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• applications(array)
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    • Application(array)
      • id1452
      • user_id693
      • trial_status_id(null)
      • abstract_of_study<div>\n <strong>BACKGROUND</strong></div>\n<div>\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>\n  </div>\n<div>\n <strong>STUDY RATIONALE</strong></div>\n<div>\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>\n  </div>\n<div>\n <strong>OBJECTIVES AND ENDPOINTS</strong></div>\n<div>\n Primary Objective:</div>\n<div>\n To evaluate the long-term safety of astegolimab</div>\n<div>\n Corresponding Endpoint:</div>\n<div>\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>\n  </div>\n<div>\n <strong>OVERALL DESIGN AND STUDY POPULATION</strong></div>\n<div>\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>\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 A PHASE III OPEN-LABEL EXTENSION STUDY TO EVALUATE THE LONG-TERM SAFETY OF ASTEGOLIMAB IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE</p>\n
      • laymans_summary<div>\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>\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>\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>\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>\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/24/08/03
      • 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_nameAstegolimab (RO7187807)
      • 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_applicantKarabo Tsoku
      • declaration_date113-08-2024
      • declaration_principal_investigatorProf Videlis Nduba
      • declaration_date213-08-2024
      • placebo_presentNo
      • study_objectives<div>\n <strong>Primary Objective</strong></div>\n<ul>\n <li>\n To evaluate the long-term safety of astegolimab</li>\n</ul>\n<div>\n <strong>Exploratory Objectives</strong></div>\n<ul>\n <li>\n To evaluate the efficacy of astegolimab</li>\n <li>\n To evaluate health status utility scores of participants treated with astegolimab</li>\n <li>\n To evaluate the long-term safety of astegolimab</li>\n <li>\n To characterize the PK profile of astegolimab</li>\n <li>\n To evaluate the immune response to astegolimab</li>\n <li>\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>\n <li>\n Signed Informed Consent Form.</li>\n <li>\n Ability to comply with the requirements of the study protocol, according to the investigator’s best judgment.</li>\n <li>\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>\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>\n <li>\n Withdrawal of consent and/or premature discontinuation from parent study</li>\n <li>\n Any permanent discontinuation of study drug in parent study</li>\n <li>\n Significant non-compliance in the parent study, specifically defined as missing scheduled visits, per investigator’s judgment</li>\n <li>\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>\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 <li>\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>\n <li>\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>\n Initiation of treatment that is considered palliative (e.g., for life expectancy < 12 months) since enrolling in the parent study</li>\n <li>\n History of severe allergic reaction or anaphylactic reaction to any biologic agent or known hypersensitivity to any component of astegolimab</li>\n </ul>\n <div>\n <ul>\n <li>\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 </ul>\n <div>\n <ul>\n <li>\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 </ul>\n <div>\n <ul>\n <li>\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>\n <div>\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</div>\n </li>\n </ul>\n </div>\n </div>\n </div>\n</div>\n
      • primary_end_points<div>\n <strong>Primary Objective Endpoints</strong></div>\n<div>\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_pharmacogenetic1
      • 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 The site has a network of health facilities and communities  that collaborate with KEMRI in clinical trials; the site reaches out to these stakeholders to refer eligible participants.</p>\n<p>\n The KEMRI-Mtwapa Clinical Research site is a fully equipped trial site. The site has a fully equipped laboratory with the ability to perform basic clinical tests including full blood count, renal and liver function tests and other chemistry tests. It has been equipped with a sponsor-provided Spirometer with ECG performance capability. Study staff have been trained on spirometry the use of the ECG component.</p>\n<p>\n The site has access to appropriate safety measures and has highly capable clinical site personnel experienced in conducting clinical trials. Site staff include the principal investigator, 4 Sub-PIs, 1 medical officer, 2 clinical officers, 1 administrator and 4 community health workers. The site is taking part in the parent 52-week placebo-controlled Phase III (GB44332) astegolimab study, a prerequisite for this  open-label extension (OLE) study. </p>\n
      • other_details_explanation<p>\n Switzerland is the host country and we already received approval in Switzerland. CEC and RA approvals were received on 17-Sep-2024</p>\n
      • other_details_regulatory_notapproved<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:589px;\" width=\"589\">\n <tbody>\n <tr>\n <td colspan=\"3\" style=\"width:589px;height:21px;\">\n <p>\n <strong>I</strong><strong>NDIA                                                                                DATE SUBMITTED</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:18px;\">\n <p>\n 30-Apr-2024</p>\n </td>\n <td style=\"width:161px;height:18px;\">\n <p>\n Pending</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:589px;height:18px;\">\n <p>\n <strong>P</strong><strong>HILIPPINES</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:18px;\">\n <p>\n 18-Apr-2024</p>\n </td>\n <td style=\"width:161px;height:18px;\">\n <p>\n Pending</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n <strong>C</strong><strong>HINA</strong></p>\n </td>\n <td style=\"width:141px;height:18px;\">\n <p>\n To be submitted</p>\n </td>\n <td style=\"width:161px;height:18px;\">\n <p>\n To be submitted</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n <strong>B</strong><strong>RAZIL</strong></p>\n </td>\n <td style=\"width:141px;height:18px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:161px;height:18px;\">\n <p>\n  </p>\n </td>\n </tr>\n </tbody>\n</table>\n<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:589px;\" width=\"589\">\n <tbody>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:18px;\">\n <p>\n 16-May-2024</p>\n </td>\n <td style=\"width:161px;height:18px;\">\n <p>\n Pending</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n <strong>K</strong><strong>ENYA</strong></p>\n </td>\n <td style=\"width:141px;height:18px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:161px;height:18px;\">\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:18px;\">\n <p>\n 13-Jun-2024 (first site)</p>\n </td>\n <td style=\"width:161px;height:18px;\">\n <p>\n Pending</p>\n </td>\n </tr>\n </tbody>\n</table>\n<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:589px;\" width=\"589\">\n <tbody>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n <strong>P</strong><strong>ERU</strong></p>\n </td>\n <td style=\"width:141px;height:18px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:161px;height:18px;\">\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:18px;\">\n <p>\n 15-Mar-2024 (first site)</p>\n </td>\n <td style=\"width:161px;height:18px;\">\n <p>\n Pending</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n AUSTRIA</td>\n <td style=\"width:141px;height:18px;\">\n 25Jun2024</td>\n <td style=\"width:161px;height:18px;\">\n Pending expected by 24-Sep2024</td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_regulatory_approved<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:589px;\" width=\"589\">\n <tbody>\n <tr>\n <td colspan=\"3\" style=\"width:589px;height:37px;\">\n <p>\n <strong>List of Competent Authorities inside the EU/EEA to which the Application has been Approved </strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:37px;\">\n <p>\n <strong>Member State </strong></p>\n </td>\n <td style=\"width:141px;height:37px;\">\n <p>\n <strong>Date Submitted</strong></p>\n </td>\n <td style=\"width:161px;height:37px;\">\n <p>\n <strong>Outcome Date</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:107px;\">\n <p>\n <strong>EU</strong> <strong>CTR</strong></p>\n <p>\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=\"width:141px;height:107px;\">\n <p>\n 30-May-2023</p>\n </td>\n <td style=\"width:161px;height:107px;\">\n <p>\n Approved, 2-Oct2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:107px;\">\n <p>\n <strong>EU</strong> <strong>CTR</strong></p>\n <p>\n GREECE, HUNGARY, ITALY, LATVIA</p>\n </td>\n <td style=\"width:141px;height:107px;\">\n <p>\n 25-Jun-2024</p>\n </td>\n <td style=\"width:161px;height:107px;\">\n <p>\n  </p>\n <p>\n GREECE – Approved, 18-Sep2024</p>\n <p>\n HUNGARY - Approved, 03-Sep2024</p>\n <p>\n ITALY - Approved, 16-Sep2024</p>\n <p>\n LATVIA - Approved, 17-Sep2024</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\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\" style=\"width:589px;\" width=\"589\">\n <tbody>\n <tr>\n <td style=\"width:287px;height:37px;\">\n <p>\n <strong>Country</strong></p>\n </td>\n <td style=\"width:141px;height:37px;\">\n <p>\n <strong>Date Submitted</strong></p>\n </td>\n <td style=\"width:161px;height:37px;\">\n <p>\n <strong>Outcome Date</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n <strong>UNITED KINGDOM (17sites)</strong></p>\n </td>\n <td style=\"width:141px;height:18px;\">\n  </td>\n <td style=\"width:161px;height:18px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:36px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:36px;\">\n <p>\n 25-May-2023</p>\n </td>\n <td style=\"width:161px;height:36px;\">\n <p>\n Approved, 31-Aug2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n <strong>ARGENTINA (40sites)</strong></p>\n </td>\n <td style=\"width:141px;height:18px;\">\n  </td>\n <td style=\"width:161px;height:18px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:18px;\">\n <p>\n 22-Jun-2023</p>\n </td>\n <td style=\"width:161px;height:18px;\">\n <p>\n 11-Sep-2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n <strong>AUSTRALIA (4 