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  • 1Recruiting
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• applications(array)
  • 0(array)
    • Application(array)
      • id1478
      • user_id693
      • trial_status_id(null)
      • abstract_of_study<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>BACKGROUND</strong></div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Chronic Obstructive Pulmonary Disease (COPD) was the third leading cause of death worldwide in 2019, accounting for approximately 6% of all deaths. Chronic obstructive pulmonary disease is distinguished by persistent respiratory symptoms and restricted airflow due to airway and/or alveolar abnormalities. COPD exacerbation, defined as an acute worsening of respiratory symptoms requiring additional therapy, is one of the key indicators of disease activity. Chronic obstructive pulmonary disease exacerbations represent the largest burden in terms of healthcare utilization, patient morbidity, and risk of mortality. Current COPD treatment options include non-pharmacologic and pharmacologic measures, which are insufficient to prevent symptoms or slow disease progression. Other safe and efficacious treatment modalities are desperately needed.</div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>STUDY RATIONALE</strong></div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n The purpose of this study is to assess the long-term safety and to explore the efficacy of astegolimab, a human IgG2 mAb that selectively inhibits the interleukin-33 (IL-33) receptor ST2, in participants with chronic obstructive pulmonary disease (COPD) who have completed the 52-week placebo-controlled treatment period in Phase III (GB44332) astegolimab study. The open-label design will allow assessment of the impact of longer treatment duration of astegolimab on safety, lung function, COPD exacerbations, and patient-reported outcomes (PROs).</div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>OBJECTIVES AND ENDPOINTS</strong></div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Primary Objective:</div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n To evaluate the long-term safety of astegolimab</div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Corresponding Endpoint:</div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Incidence and severity of adverse events, with severity determined according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (hereafter referred to as the DAIDS Toxicity Grading Scale), with slight modifications for clarity and for alignment with internal practices</div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>OVERALL DESIGN AND STUDY POPULATION</strong></div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n This is a Phase III multicenter, single group open-label extension (OLE) study to evaluate the long-term safety and explore the efficacy of astegolimab (RO7187807) in combination with standard of care (SOC). The study population will be adults aged 40-90 years (at time of consent in parent study), with Chronic obstructive pulmonary disease (COPD). Approximately 2,000 participants with COPD are expected to be enrolled globally, with the sites targeting approximately five patients with COPD who have completed the 52-week treatment period in Study GB44332 and fulfill the eligibility criteria for the OLE, for enrolment.</div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Patients who have discontinued treatment in the parent study will not be eligible to enroll into the OLE.</div>\n
      • study_title<p>\n <span style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">A PHASE III OPEN-LABEL EXTENSION STUDY TO EVALUATE THE LONG-TERM SAFETY OF ASTEGOLIMAB IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE</span></p>\n
      • laymans_summary<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Chronic Obstructive Pulmonary Disease (COPD) is a long-term lung disease that mostly affects older people who have smoked cigarettes in the past or have been exposed to or breathed in other harmful particles for a long time, like smoke from biomass fuels. It is the third leading cause of death worldwide, and the number of people who have it is growing around the world. Even though smoking cigarettes has always been the biggest risk factor for COPD, there is clear evidence that non-smokers can also get the disease.</div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n The risk of COPD goes up with age, and most people with COPD are 40 years old or older. Men are more likely to have COPD than women. COPD is a disease that affects different people in different ways and gets worse over time. The progression of the disease is strongly linked to thickening and narrowing of the airway walls, reducing the lungs' ability to stretch and reducing airflow. Patients withn COPD will present with some of the following signs and symptoms; Cough, shortness of breath and production of a thick mixture of saliva and mucus (sputum) coughed from the airways.</div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n As symptoms worsen and the disease progresses, the likelihood of death increases. Current existing treatments have been unable to significantly slow down the progression of the disease and prevent episodes of worsened symptoms. New, more effective ways to treat patients that will relieve their symptoms and change the course of the disease are urgently needed.</div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Astegolimab is a drug that is under investigation for the treatment of patients with COPD. It has been noted to potentially prevent the worsening of symptoms and improve lung function and quality of life for the respective patient populations. This study will look at the long term safety and how well astegolimab works in people with COPD who have used the drug for 1 year in a previous study.</div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n If found to be safe and efficacious, astegolimab will be recommended for market registration to make it commercially available locally so that people with COPD can have access to the drug in the market, subject to approval by relevant health authorities.</div>\n
      • short_titleALNASA
      • protocol_noECCT/24/10/01
      • version_no2
      • date_of_protocol03-04-2023
      • study_drugAstegolimab (RO7187807)
      • disease_conditionChronic Obstructive Pulmonary Disease (COPD)
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals1
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressPPDSubmissionsMembers.SM@ppd.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantPhoebe Mercy Otieno
      • declaration_date111-10-2024
      • declaration_principal_investigatorProf. Nduba
      • declaration_date211-10-2024
      • placebo_presentNo
      • study_objectives<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Primary Objective</strong></div>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n To evaluate the long-term safety of astegolimab</li>\n</ul>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Exploratory Objectives</strong></div>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n To evaluate the efficacy of astegolimab</li>\n <li style=\"line-height: 20px;\">\n To evaluate health status utility scores of participants treated with astegolimab</li>\n <li style=\"line-height: 20px;\">\n To evaluate the long-term safety of astegolimab</li>\n <li style=\"line-height: 20px;\">\n To characterize the PK profile of astegolimab</li>\n <li style=\"line-height: 20px;\">\n To evaluate the immune response to astegolimab</li>\n <li style=\"line-height: 20px;\">\n To identify and/or evaluate biomarkers that are predictive of response to astegolimab (i.e., predictive biomarkers), are early surrogates of efficacy, are associated with progression to a more severe disease state (i.e., prognostic biomarkers), can provide evidence of astegolimab activity (i.e., PD biomarkers), or can increase the knowledge and understanding of disease biology and drug safety or pharmacokinetics</li>\n</ul>\n
      • principal_inclusion_criteria<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Signed Informed Consent Form.</li>\n <li style=\"line-height: 20px;\">\n Ability to comply with the requirements of the study protocol, according to the investigator’s best judgment.</li>\n <li style=\"line-height: 20px;\">\n Completion of the 52-week treatment period in either Study GB43311 or Study GB44332. For patients in Study GB43311 eligible for the additional treatment period: Continued participation in the additional treatment period up to local availability of the OLE is required.</li>\n <li style=\"line-height: 20px;\">\n For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception. Women must remain abstinent or use contraceptive methods with a failure rate of < 1% per year during the treatment period and for 12 weeks after the final dose of astegolimab. A woman is considered to be of childbearing potential if she is postmenarchal, has not reached apostmenopausal state (at least12 continuous months of amenorrhea with no identified cause other than menopause), and is not permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, and/or uterus) or another cause as determined by the investigator (e.g., Mü llerian agenesis). The definition of childbearingpotential may be adapted for alignment with local guidelines or regulations. Examples of contraceptive methods with a failure rate of < 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-release intrauterine devices, and copper intrauterine devices. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of contraception. If required per local guidelines or regulations, locally recognized adequate methods of contraception and information about the reliability of abstinence will be described in the local Informed Consent Form.</li>\n</ul>\n
      • principal_exclusion_criteria<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Withdrawal of consent and/or premature discontinuation from parent study</li>\n <li style=\"line-height: 20px;\">\n Any permanent discontinuation of study drug in parent study</li>\n <li style=\"line-height: 20px;\">\n Significant non-compliance in the parent study, specifically defined as missing scheduled visits, per investigator’s judgment.</li>\n <li style=\"line-height: 20px;\">\n Pregnant or breastfeeding, or intending to become pregnant during the study or within 12 weeks after the final dose of study drug.\\</li>\n <li style=\"line-height: 20px;\">\n Any new diagnosis of asthma according to the Global Initiative for Asthma guidelines or other accepted guidelines since enrolling in the parent study</li>\n</ul>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Any new clinically significant pulmonary disease other than COPD (e.g., pulmonary fibrosis, sarcoidosis, chronic pulmonary embolism or primary pulmonary hypertension, alpha-1-antitrypsin deficiency) since enrolling in the parent study.</li>\n </ul>\n <div>\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Treatment with a licensed respiratory biologic agent (e.g., omalizumab, dupilumab, and/or anti-IL-5 therapies) at the time of study entry.</li>\n <li style=\"line-height: 20px;\">\n Initiation of treatment that is considered palliative (e.g., for life expectancy < 12 months) since enrolling in the parent study.</li>\n <li style=\"line-height: 20px;\">\n History of severe allergic reaction or anaphylactic reaction to any biologic agent or known hypersensitivity to any component of astegolimab.</li>\n <li style=\"line-height: 20px;\">\n Any other new serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study since enrolling in the parent study.</li>\n <li style=\"line-height: 20px;\">\n Any new unstable cardiac disease, myocardial infarction, or New York Heart Association Class III or IV heart failure since enrolling in the parent study</li>\n <li style=\"line-height: 20px;\">\n Any new abnormal ECG that is deemed clinically significant by the investigator, including complete left bundle branch block or second- or third-degree atrioventricular heart block since enrolling in the parent study</li>\n <li style=\"line-height: 20px;\">\n QT interval corrected through use of Fredericia’s formula (QTcF) > 450ms if patient is male of QTcF > 470ms if patient is female. For male or female patients with QRS > 120ms: QTcF > 480ms</li>\n </ul>\n </div>\n</div>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n
      • primary_end_points<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Primary Objective Endpoints</strong></div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Incidence and severity of all adverse events, including SAEs, AESIs and AEs leading to death or discontinuation. Severity determined according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (HHS 2017) (hereafter referred to as the DAIDS Toxicity Grading Scale), with slight modifications for clarity and for alignment with internal practices</div>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy0
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p>\n <span style=\"font-family:arial,helvetica,sans-serif;\"><span style=\"font-size:12px;\">KEMRI/CRDR Nairobi clinical research annex is located within the KNH complex. This facility has several clinical rooms available for consenting, nursing procedures, clinical exams, and dosing. There are also additional facilities that include 3 bed male and female inpatient ward for admission when required, staff work areas, a monitoring space, a pharmacy, a conference board room, a laboratory, and kitchen for preparing participant meals. Site staff include the principal investigator, 5 medical officers, 3 pharmacists, 1 pharm tech, 8 nurses, 9 lab personnel, 5 quality assurance officers, 10 clinical officers, 3 administrators and 13 community health workers.</span></span></p>\n
      • other_details_explanation<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">Switzerland is the host country and we already received approval in Switzerland. CEC and RA approvals were received on 17-Sep-2024</span></p>\n
      • other_details_regulatory_notapproved<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" font-size:=\"\" style=\"max-width: 100%; border-collapse: collapse; border-spacing: 0px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\" width=\"589\" width:=\"\">\n <tbody>\n <tr>\n <td colspan=\"3\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 589px; height: 21px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>INDIA                                                                                DATE SUBMITTED</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 287px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Competent Authority</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 141px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 30-Apr-2024</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 161px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Pending</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 589px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 287px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>C</strong><strong>HINA</strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 141px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n To be submitted</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 161px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n To be submitted</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 287px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>B</strong><strong>RAZIL</strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 141px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n  </p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 161px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n  </p>\n </td>\n </tr>\n </tbody>\n</table>\n<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" font-size:=\"\" style=\"max-width: 100%; border-collapse: collapse; border-spacing: 0px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\" width=\"589\" width:=\"\">\n <tbody>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 287px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Competent Authority</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 141px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 16-May-2024</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 161px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Pending</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 287px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>K</strong><strong>ENYA</strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 141px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n  </p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 161px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 287px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Competent Authority</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 141px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 13-Jun-2024 (first site)</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 161px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Pending</p>\n </td>\n </tr>\n </tbody>\n</table>\n<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" font-size:=\"\" style=\"max-width: 100%; border-collapse: collapse; border-spacing: 0px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\" width=\"589\" width:=\"\">\n <tbody>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 287px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>P</strong><strong>ERU</strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 141px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n  </p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 161px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 287px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Competent Authority</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 141px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 15-Mar-2024 (first site)</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 161px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Pending</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 287px; height: 18px;\">\n  </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 141px; height: 18px;\">\n  </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 161px; height: 18px;\">\n  </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_regulatory_approved<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" font-size:=\"\" style=\"max-width: 100%; border-collapse: collapse; border-spacing: 0px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\" width=\"589\" width:=\"\">\n <tbody>\n <tr>\n <td colspan=\"3\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 589px; height: 37px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>List of Competent Authorities inside the EU/EEA to which the Application Approved</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 37px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Member State </strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 37px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Date Submitted</strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 37px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Outcome Date</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 107px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>EU</strong> <strong>CTR</strong></p>\n <p style=\"margin: 0px 0px 10px;\">\n BELGIUM (11 sites), BULGARIA(25 sites), CZECH REPUBLIC (10sites), DENMARK (6sites), FRANCE (7sites), GERMANY (30sites), NETHERLANDS (5 sites), POLAND (36sites) , ROMANIA (4 sites), SPAIN (16sites), SWEDEN (6sites)</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 107px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 30-May-2023</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 107px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Approved, 2-Oct2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 107px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>EU</strong> <strong>CTR</strong></p>\n <p style=\"margin: 0px 0px 10px;\">\n GREECE, HUNGARY, ITALY, LATVIA, AUSTRIA</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 107px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 25-Jun-2024</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 107px;\">\n <p style=\"margin: 0px 0px 10px;\">\n  </p>\n <p style=\"margin: 0px 0px 10px;\">\n GREECE – Approved, 18-Sep2024</p>\n <p style=\"margin: 0px 0px 10px;\">\n HUNGARY - Approved, 03-Sep2024</p>\n <p style=\"margin: 0px 0px 10px;\">\n ITALY - Approved, 16-Sep2024</p>\n <p style=\"margin: 0px 0px 10px;\">\n LATVIA - Approved, 17-Sep2024</p>\n <p style=\"margin: 0px 0px 10px;\">\n AUSTRIA - Approved, 22Sep2024</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n<p>\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>List of Competent Authorities outside the EU/EEA to which the Application has been approved</strong></p>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" font-size:=\"\" style=\"max-width: 100%; border-collapse: collapse; border-spacing: 0px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\" width=\"589\" width:=\"\">\n <tbody>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 37px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Country</strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 37px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Date Submitted</strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 37px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Outcome Date</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>UNITED KINGDOM (17sites)</strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 18px;\">\n  </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 18px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 36px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Competent Authority</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 36px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 25-May-2023</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 36px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Approved, 31-Aug2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>ARGENTINA (40sites)</strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 18px;\">\n  </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 18px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Competent Authority</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 22-Jun-2023</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 11-Sep-2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>AUSTRALIA (4 sites)</strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 18px;\">\n  </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 18px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 37px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Competent Authority</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 37px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 02-Jun-2023</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 37px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Approved, 15-Jun2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 19px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>CHILE (10sites)</strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 19px;\">\n  </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 19px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 37px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Competent Authority</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 37px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 18-Oct-2023</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 37px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Approved, 20-Dec2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 19px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>HONG KONG (1 site)</strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 19px;\">\n  </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 19px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 37px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Competent Authority</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 37px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 24-Aug-2023</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 37px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Approved, 21-Nov2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 21px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>MEXICO (4 sites)</strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 21px;\">\n  </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 21px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 37px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Competent Authority</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 37px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 28-Jul-2023 </p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 37px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Approved, 6-Nov-2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>CANADA (14sites)</strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 18px;\">\n  </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 18px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 36px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Competent Authority</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 36px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 24-May-2023</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 36px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Approved, 23-Jun2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>NEW ZEALAND (7sites)</strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 18px;\">\n  </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 18px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 36px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Competent Authority</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 36px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 14-Jun-2023</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 36px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Approved, 7-Jul2023</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" font-size:=\"\" style=\"max-width: 100%; border-collapse: collapse; border-spacing: 0px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\" width=\"589\" width:=\"\">\n <tbody>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 37px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Country</strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 37px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Date Submitted</strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 37px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Outcome Date</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>SOUTH AFRICA (15sites)</strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 18px;\">\n  </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 18px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 36px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Competent Authority</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 36px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 30-May-2023</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 36px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Approved,12-Sep2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>SOUTH KOREA (13sites)</strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 18px;\">\n  </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 18px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 36px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Competent Authority</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 36px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 9-Jun-2023</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 36px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Approved, 10Oct2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>UNITED STATES OF AMERICA (74sites)</strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 18px;\">\n  </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 18px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Competent Authority</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 13-Feb-2023</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Approved </p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 589px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>TAIWAN (6sites)</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Competent Authority</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 29-Mar-2024</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Approved,28-May2024</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 589px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>TURKEY (3sites)</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Competent Authority</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 20-Mar-2024</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Approved，9 Aug2024</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>S</strong><strong>WITZERLAND (1site)</strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n  </p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Competent Authority</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 29-Jul-2024</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Approved,16-Sep2024</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>T</strong><strong>HAILAND (2 sites)</strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n  </p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 161px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Competent Authority</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 18px;\">\n  </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 18px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 21-May-2024</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 18px;\">\n <strong>Philippines</strong></td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 287px; height: 18px;\">\n 18Apr2024</td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 141px; height: 18px;\">\n 23Sep2024</td>\n </tr>\n </tbody>\n</table>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n
      • other_details_regulatory_rejected<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">Not applicable. None of the Regulatory Authorities or Ethics Committees have rejected this trial.</span></p>\n
      • other_details_regulatory_halted<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">Not applicable.</span></p>\n
      • estimated_durationStudy participation for each individual is expected to range from 1 day to more than 51 months
      • design_controlled_randomised
      • design_controlled_open
      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
      • design_controlled_cross_over
      • design_controlled_other
      • design_controlled_specify
      • design_controlled_comparator
      • design_controlled_other_medicinal
      • design_controlled_placebo
      • design_controlled_medicinal_other
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states39
      • number_of_sites5
      • multi_country_listAUSTRALIA, CHINA,HONG KONG,INDIA,JAPAN, NEW ZEALAND, PHILIPPINES, SOUTH KOREA, TAIWAN, THAILAND, BRAZIL, ARGENTINA, CANADA, CHILE, MEXICO, PERU, AUSTRIA, BELGIUM, BULGARIA, CZECH REPUBLIC, DENMARK, FRANCE, GERMANY, GREECE, HUNGARY, ITALY, LATVIA, NETHERLANDS, POLAND, ROMANIA, SPAIN, SWEDEN, ISRAEL, KENYA, SOUTH AFRICA, SWITZERLAND, TURKEY, UNITED KINGDOM, USA
      • data_monitoring_committeeYes
      • total_enrolment_per_siteApproximately 2 participants for this site.