sites)</strong></p>\n </td>\n <td style=\"width:141px;height:18px;\">\n  </td>\n <td style=\"width:161px;height:18px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:37px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:37px;\">\n <p>\n 02-Jun-2023</p>\n </td>\n <td style=\"width:161px;height:37px;\">\n <p>\n Approved, 15-Jun2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:19px;\">\n <p>\n <strong>CHILE (10sites)</strong></p>\n </td>\n <td style=\"width:141px;height:19px;\">\n  </td>\n <td style=\"width:161px;height:19px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:37px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:37px;\">\n <p>\n 18-Oct-2023</p>\n </td>\n <td style=\"width:161px;height:37px;\">\n <p>\n Approved, 20-Dec2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:19px;\">\n <p>\n <strong>HONG KONG (1 site)</strong></p>\n </td>\n <td style=\"width:141px;height:19px;\">\n  </td>\n <td style=\"width:161px;height:19px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:37px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:37px;\">\n <p>\n 24-Aug-2023</p>\n </td>\n <td style=\"width:161px;height:37px;\">\n <p>\n Approved, 21-Nov2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:21px;\">\n <p>\n <strong>MEXICO (4 sites)</strong></p>\n </td>\n <td style=\"width:141px;height:21px;\">\n  </td>\n <td style=\"width:161px;height:21px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:37px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:37px;\">\n <p>\n 28-Jul-2023 </p>\n </td>\n <td style=\"width:161px;height:37px;\">\n <p>\n Approved, 6-Nov-2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n <strong>CANADA (14sites)</strong></p>\n </td>\n <td style=\"width:141px;height:18px;\">\n  </td>\n <td style=\"width:161px;height:18px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:36px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:36px;\">\n <p>\n 24-May-2023</p>\n </td>\n <td style=\"width:161px;height:36px;\">\n <p>\n Approved, 23-Jun2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n <strong>NEW ZEALAND (7sites)</strong></p>\n </td>\n <td style=\"width:141px;height:18px;\">\n  </td>\n <td style=\"width:161px;height:18px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:36px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:36px;\">\n <p>\n 14-Jun-2023</p>\n </td>\n <td style=\"width:161px;height:36px;\">\n <p>\n Approved, 7-Jul2023</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:589px;\" width=\"589\">\n <tbody>\n <tr>\n <td style=\"width:287px;height:37px;\">\n <p>\n <strong>Country</strong></p>\n </td>\n <td style=\"width:141px;height:37px;\">\n <p>\n <strong>Date Submitted</strong></p>\n </td>\n <td style=\"width:161px;height:37px;\">\n <p>\n <strong>Outcome Date</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n <strong>SOUTH AFRICA (15sites)</strong></p>\n </td>\n <td style=\"width:141px;height:18px;\">\n  </td>\n <td style=\"width:161px;height:18px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:36px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:36px;\">\n <p>\n 30-May-2023</p>\n </td>\n <td style=\"width:161px;height:36px;\">\n <p>\n Approved,12-Sep2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n <strong>SOUTH KOREA (13sites)</strong></p>\n </td>\n <td style=\"width:141px;height:18px;\">\n  </td>\n <td style=\"width:161px;height:18px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:36px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:36px;\">\n <p>\n 9-Jun-2023</p>\n </td>\n <td style=\"width:161px;height:36px;\">\n <p>\n Approved, 10Oct2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n <strong>UNITED STATES OF AMERICA (74sites)</strong></p>\n </td>\n <td style=\"width:141px;height:18px;\">\n  </td>\n <td style=\"width:161px;height:18px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:18px;\">\n <p>\n 13-Feb-2023</p>\n </td>\n <td style=\"width:161px;height:18px;\">\n <p>\n Approved </p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:589px;height:18px;\">\n <p>\n <strong>TAIWAN (6sites)</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:18px;\">\n <p>\n 29-Mar-2024</p>\n </td>\n <td style=\"width:161px;height:18px;\">\n <p>\n Approved,28-May2024</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:589px;height:18px;\">\n <p>\n <strong>TURKEY (3sites)</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:18px;\">\n <p>\n 20-Mar-2024</p>\n </td>\n <td style=\"width:161px;height:18px;\">\n <p>\n Approved，9 Aug2024</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n <strong>S</strong><strong>WITZERLAND (1site)</strong></p>\n </td>\n <td style=\"width:141px;height:18px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:161px;height:18px;\">\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:18px;\">\n <p>\n 29-Jul-2024</p>\n </td>\n <td style=\"width:161px;height:18px;\">\n <p>\n Approved,16-Sep2024</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n <strong>T</strong><strong>HAILAND (2 sites)</strong></p>\n </td>\n <td style=\"width:141px;height:18px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:161px;height:18px;\">\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:18px;\">\n <p>\n 21-May-2024</p>\n </td>\n <td style=\"width:161px;height:18px;\">\n <p>\n 25-Jun2024</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_regulatory_rejected<p>\n Not applicable. None of the Regulatory Authorities or Ethics Committees have rejected this trial.</p>\n
      • other_details_regulatory_halted<p>\n Not applicable.</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_sitesApproximately 5 sites
      • 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_site 5 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_name
      • investigator1_family_nameNduba
      • 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_submitted13-08-2024
      • is_child0
      • unsubmitted1
      • initial_date_submitted13-08-2024
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonResponse to review comments satisfactory
      • 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 11:18:31
      • created2024-08-06 09:58:32
      • total_sites5
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id1127
        • application_id1452
        • given_nameMary Inziani
        • middle_name
        • family_nameMatilu
        • qualificationMedical Doctor
        • professional_addressKEMRI-Mtwapa Clinical Annex P.O. Box 428-80108, Mtwapa
        • telephone+254722523370
        • emailinzianimatilu@gmail.com
        • created2024-08-06 10:54:13
        • modified2024-11-11 13:04:51
    • SiteDetail(array)
      • 0(array)
        • id1764
        • application_id1452
        • 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)
        • created2024-08-06 10:54:13
        • modified2024-11-11 13:04:51
        • County(array)
          • id3
          • county_nameKilifi
          • created2012-05-31 16:15:49
          • modified2012-05-31 16:15:49
      • 1(array)
        • id1765
        • application_id1452
        • 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)
        • created2024-08-06 11:06:27
        • modified2024-11-11 13:04:51
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 2(array)
        • id1766
        • application_id1452
        • 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)
        • created2024-08-06 11:09:20
        • modified2024-11-11 13:04:51
        • County(array)
          • id16
          • county_nameMachakos
          • created2012-06-15 10:23:55
          • modified2012-06-15 10:23:55
      • 3(array)
        • id1767
        • application_id1452
        • 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)
        • created2024-08-06 11:09:20
        • modified2024-11-11 13:04:51
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 4(array)
        • id1768
        • application_id1452
        • 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)
        • created2024-08-06 11:09:20
        • modified2024-11-11 13:04:51
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
    • Sponsor(array)
      • 0(array)
        • id770
        • application_id1452
        • sponsorF. Hoffmann-La Roche Ltd
        • sponsor_typeIndustry
        • contact_personHeather Schofield
        • addressGrenzacherstrasse 124, 4070 Basel, Switzerland
        • telephone_number+ 41 6168 81111
        • fax_number
        • cell_number+416-930-1484
        • email_addressglobal.eudract@roche.com
        • created2024-08-06 10:54:13
        • modified2024-11-11 13:04:51
  • 1(array)
    • Application(array)
      • id1467
      • user_id693
      • trial_status_id(null)
      • abstract_of_study<div>\n <strong>BACKGROUND</strong></div>\n<div>\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>\n  </div>\n<div>\n <strong>STUDY RATIONALE</strong></div>\n<div>\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>\n  </div>\n<div>\n <strong>OBJECTIVES AND ENDPOINTS</strong></div>\n<div>\n Primary Objective:</div>\n<div>\n To evaluate the long-term safety of astegolimab</div>\n<div>\n Corresponding Endpoint:</div>\n<div>\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>\n  </div>\n<div>\n <strong>OVERALL DESIGN AND STUDY POPULATION</strong></div>\n<div>\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>\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 A PHASE III OPEN-LABEL EXTENSION STUDY TO EVALUATE THE LONG-TERM SAFETY OF ASTEGOLIMAB IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE</p>\n
      • laymans_summary<div>\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>\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>\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>\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>\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/24/09/02
      • 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_date123-09-2024
      • declaration_principal_investigatorProf. Videlis Nduba
      • declaration_date223-09-2024
      • placebo_presentNo