      • total_participants_worldwideApproximately 2000 participants
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameVidelis
      • investigator1_middle_nameNduba
      • investigator1_family_nameNzioka
      • investigator1_qualificationMedical Doctor
      • investigator1_professional_addressKenyatta National Hospital Grounds, Off Hospital Road, Behind Government Chemist, P.O. BOX 47855-00100, Nairobi, Kenya
      • investigator1_telephone+254790484654
      • investigator1_emailvnduba@gmail.com
      • organisations_transferred_Yes
      • number_participantsApproximately 18 participants
      • notification
      • approval_date21-12-2024
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted11-10-2024
      • is_child0
      • unsubmitted1
      • initial_date_submitted11-10-2024
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewers\' comments addressed satisfactorily
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-04-30 11:12:37
      • created2024-10-09 14:42:04
      • total_sites5
      • ecitizen_invoice322481
    • InvestigatorContact(array)
      • 0(array)
        • id1174
        • application_id1478
        • given_nameVidelis
        • middle_nameNduba
        • family_nameNzioka
        • qualificationMedical Doctor
        • professional_addressKenyatta National Hospital Grounds, Off Hospital Road, Behind Government Chemist, P.O. BOX 47855-00100, Nairobi, Kenya
        • telephone+254790484654
        • emailvnduba@gmail.com
        • created2024-10-09 15:03:31
        • modified2024-11-07 15:27:32
    • SiteDetail(array)
      • 0(array)
        • id1795
        • application_id1478
        • county_id47
        • site_nameKEMRI-CRDR Clinical Research Annex
        • physical_addressKenyatta National Hospital Grounds, Off Hospital Road, Behind Government Chemist, P.O. BOX 47855-00100, Nairobi, Kenya
        • contact_details+254790484654
        • contact_personProf. Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2024-10-09 15:03:31
        • modified2024-11-07 15:27:32
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 1(array)
        • id1796
        • application_id1478
        • county_id16
        • site_nameClinical Research Health Network (CREA-N)
        • physical_addressMachakos Level 5 Hospital Site P.O. Box 19 -90100 Machakos Kenya
        • contact_details+254115021107
        • contact_personDr Jacqueline Mirera
        • site_capacity(null)
        • misc(null)
        • created2024-10-10 09:21:24
        • modified2024-11-07 15:27:32
        • County(array)
          • id16
          • county_nameMachakos
          • created2012-06-15 10:23:55
          • modified2012-06-15 10:23:55
      • 2(array)
        • id1797
        • application_id1478
        • county_id47
        • site_nameCenter for Research In Tropical Medicine and Community Development
        • physical_addressP.O. Box 6387, Thika, Kenya
        • contact_details+254722425613
        • contact_personDr Jesse Gitaka
        • site_capacity(null)
        • misc(null)
        • created2024-10-10 09:22:49
        • modified2024-11-07 15:27:32
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 3(array)
        • id1798
        • application_id1478
        • county_id3
        • site_nameKEMRI-Mtwapa Clinical Annex
        • physical_addressP.O. Box 428-80108, Mtwapa
        • contact_details+254722523370
        • contact_personDr Mary Matilu
        • site_capacity(null)
        • misc(null)
        • created2024-10-10 09:24:15
        • modified2024-11-07 15:27:32
        • County(array)
          • id3
          • county_nameKilifi
          • created2012-05-31 16:15:49
          • modified2012-05-31 16:15:49
      • 4(array)
        • id1799
        • application_id1478
        • county_id47
        • site_nameUniversity of Nairobi Clinical Research Centre
        • physical_addressProf Mungai Road Off Wasawo Drive Off Riverside Drive Chiromo Campus University Of Nairobi P.O. Box 19676 00202 Nairobi Kenya
        • contact_details+254 707028067
        • contact_personDr Teresa Kinyari
        • site_capacity(null)
        • misc(null)
        • created2024-10-10 09:25:23
        • modified2024-11-07 15:27:32
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
    • Sponsor(array)
      • 0(array)
        • id786
        • application_id1478
        • sponsorF. Hoffmann-La Roche Ltd
        • sponsor_typeIndustry
        • contact_personHeather Schofield
        • addressGrenzacherstrasse 124, 4070 Basel, Switzerland
        • telephone_number+ 41 6168 81111
        • fax_numberNot available
        • cell_number+41 61 688 1111
        • email_addressglobal.eudract@roche.com
        • created2024-10-09 15:03:31
        • modified2024-11-07 15:27:32
  • 1(array)
    • Application(array)
      • id1336
      • user_id622
      • trial_status_id6
      • abstract_of_study<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\"><span style=\"color: rgb(0, 0, 0);\"><strong>PROTOCOL NUMBER</strong>: </span><span style=\"color: rgb(34, 34, 34);\">BO42452</span></span></span></div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\"><span style=\"color: rgb(0, 0, 0);\"><strong>STUDY NAME:</strong> Crosswalk A</span></span></span></div>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\"><span style=\"color: rgb(0, 0, 0);\"><strong>VERSION NUMBER</strong>: 3</span> (Africa)</span></span></div>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\"><span style=\"color: rgb(0, 0, 0);\"><strong>TEST COMPOUND(S)</strong>: </span>Crovalimab (RO7112689)</span></span></div>\n <div>\n  </div>\n <div>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">This randomized, multicenter, placebo-controlled, double-blinded Phase Ib study is designed to evaluate the safety (primary study objective), pharmacokinetics, pharmacodynamics, and efficacy of crovalimab compared with placebo for the management of an acute uncomplicated VOE in adult and adolescent patients with SCD.</span></span></div>\n <div>\n  </div>\n </div>\n</div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">This study will enroll approximately 30 patients (at approximately 10-15 sites globally), aged 12-55 years old and more than or equal to 40 kg, with SCD genotype of sickle cell anemia (HbSS) or SCD genotype of sickle cell beta zero thalassemia, presenting to the emergency room/emergency department (ER/ED) or acute medical facility with an acute uncomplicated VOE, defined as an acute episode of pain with no other medically determined cause, that requires admission to a hospital/acute medical facility and treatment with parenteral opioid analgesics.</span></span></div>\n <div>\n  </div>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">A 2-step process for screening procedures is encouraged to preliminarily identify and consent patients for the study prior to VOE presentation:</span></span></div>\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Screen Visit #1 (initial screen) is conducted at an outpatient visit (i.e., when the patient is not experiencing a VOE), where the main Informed Consent Form (ICF) is signed, and preliminary eligibility is assessed. During this visit, preliminary screening assessments can be conducted, and a steady state SCD exploratory biomarker sample will be collected (only after consent is received). Eligibility at Screen Visit #1 does not guarantee eligibility at Screen Visit #2.</span></span></li>\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Screen Visit #2 (VOE presentation screen) is then conducted when the patient presents with a VOE to the ER/ED or acute medical facility. The patient consent from Screen Visit #1 must be confirmed prior to starting study assessments (this confirmation must be documented). Once patient consent is confirmed all remaining eligibility criteria must be assessed, and all screening assessments will be conducted.</span></span></li>\n </ul>\n</div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\"><strong>NUMBER OF PATIENTS</strong></span></span></div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Approximately 30 patients (20 on crovalimab and 10 on placebo).</span></span></div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\"><strong>END OF STUDY</strong></span></span></div>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">The end of this study is defined as the date when the last patient’s last visit occurs, or the date at which the last data point is received from the last patient on study, whichever occurs later. The end of the study is expected to occur approximately 322 days or approximately 10.5 months after the last patient is enrolled.</span></span></div>\n <div>\n  </div>\n <div>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\"><strong>LENGTH OF STUDY</strong></span></span></div>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Assuming an enrollment period of approximately 2 years, the total length of the study, from screening of the first patient in the ER/ED or acute medical facility to the end of the study, is expected to be approximately 3 years.</span></span></div>\n </div>\n</div>\n<p>\n  </p>\n
      • study_title<p>\n <span style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">A PHASE IB, RANDOMIZED, PLACEBO-CONTROLLED STUDY EVALUATING THE SAFETY, PHARMACOKINETICS, PHARMACODYNAMICS, AND EFFICACY OF CROVALIMAB FOR THE MANAGEMENT OF ACUTE UNCOMPLICATED VASO‑OCCLUSIVE EPISODES (VOE) IN PATIENTS WITH SICKLE CELL DISEASE (SCD)</span></p>\n
      • laymans_summary<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">This randomized, multicenter, placebo-controlled, double-blinded Phase Ib study is designed to evaluate the safety (primary study objective), pharmacokinetics, pharmacodynamics, and efficacy of crovalimab compared with placebo for the management of an acute uncomplicated VOE in adult and adolescent patients with SCD.</span></span></div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">This study will enroll approximately 30 patients (at approximately 10-15 sites globally), aged 12-55 years old and more than or equal to 40 kg, with SCD genotype of HbSS or HbS </span></span>beta zero thalassemia<span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">, presenting to the ER/ED or acute medical facility with an acute uncomplicated VOE (as defined in Section 2.4.1 of the protocol).</span></span></div>\n <div>\n  </div>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Patients who present with acute complications such as ACS, priapism, hepatic or splenic sequestration etc., or present with pain atypical of or unrelated to an acute uncomplicated VOE will be excluded at screening.</span></span></div>\n <div>\n  </div>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Complications of the VOE that develop after study treatment administration and during hospitalization will be documented. Patients who develop complications after screening, but before study treatment administration, may no longer be eligible.</span></span></div>\n</div>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n  </p>\n
      • short_titleCROSSWALK Acute (A)
      • protocol_noECCT/23/11/02
      • version_no3 (Africa)
      • date_of_protocol06-02-2023
      • study_drugCrovalimab (RO7112689)
      • disease_conditionSickle Cell Disease (SCD)
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals1
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorYes
      • comparator_namePlacebo
      • comparator_registeredN/A
      • comparator_countriesN/A
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressfaith.wanjau@roche.con
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantDr. Faith Wanjau
      • declaration_date130-10-2023
      • declaration_principal_investigatorProf. Fredrick Chite Asirwa
      • declaration_date230-10-2023
      • placebo_presentYes
      • study_objectives<p>\n  </p>\n<table class=\"table table-condensed\" font-size:=\"\" style=\"max-width: 100%; border-collapse: collapse; border-spacing: 0px; width: 917.271px; margin-bottom: 20px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <tbody>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221);\">\n <p style=\"margin: 0px 0px 10px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">This study will evaluate the safety, pharmacokinetics, pharmacodynamics, and efficacy of crovalimab compared with placebo for the management of acute uncomplicated VOE in patients with SCD.</span></span></p>\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">The safety objective for this study is to evaluate the safety of crovalimab compared with placebo on the basis of the following endpoints:</span></span></li>\n </ul>\n <p style=\"margin: 0px 0px 10px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">- Incidence and severity of adverse events, with severity determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.0 (CTCAE v5.0)</span></span></p>\n <p style=\"margin: 0px 0px 10px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">- Change from baseline in targeted vital signs and clinical laboratory test results</span></span></p>\n <p style=\"margin: 0px 0px 10px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">- Incidence and severity of infusion-related reactions and hypersensitivity</span></span></p>\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">The PK objective for this study is to characterize the crovalimab PK profile on the basis of the following endpoints:</span></span></li>\n </ul>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">- Serum concentrations of crovalimab over time</span></span></div>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">- Relationships between drug exposure and pharmacodynamics, efficacy or safety endpoints of crovalimab (patients randomized to crovalimab)</span></span></div>\n <div>\n  </div>\n <div>\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">The PD objective for this study is to evaluate PD biomarkers that can provide evidence of crovalimab activity, on the basis of the following endpoints:</span></span></li>\n </ul>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">- Change over time in PD biomarkers, including total complement activity (CH50) measured by a LIA, total and free complement component 5 (C5) concentration, and sC5b-9 concentration</span></span></div>\n <div>\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">The efficacy objective for this study is to characterize the efficacy of crovalimab compared with placebo on the basis of the following endpoints: Time to improvement of the primary acute uncomplicated VOE (for definition, see Section 2.4.1) from baseline, defined as the first achieved from the following criteria:</span></span></li>\n </ul>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">- Confirmed decrease in pain score of at least 2 points from the maximal pre-dose pain score, that is sustained in at least two pain assessments</span></span></div>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">conducted a minimum of 6 hours apart from each other (as measured with the Numerical Rating Scale [NRS] on a 010 scale) AND transition to oral pain</span></span></div>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">medications for a minimum of 6 hours after the completion of the last dose of</span></span></div>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">parenteral opioids, OR</span></span></div>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">- Readiness for hospital discharge (as defined by the patient’s assessment that pain can be managed at home AND agreement from investigator), OR</span></span></div>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">- Hospital discharge</span></span></div>\n <ol style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Total cumulative opioid dose (parenteral and oral) in morphine equivalents per kilogram units (MEU/kg) from baseline to the time of acute uncomplicated VOE improvement</span></span></li>\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Time to discontinuation of all parenteral opioids from baseline (defined as time from baseline to the completion of the last dose of parenteral opioids)</span></span></li>\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Time to readiness for hospital discharge from baseline</span></span></li>\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Time to hospital discharge from baseline</span></span></li>\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Time to a confirmed decrease in pain score of at least 2 points from the maximal pre-dose pain score, that is sustained in at least two assessments conducted a minimum of 6 hours apart from each other, as measured with the NRS on a 010 scale</span></span></li>\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Change in pain score from the maximal pre-dose pain score to the score at hospital discharge, as measured with the NRS on a 010 scale</span></span></li>\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Proportion of patients who develop ACS from baseline to Day 28</span></span></li>\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Proportion of patients requiring intensive care unit (ICU)/critical care admission for SCD-related complications from baseline to the time of hospital discharge</span></span></li>\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Proportion of patients requiring blood transfusion for SCD-related complications from baseline to the time of hospital discharge</span></span></li>\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Readmission rate for a VOE or VOE-related event within 28 days of discharge of the primary acute uncomplicated VOE</span></span></li>\n </ol>\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">The immunogenicity objective for this study is to evaluate the immune response to crovalimab on the basis of the following endpoints:</span></span></li>\n </ul>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">- Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs during the study (patients randomized to crovalimab)</span></span></div>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">- Potential effects of ADAs on efficacy, safety, or PK endpoints</span></span></div>\n <div>\n  </div>\n <div>\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">The exploratory biomarker objective for this study is to identify and/or evaluate biomarkers that are predictive of response to crovalimab (i.e., predictive biomarkers), are early surrogates of efficacy, are associated with progression to a more severe disease state (i.e., prognostic biomarkers), are associated with resistance to crovalimab, are associated with susceptibility to developing adverse events or can lead to improved adverse event monitoring or investigation (i.e., safety biomarkers), or can increase the knowledge and understanding of disease biology and drug safety, on the basis of the following endpoints:</span></span></li>\n </ul>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">- Observed value and change over time in exploratory biomarkers including but not limited to markers of hemolysis, immune cell activation, inflammation, endothelial/vascular damage, and end-organ injury</span></span></div>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">- Relationship between biomarkers in blood and efficacy, safety, pharmacokinetics, immunogenicity, or other biomarker endpoints</span></span></div>\n </div>\n </div>\n </div>\n </td>\n </tr>\n </tbody>\n</table>\n<table class=\"table table-condensed\" font-size:=\"\" style=\"max-width: 100%; border-collapse: collapse; border-spacing: 0px; width: 917.271px; margin-bottom: 20px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <tbody>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221);\">\n <p style=\"margin: 0px 0px 10px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">This study will evaluate the safety, pharmacokinetics, pharmacodynamics, and efficacy of crovalimab compared with placebo for the management of acute uncomplicated VOE in patients with SCD.</span></span></p>\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">The safety objective for this study is to evaluate the safety of crovalimab compared with placebo on the basis of the following endpoints:</span></span></li>\n </ul>\n <p style=\"margin: 0px 0px 10px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">- Incidence and severity of adverse events, with severity determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.0 (CTCAE v5.0)</span></span></p>\n <p style=\"margin: 0px 0px 10px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">- Change from baseline in targeted vital signs and clinical laboratory test results</span></span></p>\n <p style=\"margin: 0px 0px 10px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">- Incidence and severity of infusion-related reactions and hypersensitivity</span></span></p>\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">The PK objective for this study is to characterize the crovalimab PK profile on the basis of the following endpoints:</span></span></li>\n </ul>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">- Serum concentrations of crovalimab over time</span></span></div>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">- Relationships between drug exposure and pharmacodynamics, efficacy or safety endpoints of crovalimab (patients randomized to crovalimab)</span></span></div>\n <div>\n  </div>\n <div>\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">The PD objective for this study is to evaluate PD biomarkers that can provide evidence of crovalimab activity, on the basis of the following endpoints:</span></span></li>\n </ul>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">- Change over time in PD biomarkers, including total complement activity (CH50) measured by a LIA, total and free complement component 5 (C5) concentration, and sC5b-9 concentration</span></span></div>\n <div>\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">The efficacy objective for this study is to characterize the efficacy of crovalimab compared with placebo on the basis of the following endpoints: Time to improvement of the primary acute uncomplicated VOE (for definition, see Section 2.4.1) from baseline, defined as the first achieved from the following criteria:</span></span></li>\n </ul>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">- Confirmed decrease in pain score of at least 2 points from the maximal pre-dose pain score, that is sustained in at least two pain assessments</span></span></div>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">conducted a minimum of 6 hours apart from each other (as measured with the Numerical Rating Scale [NRS] on a 010 scale) AND transition to oral pain</span></span></div>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">medications for a minimum of 6 hours after the completion of the last dose of</span></span></div>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">parenteral opioids, OR</span></span></div>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">- Readiness for hospital discharge (as defined by the patient’s assessment that pain can be managed at home AND agreement from investigator), OR</span></span></div>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">- Hospital discharge</span></span></div>\n <ol style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Total cumulative opioid dose (parenteral and oral) in morphine equivalents per kilogram units (MEU/kg) from baseline to the time of acute uncomplicated VOE improvement</span></span></li>\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Time to discontinuation of all parenteral opioids from baseline (defined as time from baseline to the completion of the last dose of parenteral opioids)</span></span></li>\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Time to readiness for hospital discharge from baseline</span></span></li>\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Time to hospital discharge from baseline</span></span></li>\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Time to a confirmed decrease in pain score of at least 2 points from the maximal pre-dose pain score, that is sustained in at least two assessments conducted a minimum of 6 hours apart from each other, as measured with the NRS on a 010 scale</span></span></li>\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Change in pain score from the maximal pre-dose pain score to the score at hospital discharge, as measured with the NRS on a 010 scale</span></span></li>\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Proportion of patients who develop ACS from baseline to Day 28</span></span></li>\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Proportion of patients requiring intensive care unit (ICU)/critical care admission for SCD-related complications from baseline to the time of hospital discharge</span></span></li>\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Proportion of patients requiring blood transfusion for SCD-related complications from baseline to the time of hospital discharge</span></span></li>\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Readmission rate for a VOE or VOE-related event within 28 days of discharge of the primary acute uncomplicated VOE</span></span></li>\n </ol>\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">The immunogenicity objective for this study is to evaluate the immune response to crovalimab on the basis of the following endpoints:</span></span></li>\n </ul>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">- Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs during the study (patients randomized to crovalimab)</span></span></div>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">- Potential effects of ADAs on efficacy, safety, or PK endpoints</span></span></div>\n <div>\n  </div>\n <div>\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">The exploratory biomarker objective for this study is to identify and/or evaluate biomarkers that are predictive of response to crovalimab (i.e., predictive biomarkers), are early surrogates of efficacy, are associated with progression to a more severe disease state (i.e., prognostic biomarkers), are associated with resistance to crovalimab, are associated with susceptibility to developing adverse events or can lead to improved adverse event monitoring or investigation (i.e., safety biomarkers), or can increase the knowledge and understanding of disease biology and drug safety, on the basis of the following endpoints:</span></span></li>\n </ul>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">- Observed value and change over time in exploratory biomarkers including but not limited to markers of hemolysis, immune cell activation, inflammation, endothelial/vascular damage, and end-organ injury</span></span></div>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">- Relationship between biomarkers in blood and efficacy, safety, pharmacokinetics, immunogenicity, or other biomarker endpoints</span></span></div>\n </div>\n </div>\n </div>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • principal_inclusion_criteria<p 1ex=\"\" box-sizing:=\"\" color:=\"\" font-size:=\"\" helvetica=\"\" line-height:=\"\" margin:=\"\" sans=\"\" source=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Inclusion Criteria:</span></span></p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 1.6; box-sizing: border-box; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Body weight >=40 kg.</span></span></li>\n <li style=\"line-height: 1.6; box-sizing: border-box; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Male or female with confirmed diagnosis of HbSS (SCD genotype of sickle cell anemia) or HbSβ0 (SCD genotype of sickle cell beta zero thalassemia).</span></span></li>\n <li style=\"line-height: 1.6; box-sizing: border-box; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Two or more (>=2) to <=10 documented VOEs in the 12 months prior to randomisation.</span></span></li>\n <li style=\"line-height: 1.6; box-sizing: border-box; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">If receiving concurrent SCD-directed therapy, the participant must have been on a stable dose for a minimum of 3 months prior to study enrollment. There should be no plans to modify the participants' dosing throughout the study duration, other than for safety reasons.</span></span></li>\n <li style=\"line-height: 1.6; box-sizing: border-box; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">If receiving erythropoietin, the participant must have been prescribed this medication for the preceding 3 months and be dose-stabilised for at least 3 months prior to study enrollment.</span></span></li>\n <li style=\"line-height: 1.6; box-sizing: border-box; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Vaccination against N. meningitides serotypes A, C, W, and Y and Vaccinations against H. influenza type B and S. pneumonia.</span></span></li>\n <li style=\"line-height: 1.6; box-sizing: border-box; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Participants who have been vaccinated (partially or in full) against SARS-CoV-2 with a locally approved vaccine are eligible to be enrolled in the study, 3 days or longer after inoculation.</span></span></li>\n <li style=\"line-height: 1.6; box-sizing: border-box; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Adequate hepatic and renal function.</span></span></li>\n <li style=\"line-height: 1.6; box-sizing: border-box; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">For women of childbearing potential: agreement to remain abstinent or use contraception during the treatment period and for 10.5 months after the final dose of study treatment.</span></span></li>\n</ul>\n