      • study_objectives<div>\n <strong>Primary Objective</strong></div>\n<ul>\n <li>\n To evaluate the long-term safety of astegolimab</li>\n</ul>\n<div>\n <strong>Exploratory Objectives</strong></div>\n<ul>\n <li>\n To evaluate the efficacy of astegolimab</li>\n <li>\n To evaluate health status utility scores of participants treated with astegolimab</li>\n <li>\n To evaluate the long-term safety of astegolimab</li>\n <li>\n To characterize the PK profile of astegolimab</li>\n <li>\n To evaluate the immune response to astegolimab</li>\n <li>\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>\n <li>\n Signed Informed Consent Form.</li>\n <li>\n Ability to comply with the requirements of the study protocol, according to the investigator’s best judgment.</li>\n <li>\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>\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>\n <li>\n Withdrawal of consent and/or premature discontinuation from parent study</li>\n <li>\n Any permanent discontinuation of study drug in parent study</li>\n <li>\n <div>\n Significant non-compliance in the parent study, specifically defined as missing scheduled visits, per investigator’s judgment.</div>\n </li>\n <li>\n <div>\n Pregnant or breastfeeding, or intending to become pregnant during the study or within 12 weeks after the final dose of study drug.\\</div>\n </li>\n <li>\n <div>\n Any new diagnosis of asthma according to the Global Initiative for Asthma guidelines or other accepted guidelines since enrolling in the parent study</div>\n </li>\n</ul>\n<div>\n <ul>\n <li>\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>\n <li>\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>\n <div>\n Initiation of treatment that is considered palliative (e.g., for life expectancy < 12 months) since enrolling in the parent study.</div>\n </li>\n <li>\n <div>\n History of severe allergic reaction or anaphylactic reaction to any biologic agent or known hypersensitivity to any component of astegolimab.</div>\n </li>\n <li>\n <div>\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.</div>\n </li>\n <li>\n <div>\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</div>\n </li>\n <li>\n <div>\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</div>\n </li>\n <li>\n <div>\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</div>\n </li>\n </ul>\n </div>\n</div>\n<p>\n  </p>\n
      • primary_end_points<div>\n <strong>Primary Objective Endpoints</strong></div>\n<div>\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<div>\n The study site is the University of Nairobi Clinical Research Centre (UNCRC) located in the Department of Human Anatomy and Medical Physiology at the Chiromo Campus of the University of Nairobi Faculty of Health Sciences. In this location administrative and archiving facilities are domiciled. The clinic facilities will be physical located in the KNH RIDU and laboratory facilities will be at the KAVI ICR. Recruitment, consenting, randomization and administration of IMP will be at the RIDU unit the chest clinic number 17.</div>\n<div>\n  </div>\n<div>\n <div>\n The research medical records unit, administrative offices, storage of the IP, laboratory testing and specimen packaging for shipping will be done at the KAVI ICR . which is well-staffed by trained personnel with expertise in the following research related tasks: Clinical officers: Participate in screening of potential patients based on the inclusion and exclusion criteria. Clinical Research Nurses: Obtain Informed consents, Make CRF entries/resolve queries; Collect medical information; Vital</div>\n <div>\n signs; Collect adverse events; Administer IP; Collect lab samples; Participant recruitment and retention. Pharmacist and Pharmacy Technologist: Investigational Drug Services: Manage IP receipt/return; Prepare and dispense IP; Unbinding procedures.</div>\n <div>\n  </div>\n <div>\n <div>\n Regulatory Affairs: Manage submissions to ethics and regulatory authorities. Maintain essential documents and ensure compliance Contracts and Budgets: Maintain legal and financial documents; Ensure appropriate invoicing to the sponsor; Ensure appropriate processes for research covered procedures versus patients’ standard of care Data Management: Make CRF entries/resolve queries; Maintain the patients’ research documents Clinical Research operations: Oversight of UNCRC studies</div>\n <div>\n and staff; support all research staff with their tasks Investigators: Obtain Informed Consent; Assess eligibility; Make CRF entries/resolve Queries; Medical decisions/review; Collect medical information; Vital signs; Assess 8 Ordinal Scale; Collect/Assess Adverse Events; Administer IP; Conduct Physical Exam; Collect Lab Samples; Maintain Essential Documents; IP processes The KNH Chest Clinic is part of the Respiratory Infectious Disease Unit (RIDU).</div>\n <div>\n  </div>\n <div>\n <div>\n The facility is designed to provide an integrated, patient-centered service across the care cycle from diagnosis, treatment, surveillance and palliative care.</div>\n <div>\n  </div>\n <div>\n <div>\n The ambulatory chest clinic also offers streamlined, efficient care by a multidisciplinary team of respiratory specialists. This coordinated approach provides comprehensive care and support for patients with lung disease and their caregivers. All patients treated at the KNH Respiratory Infectious Disease Unit (RIDU) will have access to smoking cessation, psychosocial and support counseling as well as palliative care support as part of best practice. This is not limited to non-study patients and thus is available to study patients as well. The UNCRC provides an approach to care which is guided by international standards including accreditation by the Kenya Medical Laboratory Technician and Technologist Board (KMLLTB) and IATA Shipping and Transport of Regulated Biologic Material certification.</div>\n </div>\n </div>\n </div>\n</div>\n<p>\n  </p>\n
      • other_details_explanation<p>\n Switzerland is the host country and Sponsor intends to submit study for approval in the host country.</p>\n
      • other_details_regulatory_notapproved<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" style=\"width: 589px;\" width=\"589\">\n <tbody>\n <tr>\n <td colspan=\"3\" style=\"width: 589px; height: 21px;\">\n <p>\n <strong>I</strong><strong>NDIA                                                                                DATE SUBMITTED</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 287px; height: 18px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width: 141px; height: 18px;\">\n <p>\n 30-Apr-2024</p>\n </td>\n <td style=\"width: 161px; height: 18px;\">\n <p>\n Pending</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width: 589px; height: 18px;\">\n <p>\n <strong>P</strong><strong>HILIPPINES</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 287px; height: 18px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width: 141px; height: 18px;\">\n <p>\n 18-Apr-2024</p>\n </td>\n <td style=\"width: 161px; height: 18px;\">\n <p>\n Pending</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 287px; height: 18px;\">\n <p>\n <strong>C</strong><strong>HINA</strong></p>\n </td>\n <td style=\"width: 141px; height: 18px;\">\n <p>\n To be submitted</p>\n </td>\n <td style=\"width: 161px; height: 18px;\">\n <p>\n To be submitted</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 287px; height: 18px;\">\n <p>\n <strong>B</strong><strong>RAZIL</strong></p>\n </td>\n <td style=\"width: 141px; height: 18px;\">\n <p>\n  </p>\n </td>\n <td style=\"width: 161px; height: 18px;\">\n <p>\n  </p>\n </td>\n </tr>\n </tbody>\n</table>\n<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" style=\"width: 589px;\" width=\"589\">\n <tbody>\n <tr>\n <td style=\"width: 287px; height: 18px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width: 141px; height: 18px;\">\n <p>\n 16-May-2024</p>\n </td>\n <td style=\"width: 161px; height: 18px;\">\n <p>\n Pending</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 287px; height: 18px;\">\n <p>\n <strong>K</strong><strong>ENYA</strong></p>\n </td>\n <td style=\"width: 141px; height: 18px;\">\n <p>\n  </p>\n </td>\n <td style=\"width: 161px; height: 18px;\">\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 287px; height: 18px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width: 141px; height: 18px;\">\n <p>\n 13-Jun-2024 (first site)</p>\n </td>\n <td style=\"width: 161px; height: 18px;\">\n <p>\n Pending</p>\n </td>\n </tr>\n </tbody>\n</table>\n<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" style=\"width: 589px;\" width=\"589\">\n <tbody>\n <tr>\n <td style=\"width: 287px; height: 18px;\">\n <p>\n <strong>P</strong><strong>ERU</strong></p>\n </td>\n <td style=\"width: 141px; height: 18px;\">\n <p>\n  </p>\n </td>\n <td style=\"width: 161px; height: 18px;\">\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 287px; height: 18px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width: 141px; height: 18px;\">\n <p>\n 15-Mar-2024 (first site)</p>\n </td>\n <td style=\"width: 161px; height: 18px;\">\n <p>\n Pending</p>\n </td>\n </tr>\n <tr>\n <td style=\"width: 287px; height: 18px;\">\n AUSTRIA</td>\n <td style=\"width: 141px; height: 18px;\">\n 25Jun2024</td>\n <td style=\"width: 161px; height: 18px;\">\n Pending expected by 24-Sep2024</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=\"1\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:589px;\" width=\"589\">\n <tbody>\n <tr>\n <td colspan=\"3\" style=\"width:589px;height:37px;\">\n <p>\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=\"width:287px;height:37px;\">\n <p>\n <strong>Member State </strong></p>\n </td>\n <td style=\"width:141px;height:37px;\">\n <p>\n <strong>Date Submitted</strong></p>\n </td>\n <td style=\"width:161px;height:37px;\">\n <p>\n <strong>Outcome Date</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:107px;\">\n <p>\n <strong>EU</strong> <strong>CTR</strong></p>\n <p>\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=\"width:141px;height:107px;\">\n <p>\n 30-May-2023</p>\n </td>\n <td style=\"width:161px;height:107px;\">\n <p>\n Approved, 2-Oct2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:107px;\">\n <p>\n <strong>EU</strong> <strong>CTR</strong></p>\n <p>\n GREECE, HUNGARY, ITALY, LATVIA</p>\n </td>\n <td style=\"width:141px;height:107px;\">\n <p>\n 25-Jun-2024</p>\n </td>\n <td style=\"width:161px;height:107px;\">\n <p>\n  </p>\n <p>\n GREECE – Approved, 18-Sep2024</p>\n <p>\n HUNGARY - Approved, 03-Sep2024</p>\n <p>\n ITALY - Approved, 16-Sep2024</p>\n <p>\n LATVIA - Approved, 17-Sep2024</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n<p>\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\" style=\"width:589px;\" width=\"589\">\n <tbody>\n <tr>\n <td style=\"width:287px;height:37px;\">\n <p>\n <strong>Country</strong></p>\n </td>\n <td style=\"width:141px;height:37px;\">\n <p>\n <strong>Date Submitted</strong></p>\n </td>\n <td