      • principal_exclusion_criteria<p 0ex=\"\" 0px=\"\" box-sizing:=\"\" color:=\"\" font-size:=\"\" helvetica=\"\" line-height:=\"\" margin:=\"\" sans=\"\" source=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Exclusion Criteria:</span></span></p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 1.6; box-sizing: border-box; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">History of hematopoietic stem cell transplant.</span></span></li>\n <li style=\"line-height: 1.6; box-sizing: border-box; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Participating in a chronic transfusion program and/or planning on undergoing an exchange transfusion during the duration of the study.</span></span></li>\n <li style=\"line-height: 1.6; box-sizing: border-box; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">History of hypersensitivity, allergic, or anaphylactic reactions to any ingredient contained in the study treatment.</span></span></li>\n <li style=\"line-height: 1.6; box-sizing: border-box; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Received active treatment on another investigational trial within 28 days (or within five half-lives of that agent, whichever is greater) prior to screening visit, or plans to participate in another investigational drug trial.</span></span></li>\n <li style=\"line-height: 1.6; box-sizing: border-box; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Hemoglobin <6 g/dL.</span></span></li>\n <li style=\"line-height: 1.6; box-sizing: border-box; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Known or suspected hereditary complement deficiency.</span></span></li>\n <li style=\"line-height: 1.6; box-sizing: border-box; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Active systemic bacterial, viral, or fungal infection within 14 days before first drug administration.</span></span></li>\n <li style=\"line-height: 1.6; box-sizing: border-box; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Presence of fever (>=38 degrees Celsius) within 7 days before the first drug administration.</span></span></li>\n <li style=\"line-height: 1.6; box-sizing: border-box; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Immunised with a live attenuated vaccine within 1 month before first drug administration.</span></span></li>\n <li style=\"line-height: 1.6; box-sizing: border-box; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Pregnant or breastfeeding, or intending to become pregnant during the study or within 10.5 months after the final dose of study treatment.</span></span></li>\n <li style=\"line-height: 1.6; box-sizing: border-box; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">Known HIV infection with documented CD4 count <200 cells/microliter within 24 weeks prior to screening.</span></span></li>\n <li style=\"line-height: 1.6; box-sizing: border-box; margin-bottom: 4px; margin-top: 0.7ex;\">\n <span style=\"font-size: 12px;\"><span style=\"font-family: arial, helvetica, sans-serif;\">History of N. meningitidis infection within the prior 6 months.</span></span></li>\n</ul>\n
      • primary_end_points<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">This study will evaluate the safety, pharmacokinetics, pharmacodynamics, and efficacy of crovalimab compared with placebo for the management of acute uncomplicated VOE in patients with SCD.</span></p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">The safety objective for this study is to evaluate the safety of crovalimab compared with placebo on the basis of the following endpoints:</span></li>\n</ul>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">- Incidence and severity of adverse events, with severity determined according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events, Version 5.0 (CTCAE v5.0)</span></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">- Change from baseline in targeted vital signs and clinical laboratory test results</span></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">- Incidence and severity of infusion-related reactions and hypersensitivity</span></p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">The PK objective for this study is to characterize the crovalimab PK profile on the basis of the following endpoints:</span></li>\n</ul>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">- Serum concentrations of crovalimab over time</span></div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">- Relationships between drug exposure and pharmacodynamics, efficacy or safety endpoints of crovalimab (patients randomized to crovalimab)</span></div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">The PD objective for this study is to evaluate PD biomarkers that can provide evidence of crovalimab activity, on the basis of the following endpoints:</span></li>\n </ul>\n <div>\n <span style=\"font-family: arial, helvetica, sans-serif;\">- Change over time in PD biomarkers, including total complement activity (CH50) measured by a LIA, total and free complement component 5 (C5) concentration, and sC5b-9 concentration</span></div>\n <div>\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">The efficacy objective for this study is to characterize the efficacy of crovalimab compared with placebo on the basis of the following endpoints: Time to improvement of the primary acute uncomplicated VOE (for definition, see Section 2.4.1) from baseline, defined as the first achieved from the following criteria:</span></li>\n </ul>\n <div>\n <span style=\"font-family: arial, helvetica, sans-serif;\">- Confirmed decrease in pain score of at least 2 points from the maximal pre-dose pain score, that is sustained in at least two pain assessments</span></div>\n <div>\n <span style=\"font-family: arial, helvetica, sans-serif;\">conducted a minimum of 6 hours apart from each other (as measured with the Numerical Rating Scale [NRS] on a 010 scale) AND transition to oral pain</span></div>\n <div>\n <span style=\"font-family: arial, helvetica, sans-serif;\">medications for a minimum of 6 hours after the completion of the last dose of</span></div>\n <div>\n <span style=\"font-family: arial, helvetica, sans-serif;\">parenteral opioids, OR</span></div>\n <div>\n <span style=\"font-family: arial, helvetica, sans-serif;\">- Readiness for hospital discharge (as defined by the patient’s assessment that pain can be managed at home AND agreement from investigator), OR</span></div>\n <div>\n <span style=\"font-family: arial, helvetica, sans-serif;\">- Hospital discharge</span></div>\n <ol style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Total cumulative opioid dose (parenteral and oral) in morphine equivalents per kilogram units (MEU/kg) from baseline to the time of acute uncomplicated VOE improvement</span></li>\n <li style=\"line-height: 20px;\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Time to discontinuation of all parenteral opioids from baseline (defined as time from baseline to the completion of the last dose of parenteral opioids)</span></li>\n <li style=\"line-height: 20px;\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Time to readiness for hospital discharge from baseline</span></li>\n <li style=\"line-height: 20px;\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Time to hospital discharge from baseline</span></li>\n <li style=\"line-height: 20px;\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Time to a confirmed decrease in pain score of at least 2 points from the maximal pre-dose pain score, that is sustained in at least two assessments conducted a minimum of 6 hours apart from each other, as measured with the NRS on a 010 scale</span></li>\n <li style=\"line-height: 20px;\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Change in pain score from the maximal pre-dose pain score to the score at hospital discharge, as measured with the NRS on a 010 scale</span></li>\n <li style=\"line-height: 20px;\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Proportion of patients who develop ACS from baseline to Day 28</span></li>\n <li style=\"line-height: 20px;\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Proportion of patients requiring intensive care unit (ICU)/critical care admission for SCD-related complications from baseline to the time of hospital discharge</span></li>\n <li style=\"line-height: 20px;\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Proportion of patients requiring blood transfusion for SCD-related complications from baseline to the time of hospital discharge</span></li>\n <li style=\"line-height: 20px;\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">Readmission rate for a VOE or VOE-related event within 28 days of discharge of the primary acute uncomplicated VOE</span></li>\n </ol>\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">The immunogenicity objective for this study is to evaluate the immune response to crovalimab on the basis of the following endpoints:</span></li>\n </ul>\n <div>\n <span style=\"font-family: arial, helvetica, sans-serif;\">- Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs during the study (patients randomized to crovalimab)</span></div>\n <div>\n <span style=\"font-family: arial, helvetica, sans-serif;\">- Potential effects of ADAs on efficacy, safety, or PK endpoints</span></div>\n <div>\n  </div>\n <div>\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n <span style=\"font-family: arial, helvetica, sans-serif;\">The exploratory biomarker objective for this study is to identify and/or evaluate biomarkers that are predictive of response to crovalimab (i.e., predictive biomarkers), are early surrogates of efficacy, are associated with progression to a more severe disease state (i.e., prognostic biomarkers), are associated with resistance to crovalimab, are associated with susceptibility to developing adverse events or can lead to improved adverse event monitoring or investigation (i.e., safety biomarkers), or can increase the knowledge and understanding of disease biology and drug safety, on the basis of the following endpoints:</span></li>\n </ul>\n <div>\n <span style=\"font-family: arial, helvetica, sans-serif;\">- Observed value and change over time in exploratory biomarkers including but not limited to markers of hemolysis, immune cell activation, inflammation, endothelial/vascular damage, and end-organ injury</span></div>\n <div>\n <span style=\"font-family: arial, helvetica, sans-serif;\">- Relationship between biomarkers in blood and efficacy, safety, pharmacokinetics, immunogenicity, or other biomarker endpoints</span></div>\n </div>\n </div>\n</div>\n<p>\n  </p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology1
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specifyFirst administration to patients with SCD. The clinical data for crovalimab are obtained from the primary analysis of Study BP39144, a Phase I/II study designed to assess the safety, tolerability, pharmacokinetics, pharmacodynamics, and efficacy of crovalimab in healthy subjects and patients with PNH.
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">This has been elaborated in the the respective site specific addendum attached in the checklist section.</span></p>\n
      • other_details_explanation<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">Not applicable</span></p>\n
      • other_details_regulatory_notapproved<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">Not applicable</span></p>\n
      • other_details_regulatory_approved<p>\n <img src=\"https://lh3.googleusercontent.com/1YrBIrI9WfAZ_FVMOTLmwLMms0PHlEu1V12JjOpZRN0l0f1tF39n9V8IbnXaaiw2E7bdv-V1AMtYRh9yHKkiYF4_V6S9Ja7Pd5i7cFd5RPknTmKYlw1ouWTMxx8q-lXtLERqoGgYP_LyDvIJ0tA4DA\" /></p>\n
      • other_details_regulatory_rejected<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">None</span></p>\n
      • other_details_regulatory_halted<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">None</span></p>\n
      • estimated_durationAssuming an enrollment period of approximately 2 years, the total length of the study, from screening of the first patient in the ER/ED or acute medical facility to the end of the study, is expected to be approximately 3 years.
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorN/A
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states10
      • number_of_sites2 sites: ECCT/23/09/02- Gertrude\'s Childrens Hospital already submitted
      • multi_country_listBrazil France Italy Spain Turkey USA UK Netherlands South Africa Lebanon
      • data_monitoring_committeeYes
      • total_enrolment_per_site10
      • total_participants_worldwide30
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameFredrick
      • investigator1_middle_nameChite
      • investigator1_family_nameAsirwa
      • investigator1_qualificationProfessor of Hematology and Oncology
      • investigator1_professional_addressInternational Cancer Institute, Nandi Road 8/10, Eldoret, Kenya, 8088-30100
      • investigator1_telephone+254 700 522 149
      • investigator1_emaildirector@intercancer.com
      • organisations_transferred_Yes
      • number_participants10
      • notification
      • approval_date11-01-2024
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted07-11-2023
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-02-04 15:30:46
      • created2023-10-18 14:47:00
      • total_sites(null)
      • ecitizen_invoice345527
    • InvestigatorContact(array)
      • 0(array)
        • id988
        • application_id1336
        • given_nameFredrick
        • middle_nameChite
        • family_nameAsirwa
        • qualificationProfessor of Hematology and Oncology
        • professional_addressInternational Cancer Institute, Nandi Road 8/10, Eldoret, Kenya, 8088-30100
        • telephone+254 700 522 149
        • emaildirector@intercancer.com
        • created2023-10-18 14:48:29
        • modified2023-11-07 12:43:56
    • SiteDetail(array)
      • 0(array)
        • id1613
        • application_id1336
        • county_id27
        • site_nameIn this submission: International Cancer Institute
        • physical_address Nandi Road 8/10, Eldoret, Kenya, 8088-30100
        • contact_details+254 700 522 149
        • contact_personProf. Fredrick Chite Asirwa
        • site_capacity(null)
        • misc(null)
        • created2023-10-18 14:48:29
        • modified2023-11-07 12:43:56
        • County(array)
          • id27
          • county_nameUasin Gishu
          • created2012-06-15 10:25:15
          • modified2012-06-15 10:25:15
    • Sponsor(array)
      • 0(array)
        • id702
        • application_id1336
        • sponsorHoffmann La Roche
        • sponsor_typeIndustry
        • contact_personDr. Eileen Koske
        • addressP.O. Box 44212-00100 Nairobi, Kenya
        • telephone_number+254 721375237
        • fax_number
        • cell_number+254 721375237
        • email_addresseileen.koske@roche.com
        • created2023-10-18 14:48:29
        • modified2023-11-07 12:43:56
  • 2(array)
    • Application(array)
      • id1391
      • user_id263
      • trial_status_id1
      • abstract_of_study<p class=\"SynchrogenixBodyText\">\n <span lang=\"EN-US\">Modeling suggests that the most effective contribution to TB control in high burden countries would be a vaccine that prevents pulmonary TB in adolescents and adults [</span><!--[if supportFields]><span\nlang=EN-US style=\'color:blue\'><span style=\'mso-element:field-begin\'></span></span><span\nlang=EN-US> REF WHO_2021 \\h <span style=\'color:blue\'><span style=\'mso-element:\nfield-separator\'></span></span></span><![endif]--><span lang=\"EN-US\" style=\"color:blue\">WHO<!--[if gte mso 9]><xml>\n <w:data>08D0C9EA79F9BACE118C8200AA004BA90B020000000800000009000000570048004F005F0032003000320031000000</w:data>\n</xml><![endif]--></span><!--[if supportFields]><span lang=EN-US\nstyle=\'color:blue\'><span style=\'mso-element:field-end\'></span></span><![endif]--><span lang=\"EN-US\" style=\"color:blue\">2021</span><span lang=\"EN-US\">]. In very high incidence geographies, the incidence rate of TB is highest in older adolescents and young adults (e.g., 15 to 44 years of age). In addition, pulmonary TB is the predominant form of TB in this age group (with the primary mode of TB transmission being via aerosol), and young adults are more likely to transmit to more contacts because they are active and mix extensively [</span><!--[if supportFields]><span\nlang=EN-US style=\'color:blue\'><span style=\'mso-element:field-begin\'></span> REF\nKnight_2014 \\h <span style=\'mso-element:field-separator\'></span></span><![endif]--><span lang=\"EN-US\" style=\"color:blue\">Knight<!--[if gte mso 9]><xml>\n <w:data>08D0C9EA79F9BACE118C8200AA004BA90B02000000080000000C0000004B006E0069006700680074005F0032003000310034000000</w:data>\n</xml><![endif]--></span><!--[if supportFields]><span lang=EN-US\nstyle=\'color:blue\'><span style=\'mso-element:field-end\'></span></span><![endif]--><span lang=\"EN-US\" style=\"color:blue\">2014</span><span lang=\"EN-US\">].</span></p>\n<p class=\"SynchrogenixBodyText\">\n The primary objective of this Phase 3 efficacy trial is to evaluate VE in the prevention of laboratory-confirmed pulmonary TB in IGRA-positive participants who do not have HIV. The rationale for focusing on IGRA-positive participants is based on Phase 3 trial simulations that evaluated the feasibility of demonstrating VE in an “all-comer” population (i.e., regardless of IGRA status) of young adults (15 to 44 years of age) in very high burden settings with an IGRA-positive prevalence of 67%. Based on these simulations, it appears feasible to demonstrate vaccine efficacy against tuberculosis disease (VE[D]) in an IGRA-positive, HIV-negative population, with a sample size of <span class=\"msoIns\"><ins cite=\"mailto:Debbie%20Daehnick%20(DT%20Medical%20Writing%20Corp)\" datetime=\"2024-01-08T12:19\">9</ins></span>,000 participants per arm, within 4 years from start of enrollment, whereas a trial in an all-comer population would have to be much larger, and the larger population would still be inadequate to demonstrate VE(D) in IGRA-negative participants.</p>\n<p>\n Trial simulation assumptions included an annual IGRA conversion rate of 3% per person-year, and an incidence of active pulmonary TB of 0.4% per person-year. These simulations suggested that even with a 67% IGRA-positive prevalence at enrollment, more than 90% of laboratory-confirmed cases of TB would be observed in IGRA-positive participants, and less than 10% in IGRA-negative participants; such a trial would not be powered to demonstrate VE(D) in IGRA-negative participants as a subset.</p>\n<p>\n A confirmatory trial in IGRA-negative participants is not considered feasible (in a reasonable amount of time and with a reasonable population size), given the low rate of laboratory-confirmed cases expected in baseline IGRA-negative participants. Given the inability to demonstrate VE(D) in IGRA-negative participants as a subset in an ‘all-comer’ trial, this Phase 3 trial aims to demonstrate VE(D) in IGRA-positive participants only, and to generate descriptive safety, immunogenicity, and VE(D) data in a HIV-negative, IGRA-negative Cohort  (N=1,000) and in a cohort of PLHIV (N=1,000) of either positive or negative IGRA status.</p>\n<p>\n GlaxoSmithKline Biologicals, SA (GSK) developed M72/AS01_E-4, an investigational TB vaccine, to protect against the development of TB in <em>Mtb</em>-infected adolescents and adults. The GSK Phase 2b trial (TB-018) evaluated vaccine safety and efficacy in approximately 3500 IGRA-positive adults (1:1, M72/AS01_E-4and placebo) [Van Der Meeren2018; Tait2019]. Most participants in the TB-018 trial had previously received the BCG vaccine as neonates. The observed VE against active pulmonary TB in the Phase 2b trial was 49.7% (95% CI: 2.1% to 74.2%) at 36 months and no safety signals that would prevent further development were observed [Tait2019].</p>\n<p>\n In 2020, the Bill & Melinda Gates Medical Research Institute (Gates MRI) licensed the M72/AS01_E-4investigational TB vaccine for continued development.</p>\n<p>\n  </p>\n<p class=\"SynchrogenixBodyText\">\n  </p>\n<p class=\"SynchrogenixBodyText\">\n <span lang=\"EN-US\"><o:p></o:p></span></p>\n<p class=\"SynchrogenixBodyText\">\n <span lang=\"EN-US\"><o:p></o:p></span></p>\n
      • study_title<p>\n <span style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">A Phase 3, randomized, double-blind, placebo-controlled, multicenter, clinical trial to assess the prophylactic efficacy, safety, and immunogenicity of the investigational M72/AS01</span><span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif;\">E-4</span><span style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\"> Mycobacterium tuberculosis (Mtb) vaccine when administered intramuscularly on a 0,1-month schedule to adolescents and adults.</span></p>\n
      • laymans_summary<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Tuberculosis (TB) is caused by the bacterium Mycobacterium tuberculosis (Mtb); it typically affects the lungs but can also affect other sites. TB is spread from person to person via the respiratory route and is manifested by the presence of Mtb in sputum. TB is the second leading infectious killer after COVID-19 (above HIV/AIDS). It is present in all countries and age groups, but the larger number of new cases occur in countries of the South-East Asian Region and African Region.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Bacille Calmette-Guérin, known as BCG, is the only licensed TB vaccine to date; however, the impact of BCG on the transmission of Mtb in adults is limited, since it offers minimal or no protection against pulmonary TB in adults. TB treatment is lengthy, and compliance is often incomplete, resulting in an increasing incidence of multi-drug resistant (MDR)-TB and extensively drug resistant (XDR)-TB.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Given the substantial morbidity and mortality associated with TB, the challenges associated with TB treatment, and the limited options for prevention, a vaccine is urgently needed, both to protect against disease, including the progression from latent Mtb infection to active TB, and to accelerate the end of the TB epidemic.</p>\n
      • short_titleGates MRI TBV02-301
      • protocol_noECCT/24/03/07
      • version_no2.0
      • date_of_protocol08-01-2024
      • study_drugM72/AS01E-4 investigational vaccine
      • disease_conditionTuberculosis (TB)
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorNo
      • comparator_nameN/A
      • comparator_registeredN/A
      • comparator_countriesN/A
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressamina.salim@iqvia.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantMaureen Anyango Olwero
      • declaration_date128-03-2024
      • declaration_principal_investigatorProf. Walter Jaoko _ PI - KAVI – Institute of Clinical Research (KAVI - ICR)
      • declaration_date228-03-2024
      • placebo_presentYes
      • study_objectives<div>\n <strong>Primary Efficacy Objective:</strong></div>\n<ul>\n <li>\n To evaluate the vaccine efficacy (VE) of M72/AS01_E-4 in the prevention of laboratory-confirmed pulmonary TB among IGRA-positive participants without HIV infection (IGRA-Positive Cohort) in the per-protocol (PP) analysis set</li>\n</ul>\n<p>\n <strong font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">Secondary Efficacy Objectives:</strong></p>\n<ul>\n <li>\n To evaluate the VE of M72/AS01_E-4 in the prevention of <em>Mtb</em> infection among the IGRA-Negative Cohort in the PP analysis set</li>\n <li>\n To evaluate the VE of M72/AS01_E-4 in the prevention of laboratory-confirmed pulmonary TB among the IGRA-Negative Cohort in the PP analysis set</li>\n <li>\n To evaluate the VE of M72/AS01_E-4 in the prevention of laboratory-confirmed pulmonary TB among the HIV Cohort in the PP analysis set</li>\n <li>\n To evaluate the VE of M72/AS01_E-4 in the prevention of less stringently defined laboratory-confirmed pulmonary TB among the IGRA-Positive Cohort in the PP analysis set</li>\n</ul>\n<p>\n <strong>Secondary Safety Objective:</strong></p>\n<ul>\n <li>\n To evaluate the safety and reactogenicity following administration of M72/AS01_E-4 vaccine or placebo</li>\n</ul>\n<p>\n <strong>Secondary Immunogenicity Objective:</strong></p>\n<ul>\n <li>\n To assess the humoral immunogenicity of M72/AS01_E-4 vaccination</li>\n</ul>\n<p>\n <strong>Exploratory Objectives:</strong></p>\n<ul>\n <li>\n To further explore the VE of M72/AS01_E-4 in the prevention of <strong>laboratory</strong>-confirmed pulmonary TB as defined for the primary endpoint, among the IGRA-Positive Cohort in the mITT analysis set</li>\n <li>\n To explore the effect of potential covariates on the VE of M72/AS01_E-4 in the prevention of <strong>laboratory</strong>-confirmed pulmonary TB as defined for the primary endpoint, among the IGRA-Positive Cohort in the PP analysis set</li>\n <li>\n To explore the VE of M72/AS01_E-4in the prevention of <strong>laboratory-confirmed</strong> pulmonary TB, where sputum was collected up to 28 days after treatment initiation among IGRA-positive, IGRA-negative, and HIV Cohorts, respectively, in the mITT analysis set.</li>\n <li>\n To explore the VE of M72/AS01_E-4 in the prevention of <strong>clinical</strong> TB (including extrapulmonary TB) defined as a participant for whom a clinician has diagnosed TB, and has initiated TB treatment, in the absence of laboratory-confirmed pulmonary TB, among IGRA-positive, IGRA-negative, and HIV Cohorts, respectively, in the mITT analysis set. </li>\n <li>\n To explore the VE of M72/AS01_E-4in the prevention of <strong>subclinical </strong>TB, defined as a participant with a positive result from Xpert Ultra or similar assay (excluding “trace positive”) from a single sputum sample at the EoT visit, in the absence of signs or symptoms of pulmonary TB, among IGRA-positive, IGRA-negative, and HIV Cohorts, respectively, in the mITT analysis set.</li>\n <li>\n To assess the cellular immunogenicity of M72/AS01_E-4 vaccination using M72-specific CD4+ and CD8+ T-cell responses measured by co-expression of 2 or more cytokines using intracellular cytokine staining (ICS)</li>\n <li>\n To further explore the cellular immunogenicity of M72/AS01_E-4 vaccination using M72-specific CD4+ and CD8+ T-cell responses measured by co-expression of multiple functional markers by ICS</li>\n <li>\n To confirm candidate CoP and CoR if identified in the M72 Immune Correlates Program and to explore new candidate CoP and CoR</li>\n <li>\n To explore characteristics of <em>Mtb </em>isolates, including drug susceptibility profiles and genetic diversity</li>\n</ul>\n<p>\n  </p>\n
      • principal_inclusion_criteria<p class=\"SynchrogenixBodyText\">\n <span lang=\"EN-US\">Participants are eligible for randomization and trial intervention administration only if all of the following criteria apply.</span></p>\n<p>\n    <strong>Age</strong></p>\n<ol>\n <li>\n Participant must be 15 to 44 years of age (inclusive), at the time of signing the consent or assent.</li>\n</ol>\n<p>\n <strong>Type of Participant and Disease Characteristics</strong></p>\n<ol>\n <li value=\"2\">\n Capable of giving informed consent or informed assent (as appropriate). For participants below the age of consent, the participant’s parent, or legally authorized representative (LAR) will be required to sign a statement of informed consent, in addition to the minor’s signed statement of assent.</li>\n <li value=\"3\">\n In the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of diary cards as applicable, and return for follow-up visits).</li>\n <li value=\"4\">\n Agree to actively stay in contact with the trial site for the duration of the trial for the participants own safety.</li>\n <li value=\"5\">\n Agree to provide updated contact information as necessary, and have no current plans to relocate from the trial area for the duration of the trial.</li>\n <li value=\"6\">\n Healthy, or with preexisting stable disease, as established by medical history and physical examination and as determined by the investigator. Preexisting stable disease is defined as not requiring significant change in therapy or hospitalization for worsening disease during the 28 days before enrollment.</li>\n <li value=\"7\">\n Negative sputum Xpert Ultra or similar assay result at screening </li>\n <li value=\"8\">\n Both males and females are included. Females are included with restrictions. Females must either be of non-childbearing potential, defined as pre-menarche, have a history of either current tubal ligation, hysterectomy, or ovariectomy, or post-menopause, <strong>or</strong>, if she is of childbearing potential, she has practiced abstinence from penile-vaginal intercourse or adequate contraception for 28 days prior to vaccination, has a negative pregnancy test on the day of screening and the day of first vaccination, and agrees to continue abstinence or adequate contraception until 2 months after the second dose of trial intervention.</li>\n <li value=\"9\">\n HIV-negative test result at screening (IGRA-Positive Cohort and IGRA-Negative Cohort only)</li>\n <li value=\"10\">\n HIV Cohort only: Participants with documented<ins cite=\"mailto:Debbie%20Daehnick%20(DT%20Medical%20Writing%20Corp)\" datetime=\"2024-01-08T12:19\">*</ins> HIV infection who fulfill all of the following criteria:</li>\n</ol>\n<ul>\n <li>\n have reactive anti-HIV antibody at screening</li>\n <li>\n have been on ART for at least 3 consecutive months at screening and agree to remain on ART throughout the trial</li>\n <li>\n have documented HIV RNA <200 copies/mL at screening</li>\n <li>\n have CD4+ cell count ≥200 cells/µL at screening</li>\n <li>\n have had TPT in the past and are not receiving TPT at the time of screening, according to the judgment of the investigators</li>\n <li>\n have an IGRA-positive or negative result at screening.</li>\n</ul>\n<p>\n <ins cite=\"mailto:Debbie%20Daehnick%20(DT%20Medical%20Writing%20Corp)\" datetime=\"2024-01-08T12:19\">*Note that ‘documented’ refers to documentation from the site personnel’s review of the participant’s medical records, medical examination, or medical history interview.</ins></p>\n<p class=\"SynchrogenixBodyText\">\n <span lang=\"EN-US\"><o:p></o:p></span></p>\n
      • principal_exclusion_criteria<p>\n Participants are excluded from the trial if any of the following criteria apply:</p>\n<p>\n <strong>Medical Conditions</strong></p>\n<p>\n 1. Current TB, or history of TB or treatment for TB disease</p>\n<p>\n 2. Clinical suspicion of pulmonary TB at screening, defined as a participant presenting with one or more of the following signs or symptoms: unexplained cough, unexplained fever, night sweats, unintentional weight loss, hemoptysis, pleuritic chest pain</p>\n<p>\n 3. Any current medical, psychiatric, occupational, or substance abuse problems that, in the opinion of the investigator, will make it unlikely that the participant will comply with the protocol, or that will interfere with the assessments or the safety of the participant</p>\n<p>\n 4. Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (e.g., invasive, or malignant cancers), other than HIV infection in the HIV Cohort</p>\n<p>\n 5. Known bleeding disorder that is considered a contracindication to intramuscular injection or phlebotomy </p>\n<p>\n <strong>Prior/Concomitant Therapy</strong></p>\n<p>\n 6. Any cytotoxic drugs or administration of medications known to have a major impact on the immune system, as determined by the investigator, within 90 days prior to Day 1. These include immune globulin, blood, or blood products, potent immunosuppressants and immunomodulators, and systemic corticosteroids (exceeding 20 mg/day prednisone equivalent). Inhaled, topical, and intra-articular corticosteroids are allowed.</p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n <strong>Prior/Concurrent Clinical Trial Experience</strong></p>\n<p>\n 7. Planned receipt of blood, or blood products during the trial period</p>\n<p>\n 8. Receipt or planned receipt of any vaccine in the period starting 28 days before, and ending 28 days after, each dose of the trial vaccine</p>\n<p>\n 9. History of previous administration of an experimental <em>Mtb</em> vaccine including M72/AS01_Ein a previous trial</p>\n<p>\n 10. History of allergy or hypersensitivity to the trial intervention, excipients, or related substances</p>\n<p>\n <strong>Diagnostic assessments</strong></p>\n<p>\n 11. An indeterminate IGRA test result at screening</p>\n<p>\n 12. Female participants with any one of the following conditions: currently pregnant or lactating; having positive serum pregnancy test during the screening window, positive urine pregnancy test on Day 1, planning a pregnancy within 2 months after completion of the vaccination series</p>\n<p>\n 13. Only in the HIV Cohort: Safety laboratory values at screening that are of concern, based on investigator’s judgment. Note that preexisting stable chronic disease will not necessarily lead to exclusion, especially if laboratory values are graded as mild (Section 13).</p>\n<p>\n <strong>Other Exclusions</strong></p>\n<p>\n 14. Participation in an interventional clinical trial in which the participant has been or will be exposed to an investigational product (pharmaceutical product or device), within 28 days prior to signing consent or assent, or during the trial period.</p>\n<p>\n 15. Individuals who are acting as personnel for this trial, or who have immediate family members (brother, sister, child, parent, or the spouse/partner) who are acting as personnel for this trial.</p>\n<p>\n 16. Child in Care, defined as a child who is under the care (control or protection) of an agency, organization, institution or entity by the courts, the government body, acting in accordance with powers conferred in them by law or regulations. The definition of a child in care can include a child who is cared for by foster parents or living in a care home or institution, provided that the arrangements fall within the definition above. The definition of a child in care <strong>does not include</strong> a child who is adopted or has an appointed LAR.</p>\n<p>\n 17. Participants who had a Tuberculin Skin Test (TST) within 6 months prior to Day 1</p>\n<p>\n  </p>\n
      • primary_end_points<p>\n <strong>Primary Efficacy Endpoint:</strong></p>\n<p>\n Laboratory-confirmed pulmonary TB over a period starting 1 month post Dose 2 and lasting up to End of Trial (EoT) where a laboratory-confirmed pulmonary TB case is defined as a participant with:</p>\n<p style=\"margin-left:21.6pt;\">\n ·       Suspected pulmonary TB as defined as a participant presenting with one or more of the following signs or symptoms:</p>\n<p style=\"margin-left:39.7pt;\">\n o   unexplained cough, unintentional weight loss, hemoptysis, unexplained fever, night sweats, pleuritic chest pain</p>\n<p>\n who has</p>\n<p>\n At least 2 positive <em>Mtb</em> test results (positive <em>Mtb</em> culture and/or positive test result from Xpert Ultra or similar assay, excluding “trace positive”), from the same or from different sputum samples collected during 3 suspected TB visits, preferably within a 7-day time frame, before initiation of TB treatment</p>\n<p>\n <strong>Secondary Efficacy Endpoints:</strong></p>\n<p>\n Sustained QuantiFERON®-TB Gold Plus assay (or similar) conversion (i.e., initial conversion and IGRA-positive test result at next attended scheduled visit) over a period starting 1 month post dose 2 and lasting up to EoT </p>\n<p>\n Laboratory-confirmed pulmonary TB over a period starting 1 month post Dose 2 and lasting up to EoT, where a laboratory-confirmed pulmonary TB case follows the same definition as the primary endpoint</p>\n<p>\n Laboratory-confirmed pulmonary TB over a period starting 1 month post Dose 2 and lasting up to EoT, where a laboratory-confirmed pulmonary TB case follows the same definition as the primary endpoint</p>\n<p>\n Laboratory-confirmed pulmonary TB over a period starting 1 month post Dose 2 and lasting up to EoT, where a laboratory-confirmed pulmonary TB case is defined less stringently as a participant with:</p>\n<p style=\"margin-left:17.3pt;\">\n ·       Suspected pulmonary TB as defined for the primary efficacy endpoint, and</p>\n<p>\n At least 1 positive <em>Mtb</em> culture or at least 1 positive result from Xpert Ultra or similar assay (excluding “trace positive”),from the same or from different sputum samples collected during the 3 suspected TB visits, preferably within a 7-day time frame, before initiation of TB treatment</p>\n<p>\n <strong>Secondary Safety Endpoints:</strong></p>\n<p>\n Occurrence of solicited AEs during the 7 days following each vaccination (starting on day of vaccination and 6 subsequent days after each vaccine dose) Safety analysis set</p>\n<p>\n Occurrence of unsolicited AEs during the 28 days following each vaccination (starting on day of vaccination and 27 subsequent days after each vaccine dose) Safety analysis set</p>\n<p>\n Occurrence of all serious adverse events (SAEs) and potential immune-mediated diseases (pIMDs) from Day 1 through Month 13, Safety analysis set</p>\n<p>\n Occurrence of SAEs related to trial participation through <ins cite=\"mailto:Debbie%20Daehnick%20(DT%20Medical%20Writing%20Corp)\" datetime=\"2024-01-08T12:19\">trial</ins> end, Safety analysis set</p>\n<p>\n <strong>Secondary Immunogenicity Endpoint:</strong></p>\n<p>\n Geometric mean concentration (GMC) and seropositivity of M72-specific antibodies at Day 1, Month 1, Month 2, Month 7, Month 13, Month 37, and Month 49 among each of the IGRA-Positive Cohort, IGRA-Negative Cohort, and HIV Cohorts in the per-protocol for immunogenicity (PPI) analyses set</p>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Site 1201_</strong> <strong>KAVI – Institute of Clinical Research (KAVI - ICR)</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n KAVI- ICR Kenyatta National Hospital (KAVI-ICR KNH) clinical trial site is located at the Faculty of Health Sciences, University of Nairobi at Kenyatta National Hospital complex.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Clinic - </strong>The KAVI-ICR clinic is located on 3<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; top: -0.5em;\">rd</span> floor the Faculty of Health Sciences Building, University of Nairobi, occupying the floor above the Department of Obstetrics and Gynaecology. It comprises 10 clinic rooms, which serve multiple purposes depending on study needs. The clinic also has an investigational product (IP) pharmacy, a general pharmacy, a data management room, a community meeting board room, and administrative offices. Routine medical care for trial participants is provided on-site at the clinic, including general medical care. The clinic also has an emergency room with resuscitation equipment including a cardiac defibrillator, oxygen delivery system, and supplies for intravenous access in the event of anaphylaxis. It is equipped for protocol specific requirements.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Onsite study visits including screening, enrolment, study product administration and follow-up visits will be conducted at both the KAVI-ICR clinic.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Pharmacy - </strong>The vaccine pharmacy at KAVI-ICR is located on 3<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; top: -0.5em;\">rd</span> floor and measures 18.792m<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; top: -0.5em;\">2</span>. It has 2 Sanyo MDF freezers that operate at -80°C, a 2 to 8 degrees Celsius fridge and two class II biosafety cabinet for use in preparation of study products. The room is fitted with air conditioners and telemetry-based temperature monitoring of study product storage units. Access to the pharmacy storage room is controlled and is restricted to the pharmacy staff only. A back-up pharmacy is available at the KAVI-ICR Kangemi site (located at Kangemi Health Center) for emergency transfer of Investigational Product. The pharmacy is served by two standby generators with automatic changeover in case of power loss.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Laboratory - </strong>The laboratory located on 2nd floor of KAVI-ICR building, Faculty of Health Sciences, University of Nairobi is accredited to Good Clinical Laboratory Practice (GCLP) standards. It comprises of safety and level-2 immunology laboratories equipped for conduct of clinical trials and basic science experiments. The lab has capacity to perform Hematology (CBC and differential count), biochemistry (liver and renal function tests), urinalysis and pregnancy tests, serological assays for HIV, HBV, HCV, RPR (syphilis) and TPHA, PBMC isolation, Flow cytometry (CD4/CD8 counts, T cells & B cells sorting), ELISpot assays, HLA molecular tissue typing, intracellular cytokine staining, mucosal sample processing, Binding Antibodies Multiples Assays (BAMA) and sequencing using Illumina Miseq platform. The turn-around time for safety tests results is approximately 3 days but more urgent/critical results can be provided within 24 hours.</p>\n
      • other_details_explanation<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">This Phase 3 TB vaccine trial will be conducted in adolescents and adults in communities with a high burden of pulmonary tuberculosis (TB). The trial is being conducted in Kenya because TB is significantly more prevalent (>200 cases per 100,000 population) than the USA (<3 cases per 100,000 population).  </span></p>\n
      • other_details_regulatory_notapproved<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td rowspan=\"2\" style=\"width:97px;height:19px;\">\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n <strong>C</strong><strong>o</strong><strong>u</strong><strong>ntry</strong></p>\n </td>\n <td colspan=\"2\" rowspan=\"2\" style=\"width:213px;height:19px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n <strong>N</strong><strong>ame of Competent Authority</strong></p>\n </td>\n <td rowspan=\"2\" style=\"width:124px;height:19px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n <strong>Submission status</strong></p>\n </td>\n <td rowspan=\"2\" style=\"width:130px;height:19px;\">\n <p style=\"margin-left:4.85pt;\">\n <strong>C</strong><strong>ompetent</strong></p>\n <p style=\"margin-left:4.85pt;\">\n <strong>A</strong><strong>uthority decision</strong></p>\n </td>\n <td height=\"29\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:97px;height:63px;\">\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n <strong>Kenya</strong></p>\n </td>\n <td colspan=\"2\" style=\"width:213px;height:63px;\">\n <p>\n  </p>\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n Kenya Pharmacy and Poison</p>\n <p style=\"margin-left:5.0pt;\">\n Board (KPPB)</p>\n </td>\n <td style=\"width:124px;height:63px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n Pending</p>\n </td>\n <td style=\"width:130px;height:63px;\">\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n Pending</p>\n </td>\n <td height=\"94\" style=\"height:63px;\">\n  </td>\n </tr>\n <tr>\n <td rowspan=\"2\" style=\"width:97px;height:20px;\">\n <p style=\"margin-left:2.6pt;\">\n <strong>I</strong><strong>ndonesia</strong></p>\n </td>\n <td colspan=\"2\" rowspan=\"2\" style=\"width:213px;height:20px;\">\n <p style=\"margin-left:5.0pt;\">\n Indonesian Food and Drug Authority</p>\n <p style=\"margin-left:5.0pt;\">\n (Indonesia NADFC-BPOM)</p>\n </td>\n <td style=\"width:124px;height:20px;\">\n <p style=\"margin-left:5.0pt;\">\n V1,0 Submitted –</p>\n </td>\n <td rowspan=\"2\" style=\"width:130px;height:20px;\">\n <p style=\"margin-left:4.85pt;\">\n V1.0 - Pending</p>\n </td>\n <td height=\"30\" style=\"height:20px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:124px;height:75px;\">\n <p style=\"margin-left:5.0pt;\">\n 07Sep2023</p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n V2.0 – Pending</p>\n </td>\n <td height=\"113\" style=\"height:75px;\">\n  </td>\n </tr>\n <tr>\n <td rowspan=\"2\" style=\"width:97px;height:62px;\">\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n <strong>Z</strong><strong>a</strong><strong>mbia</strong></p>\n </td>\n <td style=\"width:15px;height:62px;\">\n <p style=\"margin-left:.05pt;\">\n §</p>\n </td>\n <td style=\"width:198px;height:62px;\">\n <p style=\"margin-left:6.1pt;\">\n Zambia Medicines Regulatory</p>\n <p style=\"margin-left:6.1pt;\">\n Authority (ZAMRA)</p>\n </td>\n <td style=\"width:124px;height:62px;\">\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n V1.0 Submitted- 31 Oct 2023</p>\n </td>\n <td rowspan=\"2\" style=\"width:130px;height:62px;\">\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n V1.0 N/A</p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p style=\"margin-left:4.85pt;\">\n V2.0 Pending</p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n </td>\n <td height=\"94\" style=\"height:62px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:15px;height:43px;\">\n <p style=\"margin-left:.05pt;\">\n §</p>\n </td>\n <td style=\"width:198px;height:43px;\">\n <p style=\"margin-left:6.1pt;\">\n National Health Research</p>\n <p style=\"margin-left:6.1pt;\">\n Authoirty (NHRA)</p>\n </td>\n <td style=\"width:124px;height:43px;\">\n <p>\n V2.0 – Pending</p>\n </td>\n <td height=\"64\" style=\"height:43px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:97px;height:90px;\">\n <p style=\"margin-left:4.85pt;\">\n <strong>M</strong><strong>alawi</strong></p>\n </td>\n <td colspan=\"2\" style=\"width:213px;height:90px;\">\n <p style=\"margin-left:5.0pt;\">\n Pharmacy and Medicines Regulatory</p>\n <p style=\"margin-left:5.0pt;\">\n Authority (PMRA)</p>\n </td>\n <td style=\"width:124px;height:90px;\">\n <p style=\"margin-left:5.0pt;\">\n V1.0 Submitted – 08 Dec 2023</p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n V2.0 Submitted – 15 Mar 2024</p>\n </td>\n <td style=\"width:130px;height:90px;\">\n <p style=\"margin-left:4.85pt;\">\n V1.0  n/a</p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p style=\"margin-left:4.85pt;\">\n V2.0 Pending</p>\n </td>\n <td height=\"135\" style=\"height:90px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:97px;height:69px;\">\n <p>\n  </p>\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n <strong>M</strong><strong>o</strong><strong>z</strong><strong>a</strong><strong>m</strong><strong>bi</strong><strong>que</strong></p>\n </td>\n <td colspan=\"2\" style=\"width:213px;height:69px;\">\n <p>\n  </p>\n <p>\n  </p>\n <p style=\"margin-left:2.7pt;\">\n National Medicines Regulatory</p>\n <p style=\"margin-left:.05pt;\">\n Authority (ANARME)</p>\n </td>\n <td style=\"width:124px;height:69px;\">\n <p>\n  </p>\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n Pending</p>\n </td>\n <td style=\"width:130px;height:69px;\">\n <p>\n  </p>\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n Pending</p>\n </td>\n <td height=\"104\" style=\"height:69px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:97px;height:81px;\">\n <p style=\"margin-left:4.85pt;\">\n <strong>V</strong><strong>ietnam</strong></p>\n </td>\n <td colspan=\"2\" style=\"width:213px;height:81px;\">\n <p style=\"margin-left:5.0pt;\">\n Vietnam Ministry of Health</p>\n </td>\n <td style=\"width:124px;height:81px;\">\n <p style=\"margin-left:5.0pt;\">\n V1.0 Submitted 08 Jan 2024</p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n V2.0 Pending</p>\n </td>\n <td style=\"width:130px;height:81px;\">\n <p style=\"margin-left:4.85pt;\">\n Pending</p>\n </td>\n <td height=\"122\" style=\"height:81px;\">\n  </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_regulatory_approved<p>\n  </p>\n<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td rowspan=\"2\" style=\"width:97px;height:19px;\">\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n <strong>C</strong><strong>o</strong><strong>u</strong><strong>ntry</strong></p>\n </td>\n <td rowspan=\"2\" style=\"width:213px;height:19px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n <strong>N</strong><strong>ame of Competent Authority</strong></p>\n </td>\n <td rowspan=\"2\" style=\"width:124px;height:19px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n <strong>Submission status</strong></p>\n </td>\n <td rowspan=\"2\" style=\"width:130px;height:19px;\">\n <p style=\"margin-left:4.85pt;\">\n <strong>C</strong><strong>ompetent</strong></p>\n <p style=\"margin-left:4.85pt;\">\n <strong>A</strong><strong>uthority decision</strong></p>\n </td>\n <td height=\"29\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td rowspan=\"2\" style=\"width:97px;height:28px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.25pt;\">\n <strong>South Africa</strong></p>\n <p style=\"margin-left:5.25pt;\">\n <b>34 Sites</b></p>\n </td>\n <td rowspan=\"2\" style=\"width:213px;height:28px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n South Africa Health Products</p>\n <p style=\"margin-left:5.0pt;\">\n Regulatory Authority (SAHPRA)</p>\n </td>\n <td style=\"width:124px;height:28px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n V1.0 Submitted -</p>\n <p style=\"margin-left:5.0pt;\">\n 11Aug2023</p>\n </td>\n <td style=\"width:130px;height:28px;\">\n <p>\n  </p>\n <p>\n Approved: 15 Nov 2023</p>\n <p>\n  </p>\n </td>\n <td height=\"42\" style=\"height:28px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:124px;height:63px;\">\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n V2.0 Submitted –</p>\n <p style=\"margin-left:5.0pt;\">\n 19 Jan 2024</p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n </td>\n <td style=\"width:130px;height:63px;\">\n <p>\n  </p>\n <p>\n Approved: 02 Feb 2024</p>\n <p>\n  </p>\n </td>\n <td height=\"95\" style=\"height:63px;\">\n  </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration4 years
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states7
      • number_of_sites9
      • multi_country_listKenya, South Africa, Malawi, Zambia, Mozambique, Indonesia and Vietnam
      • data_monitoring_committeeYes
      • total_enrolment_per_siteCompetitive enrolment approximated at 500 per Site
      • total_participants_worldwide20,000
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameDr Videlis
      • investigator1_middle_name
      • investigator1_family_nameNduba
      • investigator1_qualificationMBChB, MPH,PhD
      • investigator1_professional_addressKEMRI Centre for Clinical Respiratory Diseases Research (KEMRI CRDR), KEMRI/ CRDR Clinical Research Annex, KNH Complex Behind Government Chemist and Off Raila Odinga Way, P.O Box 47855 - 00100,Nairobi Kenya.