style=\"width:161px;height:37px;\">\n <p>\n <strong>Outcome Date</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n <strong>UNITED KINGDOM (17sites)</strong></p>\n </td>\n <td style=\"width:141px;height:18px;\">\n  </td>\n <td style=\"width:161px;height:18px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:36px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:36px;\">\n <p>\n 25-May-2023</p>\n </td>\n <td style=\"width:161px;height:36px;\">\n <p>\n Approved, 31-Aug2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n <strong>ARGENTINA (40sites)</strong></p>\n </td>\n <td style=\"width:141px;height:18px;\">\n  </td>\n <td style=\"width:161px;height:18px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:18px;\">\n <p>\n 22-Jun-2023</p>\n </td>\n <td style=\"width:161px;height:18px;\">\n <p>\n 11-Sep-2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n <strong>AUSTRALIA (4 sites)</strong></p>\n </td>\n <td style=\"width:141px;height:18px;\">\n  </td>\n <td style=\"width:161px;height:18px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:37px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:37px;\">\n <p>\n 02-Jun-2023</p>\n </td>\n <td style=\"width:161px;height:37px;\">\n <p>\n Approved, 15-Jun2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:19px;\">\n <p>\n <strong>CHILE (10sites)</strong></p>\n </td>\n <td style=\"width:141px;height:19px;\">\n  </td>\n <td style=\"width:161px;height:19px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:37px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:37px;\">\n <p>\n 18-Oct-2023</p>\n </td>\n <td style=\"width:161px;height:37px;\">\n <p>\n Approved, 20-Dec2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:19px;\">\n <p>\n <strong>HONG KONG (1 site)</strong></p>\n </td>\n <td style=\"width:141px;height:19px;\">\n  </td>\n <td style=\"width:161px;height:19px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:37px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:37px;\">\n <p>\n 24-Aug-2023</p>\n </td>\n <td style=\"width:161px;height:37px;\">\n <p>\n Approved, 21-Nov2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:21px;\">\n <p>\n <strong>MEXICO (4 sites)</strong></p>\n </td>\n <td style=\"width:141px;height:21px;\">\n  </td>\n <td style=\"width:161px;height:21px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:37px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:37px;\">\n <p>\n 28-Jul-2023 </p>\n </td>\n <td style=\"width:161px;height:37px;\">\n <p>\n Approved, 6-Nov-2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n <strong>CANADA (14sites)</strong></p>\n </td>\n <td style=\"width:141px;height:18px;\">\n  </td>\n <td style=\"width:161px;height:18px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:36px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:36px;\">\n <p>\n 24-May-2023</p>\n </td>\n <td style=\"width:161px;height:36px;\">\n <p>\n Approved, 23-Jun2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n <strong>NEW ZEALAND (7sites)</strong></p>\n </td>\n <td style=\"width:141px;height:18px;\">\n  </td>\n <td style=\"width:161px;height:18px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:36px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:36px;\">\n <p>\n 14-Jun-2023</p>\n </td>\n <td style=\"width:161px;height:36px;\">\n <p>\n Approved, 7-Jul2023</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:589px;\" width=\"589\">\n <tbody>\n <tr>\n <td style=\"width:287px;height:37px;\">\n <p>\n <strong>Country</strong></p>\n </td>\n <td style=\"width:141px;height:37px;\">\n <p>\n <strong>Date Submitted</strong></p>\n </td>\n <td style=\"width:161px;height:37px;\">\n <p>\n <strong>Outcome Date</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n <strong>SOUTH AFRICA (15sites)</strong></p>\n </td>\n <td style=\"width:141px;height:18px;\">\n  </td>\n <td style=\"width:161px;height:18px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:36px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:36px;\">\n <p>\n 30-May-2023</p>\n </td>\n <td style=\"width:161px;height:36px;\">\n <p>\n Approved,12-Sep2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n <strong>SOUTH KOREA (13sites)</strong></p>\n </td>\n <td style=\"width:141px;height:18px;\">\n  </td>\n <td style=\"width:161px;height:18px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:36px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:36px;\">\n <p>\n 9-Jun-2023</p>\n </td>\n <td style=\"width:161px;height:36px;\">\n <p>\n Approved, 10Oct2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n <strong>UNITED STATES OF AMERICA (74sites)</strong></p>\n </td>\n <td style=\"width:141px;height:18px;\">\n  </td>\n <td style=\"width:161px;height:18px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:18px;\">\n <p>\n 13-Feb-2023</p>\n </td>\n <td style=\"width:161px;height:18px;\">\n <p>\n Approved </p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:589px;height:18px;\">\n <p>\n <strong>TAIWAN (6sites)</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:18px;\">\n <p>\n 29-Mar-2024</p>\n </td>\n <td style=\"width:161px;height:18px;\">\n <p>\n Approved,28-May2024</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"3\" style=\"width:589px;height:18px;\">\n <p>\n <strong>TURKEY (3sites)</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:18px;\">\n <p>\n 20-Mar-2024</p>\n </td>\n <td style=\"width:161px;height:18px;\">\n <p>\n Approved，9 Aug2024</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n <strong>S</strong><strong>WITZERLAND (1site)</strong></p>\n </td>\n <td style=\"width:141px;height:18px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:161px;height:18px;\">\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:18px;\">\n <p>\n 29-Jul-2024</p>\n </td>\n <td style=\"width:161px;height:18px;\">\n <p>\n Approved,16-Sep2024</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n <strong>T</strong><strong>HAILAND (2 sites)</strong></p>\n </td>\n <td style=\"width:141px;height:18px;\">\n <p>\n  </p>\n </td>\n <td style=\"width:161px;height:18px;\">\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:287px;height:18px;\">\n <p>\n Competent Authority</p>\n </td>\n <td style=\"width:141px;height:18px;\">\n <p>\n 21-May-2024</p>\n </td>\n <td style=\"width:161px;height:18px;\">\n <p>\n 25-Jun2024</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_regulatory_rejected<p>\n Not applicable. None of the Regulatory Authorities or Ethics Committees have rejected this trial.</p>\n
      • other_details_regulatory_halted<p>\n Not applicable.</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 4 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_name
      • investigator1_family_nameNduba
      • 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_date13-11-2024
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted23-09-2024
      • is_child0
      • unsubmitted1
      • initial_date_submitted23-09-2024
      • 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)
      • modified2025-04-30 11:14:30
      • created2024-09-06 06:58:08
      • total_sites
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id1153
        • application_id1467
        • given_nameTeresa
        • middle_name
        • family_nameKinyari
        • qualificationMedical Doctor
        • professional_addressProf Mungai Road Off Wasawo Drive Off Riverside Drive Chiromo Campus University Of Nairobi P.O. Box 19676 00202 Nairobi Kenya
        • telephone+254 707028067
        • emailtmwendwa@uonbi.ac.ke
        • created2024-09-06 07:06:21
        • modified2024-11-06 10:00:24
    • SiteDetail(array)
      • 0(array)
        • id1779
        • application_id1467
        • 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)
        • created2024-09-06 07:06:21
        • modified2024-11-06 10:00:24
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 1(array)
        • id1780
        • application_id1467
        • 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)
        • created2024-09-06 07:17:55
        • modified2024-11-06 10:00:24
        • County(array)
          • id3
          • county_nameKilifi
          • created2012-05-31 16:15:49
          • modified2012-05-31 16:15:49
      • 2(array)
        • id1781
        • application_id1467
        • 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)
        • created2024-09-06 07:17:55
        • modified2024-11-06 10:00:24
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 3(array)
        • id1782
        • application_id1467
        • 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)
        • created2024-09-06 07:17:55
        • modified2024-11-06 10:00:24
        • County(array)
          • id16
          • county_nameMachakos
          • created2012-06-15 10:23:55
          • modified2012-06-15 10:23:55
      • 4(array)
        • id1783
        • application_id1467
        • 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)
        • created2024-09-06 07:17:55
        • modified2024-11-06 10:00:24
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
    • Sponsor(array)
      • 0(array)
        • id779
        • application_id1467
        • 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
        • created2024-09-06 07:06:21
        • modified2024-11-06 10:00:24
  • 2(array)
    • Application(array)
      • id979
      • user_id81
      • trial_status_id6