      • investigator1_telephone+254 724 522 474
      • investigator1_emailvnduba@gmail.com
      • organisations_transferred_Yes
      • number_participants4,500
      • notification
      • approval_date25-04-2024
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted28-03-2024
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonhe application was reviewed under the AVAREF pathway, and the version 2 has been reviewed and considered acceptable.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-04-24 14:10:48
      • created2024-03-28 10:31:40
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id1051
        • application_id1391
        • given_nameProf Walter
        • middle_nameGodfrey
        • family_nameJaoko
        • qualificationMBChB,MTropMed, PGDip, MSc, PhD, FAAS
        • professional_addressKAVI – Institute of Clinical Research (KAVI - ICR),College of Health Science, University of Nairobi, KNH Complex, Upper Hill, P.O. Box 19676 – 00202, Nairobi Kenya
        • telephone+254 727 555 254
        • emailwjaoko07@gmail.com
        • created2024-03-28 11:38:43
        • modified2024-03-28 21:01:45
    • SiteDetail(array)
      • 0(array)
        • id1690
        • application_id1391
        • county_id47
        • site_nameKAVI – Institute of Clinical Research (KAVI - ICR)
        • physical_addressCollege of Health Science, University of Nairobi, KNH Complex, Upper Hill
        • contact_details+254 727 555 254 ; P.O. Box 19676 – 00202
        • contact_personProf Walter Jaoko
        • site_capacity(null)
        • misc(null)
        • created2024-03-28 11:38:43
        • modified2024-03-28 21:01:45
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
    • Sponsor(array)
      • 0(array)
        • id735
        • application_id1391
        • sponsorBill & Melinda Gates Medical Research Institute (Gates MRI)
        • sponsor_typeResearch Institution
        • contact_personKristen Mayer
        • addressOne Kendall Square, Building 600, Suite 6-301, Cambridge, MA 02139, USA
        • telephone_number+1 617-465-0089
        • fax_numberN/A
        • cell_number+1 617-465-0089
        • email_addressKristen.mayer@gatesmri.org
        • created2024-03-28 11:38:43
        • modified2024-03-28 21:01:45
  • 3(array)
    • Application(array)
      • id1402
      • user_id263
      • trial_status_id1
      • abstract_of_study<p class=\"SynchrogenixBodyText\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <span lang=\"EN-US\">Modeling suggests that the most effective contribution to TB control in high burden countries would be a vaccine that prevents pulmonary TB in adolescents and adults [</span><span lang=\"EN-US\" style=\"color: blue;\">WHO</span><span lang=\"EN-US\" style=\"color: blue;\">2021</span><span lang=\"EN-US\">]. In very high incidence geographies, the incidence rate of TB is highest in older adolescents and young adults (e.g., 15 to 44 years of age). In addition, pulmonary TB is the predominant form of TB in this age group (with the primary mode of TB transmission being via aerosol), and young adults are more likely to transmit to more contacts because they are active and mix extensively [</span><span lang=\"EN-US\" style=\"color: blue;\">Knight</span><span lang=\"EN-US\" style=\"color: blue;\">2014</span><span lang=\"EN-US\">].</span></p>\n<p class=\"SynchrogenixBodyText\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n The primary objective of this Phase 3 efficacy trial is to evaluate VE in the prevention of laboratory-confirmed pulmonary TB in IGRA-positive participants who do not have HIV. The rationale for focusing on IGRA-positive participants is based on Phase 3 trial simulations that evaluated the feasibility of demonstrating VE in an “all-comer” population (i.e., regardless of IGRA status) of young adults (15 to 44 years of age) in very high burden settings with an IGRA-positive prevalence of 67%. Based on these simulations, it appears feasible to demonstrate vaccine efficacy against tuberculosis disease (VE[D]) in an IGRA-positive, HIV-negative population, with a sample size of <span class=\"msoIns\"><ins cite=\"mailto:Debbie%20Daehnick%20(DT%20Medical%20Writing%20Corp)\" datetime=\"2024-01-08T12:19\">9</ins></span>,000 participants per arm, within 4 years from start of enrollment, whereas a trial in an all-comer population would have to be much larger, and the larger population would still be inadequate to demonstrate VE(D) in IGRA-negative participants.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Trial simulation assumptions included an annual IGRA conversion rate of 3% per person-year, and an incidence of active pulmonary TB of 0.4% per person-year. These simulations suggested that even with a 67% IGRA-positive prevalence at enrollment, more than 90% of laboratory-confirmed cases of TB would be observed in IGRA-positive participants, and less than 10% in IGRA-negative participants; such a trial would not be powered to demonstrate VE(D) in IGRA-negative participants as a subset.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n A confirmatory trial in IGRA-negative participants is not considered feasible (in a reasonable amount of time and with a reasonable population size), given the low rate of laboratory-confirmed cases expected in baseline IGRA-negative participants. Given the inability to demonstrate VE(D) in IGRA-negative participants as a subset in an ‘all-comer’ trial, this Phase 3 trial aims to demonstrate VE(D) in IGRA-positive participants only, and to generate descriptive safety, immunogenicity, and VE(D) data in a HIV-negative, IGRA-negative Cohort  (N=1,000) and in a cohort of PLHIV (N=1,000) of either positive or negative IGRA status.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n GlaxoSmithKline Biologicals, SA (GSK) developed M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span>, an investigational TB vaccine, to protect against the development of TB in <em>Mtb</em>-infected adolescents and adults. The GSK Phase 2b trial (TB-018) evaluated vaccine safety and efficacy in approximately 3500 IGRA-positive adults (1:1, M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4 </span>and placebo) [Van Der Meeren2018; Tait2019]. Most participants in the TB-018 trial had previously received the BCG vaccine as neonates. The observed VE against active pulmonary TB in the Phase 2b trial was 49.7% (95% CI: 2.1% to 74.2%) at 36 months and no safety signals that would prevent further development were observed [Tait2019].</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n In 2020, the Bill & Melinda Gates Medical Research Institute (Gates MRI) licensed the M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4 </span>investigational TB vaccine for continued development.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n  </p>\n
      • study_title<p>\n <span style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">A Phase 3, randomized, double-blind, placebo-controlled, multicenter, clinical trial to assess the prophylactic efficacy, safety, and immunogenicity of the investigational M72/AS01</span><span style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span><span style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\"> Mycobacterium tuberculosis (Mtb) vaccine when administered intramuscularly on a 0,1-month schedule to adolescents and adults.</span></p>\n
      • laymans_summary<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Tuberculosis (TB) is caused by the bacterium Mycobacterium tuberculosis (Mtb); it typically affects the lungs but can also affect other sites. TB is spread from person to person via the respiratory route and is manifested by the presence of Mtb in sputum. TB is the second leading infectious killer after COVID-19 (above HIV/AIDS). It is present in all countries and age groups, but the larger number of new cases occur in countries of the South-East Asian Region and African Region.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Bacille Calmette-Guérin, known as BCG, is the only licensed TB vaccine to date; however, the impact of BCG on the transmission of Mtb in adults is limited, since it offers minimal or no protection against pulmonary TB in adults. TB treatment is lengthy, and compliance is often incomplete, resulting in an increasing incidence of multi-drug resistant (MDR)-TB and extensively drug resistant (XDR)-TB.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Given the substantial morbidity and mortality associated with TB, the challenges associated with TB treatment, and the limited options for prevention, a vaccine is urgently needed, both to protect against disease, including the progression from latent Mtb infection to active TB, and to accelerate the end of the TB epidemic.</p>\n
      • short_titleGates MRI TBV02-301
      • protocol_noECCT/24/04/08
      • version_no2.0
      • date_of_protocol08-01-2024
      • study_drugM72/AS01E-4 investigational vaccine
      • disease_conditionTuberculosis (TB)
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorNo
      • comparator_nameN/A
      • comparator_registeredN/A
      • comparator_countriesN/A
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressamina.salim@iqvia.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantMaureen Anyango Olwero
      • declaration_date130-04-2024
      • declaration_principal_investigatorDr Wilson Muraya_PI_Kemri-Mtwapa Clinical Research Annex
      • declaration_date230-04-2024
      • placebo_presentYes
      • study_objectives<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <div>\n <strong>Primary Efficacy Objective:</strong></div>\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate the vaccine efficacy (VE) of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> in the prevention of laboratory-confirmed pulmonary TB among IGRA-positive participants without HIV infection (IGRA-Positive Cohort) in the per-protocol (PP) analysis set</li>\n </ul>\n <p style=\"margin: 0px 0px 10px;\">\n <strong font-size:=\"\" trebuchet=\"\">Secondary Efficacy Objectives:</strong></p>\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate the VE of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> in the prevention of <em>Mtb</em> infection among the IGRA-Negative Cohort in the PP analysis set</li>\n <li style=\"line-height: 20px;\">\n To evaluate the VE of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> in the prevention of laboratory-confirmed pulmonary TB among the IGRA-Negative Cohort in the PP analysis set</li>\n <li style=\"line-height: 20px;\">\n To evaluate the VE of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> in the prevention of laboratory-confirmed pulmonary TB among the HIV Cohort in the PP analysis set</li>\n <li style=\"line-height: 20px;\">\n To evaluate the VE of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> in the prevention of less stringently defined laboratory-confirmed pulmonary TB among the IGRA-Positive Cohort in the PP analysis set</li>\n </ul>\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Secondary Safety Objective:</strong></p>\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate the safety and reactogenicity following administration of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> vaccine or placebo</li>\n </ul>\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Secondary Immunogenicity Objective:</strong></p>\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To assess the humoral immunogenicity of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> vaccination</li>\n </ul>\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Exploratory Objectives:</strong></p>\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To further explore the VE of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> in the prevention of <strong>laboratory</strong>-confirmed pulmonary TB as defined for the primary endpoint, among the IGRA-Positive Cohort in the mITT analysis set</li>\n <li style=\"line-height: 20px;\">\n To explore the effect of potential covariates on the VE of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> in the prevention of <strong>laboratory</strong>-confirmed pulmonary TB as defined for the primary endpoint, among the IGRA-Positive Cohort in the PP analysis set</li>\n <li style=\"line-height: 20px;\">\n To explore the VE of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4 </span>in the prevention of <strong>laboratory-confirmed</strong> pulmonary TB, where sputum was collected up to 28 days after treatment initiation among IGRA-positive, IGRA-negative, and HIV Cohorts, respectively, in the mITT analysis set.</li>\n <li style=\"line-height: 20px;\">\n To explore the VE of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> in the prevention of <strong>clinical</strong> TB (including extrapulmonary TB) defined as a participant for whom a clinician has diagnosed TB, and has initiated TB treatment, in the absence of laboratory-confirmed pulmonary TB, among IGRA-positive, IGRA-negative, and HIV Cohorts, respectively, in the mITT analysis set. </li>\n <li style=\"line-height: 20px;\">\n To explore the VE of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4 </span>in the prevention of <strong>subclinical </strong>TB, defined as a participant with a positive result from Xpert Ultra or similar assay (excluding “trace positive”) from a single sputum sample at the EoT visit, in the absence of signs or symptoms of pulmonary TB, among IGRA-positive, IGRA-negative, and HIV Cohorts, respectively, in the mITT analysis set.</li>\n <li style=\"line-height: 20px;\">\n To assess the cellular immunogenicity of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> vaccination using M72-specific CD4+ and CD8+ T-cell responses measured by co-expression of 2 or more cytokines using intracellular cytokine staining (ICS)</li>\n <li style=\"line-height: 20px;\">\n To further explore the cellular immunogenicity of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> vaccination using M72-specific CD4+ and CD8+ T-cell responses measured by co-expression of multiple functional markers by ICS</li>\n <li style=\"line-height: 20px;\">\n To confirm candidate CoP and CoR if identified in the M72 Immune Correlates Program and to explore new candidate CoP and CoR</li>\n <li style=\"line-height: 20px;\">\n To explore characteristics of <em>Mtb </em>isolates, including drug susceptibility profiles and genetic diversity</li>\n </ul>\n</div>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n
      • principal_inclusion_criteria<p class=\"SynchrogenixBodyText\" font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <span lang=\"EN-US\">Participants are eligible for randomization and trial intervention administration only if all of the following criteria apply.</span></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n    <strong>Age</strong></p>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Participant must be 15 to 44 years of age (inclusive), at the time of signing the consent or assent.</li>\n</ol>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Type of Participant and Disease Characteristics</strong></p>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"2\">\n Capable of giving informed consent or informed assent (as appropriate). For participants below the age of consent, the participant’s parent, or legally authorized representative (LAR) will be required to sign a statement of informed consent, in addition to the minor’s signed statement of assent.</li>\n <li style=\"line-height: 20px;\" value=\"3\">\n In the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of diary cards as applicable, and return for follow-up visits).</li>\n <li style=\"line-height: 20px;\" value=\"4\">\n Agree to actively stay in contact with the trial site for the duration of the trial for the participants own safety.</li>\n <li style=\"line-height: 20px;\" value=\"5\">\n Agree to provide updated contact information as necessary, and have no current plans to relocate from the trial area for the duration of the trial.</li>\n <li style=\"line-height: 20px;\" value=\"6\">\n Healthy, or with preexisting stable disease, as established by medical history and physical examination and as determined by the investigator. Preexisting stable disease is defined as not requiring significant change in therapy or hospitalization for worsening disease during the 28 days before enrollment.</li>\n <li style=\"line-height: 20px;\" value=\"7\">\n Negative sputum Xpert Ultra or similar assay result at screening </li>\n <li style=\"line-height: 20px;\" value=\"8\">\n Both males and females are included. Females are included with restrictions. Females must either be of non-childbearing potential, defined as pre-menarche, have a history of either current tubal ligation, hysterectomy, or ovariectomy, or post-menopause, <strong>or</strong>, if she is of childbearing potential, she has practiced abstinence from penile-vaginal intercourse or adequate contraception for 28 days prior to vaccination, has a negative pregnancy test on the day of screening and the day of first vaccination, and agrees to continue abstinence or adequate contraception until 2 months after the second dose of trial intervention.</li>\n <li style=\"line-height: 20px;\" value=\"9\">\n HIV-negative test result at screening (IGRA-Positive Cohort and IGRA-Negative Cohort only)</li>\n <li style=\"line-height: 20px;\" value=\"10\">\n HIV Cohort only: Participants with documented<ins cite=\"mailto:Debbie%20Daehnick%20(DT%20Medical%20Writing%20Corp)\" datetime=\"2024-01-08T12:19\">*</ins> HIV infection who fulfill all of the following criteria:</li>\n</ol>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n have reactive anti-HIV antibody at screening</li>\n <li style=\"line-height: 20px;\">\n have been on ART for at least 3 consecutive months at screening and agree to remain on ART throughout the trial</li>\n <li style=\"line-height: 20px;\">\n have documented HIV RNA <200 copies/mL at screening</li>\n <li style=\"line-height: 20px;\">\n have CD4+ cell count ≥200 cells/µL at screening</li>\n <li style=\"line-height: 20px;\">\n have had TPT in the past and are not receiving TPT at the time of screening, according to the judgment of the investigators</li>\n <li style=\"line-height: 20px;\">\n have an IGRA-positive or negative result at screening.</li>\n</ul>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <ins cite=\"mailto:Debbie%20Daehnick%20(DT%20Medical%20Writing%20Corp)\" datetime=\"2024-01-08T12:19\">*Note that ‘documented’ refers to documentation from the site personnel’s review of the participant’s medical records, medical examination, or medical history interview.</ins></p>\n
      • principal_exclusion_criteria<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Participants are excluded from the trial if any of the following criteria apply:</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Medical Conditions</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 1. Current TB, or history of TB or treatment for TB disease</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 2. Clinical suspicion of pulmonary TB at screening, defined as a participant presenting with one or more of the following signs or symptoms: unexplained cough, unexplained fever, night sweats, unintentional weight loss, hemoptysis, pleuritic chest pain</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 3. Any current medical, psychiatric, occupational, or substance abuse problems that, in the opinion of the investigator, will make it unlikely that the participant will comply with the protocol, or that will interfere with the assessments or the safety of the participant</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 4. Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (e.g., invasive, or malignant cancers), other than HIV infection in the HIV Cohort</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 5. Known bleeding disorder that is considered a contracindication to intramuscular injection or phlebotomy </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Prior/Concomitant Therapy</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 6. Any cytotoxic drugs or administration of medications known to have a major impact on the immune system, as determined by the investigator, within 90 days prior to Day 1. These include immune globulin, blood, or blood products, potent immunosuppressants and immunomodulators, and systemic corticosteroids (exceeding 20 mg/day prednisone equivalent). Inhaled, topical, and intra-articular corticosteroids are allowed.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Prior/Concurrent Clinical Trial Experience</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 7. Planned receipt of blood, or blood products during the trial period</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 8. Receipt or planned receipt of any vaccine in the period starting 28 days before, and ending 28 days after, each dose of the trial vaccine</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 9. History of previous administration of an experimental <em>Mtb</em> vaccine including M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E </span>in a previous trial</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 10. History of allergy or hypersensitivity to the trial intervention, excipients, or related substances</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Diagnostic assessments</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 11. An indeterminate IGRA test result at screening</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 12. Female participants with any one of the following conditions: currently pregnant or lactating; having positive serum pregnancy test during the screening window, positive urine pregnancy test on Day 1, planning a pregnancy within 2 months after completion of the vaccination series</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 13. Only in the HIV Cohort: Safety laboratory values at screening that are of concern, based on investigator’s judgment. Note that preexisting stable chronic disease will not necessarily lead to exclusion, especially if laboratory values are graded as mild (Section 13).</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Other Exclusions</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 14. Participation in an interventional clinical trial in which the participant has been or will be exposed to an investigational product (pharmaceutical product or device), within 28 days prior to signing consent or assent, or during the trial period.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 15. Individuals who are acting as personnel for this trial, or who have immediate family members (brother, sister, child, parent, or the spouse/partner) who are acting as personnel for this trial.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 16. Child in Care, defined as a child who is under the care (control or protection) of an agency, organization, institution or entity by the courts, the government body, acting in accordance with powers conferred in them by law or regulations. The definition of a child in care can include a child who is cared for by foster parents or living in a care home or institution, provided that the arrangements fall within the definition above. The definition of a child in care <strong>does not include</strong> a child who is adopted or has an appointed LAR.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 17. Participants who had a Tuberculin Skin Test (TST) within 6 months prior to Day 1</p>\n
      • primary_end_points<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Primary Efficacy Endpoint:</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Laboratory-confirmed pulmonary TB over a period starting 1 month post Dose 2 and lasting up to End of Trial (EoT) where a laboratory-confirmed pulmonary TB case is defined as a participant with:</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 21.6pt; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n ·       Suspected pulmonary TB as defined as a participant presenting with one or more of the following signs or symptoms:</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 39.7pt; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n o   unexplained cough, unintentional weight loss, hemoptysis, unexplained fever, night sweats, pleuritic chest pain</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n who has</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n At least 2 positive <em>Mtb</em> test results (positive <em>Mtb</em> culture and/or positive test result from Xpert Ultra or similar assay, excluding “trace positive”), from the same or from different sputum samples collected during 3 suspected TB visits, preferably within a 7-day time frame, before initiation of TB treatment</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Secondary Efficacy Endpoints:</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Sustained QuantiFERON®-TB Gold Plus assay (or similar) conversion (i.e., initial conversion and IGRA-positive test result at next attended scheduled visit) over a period starting 1 month post dose 2 and lasting up to EoT </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Laboratory-confirmed pulmonary TB over a period starting 1 month post Dose 2 and lasting up to EoT, where a laboratory-confirmed pulmonary TB case follows the same definition as the primary endpoint</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Laboratory-confirmed pulmonary TB over a period starting 1 month post Dose 2 and lasting up to EoT, where a laboratory-confirmed pulmonary TB case follows the same definition as the primary endpoint</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Laboratory-confirmed pulmonary TB over a period starting 1 month post Dose 2 and lasting up to EoT, where a laboratory-confirmed pulmonary TB case is defined less stringently as a participant with:</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 17.3pt; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n ·       Suspected pulmonary TB as defined for the primary efficacy endpoint, and</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n At least 1 positive <em>Mtb</em> culture or at least 1 positive result from Xpert Ultra or similar assay (excluding “trace positive”),from the same or from different sputum samples collected during the 3 suspected TB visits, preferably within a 7-day time frame, before initiation of TB treatment</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Secondary Safety Endpoints:</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Occurrence of solicited AEs during the 7 days following each vaccination (starting on day of vaccination and 6 subsequent days after each vaccine dose) Safety analysis set</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Occurrence of unsolicited AEs during the 28 days following each vaccination (starting on day of vaccination and 27 subsequent days after each vaccine dose) Safety analysis set</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Occurrence of all serious adverse events (SAEs) and potential immune-mediated diseases (pIMDs) from Day 1 through Month 13, Safety analysis set</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Occurrence of SAEs related to trial participation through <ins cite=\"mailto:Debbie%20Daehnick%20(DT%20Medical%20Writing%20Corp)\" datetime=\"2024-01-08T12:19\">trial</ins> end, Safety analysis set</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Secondary Immunogenicity Endpoint:</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Geometric mean concentration (GMC) and seropositivity of M72-specific antibodies at Day 1, Month 1, Month 2, Month 7, Month 13, Month 37, and Month 49 among each of the IGRA-Positive Cohort, IGRA-Negative Cohort, and HIV Cohorts in the per-protocol for immunogenicity (PPI) analyses set</p>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n KEMRI-Mtwapa  clinical research annex is located within the Kilifi county. The site is well equipped with the facilities required to conduct a drug study. The facility has several clinical rooms available for consenting, nursing procedures, clinical exams, and dosing.</p>\n<p>\n There are also additional facilities that include staff work areas, a monitoring space, a pharmacy, a conference board room, a laboratory, standby generator and kitchen for preparing participant meals. The site has access to appropriate safety measures and has highly capable clinical site personnel experienced in conducting clinical trials for more than 15 years. The Site staff include the principal investigator, 4 Sub-PIs, 1 medical officer, 2 study coordinator, 2 pharmacists, 2 pharm tech, 4 nurses, 4 lab personnel, 2 quality assurance officers, 3 clinical officers, 2 data/ICT staff, 1 administrator and 4 community health workers. All study related activities will occur at the site.</p>\n
      • other_details_explanation<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">This Phase 3 TB vaccine trial will be conducted in adolescents and adults in communities with a high burden of pulmonary tuberculosis (TB). The trial is being conducted in Kenya because TB is significantly more prevalent (>200 cases per 100,000 population) than the USA (<3 cases per 100,000 population).  </span></p>\n
      • other_details_regulatory_notapproved<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"648\">\n <tbody>\n <tr>\n <td rowspan=\"2\" style=\"width:97px;height:19px;\">\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n <strong>C</strong><strong>o</strong><strong>u</strong><strong>ntry</strong></p>\n </td>\n <td colspan=\"2\" rowspan=\"2\" style=\"width:213px;height:19px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n <strong>N</strong><strong>ame of Competent Authority</strong></p>\n </td>\n <td rowspan=\"2\" style=\"width:205px;height:19px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n <strong>Submission status</strong></p>\n </td>\n <td rowspan=\"2\" style=\"width:132px;height:19px;\">\n <p style=\"margin-left:4.85pt;\">\n <strong>C</strong><strong>ompetent</strong></p>\n <p style=\"margin-left:4.85pt;\">\n <strong>A</strong><strong>uthority decision</strong></p>\n </td>\n <td height=\"29\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td rowspan=\"9\" style=\"width:97px;height:51px;\">\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n <strong>Kenya</strong></p>\n </td>\n <td colspan=\"4\" style=\"width:551px;height:51px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n Kenya Pharmacy and Poison</p>\n <p style=\"margin-left:5.0pt;\">\n Board (KPPB)</p>\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p>\n  </p>\n </td>\n <td height=\"76\" style=\"height:51px;\">\n  </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:213px;height:19px;\">\n <p style=\"margin-left:5.0pt;\">\n Site 1202</p>\n <p>\n  </p>\n </td>\n <td style=\"width:205px;height:19px;\">\n <p>\n Pending</p>\n </td>\n <td style=\"width:132px;height:19px;\">\n <p>\n Pending</p>\n </td>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:213px;height:19px;\">\n <p style=\"margin-left:5.0pt;\">\n Site 1203</p>\n <p>\n  </p>\n </td>\n <td style=\"width:205px;height:19px;\">\n <p>\n Pending</p>\n </td>\n <td style=\"width:132px;height:19px;\">\n <p>\n Pending</p>\n </td>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:213px;height:19px;\">\n <p style=\"margin-left:5.0pt;\">\n Site 1204</p>\n <p>\n  </p>\n </td>\n <td style=\"width:205px;height:19px;\">\n <p>\n Pending</p>\n </td>\n <td style=\"width:132px;height:19px;\">\n <p>\n Pending</p>\n </td>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:213px;height:19px;\">\n <p style=\"margin-left:5.0pt;\">\n Site 1205</p>\n <p>\n  </p>\n </td>\n <td style=\"width:205px;height:19px;\">\n <p>\n Pending</p>\n </td>\n <td style=\"width:132px;height:19px;\">\n <p>\n Pending</p>\n </td>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:213px;height:19px;\">\n <p style=\"margin-left:5.0pt;\">\n Site 1206</p>\n <p>\n  </p>\n </td>\n <td style=\"width:205px;height:19px;\">\n <p>\n Pending</p>\n </td>\n <td style=\"width:132px;height:19px;\">\n <p>\n Pending</p>\n </td>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:213px;height:19px;\">\n <p style=\"margin-left:5.0pt;\">\n Site 1207 </p>\n <p>\n  </p>\n </td>\n <td style=\"width:205px;height:19px;\">\n <p>\n Submitted with this application</p>\n <p>\n  </p>\n </td>\n <td style=\"width:132px;height:19px;\">\n <p>\n Pending</p>\n </td>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:213px;height:19px;\">\n <p style=\"margin-left:5.0pt;\">\n Site 1208</p>\n <p>\n  </p>\n </td>\n <td style=\"width:205px;height:19px;\">\n <p>\n Pending</p>\n </td>\n <td style=\"width:132px;height:19px;\">\n <p>\n Pending</p>\n </td>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:213px;height:19px;\">\n <p style=\"margin-left:5.0pt;\">\n Site 1209</p>\n </td>\n <td style=\"width:205px;height:19px;\">\n <p>\n Pending</p>\n </td>\n <td style=\"width:132px;height:19px;\">\n <p>\n Pending</p>\n </td>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td rowspan=\"2\" style=\"width:97px;height:62px;\">\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n <strong>Z</strong><strong>a</strong><strong>mbia</strong></p>\n </td>\n <td style=\"width:15px;height:62px;\">\n <p style=\"margin-left:.05pt;\">\n §</p>\n </td>\n <td style=\"width:198px;height:62px;\">\n <p style=\"margin-left:6.1pt;\">\n Zambia Medicines Regulatory</p>\n <p style=\"margin-left:6.1pt;\">\n Authority (ZAMRA)</p>\n </td>\n <td style=\"width:205px;height:62px;\">\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n V1.0 Submitted- 31 Oct 2023</p>\n </td>\n <td rowspan=\"2\" style=\"width:132px;height:62px;\">\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n V1.0 N/A</p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p style=\"margin-left:4.85pt;\">\n V2.0 Pending</p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n </td>\n <td height=\"94\" style=\"height:62px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:15px;height:43px;\">\n <p style=\"margin-left:.05pt;\">\n §</p>\n </td>\n <td style=\"width:198px;height:43px;\">\n <p style=\"margin-left:6.1pt;\">\n National Health Research</p>\n <p style=\"margin-left:6.1pt;\">\n Authority (NHRA)</p>\n </td>\n <td style=\"width:205px;height:43px;\">\n <p>\n V2.0 – Submitted  05 Apr 2024</p>\n </td>\n <td height=\"64\" style=\"height:43px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:97px;height:90px;\">\n <p style=\"margin-left:4.85pt;\">\n <strong>M</strong><strong>alawi</strong></p>\n </td>\n <td colspan=\"2\" style=\"width:213px;height:90px;\">\n <p style=\"margin-left:5.0pt;\">\n Pharmacy and Medicines Regulatory</p>\n <p style=\"margin-left:5.0pt;\">\n Authority (PMRA)</p>\n </td>\n <td style=\"width:205px;height:90px;\">\n <p style=\"margin-left:5.0pt;\">\n V1.0 Submitted – 08 Dec 2023</p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n V2.0 Submitted – 15 Mar 2024</p>\n </td>\n <td style=\"width:132px;height:90px;\">\n <p style=\"margin-left:4.85pt;\">\n V1.0  n/a</p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p style=\"margin-left:4.85pt;\">\n V2.0 Pending</p>\n </td>\n <td height=\"135\" style=\"height:90px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:97px;height:69px;\">\n <p>\n  </p>\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n <strong>M</strong><strong>o</strong><strong>z</strong><strong>a</strong><strong>m</strong><strong>bi</strong><strong>que</strong></p>\n </td>\n <td colspan=\"2\" style=\"width:213px;height:69px;\">\n <p>\n  </p>\n <p>\n  </p>\n <p style=\"margin-left:2.7pt;\">\n National Medicines Regulatory</p>\n <p style=\"margin-left:.05pt;\">\n Authority (ANARME)</p>\n </td>\n <td style=\"width:205px;height:69px;\">\n <p>\n  </p>\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n Pending</p>\n </td>\n <td style=\"width:132px;height:69px;\">\n <p>\n  </p>\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n Pending</p>\n </td>\n <td height=\"104\" style=\"height:69px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:97px;height:81px;\">\n <p style=\"margin-left:4.85pt;\">\n <strong>V</strong><strong>ietnam</strong></p>\n </td>\n <td colspan=\"2\" style=\"width:213px;height:81px;\">\n <p style=\"margin-left:5.0pt;\">\n Vietnam Ministry of Health</p>\n </td>\n <td style=\"width:205px;height:81px;\">\n <p style=\"margin-left:5.0pt;\">\n V1.0 Submitted 08 Jan 2024</p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n V2.0 Pending</p>\n </td>\n <td style=\"width:132px;height:81px;\">\n <p style=\"margin-left:4.85pt;\">\n Pending</p>\n </td>\n <td height=\"122\" style=\"height:81px;\">\n  </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n
      • other_details_regulatory_approved<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"648\">\n <tbody>\n <tr>\n <td rowspan=\"2\" style=\"width:97px;height:19px;\">\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n <strong>C</strong><strong>o</strong><strong>u</strong><strong>ntry</strong></p>\n </td>\n <td rowspan=\"2\" style=\"width:213px;height:19px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n <strong>N</strong><strong>ame of Competent Authority</strong></p>\n </td>\n <td rowspan=\"2\" style=\"width:205px;height:19px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n <strong>Submission status</strong></p>\n </td>\n <td rowspan=\"2\" style=\"width:132px;height:19px;\">\n <p style=\"margin-left:4.85pt;\">\n <strong>C</strong><strong>ompetent</strong></p>\n <p style=\"margin-left:4.85pt;\">\n <strong>A</strong><strong>uthority decision</strong></p>\n </td>\n <td height=\"29\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td rowspan=\"2\" style=\"width:97px;height:51px;\">\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n <strong>Kenya</strong></p>\n </td>\n <td colspan=\"3\" style=\"width:551px;height:51px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n Kenya Pharmacy and Poison</p>\n <p style=\"margin-left:5.0pt;\">\n Board (KPPB)</p>\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p>\n  </p>\n </td>\n <td height=\"76\" style=\"height:51px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:213px;height:19px;\">\n <p style=\"margin-left:5.0pt;\">\n Site 1201</p>\n <p>\n  </p>\n </td>\n <td style=\"width:205px;height:19px;\">\n <p>\n V2.0 Submitted 28 Mar 2024</p>\n <p>\n  </p>\n </td>\n <td style=\"width:132px;height:19px;\">\n <p>\n Approved: 25 Apr 2024</p>\n <p>\n  </p>\n </td>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td rowspan=\"2\" style=\"width:97px;height:28px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.25pt;\">\n <strong>South Africa</strong></p>\n </td>\n <td rowspan=\"2\" style=\"width:213px;height:28px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n South Africa Health Products</p>\n <p style=\"margin-left:5.0pt;\">\n Regulatory Authority (SAHPRA)</p>\n </td>\n <td style=\"width:205px;height:28px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n V1.0 Submitted - 11 Aug 2023</p>\n </td>\n <td style=\"width:132px;height:28px;\">\n <p>\n Approved: 15 Nov 2023</p>\n <p>\n  </p>\n <p>\n  </p>\n </td>\n <td height=\"42\" style=\"height:28px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:205px;height:63px;\">\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n V2.0 Submitted – 19 Jan 2024</p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n </td>\n <td style=\"width:132px;height:63px;\">\n <p>\n  </p>\n <p>\n  </p>\n <p>\n Approved: 02 Feb 2024</p>\n </td>\n <td height=\"95\" style=\"height:63px;\">\n  </td>\n </tr>\n <tr>\n <td rowspan=\"2\" style=\"width:97px;height:20px;\">\n <p style=\"margin-left:2.6pt;\">\n <strong>I</strong><strong>ndonesia</strong></p>\n </td>\n <td rowspan=\"2\" style=\"width:213px;height:20px;\">\n <p style=\"margin-left:5.0pt;\">\n Indonesian Food and Drug Authority</p>\n <p style=\"margin-left:5.0pt;\">\n (Indonesia NADFC-BPOM)</p>\n </td>\n <td style=\"width:205px;height:20px;\">\n <p style=\"margin-left:5.0pt;\">\n V1.0 Submitted – 07Sep2023</p>\n </td>\n <td rowspan=\"2\" style=\"width:132px;height:20px;\">\n <p style=\"margin-left:4.85pt;\">\n V1.0 – N/A</p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p style=\"margin-left:4.85pt;\">\n V2.0 – Approved 19 Apr 2024  </p>\n </td>\n <td height=\"30\" style=\"height:20px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:205px;height:75px;\">\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n V2.0 – Submitted  16 Apr 2024</p>\n </td>\n <td height=\"113\" style=\"height:75px;\">\n  </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration4 years
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states7
      • number_of_sites9
      • multi_country_listKenya, South Africa, Malawi, Zambia, Mozambique, Indonesia and Vietnam
      • data_monitoring_committeeYes
      • total_enrolment_per_siteCompetitive enrolment approximated at 500 per Site
      • total_participants_worldwide20,000
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameDr Videlis
      • investigator1_middle_name
      • investigator1_family_nameNduba
      • investigator1_qualificationMBChB, MPH,PhD
      • investigator1_professional_addressKEMRI Centre for Clinical Respiratory Diseases Research (KEMRI CRDR), KEMRI/ CRDR Clinical Research Annex, KNH Complex Behind Government Chemist and Off Raila Odinga Way, P.O Box 47855 - 00100,Nairobi Kenya.