      • abstract_of_study<p>\n In 2018, there were an estimated 228 million malaria cases worldwide, resulting in 405, 000 deaths. 93% of these occurred in the WHO African Region. In this region, Plasmodium falciparum is the most prevalent malaria parasite causing 99.7% of the estimated malaria cases. In the era of emerging possible parasite resistance to artemisinin-based drugs and wide-spread resistance among malaria vectors to insecticide classes used to treat bed nets or for indoor residual house-spraying, there is an urgent need for a highly efficacious vaccine to combat the stalling reductions in the malaria burden in Africa. Currently, RTS,S/AS01E is the most advanced malaria vaccine. However, the vaccine demonstrated moderate efficacy against clinical malaria in infants (28.3%; 95% CI 23.3-32.9) aged 6-12 weeks who received 3 vaccinations 4 weeks apart with or without a booster vaccination at 20 months. Implementation of the vaccine is currently under evaluation in Kenya, Malawi and Ghana to establish safety when distributed at scale and impact on mortality. Vaccines against malaria offer real hope for the continent, as resistance and difficulties in sustaining a complete coverage of vector control continue to pose major challenges. While RTS,S/AS01E offers some early hope, this is the only registered malaria vaccine and it is expensive. The estimated cost of RTS,S/AS01E at 7$ per dose will also be substantial if a 3-dose regime and booster(s) are considered in the KEPI schedule. The provision of an alternative, safe and efficacious vaccine candidate would increase Kenya’s options and notably related to the sustainable cost implications. One option in the development pipeline is R21/MM. Preliminary data suggest R21/MM is safe, immunogenic and prevents disease in African infants. R21 was designed to have a higher ratio of malaria antigen (i.e. circumsporozoite protein (CS)) to hepatitis B surface antigen. This allows immunogenicity to be sustained with lower doses than with RTS,S/AS01E, but does not translate into higher levels of immunogenicity than RTS,S/AS01E when judged by antibody concentrations. However, it appears that the antibody is of improved quality, since protective efficacy in both mouse and human challenge studies is higher than that observed with RTS, S/AS01E. Furthermore, the manufacture process for R21 is improved and likely to be less costly than RTS,S/AS01E. Overall, R21/MM has been shown to be safe and well tolerated across the UK and Africa (Kenya and Burkina Faso) in phase I and II trials. We will conduct a phase III randomized control trial to evaluate the efficacy of R21/MM vaccine in children (aged 5-17 months at enrolment) against clinical malaria. This is a multicentre trial with sites in Bougouni; Mali, Nanoro; Burkina Faso, Dande; Burkina Faso, Bagamoyo; Tanzania as well as Kilifi; Kenya. Each participant will be screened to ensure they are in good health based on clinical assessment and laboratory results. Each participant will have 10 clinic visits and additional safety assessments in the week following vaccination for the safety cohort. Of approximately 600 participants to be enrolled in Kilifi, 50% will be randomised to the safety cohort. Participants will receive three vaccinations at day 0, 28, and 56 and a booster dose at 12 months post third vaccination. For the safety cohort; 1) Following each vaccination, participants will be assessed for solicited and unsolicited adverse events either at home or on the phone, 2) Blood will be taken during the clinic visits for safety and/or immunological analysis. </p>\n
      • study_title<p>\n A Phase III randomized, controlled, multi-centre trial to evaluate the efficacy of the R21/Matrix-M vaccine in African children against clinical malaria.</p>\n
      • laymans_summary<p>\n What is the problem/background?</p>\n<p>\n Malaria remains one of the leading causes of infectious disease and deaths worldwide mostly affecting children and pregnant women in sub-Saharan Africa. While globally, the number of new cases of malaria per year decreased between 2010 and 2018, the rate of change slowed from 2014 to 2018. There are several threats to controlling malaria; drug and insecticide resistance, the absence of a licensed vaccine in use and currently the COVID-19 pandemic. Mosquirix™ (RTS, S/AS01E) remains under evaluation in Africa (including studies ongoing in Western Kenya). RTS,S/AS01E is likely to be expensive due to the manufacture process, and even if the current trials in Western Kenya confirm that RTS,S is safe and efficacious when delivered at scale, sustaining funding for ongoing vaccination will be a challenge. R21/Matrix-M (R21/MM) is a candidate malaria vaccine and biologically similar to RTS,S/AS01E. R21/MM vaccine has been found to be safe and well tolerated in children and infants (n=470) when evaluated using 3 vaccinations 4 weeks apart in Burkina Faso (Nanoro-Phase IIb trial, NCT03896724) and Kenya (Kilifi-Phase Ib trial, NCT03580824). The vaccine is manufactured by the Serum Institute of India (SII) and if found to be efficacious will likely be a cost-effective alternative to RTS,S/AS01E given the good immune response seen in these studies. Since R21/MM has been found to be safe, tolerable and elicits good immune responses comparable to the RTS,S/AS01E vaccine, it is important that its efficacy is assessed to provide evidence for further clinical development and licensure with phase III trials in Africa. The option of a second licensed malaria vaccine, likely at lower price than RTS,S/AS01E and higher efficacy, would be beneficial for Kenya.</p>\n<p>\n What question are we trying to answer?</p>\n<p>\n We plan to evaluate if R21/MM, protects infants enrolled at 5-17 months of age from malaria and is safe and well tolerated. Infants will receive a three-dose vaccination course at day 0, 28 and 56 followed by a booster dose at 1 year post the third vaccination and will be followed up at 12 and 24 months following the 3 primary vaccinations.</p>\n<p>\n Where is the study taking place, how many people does it involve and how are they selected?</p>\n<p>\n The study will take place at the KEMRI Centre for Geographic Medicine Research, Coast (KEMRICGMRC). We will recruit approximately 600 healthy infants from the Kilifi population surveillance platform, the Kilifi Health and Demographic Surveillance System (KHDSS), and they should be 5-17 months at enrolment. Approximately 400 of the infants will receive the R21/MM vaccine whilst approximately 200 will receive the control rabies vaccine. Participants will be identified based on their date of birth and locator information available through the KHDSS. The decision on which vaccine they will receive will be based on chance with 2:1 participants receiving the R21/MM vaccine to ensure the results of the study can be reasonably interpreted. We will screen potential participants until we identify the required number of healthy participants. These children will be followed up for 2 years and malaria detected if children present to the KEMRI-CGMRC out-patient facilities at Junju, Pingilikani and Chasimba and the Kilifi County Hospital.</p>\n<p>\n What does the study involve for those who are in it?</p>\n<p>\n Children, whose parents/guardians provide consent and their children pass screening assessments will be enrolled into the study. Blood samples will be taken at up to 7 clinic visits (safety cohort) and additionally 3 finger prick tests to check for evidence of malaria on the days of vaccination in the event of fever or history of fever. Screening will involve a series of blood tests and clinical assessment to check for good health. For individuals who are selected for participation, blood will be drawn at different timepoints as outlined in the schedule of procedures (Table 2) and the amount of blood collected throughout the study will be approximately 30-60 mls depending on the child’s weight and within the limits regarded as appropriate by the World Health Organization (WHO). Repeat blood samples may be taken to verify abnormal results or if clinically indicated. Medical history will also be obtained and a clinical assessment performed to exclude any major health conditions. Those that pass screening will be enrolled in the trial and if a clinically significant condition is identified participants will be counselled as appropriate then referred to a government facility for further management. Once the participants are successfully screened, they will be invited for the first vaccination (Day 0). Following vaccination, participants will be observed for at least 30 minutes to check for any reactions. There will be a total of 10 clinic visits; 6 clinic visits, 4 vaccinations visits and up to 10 telephone calls to document any medical events post vaccination. In the 6 days following vaccination information will be gathered on any side effects to vaccination either over the phone or in person. The three vaccinations will occur on day 0, 28 and 56 and a booster vaccination one year after the third vaccination. The study duration for each participant will be 2 years.</p>\n<p>\n What are the benefits and risks/costs of the study for those involved?</p>\n<p>\n Studies in Kenya and Burkina Faso have shown that the vaccine is safe, tolerable and elicits good immune responses in children and infants. Participants may benefit from receipt of the vaccine given the promising efficacy data (up to 77% protected from disease) seen from the previous trial in 450 children in Burkina Faso. It remains to be demonstrated in large scale trials if the vaccine effectively prevents malarial disease and its complications. Participants will also have close oversight and treatment support from the study team although this will primarily be for risk monitoring. There will also be wider benefit in the field of malaria vaccine research in building on data available on safety, efficacy and immune responses to R21/MM which will help with the WHO’s aim to identify a malaria vaccine with high protection rates. Although the administration schedule of the rabies vaccine being used has been evaluated in clinical trials it is currently not standard practice, therefore for all children we will recommend that should they have exposure to high risk bite during the trial they get full post-exposure prophylaxis. There are also minor risks of bruising and infection associated with venepuncture and vaccination but these are minimised by appropriate training of study staff and use of sterile equipment. Participants will not bear any costs as a result of participation in this trial. Participants will also be compensated for transport costs based on distance travelled according to rates for public transport and compensated for out of pocket expenses (350 KSH). These costs will vary but may be up to approximately 2000/- per visit when catering for refreshments and additional transport requirements (spouse, siblings, impartial witness etc.).</p>\n<div>\n  </div>\n<div>\n How will the study benefit society?</div>\n<div>\n  This study will build on efficacy and immune response data of R21/Matrix M from previous phase 1 and 2 vaccine trials in Africa and will inform further clinical development of this vaccine. There is reason to believe this is a promising candidate vaccine given that a smaller dose is required to illicit a similar vaccine response to RTS,S/AS01E, manufacture is cheaper, and the data thus far on the vaccine and adjuvant Matrix-M demonstrates they are safe. </div>\n<div>\n  </div>\n<div>\n When does the study start and finish? </div>\n<div>\n The study will start upon receipt of ethical clearance; conduct of the trial including data collection, analysis and final write up will take up to 3.5 years.</div>\n