      • investigator1_telephone+254 724 522 474
      • investigator1_emailvnduba@gmail.com
      • organisations_transferred_Yes
      • number_participants4,500
      • notification
      • approval_date08-05-2024
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted30-04-2024
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonApproved based on the AVAREF report of Jan 2024. The report has been attached to the application.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-03-27 16:55:55
      • created2024-04-29 13:07:13
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id1066
        • application_id1402
        • given_nameWilson
        • middle_name
        • family_nameMuraya
        • qualificationMBChB
        • professional_addressKemri-Mtwapa Clinical Research Annex, P.O. Box 428-80108
        • telephone+254721299093
        • emailwmuraya07@gmail.com
        • created2024-04-29 13:22:35
        • modified2024-04-30 12:01:21
    • SiteDetail(array)
      • 0(array)
        • id1705
        • application_id1402
        • county_id3
        • site_nameKEMRI Mtwapa Clinical Research Site- Kilifi
        • physical_addressKemri-Mtwapa Clinical Research Annex
        • contact_details+254721299093; P.O. Box 428-80108
        • contact_personDr Wilson Muraya
        • site_capacity(null)
        • misc(null)
        • created2024-04-29 13:22:35
        • modified2024-04-30 12:01:21
        • County(array)
          • id3
          • county_nameKilifi
          • created2012-05-31 16:15:49
          • modified2012-05-31 16:15:49
    • Sponsor(array)
      • 0(array)
        • id743
        • application_id1402
        • sponsorBill & Melinda Gates Medical Research Institute (Gates MRI)
        • sponsor_typeResearch Institution
        • contact_personKristen Mayer
        • addressOne Kendall Square, Building 600, Suite 6-301, Cambridge, MA 02139, USA
        • telephone_number+1 617-465-0089
        • fax_numberN/A
        • cell_number+1 617-465-0089
        • email_addressKristen.mayer@gatesmri.org
        • created2024-04-29 13:22:35
        • modified2024-04-30 12:01:21
  • 4(array)
    • Application(array)
      • id1403
      • user_id263
      • trial_status_id1
      • abstract_of_study<p class=\"SynchrogenixBodyText\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <span lang=\"EN-US\">Modeling suggests that the most effective contribution to TB control in high burden countries would be a vaccine that prevents pulmonary TB in adolescents and adults [</span><span lang=\"EN-US\" style=\"color: blue;\">WHO</span><span lang=\"EN-US\" style=\"color: blue;\">2021</span><span lang=\"EN-US\">]. In very high incidence geographies, the incidence rate of TB is highest in older adolescents and young adults (e.g., 15 to 44 years of age). In addition, pulmonary TB is the predominant form of TB in this age group (with the primary mode of TB transmission being via aerosol), and young adults are more likely to transmit to more contacts because they are active and mix extensively [</span><span lang=\"EN-US\" style=\"color: blue;\">Knight</span><span lang=\"EN-US\" style=\"color: blue;\">2014</span><span lang=\"EN-US\">].</span></p>\n<p class=\"SynchrogenixBodyText\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n The primary objective of this Phase 3 efficacy trial is to evaluate VE in the prevention of laboratory-confirmed pulmonary TB in IGRA-positive participants who do not have HIV. The rationale for focusing on IGRA-positive participants is based on Phase 3 trial simulations that evaluated the feasibility of demonstrating VE in an “all-comer” population (i.e., regardless of IGRA status) of young adults (15 to 44 years of age) in very high burden settings with an IGRA-positive prevalence of 67%. Based on these simulations, it appears feasible to demonstrate vaccine efficacy against tuberculosis disease (VE[D]) in an IGRA-positive, HIV-negative population, with a sample size of <span class=\"msoIns\"><ins cite=\"mailto:Debbie%20Daehnick%20(DT%20Medical%20Writing%20Corp)\" datetime=\"2024-01-08T12:19\">9</ins></span>,000 participants per arm, within 4 years from start of enrollment, whereas a trial in an all-comer population would have to be much larger, and the larger population would still be inadequate to demonstrate VE(D) in IGRA-negative participants.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Trial simulation assumptions included an annual IGRA conversion rate of 3% per person-year, and an incidence of active pulmonary TB of 0.4% per person-year. These simulations suggested that even with a 67% IGRA-positive prevalence at enrollment, more than 90% of laboratory-confirmed cases of TB would be observed in IGRA-positive participants, and less than 10% in IGRA-negative participants; such a trial would not be powered to demonstrate VE(D) in IGRA-negative participants as a subset.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n A confirmatory trial in IGRA-negative participants is not considered feasible (in a reasonable amount of time and with a reasonable population size), given the low rate of laboratory-confirmed cases expected in baseline IGRA-negative participants. Given the inability to demonstrate VE(D) in IGRA-negative participants as a subset in an ‘all-comer’ trial, this Phase 3 trial aims to demonstrate VE(D) in IGRA-positive participants only, and to generate descriptive safety, immunogenicity, and VE(D) data in a HIV-negative, IGRA-negative Cohort  (N=1,000) and in a cohort of PLHIV (N=1,000) of either positive or negative IGRA status.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n GlaxoSmithKline Biologicals, SA (GSK) developed M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span>, an investigational TB vaccine, to protect against the development of TB in <em>Mtb</em>-infected adolescents and adults. The GSK Phase 2b trial (TB-018) evaluated vaccine safety and efficacy in approximately 3500 IGRA-positive adults (1:1, M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4 </span>and placebo) [Van Der Meeren2018; Tait2019]. Most participants in the TB-018 trial had previously received the BCG vaccine as neonates. The observed VE against active pulmonary TB in the Phase 2b trial was 49.7% (95% CI: 2.1% to 74.2%) at 36 months and no safety signals that would prevent further development were observed [Tait2019].</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n In 2020, the Bill & Melinda Gates Medical Research Institute (Gates MRI) licensed the M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4 </span>investigational TB vaccine for continued development.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n  </p>\n
      • study_title<p>\n <span style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">A Phase 3, randomized, double-blind, placebo-controlled, multicenter, clinical trial to assess the prophylactic efficacy, safety, and immunogenicity of the investigational M72/AS01</span><span style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span><span style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\"> Mycobacterium tuberculosis (Mtb) vaccine when administered intramuscularly on a 0,1-month schedule to adolescents and adults.</span></p>\n
      • laymans_summary<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Tuberculosis (TB) is caused by the bacterium Mycobacterium tuberculosis (Mtb); it typically affects the lungs but can also affect other sites. TB is spread from person to person via the respiratory route and is manifested by the presence of Mtb in sputum. TB is the second leading infectious killer after COVID-19 (above HIV/AIDS). It is present in all countries and age groups, but the larger number of new cases occur in countries of the South-East Asian Region and African Region.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Bacille Calmette-Guérin, known as BCG, is the only licensed TB vaccine to date; however, the impact of BCG on the transmission of Mtb in adults is limited, since it offers minimal or no protection against pulmonary TB in adults. TB treatment is lengthy, and compliance is often incomplete, resulting in an increasing incidence of multi-drug resistant (MDR)-TB and extensively drug resistant (XDR)-TB.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Given the substantial morbidity and mortality associated with TB, the challenges associated with TB treatment, and the limited options for prevention, a vaccine is urgently needed, both to protect against disease, including the progression from latent Mtb infection to active TB, and to accelerate the end of the TB epidemic.</p>\n
      • short_titleGates MRI TBV02-301
      • protocol_noECCT/24/05/01
      • version_no2.0
      • date_of_protocol08-01-2024
      • study_drugM72/AS01E-4 investigational vaccine
      • disease_conditionTuberculosis (TB)
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorNo
      • comparator_nameN/A
      • comparator_registeredN/A
      • comparator_countriesN/A
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressamina.salim@iqvia.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantMaureen Anyango Olwero
      • declaration_date102-05-2024
      • declaration_principal_investigatorVidelis Nduba
      • declaration_date202-05-2024
      • placebo_presentYes
      • study_objectives<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Primary Efficacy Objective:</strong></div>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n To evaluate the vaccine efficacy (VE) of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> in the prevention of laboratory-confirmed pulmonary TB among IGRA-positive participants without HIV infection (IGRA-Positive Cohort) in the per-protocol (PP) analysis set</li>\n</ul>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong font-size:=\"\" trebuchet=\"\">Secondary Efficacy Objectives:</strong></p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n To evaluate the VE of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> in the prevention of <em>Mtb</em> infection among the IGRA-Negative Cohort in the PP analysis set</li>\n <li style=\"line-height: 20px;\">\n To evaluate the VE of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> in the prevention of laboratory-confirmed pulmonary TB among the IGRA-Negative Cohort in the PP analysis set</li>\n <li style=\"line-height: 20px;\">\n To evaluate the VE of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> in the prevention of laboratory-confirmed pulmonary TB among the HIV Cohort in the PP analysis set</li>\n <li style=\"line-height: 20px;\">\n To evaluate the VE of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> in the prevention of less stringently defined laboratory-confirmed pulmonary TB among the IGRA-Positive Cohort in the PP analysis set</li>\n</ul>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Secondary Safety Objective:</strong></p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n To evaluate the safety and reactogenicity following administration of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> vaccine or placebo</li>\n</ul>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Secondary Immunogenicity Objective:</strong></p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n To assess the humoral immunogenicity of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> vaccination</li>\n</ul>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Exploratory Objectives:</strong></p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n To further explore the VE of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> in the prevention of <strong>laboratory</strong>-confirmed pulmonary TB as defined for the primary endpoint, among the IGRA-Positive Cohort in the mITT analysis set</li>\n <li style=\"line-height: 20px;\">\n To explore the effect of potential covariates on the VE of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> in the prevention of <strong>laboratory</strong>-confirmed pulmonary TB as defined for the primary endpoint, among the IGRA-Positive Cohort in the PP analysis set</li>\n <li style=\"line-height: 20px;\">\n To explore the VE of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4 </span>in the prevention of <strong>laboratory-confirmed</strong> pulmonary TB, where sputum was collected up to 28 days after treatment initiation among IGRA-positive, IGRA-negative, and HIV Cohorts, respectively, in the mITT analysis set.</li>\n <li style=\"line-height: 20px;\">\n To explore the VE of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> in the prevention of <strong>clinical</strong> TB (including extrapulmonary TB) defined as a participant for whom a clinician has diagnosed TB, and has initiated TB treatment, in the absence of laboratory-confirmed pulmonary TB, among IGRA-positive, IGRA-negative, and HIV Cohorts, respectively, in the mITT analysis set. </li>\n <li style=\"line-height: 20px;\">\n To explore the VE of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4 </span>in the prevention of <strong>subclinical </strong>TB, defined as a participant with a positive result from Xpert Ultra or similar assay (excluding “trace positive”) from a single sputum sample at the EoT visit, in the absence of signs or symptoms of pulmonary TB, among IGRA-positive, IGRA-negative, and HIV Cohorts, respectively, in the mITT analysis set.</li>\n <li style=\"line-height: 20px;\">\n To assess the cellular immunogenicity of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> vaccination using M72-specific CD4+ and CD8+ T-cell responses measured by co-expression of 2 or more cytokines using intracellular cytokine staining (ICS)</li>\n <li style=\"line-height: 20px;\">\n To further explore the cellular immunogenicity of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> vaccination using M72-specific CD4+ and CD8+ T-cell responses measured by co-expression of multiple functional markers by ICS</li>\n <li style=\"line-height: 20px;\">\n To confirm candidate CoP and CoR if identified in the M72 Immune Correlates Program and to explore new candidate CoP and CoR</li>\n <li style=\"line-height: 20px;\">\n To explore characteristics of <em>Mtb </em>isolates, including drug susceptibility profiles and genetic diversity</li>\n</ul>\n
      • principal_inclusion_criteria<p class=\"SynchrogenixBodyText\" font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <span lang=\"EN-US\">Participants are eligible for randomization and trial intervention administration only if all of the following criteria apply.</span></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n    <strong>Age</strong></p>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Participant must be 15 to 44 years of age (inclusive), at the time of signing the consent or assent.</li>\n</ol>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Type of Participant and Disease Characteristics</strong></p>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"2\">\n Capable of giving informed consent or informed assent (as appropriate). For participants below the age of consent, the participant’s parent, or legally authorized representative (LAR) will be required to sign a statement of informed consent, in addition to the minor’s signed statement of assent.</li>\n <li style=\"line-height: 20px;\" value=\"3\">\n In the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of diary cards as applicable, and return for follow-up visits).</li>\n <li style=\"line-height: 20px;\" value=\"4\">\n Agree to actively stay in contact with the trial site for the duration of the trial for the participants own safety.</li>\n <li style=\"line-height: 20px;\" value=\"5\">\n Agree to provide updated contact information as necessary, and have no current plans to relocate from the trial area for the duration of the trial.</li>\n <li style=\"line-height: 20px;\" value=\"6\">\n Healthy, or with preexisting stable disease, as established by medical history and physical examination and as determined by the investigator. Preexisting stable disease is defined as not requiring significant change in therapy or hospitalization for worsening disease during the 28 days before enrollment.</li>\n <li style=\"line-height: 20px;\" value=\"7\">\n Negative sputum Xpert Ultra or similar assay result at screening </li>\n <li style=\"line-height: 20px;\" value=\"8\">\n Both males and females are included. Females are included with restrictions. Females must either be of non-childbearing potential, defined as pre-menarche, have a history of either current tubal ligation, hysterectomy, or ovariectomy, or post-menopause, <strong>or</strong>, if she is of childbearing potential, she has practiced abstinence from penile-vaginal intercourse or adequate contraception for 28 days prior to vaccination, has a negative pregnancy test on the day of screening and the day of first vaccination, and agrees to continue abstinence or adequate contraception until 2 months after the second dose of trial intervention.</li>\n <li style=\"line-height: 20px;\" value=\"9\">\n HIV-negative test result at screening (IGRA-Positive Cohort and IGRA-Negative Cohort only)</li>\n <li style=\"line-height: 20px;\" value=\"10\">\n HIV Cohort only: Participants with documented<ins cite=\"mailto:Debbie%20Daehnick%20(DT%20Medical%20Writing%20Corp)\" datetime=\"2024-01-08T12:19\">*</ins> HIV infection who fulfill all of the following criteria:</li>\n</ol>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n have reactive anti-HIV antibody at screening</li>\n <li style=\"line-height: 20px;\">\n have been on ART for at least 3 consecutive months at screening and agree to remain on ART throughout the trial</li>\n <li style=\"line-height: 20px;\">\n have documented HIV RNA <200 copies/mL at screening</li>\n <li style=\"line-height: 20px;\">\n have CD4+ cell count ≥200 cells/µL at screening</li>\n <li style=\"line-height: 20px;\">\n have had TPT in the past and are not receiving TPT at the time of screening, according to the judgment of the investigators</li>\n <li style=\"line-height: 20px;\">\n have an IGRA-positive or negative result at screening.</li>\n</ul>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <ins cite=\"mailto:Debbie%20Daehnick%20(DT%20Medical%20Writing%20Corp)\" datetime=\"2024-01-08T12:19\">*Note that ‘documented’ refers to documentation from the site personnel’s review of the participant’s medical records, medical examination, or medical history interview.</ins></p>\n
      • principal_exclusion_criteria<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Participants are excluded from the trial if any of the following criteria apply:</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Medical Conditions</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 1. Current TB, or history of TB or treatment for TB disease</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 2. Clinical suspicion of pulmonary TB at screening, defined as a participant presenting with one or more of the following signs or symptoms: unexplained cough, unexplained fever, night sweats, unintentional weight loss, hemoptysis, pleuritic chest pain</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 3. Any current medical, psychiatric, occupational, or substance abuse problems that, in the opinion of the investigator, will make it unlikely that the participant will comply with the protocol, or that will interfere with the assessments or the safety of the participant</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 4. Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (e.g., invasive, or malignant cancers), other than HIV infection in the HIV Cohort</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 5. Known bleeding disorder that is considered a contracindication to intramuscular injection or phlebotomy </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Prior/Concomitant Therapy</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 6. Any cytotoxic drugs or administration of medications known to have a major impact on the immune system, as determined by the investigator, within 90 days prior to Day 1. These include immune globulin, blood, or blood products, potent immunosuppressants and immunomodulators, and systemic corticosteroids (exceeding 20 mg/day prednisone equivalent). Inhaled, topical, and intra-articular corticosteroids are allowed.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Prior/Concurrent Clinical Trial Experience</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 7. Planned receipt of blood, or blood products during the trial period</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 8. Receipt or planned receipt of any vaccine in the period starting 28 days before, and ending 28 days after, each dose of the trial vaccine</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 9. History of previous administration of an experimental <em>Mtb</em> vaccine including M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E </span>in a previous trial</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 10. History of allergy or hypersensitivity to the trial intervention, excipients, or related substances</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Diagnostic assessments</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 11. An indeterminate IGRA test result at screening</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 12. Female participants with any one of the following conditions: currently pregnant or lactating; having positive serum pregnancy test during the screening window, positive urine pregnancy test on Day 1, planning a pregnancy within 2 months after completion of the vaccination series</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 13. Only in the HIV Cohort: Safety laboratory values at screening that are of concern, based on investigator’s judgment. Note that preexisting stable chronic disease will not necessarily lead to exclusion, especially if laboratory values are graded as mild (Section 13).</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Other Exclusions</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 14. Participation in an interventional clinical trial in which the participant has been or will be exposed to an investigational product (pharmaceutical product or device), within 28 days prior to signing consent or assent, or during the trial period.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 15. Individuals who are acting as personnel for this trial, or who have immediate family members (brother, sister, child, parent, or the spouse/partner) who are acting as personnel for this trial.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 16. Child in Care, defined as a child who is under the care (control or protection) of an agency, organization, institution or entity by the courts, the government body, acting in accordance with powers conferred in them by law or regulations. The definition of a child in care can include a child who is cared for by foster parents or living in a care home or institution, provided that the arrangements fall within the definition above. The definition of a child in care <strong>does not include</strong> a child who is adopted or has an appointed LAR.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 17. Participants who had a Tuberculin Skin Test (TST) within 6 months prior to Day 1</p>\n
      • primary_end_points<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Primary Efficacy Endpoint:</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Laboratory-confirmed pulmonary TB over a period starting 1 month post Dose 2 and lasting up to End of Trial (EoT) where a laboratory-confirmed pulmonary TB case is defined as a participant with:</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 21.6pt; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n ·       Suspected pulmonary TB as defined as a participant presenting with one or more of the following signs or symptoms:</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 39.7pt; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n o   unexplained cough, unintentional weight loss, hemoptysis, unexplained fever, night sweats, pleuritic chest pain</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n who has</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n At least 2 positive <em>Mtb</em> test results (positive <em>Mtb</em> culture and/or positive test result from Xpert Ultra or similar assay, excluding “trace positive”), from the same or from different sputum samples collected during 3 suspected TB visits, preferably within a 7-day time frame, before initiation of TB treatment</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Secondary Efficacy Endpoints:</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Sustained QuantiFERON®-TB Gold Plus assay (or similar) conversion (i.e., initial conversion and IGRA-positive test result at next attended scheduled visit) over a period starting 1 month post dose 2 and lasting up to EoT </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Laboratory-confirmed pulmonary TB over a period starting 1 month post Dose 2 and lasting up to EoT, where a laboratory-confirmed pulmonary TB case follows the same definition as the primary endpoint</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Laboratory-confirmed pulmonary TB over a period starting 1 month post Dose 2 and lasting up to EoT, where a laboratory-confirmed pulmonary TB case follows the same definition as the primary endpoint</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Laboratory-confirmed pulmonary TB over a period starting 1 month post Dose 2 and lasting up to EoT, where a laboratory-confirmed pulmonary TB case is defined less stringently as a participant with:</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 17.3pt; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n ·       Suspected pulmonary TB as defined for the primary efficacy endpoint, and</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n At least 1 positive <em>Mtb</em> culture or at least 1 positive result from Xpert Ultra or similar assay (excluding “trace positive”),from the same or from different sputum samples collected during the 3 suspected TB visits, preferably within a 7-day time frame, before initiation of TB treatment</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Secondary Safety Endpoints:</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Occurrence of solicited AEs during the 7 days following each vaccination (starting on day of vaccination and 6 subsequent days after each vaccine dose) Safety analysis set</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Occurrence of unsolicited AEs during the 28 days following each vaccination (starting on day of vaccination and 27 subsequent days after each vaccine dose) Safety analysis set</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Occurrence of all serious adverse events (SAEs) and potential immune-mediated diseases (pIMDs) from Day 1 through Month 13, Safety analysis set</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Occurrence of SAEs related to trial participation through <ins cite=\"mailto:Debbie%20Daehnick%20(DT%20Medical%20Writing%20Corp)\" datetime=\"2024-01-08T12:19\">trial</ins> end, Safety analysis set</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Secondary Immunogenicity Endpoint:</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Geometric mean concentration (GMC) and seropositivity of M72-specific antibodies at Day 1, Month 1, Month 2, Month 7, Month 13, Month 37, and Month 49 among each of the IGRA-Positive Cohort, IGRA-Negative Cohort, and HIV Cohorts in the per-protocol for immunogenicity (PPI) analyses set</p>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p style=\"margin-bottom: 8px;\">\n <span class=\"ui-provider a b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\"><span style=\"font-size: inherit;\">Site activities are located in Nairobi City County, at the Centre for Respiratory Disease Research within the Kenyatta National Referral Hospital Complex. The facility has clinical rooms available for consenting, nursing procedures and clinical reviews. There are also additional facilities that include an inpatient ward, temperature and access-controlled pharmacy, study record archival space, a laboratory, staff work stations, a monitoring space and kitchen for preparing participants’ meals. The site has been identified for this study due to high TB burden in the catchment area.</span></span></p>\n<p style=\"margin-bottom: 8px;\">\n <span class=\"ui-provider a b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\"><span style=\"font-size: inherit;\">Nairobi is a cosmopolitan city with a population of >3 million. A 2017 national TB prevalence survey report, 50 years after the last TB prevalence report was done, indicated that the burden of TB in Kenya was higher than previously thought, with a prevalence of 558/100,000 population against WHO 2015 estimates of 233/100,000 population (Center for Health Solutions, 2017) and compared to rural settings (453 per 100,000 population) which is consistent with routine TB data which shows higher notification in the big cities. The clinical trial site is also well-equipped with the requisite infrastructure for the conduct of a TB vaccine study. These include good internet connectivity, computers and laptops for data management, laboratories for collection and processing of sputum, safety and immunogenicity samples, sputum culture, Good Clinical Practice (GCP) trained and experienced staff including the principal investigator, 6 medical officers, 2 pharmacists, 1 pharmaceutical technician, 6 nurses, 13 quality control officers, 9 clinical officers, 3 phlebotomist, 8 laboratory scientists, 4 laboratory technologists, 6 data management officers, 8 administrators and 14 community interviewers.</span></span></p>\n
      • other_details_explanation<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">This Phase 3 TB vaccine trial will be conducted in adolescents and adults in communities with a high burden of pulmonary tuberculosis (TB). The trial is being conducted in Kenya because TB is significantly more prevalent (>200 cases per 100,000 population) than the USA (<3 cases per 100,000 population).  </span></p>\n
      • other_details_regulatory_notapproved<p>\n  </p>\n<p>\n  </p>\n<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"648\">\n <tbody>\n <tr>\n <td rowspan=\"2\" style=\"width:97px;height:19px;\">\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n <strong>C</strong><strong>o</strong><strong>u</strong><strong>ntry</strong></p>\n </td>\n <td colspan=\"2\" rowspan=\"2\" style=\"width:213px;height:19px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n <strong>N</strong><strong>ame of Competent Authority</strong></p>\n </td>\n <td rowspan=\"2\" style=\"width:205px;height:19px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n <strong>Submission status</strong></p>\n </td>\n <td rowspan=\"2\" style=\"width:132px;height:19px;\">\n <p style=\"margin-left:4.85pt;\">\n <strong>C</strong><strong>ompetent</strong></p>\n <p style=\"margin-left:4.85pt;\">\n <strong>A</strong><strong>uthority decision</strong></p>\n </td>\n <td height=\"29\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td rowspan=\"9\" style=\"width:97px;height:51px;\">\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n <strong>Kenya</strong></p>\n </td>\n <td colspan=\"4\" style=\"width:551px;height:51px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n Kenya Pharmacy and Poison</p>\n <p style=\"margin-left:5.0pt;\">\n Board (KPPB)</p>\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p>\n  </p>\n </td>\n <td height=\"76\" style=\"height:51px;\">\n  </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:213px;height:19px;\">\n <p style=\"margin-left:5.0pt;\">\n Site 1202</p>\n <p>\n  </p>\n </td>\n <td style=\"width:205px;height:19px;\">\n <p>\n Pending</p>\n </td>\n <td style=\"width:132px;height:19px;\">\n <p>\n Pending</p>\n </td>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:213px;height:19px;\">\n <p style=\"margin-left:5.0pt;\">\n Site 1203</p>\n <p>\n  </p>\n </td>\n <td style=\"width:205px;height:19px;\">\n <p>\n Pending</p>\n </td>\n <td style=\"width:132px;height:19px;\">\n <p>\n Pending</p>\n </td>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:213px;height:19px;\">\n <p style=\"margin-left:5.0pt;\">\n Site 1204</p>\n <p>\n  </p>\n </td>\n <td style=\"width:205px;height:19px;\">\n <p>\n Pending</p>\n </td>\n <td style=\"width:132px;height:19px;\">\n <p>\n Pending</p>\n </td>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:213px;height:19px;\">\n <p style=\"margin-left:5.0pt;\">\n Site 1205</p>\n <p>\n  </p>\n </td>\n <td style=\"width:205px;height:19px;\">\n <p>\n Pending</p>\n </td>\n <td style=\"width:132px;height:19px;\">\n <p>\n Pending</p>\n </td>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:213px;height:19px;\">\n <p style=\"margin-left:5.0pt;\">\n Site 1206</p>\n <p>\n  </p>\n </td>\n <td style=\"width:205px;height:19px;\">\n <p>\n Pending</p>\n </td>\n <td style=\"width:132px;height:19px;\">\n <p>\n Pending</p>\n </td>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:213px;height:19px;\">\n <p style=\"margin-left:5.0pt;\">\n Site 1207 </p>\n <p>\n  </p>\n </td>\n <td style=\"width:205px;height:19px;\">\n <p>\n Submitted_30 Apr 2024</p>\n <p>\n  </p>\n </td>\n <td style=\"width:132px;height:19px;\">\n <p>\n Pending</p>\n </td>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:213px;height:19px;\">\n <p style=\"margin-left:5.0pt;\">\n Site 1208</p>\n <p>\n  </p>\n </td>\n <td style=\"width:205px;height:19px;\">\n <p>\n Pending</p>\n </td>\n <td style=\"width:132px;height:19px;\">\n <p>\n Pending</p>\n </td>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:213px;height:19px;\">\n <p style=\"margin-left:5.0pt;\">\n Site 1209</p>\n </td>\n <td style=\"width:205px;height:19px;\">\n <p>\n Submitted with this application</p>\n </td>\n <td style=\"width:132px;height:19px;\">\n <p>\n Pending</p>\n </td>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td rowspan=\"2\" style=\"width:97px;height:62px;\">\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n <strong>Z</strong><strong>a</strong><strong>mbia</strong></p>\n </td>\n <td style=\"width:15px;height:62px;\">\n <p style=\"margin-left:.05pt;\">\n §</p>\n </td>\n <td style=\"width:198px;height:62px;\">\n <p style=\"margin-left:6.1pt;\">\n Zambia Medicines Regulatory</p>\n <p style=\"margin-left:6.1pt;\">\n Authority (ZAMRA)</p>\n </td>\n <td style=\"width:205px;height:62px;\">\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n V1.0 Submitted- 31 Oct 2023</p>\n </td>\n <td rowspan=\"2\" style=\"width:132px;height:62px;\">\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n V1.0 N/A</p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p style=\"margin-left:4.85pt;\">\n V2.0 Pending</p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n </td>\n <td height=\"94\" style=\"height:62px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:15px;height:43px;\">\n <p style=\"margin-left:.05pt;\">\n §</p>\n </td>\n <td style=\"width:198px;height:43px;\">\n <p style=\"margin-left:6.1pt;\">\n National Health Research</p>\n <p style=\"margin-left:6.1pt;\">\n Authority (NHRA)</p>\n </td>\n <td style=\"width:205px;height:43px;\">\n <p>\n V2.0 – Submitted  05 Apr 2024</p>\n </td>\n <td height=\"64\" style=\"height:43px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:97px;height:90px;\">\n <p style=\"margin-left:4.85pt;\">\n <strong>M</strong><strong>alawi</strong></p>\n </td>\n <td colspan=\"2\" style=\"width:213px;height:90px;\">\n <p style=\"margin-left:5.0pt;\">\n Pharmacy and Medicines Regulatory</p>\n <p style=\"margin-left:5.0pt;\">\n Authority (PMRA)</p>\n </td>\n <td style=\"width:205px;height:90px;\">\n <p style=\"margin-left:5.0pt;\">\n V1.0 Submitted – 08 Dec 2023</p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n V2.0 Submitted – 15 Mar 2024</p>\n </td>\n <td style=\"width:132px;height:90px;\">\n <p style=\"margin-left:4.85pt;\">\n V1.0  n/a</p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p style=\"margin-left:4.85pt;\">\n V2.0 Pending</p>\n </td>\n <td height=\"135\" style=\"height:90px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:97px;height:69px;\">\n <p>\n  </p>\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n <strong>M</strong><strong>o</strong><strong>z</strong><strong>a</strong><strong>m</strong><strong>bi</strong><strong>que</strong></p>\n </td>\n <td colspan=\"2\" style=\"width:213px;height:69px;\">\n <p>\n  </p>\n <p>\n  </p>\n <p style=\"margin-left:2.7pt;\">\n National Medicines Regulatory</p>\n <p style=\"margin-left:.05pt;\">\n Authority (ANARME)</p>\n </td>\n <td style=\"width:205px;height:69px;\">\n <p>\n  </p>\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n Pending</p>\n </td>\n <td style=\"width:132px;height:69px;\">\n <p>\n  </p>\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n Pending</p>\n </td>\n <td height=\"104\" style=\"height:69px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:97px;height:81px;\">\n <p style=\"margin-left:4.85pt;\">\n <strong>V</strong><strong>ietnam</strong></p>\n </td>\n <td colspan=\"2\" style=\"width:213px;height:81px;\">\n <p style=\"margin-left:5.0pt;\">\n Vietnam Ministry of Health</p>\n </td>\n <td style=\"width:205px;height:81px;\">\n <p style=\"margin-left:5.0pt;\">\n V1.0 Submitted 08 Jan 2024</p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n V2.0 Pending</p>\n </td>\n <td style=\"width:132px;height:81px;\">\n <p style=\"margin-left:4.85pt;\">\n Pending</p>\n </td>\n <td height=\"122\" style=\"height:81px;\">\n  </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_regulatory_approved<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" width=\"648\">\n <tbody>\n <tr>\n <td rowspan=\"2\" style=\"width:97px;height:19px;\">\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n <strong>C</strong><strong>o</strong><strong>u</strong><strong>ntry</strong></p>\n </td>\n <td rowspan=\"2\" style=\"width:213px;height:19px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n <strong>N</strong><strong>ame of Competent Authority</strong></p>\n </td>\n <td rowspan=\"2\" style=\"width:205px;height:19px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n <strong>Submission status</strong></p>\n </td>\n <td rowspan=\"2\" style=\"width:132px;height:19px;\">\n <p style=\"margin-left:4.85pt;\">\n <strong>C</strong><strong>ompetent</strong></p>\n <p style=\"margin-left:4.85pt;\">\n <strong>A</strong><strong>uthority decision</strong></p>\n </td>\n <td height=\"29\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td rowspan=\"2\" style=\"width:97px;height:51px;\">\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n <strong>Kenya</strong></p>\n </td>\n <td colspan=\"3\" style=\"width:551px;height:51px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n Kenya Pharmacy and Poison</p>\n <p style=\"margin-left:5.0pt;\">\n Board (KPPB)</p>\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p>\n  </p>\n </td>\n <td height=\"76\" style=\"height:51px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:213px;height:19px;\">\n <p style=\"margin-left:5.0pt;\">\n Site 1201</p>\n <p>\n  </p>\n </td>\n <td style=\"width:205px;height:19px;\">\n <p>\n V2.0 Submitted 28 Mar 2024</p>\n </td>\n <td style=\"width:132px;height:19px;\">\n <p>\n Approved: 25Apr2024</p>\n <p>\n  </p>\n </td>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td rowspan=\"2\" style=\"width:97px;height:28px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.25pt;\">\n <strong>South Africa</strong></p>\n </td>\n <td rowspan=\"2\" style=\"width:213px;height:28px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n South Africa Health Products</p>\n <p style=\"margin-left:5.0pt;\">\n Regulatory Authority (SAHPRA)</p>\n </td>\n <td style=\"width:205px;height:28px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n V1.0 Submitted - 11Aug2023</p>\n </td>\n <td style=\"width:132px;height:28px;\">\n <p>\n Approved: 15 Nov 2023</p>\n <p>\n  </p>\n <p>\n  </p>\n </td>\n <td height=\"42\" style=\"height:28px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:205px;height:63px;\">\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n V2.0 Submitted – 19 Jan 2024</p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n </td>\n <td style=\"width:132px;height:63px;\">\n <p>\n  </p>\n <p>\n  </p>\n <p>\n Approved: 02 Feb 2024</p>\n </td>\n <td height=\"95\" style=\"height:63px;\">\n  </td>\n </tr>\n <tr>\n <td rowspan=\"2\" style=\"width:97px;height:20px;\">\n <p style=\"margin-left:2.6pt;\">\n <strong>I</strong><strong>ndonesia</strong></p>\n </td>\n <td rowspan=\"2\" style=\"width:213px;height:20px;\">\n <p style=\"margin-left:5.0pt;\">\n Indonesian Food and Drug Authority</p>\n <p style=\"margin-left:5.0pt;\">\n (Indonesia NADFC-BPOM)</p>\n </td>\n <td style=\"width:205px;height:20px;\">\n <p style=\"margin-left:5.0pt;\">\n V1,0 Submitted – 07Sep2023</p>\n </td>\n <td rowspan=\"2\" style=\"width:132px;height:20px;\">\n <p style=\"margin-left:4.85pt;\">\n V1.0 – N/A</p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p style=\"margin-left:4.85pt;\">\n V2.0 – Approved 19 Apr 2024  </p>\n </td>\n <td height=\"30\" style=\"height:20px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:205px;height:75px;\">\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n V2.0 – Submitted -16Apr2024</p>\n </td>\n <td height=\"113\" style=\"height:75px;\">\n  </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n<p>\n  </p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration4 years
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states7
      • number_of_sites9
      • multi_country_listKenya, South Africa, Malawi, Zambia, Mozambique, Indonesia and Vietnam
      • data_monitoring_committeeYes
      • total_enrolment_per_siteCompetitive enrolment approximated at 500 per Site
      • total_participants_worldwide20,000
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameDr Videlis
      • investigator1_middle_name
      • investigator1_family_nameNduba
      • investigator1_qualificationMBChB, MPH,PhD
      • investigator1_professional_addressKEMRI Centre for Clinical Respiratory Diseases Research (KEMRI CRDR), KEMRI/ CRDR Clinical Research Annex, KNH Complex Behind Government Chemist and Off Raila Odinga Way, P.O Box 47855 - 00100,Nairobi Kenya.
      • investigator1_telephone+254 724 522 474
      • investigator1_emailvnduba@gmail.com
      • organisations_transferred_Yes
      • number_participants4,500
      • notification
      • approval_date08-05-2024
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted02-05-2024
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonApproved after compliance with AVAREF Joint review recommendations.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-04-08 13:56:03
      • created2024-05-02 12:52:38
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id1067
        • application_id1403
        • given_nameDr Videlis
        • middle_name
        • family_nameNduba
        • qualificationMBChB, MPH,PhD
        • professional_addressKEMRI Centre for Clinical Respiratory Diseases Research (KEMRI CRDR), KEMRI/ CRDR Clinical Research Annex, KNH Complex Behind Government Chemist and Off Raila Odinga Way, P.O Box 47855 - 00100,Nairobi Kenya.
        • telephone+254 724 522 474
        • emailvnduba@gmail.com
        • created2024-05-02 12:55:32
        • modified2024-05-02 15:23:57
    • SiteDetail(array)
      • 0(array)
        • id1706
        • application_id1403
        • county_id47
        • site_nameKEMRI Centre for Clinical Respiratory Diseases Research (KEMRI CRDR)-Nairobi
        • physical_address KEMRI/ CRDR Clinical Research Annex, KNH Complex Behind Government Chemist and Off Raila Odinga Way
        • contact_details+254 724 522 474; P.O Box 47855 - 00100,Nairobi Kenya.
        • contact_personDr Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2024-05-02 12:55:32
        • modified2024-05-02 15:23:57
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
    • Sponsor(array)
      • 0(array)
        • id744
        • application_id1403
        • sponsorBill & Melinda Gates Medical Research Institute (Gates MRI)
        • sponsor_typeResearch Institution
        • contact_personKristen Mayer
        • addressOne Kendall Square, Building 600, Suite 6-301, Cambridge, MA 02139, USA
        • telephone_number+1 617-465-0089
        • fax_numberN/A
        • cell_number+1 617-465-0089
        • email_addressKristen.mayer@gatesmri.org
        • created2024-05-02 12:55:32
        • modified2024-05-02 15:23:57
• page_options(array)
  • 55
  • 1010
• redir
• $request->data(array)
  • Application(array)
    • approved1
• $this->validationErrors(array)
  • Permission(empty)
  • Aro(empty)
  • Aco(empty)
  • Application(empty)
  • User(empty)
  • TrialStatus(empty)
  • InvestigatorContact(empty)
  • Sponsor(empty)
  • SiteDetail(empty)
  • County(empty)
• Loaded Helpers(array)
  • 0Html
  • 1Form
  • 2Session
  • 3Text
  • 4Number
  • 5SimpleGraph
  • 6Paginator
  • 7DebugTimer
  • 8Toolbar
  • 9HtmlToolbar

App Constants

CakePHP Constants

PHP Environment

Included Files

Include Paths

• 0/var/www/html/ctr/app/Plugin/Media/Lib/mm/src
• 1/var/www/html/ctr/lib
• 3/usr/share/php
• 4-> /var/www/html/ctr/lib/Cake/

Included Files

• core(array)
  • Behavior(array)
    • 0CORE/Model/Behavior/TreeBehavior.php
    • 1CORE/Model/Behavior/ContainableBehavior.php
    • 2CORE/Model/Behavior/AclBehavior.php
  • Cache(array)
    • 0CORE/Cache/Cache.php
    • 1CORE/Cache/Engine/FileEngine.php
    • 2CORE/Cache/CacheEngine.php
  • Component(array)
    • 0CORE/Controller/Component/AclComponent.php
    • 1CORE/Controller/Component/Acl/DbAcl.php
    • 2CORE/Controller/Component/Acl/AclInterface.php
    • 3CORE/Controller/Component/AuthComponent.php
    • 4CORE/Controller/Component/RequestHandlerComponent.php
    • 5CORE/Controller/Component/SessionComponent.php
    • 6CORE/Controller/Component/PaginatorComponent.php
  • Config(array)
    • 0CORE/Config/routes.php
    • 1CORE/Config/config.php
  • Controller(array)
    • 0CORE/Controller/Controller.php
    • 1CORE/Controller/ComponentCollection.php
    • 2CORE/Controller/Component.php
  • Datasource(array)
    • 0CORE/Model/Datasource/CakeSession.php
    • 1CORE/Model/Datasource/Database/Mysql.php
    • 2CORE/Model/Datasource/DboSource.php
    • 3CORE/Model/Datasource/DataSource.php
  • Error(array)
    • 0CORE/Error/exceptions.php
    • 1CORE/Error/ErrorHandler.php
  • I18n(array)
    • 0CORE/I18n/I18n.php
    • 1CORE/I18n/L10n.php
  • Log(array)
    • 0CORE/Log/CakeLog.php
    • 1CORE/Log/LogEngineCollection.php
    • 2CORE/Log/Engine/FileLog.php
    • 3CORE/Log/Engine/BaseLog.php
    • 4CORE/Log/CakeLogInterface.php
  • Model(array)
    • 0CORE/Model/ConnectionManager.php
    • 1CORE/Model/Permission.php
    • 2CORE/Model/Model.php
    • 3CORE/Model/BehaviorCollection.php
    • 4CORE/Model/Aro.php
    • 5CORE/Model/AclNode.php
    • 6CORE/Model/Aco.php
    • 7CORE/Model/ModelBehavior.php
  • Network(array)
    • 0CORE/Network/CakeRequest.php
    • 1CORE/Network/CakeResponse.php
  • Other(array)
    • 0CORE/bootstrap.php
    • 1CORE/basics.php
    • 2CORE/Core/App.php
    • 3CORE/Core/Configure.php
    • 4CORE/Core/CakePlugin.php
    • 5CORE/Event/CakeEventListener.php
    • 6CORE/Event/CakeEvent.php
    • 7CORE/Event/CakeEventManager.php
    • 8CORE/Core/Object.php
  • Routing(array)
    • 0CORE/Routing/Dispatcher.php
    • 1CORE/Routing/Filter/AssetDispatcher.php
    • 2CORE/Routing/DispatcherFilter.php
    • 3CORE/Routing/Filter/CacheDispatcher.php
    • 4CORE/Routing/Router.php
    • 5CORE/Routing/Route/CakeRoute.php
    • 6CORE/Routing/Route/PluginShortRoute.php
  • Utility(array)
    • 0CORE/Utility/Hash.php
    • 1CORE/Utility/Inflector.php
    • 2CORE/Utility/ObjectCollection.php
    • 3CORE/Utility/Debugger.php
    • 4CORE/Utility/String.php
    • 5CORE/Utility/ClassRegistry.php
    • 6CORE/Utility/Set.php
    • 7CORE/Utility/Sanitize.php
  • View(array)
    • 0CORE/View/HelperCollection.php
• app(array)
  • Behavior(array)
    • 0APP/Model/Behavior/SoftDeleteBehavior.php
  • Config(array)
    • 0APP/Config/core.php
    • 1APP/Config/bootstrap.php
    • 2APP/Config/routes.php
    • 3APP/Config/database.php
  • Controller(array)
    • 0APP/Controller/ApplicationsController.php
    • 1APP/Controller/AppController.php
  • Model(array)
    • 0APP/Model/AppModel.php
    • 1APP/Model/Application.php
    • 2APP/Model/User.php
    • 3APP/Model/TrialStatus.php
    • 4APP/Model/InvestigatorContact.php
    • 5APP/Model/Sponsor.php
    • 6APP/Model/SiteDetail.php
    • 7APP/Model/County.php
  • Other(array)
    • 0APP/webroot/index.php
• plugins(array)
  • CakePdf(array)
    • Config(array)
      • 0CakePdf/Config/bootstrap.php
      • 1CakePdf/Config/routes.php
  • CakeResque(array)
    • Config(array)
      • 0CakeResque/Config/bootstrap.php
    • Plugin(array)
      • 0CakeResque/Lib/CakeResque.php
      • 1CakeResque/vendor/kamisama/php-resque-ex/lib/Resque.php
      • 2CakeResque/vendor/kamisama/php-resque-ex/lib/Resque/Event.php
      • 3CakeResque/vendor/kamisama/php-resque-ex/lib/Resque/Exception.php
  • DebugKit(array)
    • Component(array)
      • 0DebugKit/Controller/Component/ToolbarComponent.php
    • Plugin(array)
      • 0DebugKit/Lib/DebugMemory.php
      • 1DebugKit/Lib/Panel/HistoryPanel.php
      • 2DebugKit/Lib/DebugPanel.php
      • 3DebugKit/Lib/Panel/SessionPanel.php
      • 4DebugKit/Lib/Panel/RequestPanel.php
      • 5DebugKit/Lib/Panel/SqlLogPanel.php
      • 6DebugKit/Lib/Panel/TimerPanel.php
      • 7DebugKit/Lib/Panel/LogPanel.php
      • 8DebugKit/Lib/Log/Engine/DebugKitLog.php
      • 9DebugKit/Lib/Panel/VariablesPanel.php
      • 10DebugKit/Lib/Panel/EnvironmentPanel.php
      • 11DebugKit/Lib/Panel/IncludePanel.php
      • 12DebugKit/Lib/DebugTimer.php
  • Media(array)
    • Config(array)
      • 0Media/Config/bootstrap.php
    • Plugin(array)
      • 0Media/Lib/mm/src/Mime/Type.php
      • 1Media/Lib/mm/src/Mime/Type/Magic/Adapter/Fileinfo.php
      • 2Media/Lib/mm/src/Mime/Type/Magic/Adapter.php
      • 3Media/Lib/mm/src/Mime/Type/Glob/Adapter/Memory.php
      • 4Media/Lib/mm/src/Mime/Type/Glob/Adapter.php
      • 5Media/Lib/mm/src/Media/Process.php
      • 6Media/Lib/mm/src/Media/Info.php
  • Search(array)
    • Component(array)
      • 0Search/Controller/Component/PrgComponent.php
    • Behavior(array)
      • 0Search/Model/Behavior/SearchableBehavior.php
  • Shim(array)
    • Config(array)
      • 0Shim/Config/bootstrap.php
  • Tools(array)
    • Config(array)
      • 0Tools/Config/bootstrap.php