      • short_titleVAC078
      • protocol_noECCT/21/02/03
      • version_no2.0
      • date_of_protocol05-01-2021
      • study_drugR21/Matrix-M vaccine
      • disease_conditionMALARIA
      • 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
      • comparatorYes
      • comparator_nameAbhayrab
      • comparator_registeredYes
      • comparator_countriesRegistered in Kenya
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressCGMRCCSC@kemri-wellcome.org
      • 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_applicantDr. Mainga Hamaluba
      • declaration_date118-02-2021
      • declaration_principal_investigatorDr. Mainga Hamaluba
      • declaration_date218-02-2021
      • placebo_presentNo
      • study_objectives<p>\n Primary objectives:</p>\n<div>\n Efficacy:</div>\n<div>\n To assess the protective efficacy of R21/Matrix-M against clinical malaria caused by Plasmodium falciparum, in 5-17 month old children living in a malaria endemic area, 12 months after completion of the primary course (standard vaccination regime).</div>\n<div>\n To assess the protective efficacy of R21/Matrix-M against clinical malaria caused by Plasmodium falciparum, in 5-48 month old children living in a malaria endemic area, 12 months after completion of the primary course (seasonal vaccination regime).</div>\n<div>\n  </div>\n<div>\n Safety:</div>\n<div>\n To assess the safety and reactogenicity of R21/Matrix-M, in both vaccination regimes, of children living in a malaria endemic area, in the month following each vaccination, and 12 months after completion of the primary course.</div>\n<div>\n  </div>\n<div>\n Secondary objectives</div>\n<div>\n <div>\n Protective efficacy</div>\n <div>\n To assess the protective efficacy of R21/Matrix-M against clinical malaria caused by P. falciparum, in 5-17 month old children living in a malaria endemic area, 12 months after administration of a booster vaccination (standard vaccination regime).</div>\n <div>\n To assess the protective efficacy of R21/Matrix-M against clinical malaria caused by P. falciparum, in 5-48 month old children living in a malaria endemic area, 12 months after administration of a booster vaccination (seasonal vaccination regime).</div>\n <div>\n  </div>\n <div>\n Efficacy against asymptomatic P. falciparum infection</div>\n <div>\n To assess the protective efficacy of R21/Matrix-M against asymptomatic P. falciparum infection employing either vaccination regime, in children living in a malaria endemic area, 12 months after completion of the primary course.</div>\n <div>\n To assess the protective efficacy of R21/Matrix-M against asymptomatic P. falciparum infection employing either vaccination regime, in children living in a malaria endemic area, 12 months after administration of a booster vaccination.</div>\n <div>\n  </div>\n <div>\n Efficacy against severe malaria disease</div>\n <div>\n To assess the protective efficacy of R21/Matrix-M against severe malaria disease employing either vaccination regime, in children living in a malaria endemic area, 12 months after completion of the primary course.</div>\n <div>\n To assess the protective efficacy of R21/Matrix-M against severe malaria disease employing either vaccination regime, in children living in a malaria endemic area, 12 months after administration of a booster vaccinattion.</div>\n <div>\n  </div>\n <div>\n Efficacy according to different transmission settings</div>\n <div>\n To describe the protective efficacy of R21/Matrix-M given in the primary course, in both vaccination regimes, and with an additional booster vaccination, against clinical malaria caused by P. falciparum in different transmission settings.</div>\n <div>\n  </div>\n <div>\n <div>\n Efficacy against incident severe anaemia</div>\n <div>\n To assess the protective efficacy of R21/Matrix-M, in both vaccination regimes, against incident severe anaemia after the primary course and 12 months after the booster vaccination.</div>\n <div>\n To assess the protective efficacy of R21/Matrix-M, in both vaccination regimes in preventing the need for blood transfusiion</div>\n <div>\n  </div>\n <div>\n Efficacy against malaria hospitalisation</div>\n <div>\n To assess the protective efficacy of R21/Matrix-M, in both vaccination regimes, against malaria hospitalisation after the primary course and 12 months after the booster vaccination.</div>\n <div>\n  </div>\n <div>\n Safety</div>\n <div>\n To assess the safety and reactogenicity of R21/Matrix-M, in both vaccination regimes, of children living in a malaria endemic area, in the month following booster vaccination, and 12 months after administration of booster vaccination.</div>\n <div>\n  </div>\n <div>\n Immunogenicity</div>\n <div>\n To assess the humoral immunogenicity of R21/Matrix-M, in both vaccination regimes, of children living in a malaria endemic area, 28 days and 12 months after completion of the primary course.</div>\n <div>\n To assess the humoral immunogenicity of R21/Matrix-M, in both vaccination regimes, of children living in a malaria endemic area, 28 days and 12 months after administration of booster vaccination.</div>\n <div>\n  </div>\n <div>\n <div>\n Exploratory objectives:</div>\n <div>\n  </div>\n <div>\n Efficacy against prevalence of severe anaemia</div>\n <div>\n To assess the protective efficacy of R21/Matrix-M, in both vaccination regimes, against prevalence of severe anaemia 12 months after the primary course and 12 months after the booster vaccination.</div>\n <div>\n  </div>\n <div>\n Efficacy against other serious illnesses</div>\n <div>\n To assess the protective efficacy of R21/Matrix-M, in both vaccination regimes, against other serious illnesses (pneumonia, sepsis, all-case hospitalisation*) 12 months after the primary course and 12 months after the booster vaccination.</div>\n <div>\n * Excluding hospitalisation as a result of trauma or elective surgery</div>\n <div>\n  </div>\n <div>\n Efficacy against fatal malaria and all-cause mortality</div>\n <div>\n To assess the protective efficacy of R21/Matrix-M, in both vaccination regimes, against fatal malaria and all-cause mortality** 12 months after the primary course and 12 months after the booster vaccination.</div>\n <div>\n ** Excluding mortality as a result of trauma or elective surgery</div>\n <div>\n  </div>\n <div>\n Gender-specific efficacy</div>\n <div>\n To assess the vaccine efficacy of R21/Matrix-M, in both vaccination regimes, with or without a booster vaccination, according to gender.</div>\n <div>\n  </div>\n <div>\n <div>\n Effect of vaccine on growth</div>\n <div>\n To assess the effect of R21/Matrix-M, in both vaccination regime, with or without a booster vaccination, on growth of children.</div>\n <div>\n  </div>\n <div>\n Safety and immunogenicity in specific groups</div>\n <div>\n To assess safety and immunogenicity of R21/Matrix-M, in both vaccination regimes, with or without a booster vaccination, of children with low weight and very low weight according to z-score.</div>\n <div>\n To assess safety and immunogenicity of R21/Matrix-M, in both vaccination regimes, with or without a booster vaccination, in HIV-infected child</div>\n <div>\n  </div>\n <div>\n Immunogenicity</div>\n <div>\n To evaluate immunogenicity, magnitude, quality and functionality of induced antibodies to the circumsporozoite protein, antibodies to HBsAg and other exploratory immunological end points in all vaccination groups.</div>\n <div>\n  </div>\n <div>\n Genotypes</div>\n <div>\n To evaluate any potential impact of parasite genetic variation sequence in the P. falciparum circumsporozoite protein (CSP). Other relevant Plasmodium gene analysis may be undertaken to define local parasite populations, define the strain of parasites against which efficacy is being measured, and search for any evidence of differential efficacy of the R21/MM vaccine against different parasite genotypes. In studies of participant human DNA samples, genotyping may be undertaken to evaluate impact of host genetics on risk of malaria disease, the magnitude and quality of immune responses to vaccination and vaccine efficacy.</div>\n </div>\n </div>\n </div>\n</div>\n<div>\n  </div>\n
      • principal_inclusion_criteria<div>\n Inclusion criteria</div>\n<div>\n All participants must satisfy the following criteria at study entry:</div>\n<div>\n For standard vaccination regime, the child is 5-17 months of age at the time of first vaccination.</div>\n<div>\n For seasonal vaccination regime, the child is 5-48 months of age at the time of first vaccination.</div>\n<div>\n Signed informed consent/thumb-printed and witnessed informed consent obtained from the parent(s)/guardian(s) of the child to join the trial.</div>\n<div>\n The investigator believes that the parents/guardians can and will comply with the requirements of the protocol if the child is enrolled in the study.</div>\n<div>\n The child is a permanent resident of the study area and likely to remain a resident for the duration of the trial.</div>\n
      • principal_exclusion_criteria<div>\n  Exclusion criteria for enrolment:</div>\n<div>\n  </div>\n<div>\n The following criteria should be checked at the time of study entry. If any apply, the participant must not be included:</div>\n<div>\n The child has previously received a malaria vaccine.</div>\n<div>\n The child is enrolled in another malaria intervention trial.</div>\n<div>\n The child has a history of allergic disease or reactions likely to be exacerbated by any component of the malaria or control vaccine.</div>\n<div>\n The child has a history of allergic reactions, significant IgE-mediated events or anaphylaxis to previous immunisations.</div>\n<div>\n The child has major congenital defects.</div>\n<div>\n The child has anaemia associated with clinical signs of symptoms of decompensation, or a haemoglobin of ≤ 5.0 g/dL.</div>\n<div>\n The child has had a blood transfusion within one month of enrolment.</div>\n<div>\n The child has been administered immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate.</div>\n<div>\n The child has malnutrition requiring hospital admission.</div>\n<div>\n The child has an acute or chronic, clinically significant pulmonary, cardiovascular, gastrointestinal, endocrine, neurological, skin, hepatic or renal functional abnormality, as determined by medical history, physical examination or laboratory tests.</div>\n<div>\n Children currently meeting the WHO criteria for HIV disease of stage 3 or 4 severity. A previous history of stage 3 or 4 disease is not an exclusion. Note: There will be no routine testing for HIV. Positive diagnoses will be recorded at screening if known.</div>\n<div>\n The child has received an investigational drug or vaccine other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period.</div>\n<div>\n The child is currently participating in another clinical trial if likely to affect data interpretation of this trial</div>\n<div>\n The child has any significant disease, disorder or situation which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant’s ability to participate in the trial.</div>\n<div>\n  </div>\n<div>\n <div>\n Exclusion criteria during the study</div>\n <div>\n The following criteria should be checked during the study, prior to each vaccination:</div>\n <div>\n Any significant disease, disorder or situation which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant’s ability to participate in the trial.</div>\n</div>\n<p>\n  </p>\n
      • primary_end_points<p>\n <span style=\"font-size:14px;\">Primary efficacy endpoint: efficacy against clinical malaria disease over one year for each of the two vaccination regimes as well as in the trial population as a whole.</span></p>\n<p>\n Primary Outcome Measures:</p>\n<ol font-size:=\"\" helvetica=\"\" margin-bottom:=\"\" margin-top:=\"\" sans=\"\" source=\"\" style=\"box-sizing: border-box; font-family: \">\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Efficacy To assess the protective efficacy of R21/Matrix-M against clinical malaria caused by Plasmodium falciparum, in 5-48 month old children living in a malaria endemic area, 12 months after completion of the primary course. [ Time Frame: 2 years ]\n <div class=\"tr-indent2\" style=\"box-sizing: border-box; line-height: 1.6; clear: both; margin-left: 1em; margin-top: 1ex;\">\n <p style=\"box-sizing: border-box; line-height: 1.6; margin: 0ex 0px 1ex;\">\n Assessment for all efficacy outcomes will begin from 14 days after primary course of vaccination to specified time point.</p>\n <p style=\"box-sizing: border-box; line-height: 1.6; margin: 0ex 0px 1ex;\">\n Clinical malaria Primary case definition: Presence of axillary temperature ≥37.5°C and/ or history of fever within the last 24 hours AND P. falciparum asexual parasitaemia > 5000 parasites/µL Secondary case definitions: Presence of axillary temperature ≥37.5°C and/ or history of fever within the last 24 hours AND P. falciparum asexual parasitaemia > 0 parasites/µL Presence of axillary temperature ≥37.5°C and/ or history of fever within the last 24 hours AND P. falciparum asexual parasitaemia > 2500 parasites/µL Tertiary case definitions: Presence of axillary temperature ≥37.5°C and/ or history of fever within the last 24 hours AND P. falciparum asexual parasitaemia > 500 parasites/µL Presence of axillary temperature ≥37.5°C and/ or history of fever within the last 24 hours AND P. falciparum asexual parasitaemia > 20,000 parasites/µL or RDT positive.</p>\n <p style=\"box-sizing: border-box; line-height: 1.6; margin: 0ex 0px 1ex;\">\n  </p>\n </div>\n </li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Safety • To assess the safety and reactogenicity of R21/Matrix-M, in both vaccination regimes, of children living in a malaria endemic area, in the month following each vaccination, and 12 months after completion of the primary course. [ Time Frame: 2 years ]\n <div class=\"tr-indent2\" style=\"box-sizing: border-box; line-height: 1.6; clear: both; margin-left: 1em; margin-top: 1ex;\">\n <p style=\"box-sizing: border-box; line-height: 1.6; margin: 0ex 0px 1ex;\">\n Solicited adverse events</p>\n <ul style=\"box-sizing: border-box; margin-top: 1ex; margin-left: 0px; padding-left: 24px; margin-bottom: 1ex;\">\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Occurrence of solicited local reactogenicity signs and symptoms for 7 days following the vaccination.</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Occurrence of solicited systemic reactogenicity signs and symptoms for 7 days following the vaccination. Unsolicited adverse events</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Occurrence of unsolicited adverse events for 28 days following the vaccination. Laboratory adverse events</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Change from baseline for safety laboratory measures thought to be clinically significant. Serious adverse events</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Occurrence of serious adverse events for the whole study duration.</li>\n </ul>\n </div>\n </li>\n</ol>\n<p>\n  </p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • 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 The site has long standing experience in conducting clinical research with currently over 200 studies in clinical research including phase I - IV trials, human infection studies, cohort studies in children and surveillance of paediatric and maternity admissions at delivery. KEMRI-CGMRC has close to 1000 employees and about a third of them are scientists. All clinical trial staff are trained in acute resuscitation and in the event of emergencies provisions are in place for resuscitation and ambulance transfer to either the KEMRI-HDU ward or Intensive Care at the Aga Khan Hospital, Mombasa. KEMRI HDU is fully staffed with Paediatricians and adult physicians (up to 10 staff contribute to the on-call rota), nurses including a nurse manager, 6 clinical officers, 2 pharmacists, 4 pharmaceutical technologists and 5 pharmacy dispensing clerks as well as study specific staff. If participants require non-critical care they will be admitted to the general wards where KEMRI staff will also oversee their care. The following staff will be supporting this trial:</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Medical officer-1</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Clinical officer - 3</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Nurses -3</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Fieldworkers - 15</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Study Coordinator -1</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Pharmacisit-2</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Data Manager-1</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Data Clerk-3</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n All staff are trained in basic life support and resuscitation facilities are available</p>\n
      • other_details_explanation<p>\n The sponsor of the trial is the University of Oxford. Since  this is on efficacy and effectiveness in a malaria endemic setting, it could not be conducted in the United Kingdom.</p>\n
      • other_details_regulatory_notapproved<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">A joint submission has been initiated by the Sponsor through AVAREF.</span></p>\n
      • other_details_regulatory_approved<p>\n <span style=\"color: rgb(51, 51, 51); font-family: \">A joint submission has been initiated by the Sponsor through AVAREF. This will cater for Burkina Faso, Kenya, Mali and Tanzania.</span></p>\n
      • other_details_regulatory_rejected<p>\n Not applicable</p>\n
      • other_details_regulatory_halted<p>\n Not applicable</p>\n
      • estimated_durationTwo and a half 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_comparatorRabivax-S Rabies vaccine
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKEMRI Wellcome Trust Research Programme
      • single_site_physical_addressHospital Grounds, Off Bofa Road, Kilifi, Kenya
      • single_site_contact_personMainga Hamaluba
      • single_site_telephone+254709983946
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states4
      • number_of_sites
      • multi_country_listKenya, Tanzania, Mali and Burkina Faso
      • data_monitoring_committeeYes
      • total_enrolment_per_site600
      • total_participants_worldwide4800
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerYes
      • population_childrenYes
      • population_adolescentNo
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyIn the standard vaccination regimen, we will enroll children aged 5-17 months old and 5-48 months old in the seasonal vaccination regime.
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameProf. Adrian Vivian Sinton
      • investigator1_middle_name
      • investigator1_family_nameHill
      • investigator1_qualificationProfessor of Human Genetics at the University of Oxford
      • investigator1_professional_addressJenner Institute, University of Oxford. ORCRB, Roosevelt Drive OX3 7DQ
      • investigator1_telephone+ 44 7881826377
      • investigator1_emailadrian.hill@ndm.ox.ac.uk
      • organisations_transferred_Yes
      • number_participants600
      • notification
      • approval_date02-04-2021
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted11-06-2021
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonApplication has been approved by the experts
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-04-11 21:27:01
      • created2021-02-16 16:28:13
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id619
        • application_id979
        • given_nameMainga Patience Mayeso
        • middle_name
        • family_nameHamaluba
        • qualificationMBChB MRCPCH MD
        • professional_addressP.O.Box 230, Kilifi 80108, Kenya
        • telephone(+254) 795 3204 22
        • emailMHamaluba@kemri-wellcome.org
        • created2021-02-16 16:38:00
        • modified2021-06-11 17:40:38
      • 1(array)
        • id620
        • application_id979
        • given_nameJean Bosco
        • middle_name
        • family_nameOuedraogo
        • qualificationMD Parasitologist and Medical Researcher
        • professional_addressInstitut des Sciences et Techniques (INSTech), 540 Avenue de Sya, 01 BP 2779, Bobo-Dioulasso, Burkina Faso
        • telephone(226) 20981880
        • emailjbouedraogo.irssbobo@fasonet.bf
        • created2021-02-16 16:45:58
        • modified2021-06-11 17:40:38
      • 2(array)
        • id621
        • application_id979
        • given_nameHalidou
        • middle_name
        • family_nameTinto
        • qualificationProfessor of Parasitology, Pharm D, PhD
        • professional_addressUnité de Recherche Clinique de Nanoro (URCN), Institut de Recherche en Sciences de la Santé, Direction Régionale du Centre-Ouest (IRSS-DRCO), 42 Avenue Kumda-Yonre, 11 BP218 Ouagadougou CMS 11 Burkina Faso.
        • telephone+226 70346354
        • emailtintoh@fasonet.bf
        • created2021-02-16 16:47:23
        • modified2021-06-11 17:40:38
      • 3(array)
        • id622
        • application_id979
        • given_nameAlassane
        • middle_name
        • family_nameDicko
        • qualificationProfessor Department of Research Institute of Health Science
        • professional_addressMalaria Research & Training Center, Department of Epidemiology of Parasitic Diseases, Faculty of Medicine, Pharmacy and Dentistry, University of Sciences Techniques and Technologies of Bamako, P.O. Box 1805 Bamako, Mali
        • telephone+223 2022 8109
        • emailadicko@icermali.org
        • created2021-02-16 16:48:21
        • modified2021-06-11 17:40:38
      • 4(array)
        • id623
        • application_id979
        • given_nameAlly
        • middle_name
        • family_nameOlotu
        • qualificationclinical epidemiology and vaccinology
        • professional_addressIfakara Health Institute, Bagamoyo Research and Training centre, PO Box 74, Bagamoyo, Tanzania
        • telephone+255 718 927 104
        • emailndaskoiolotu@gmail.com
        • created2021-02-16 16:49:37
        • modified2021-06-11 17:40:38
    • SiteDetail(array)
      • 0(array)
        • id857
        • application_id979
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2021-02-16 16:38:00
        • modified2021-06-11 17:40:38
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id479
        • application_id979
        • sponsorUniversity of Oxford
        • sponsor_typeResearch Institution
        • contact_personAdrian Hill (Chief Invetigator)
        • addressUniversity Offices, Wellington Square, Oxford, OX1 2JD, UK
        • telephone_number+44 1865 270000
        • fax_number
        • cell_number+44 1865 270000
        • email_addressadrian.hill@ndm.ox.ac.uk
        • created2021-02-16 16:38:00
        • modified2021-06-11 17:40:38
  • 3(array)
    • Application(array)
      • id1396
      • user_id729
      • trial_status_id7
      • abstract_of_study<p>\n Measles is one of the most contagious diseases for humans. It is caused by a paramyxovirus virus, manifesting as a febrile illness with rash.1 Initial symptoms (prodrome) generally consist of fever, malaise, cough, conjunctivitis, and coryza appear 10-12 days after infection. The characteristic maculopapular rash appears two to four days after onset of the prodrome. Measles complications such as pneumonia, diarrhea and encephalitis can occur in up to 30% of persons depending on age and predisposing conditions, such as young age, malnutrition and immunocompromising conditions. Measles can infect anyone of any age, but most of the burden of disease globally is still among children < 5 years of age. There is no specific antiviral treatment against the measles virus. Measles can be prevented by immunization. The measles vaccine is a live attenuated virus vaccine which is available since 1963; two doses are recommended by WHO to provide protection from disease. Accelerated immunization activities have had a major impact on reducing measles deaths including Kenya. Post introduction of vaccine global measles deaths have decreased by 73% from an estimated 536 000 in 2000 to 142,000 in 2018. During 2000– 2018, measles vaccination prevented an estimated 23.2 million deaths.2All six WHO regions had a measles elimination goals by or before 2020, and surveillance was considered a key element to achieve elimination.3 Mumps is an infectious viral disease transmitted via respiratory droplets, fomites, or personal contact. Symptoms often begin with chilly sensations, headache, loss of appetite, feeling of not being well and fever. Once symptoms appear, a typical mumps infection is characterized by inflammation of the parotid glands. Some infected individuals develop severe complications such as orchitis, pancreatitis, septic meningitis, and deafness. The first mumps vaccine was licensed in 1967. Soon after, the mumps vaccine was included as part of the trivalent measles, mumps, and rubella (MMR) vaccine. Currently, the MMR vaccine is given in two doses as part of a routine immunization schedule in many countries. Although widespread use of the two-dose MMR vaccine largely reduced mumps incidence among school children by the 1990s, there has been a significant increase in the number of mumps outbreaks since. Additionally, vaccine efficacy and safety remain a concern.4 Rubella, or German measles, is a mild viral infection that typically occurs in children and non-immune young adults. The prodromal illness is characterized by low-grade fever, malaise, anorexia, headaches, sore throat, and lymphadenopathy. The exanthem could be the first manifestation in children and consists of short-lived pinpoint pink macules and papules that classically begins on the face and rapidly spreads to involve the trunk and extremities. In nonpregnant individuals, rubella is generally a selflimited and benign infection. However, maternal rubella infection, especially during embryogenesis leads to the classic triad of cataracts, congenital heart defects, and sensorineural deafness; however, other defects may be seen including miscarriages, fetal death, or severe birth defects collectively known as Congenital Rubella Syndrome (CRS). Of all the manifestations, deafness in the newborn is the most common finding and could be the only defect observed. Individuals that survive the neonatal period may face severe disabilities (e.g., visual and hearing impairments) and have an increased risk for developmental disorders, including autism. Universal immunization of all susceptible individuals with rubella vaccines is the cornerstone to the prevention of rubella and, more importantly, congenital rubella syndrome. The vaccine is usually administered in combination with measles and mumps (MMR) or measles, mumps, Rubella and varicella (MMRV), with the first dose at ages 12-15 months and the second dose at ages 4-6 years.5 Immunization of all unvaccinated adolescents and adults with at least one dose of rubella vaccine is also recommended. Before the introduction of the rubella vaccine, outbreaks of rubella occurred at variable intervals of 3 to 7 years, with the highest incidence among school children. Steep declines in rubella cases occurred with the routine immunization of young children, and countries with high rates of rubella immunizations no longer see cases of rubella or CRS.6 After the introduction of the live-virus vaccine, outbreaks occurred more commonly among older adolescents and young adults.7,8 The currently used Yellow Fever Vaccine (Stamaril) is a licensed live, attenuated, lyophilized yellow fever vaccine manufactured by Sanofi Pasteur Europe, Lyon, France. A single dose of 0.5 mL contains not less than 1000 IU of yellow fever virus 17D-204 strain. The vaccine is produced in specific pathogen-free chick embryos. YF vaccine is incorporated in the Kenya Expanded Programme for Immunization (KEPI) schedule and is given at 9 months in selected endemic counties. The results of a study R01 (comparison with a prequalified MMR vaccine (Merck Sharp & Dohme or MSD) and R04 (comparison with GlaxoSmithKline’s (GSK’s) MMR vaccine) in China have sufficiently demonstrated the non-inferiority of SIBP MMR with that of licensed vaccine. However, given that these studies were carried out in an Asian population, this study could better support future use in additional jurisdictions such as Africa. The WHO Prequalification supports the specific needs of national immunization programs. Studies R05 and R06 (co-administration with varicella vaccine or with rotavirus vaccine) have also sufficiently demonstrated non-interference when co-administered with these vaccines. Since earlier studies have already assessed the immunogenicity of the vaccine in different age groups and the fact that the vaccine is in wide use in EPI of China supports not conducting any additional studies in other age groups. It is also expected that no additional studies will be required demonstrating non-inferiority between the vaccines produced from old process versus that produced by new process as the change is only in the method of cultivation of the strain virus without any change in excipients or downstream manufacturing process. The current study is designed to demonstrate non-inferiority based on the immune response of SIBP MMR vaccine when compared against an already licensed and WHO prequalified GSK MMR vaccine. In addition, the study will evaluate the interaction of co-administration of SIBP MMR vaccine with a licensed Yellow Fever (YF) vaccine in children 9-11months of age, in terms of immune responses against antigens contained in both vaccines. To study this interaction, the study is designed such that one group of children will concomitantly receive SIBP MMR and YF vaccine whereas the comparator groups will either receive SIBP MMR followed by YF vaccine six weeks later. The study is designed as an observer-blind for Group 1 vs Group 2 until Day 43 and an open label study for Group 3 from Day 1 since the number of vaccinations to be administered, the appearance of the vaccine and their containers are different in the study arms. A blood draw has been planned prior to vaccination on Day 1 and Day 43 after vaccination to measure the immune responses in the study arm as done in many prior clinical trials for licensure of the vaccine. An extended solicitation period has been included to capture solicited systemic reactions as the reaction of fever and rash are most seen in second week following vaccination. The result of this study is expected to complete the package required for applying for WHO pre- qualification for the SIBP MMR vaccine.</p>\n
      • study_title<p>\n A Phase III, Multi-Center, Randomized, Observer-Blind, Active Controlled Non-Inferiority Study to Evaluate the Immunogenicity and Safety of Shanghai Institute of Biological Products Co., Ltd.’s Measles, Mumps and Rubella (MMR) Vaccine Compared to a Licensed and WHO Prequalified GSK MMR Vaccine in Healthy African Children, 9- 11 Months of Age</p>\n
      • laymans_summary<p>\n Measles is one of the most contagious diseases for humans. Measles complications such as pneumonia, diarrhea and encephalitis can occur in up to 30% of persons depending on age and predisposing conditions, such as young age, malnutrition and immunocompromising conditions. Mumps is an infectious viral disease transmitted via respiratory droplets, fomites, or personal contact. Some infected individuals develop severe complications such as orchitis, pancreatitis, septic meningitis, and deafness. Rubella is a mild viral infection that typically occurs in children and non-immune young adults. In nonpregnant individuals, rubella is generally a self-limited and benign infection. However, maternal rubella infection, especially during embryogenesis leads to the classic triad of cataracts, congenital heart defects, and sensorineural deafness; however, other defects may be seen including miscarriages, fetal death, or severe birth defects collectively known as Congenital Rubella Syndrome (CRS). Yellow fever (YF) is a mosquito borne viral disease caused by RNA virus belonging to Flavivirus genus of the Flaviviridae family. This virus is transmitted by Aedes aegypti and Haemagogous species mosquitoes, during the rainy season. This disease is endemic in the tropical and subtropical areas in South America and Africa. The current study is designed to compare the safety and immunogenicity of SIBP MMR administered alone with that of GSK MMR vaccine administered alone in the African context and to evaluate the interaction of co-administration of SIBP MMR vaccine with YF vaccine in children 9-11months of age, in terms of immune responses against antigens contained in both vaccines The results of this study is expected to complete the package required for applying for WHO pre-qualification for the SIBP MMR vaccine.</p>\n
      • short_titleSIBP-MMR-02
      • protocol_noECCT/24/05/03
      • version_no3.0
      • date_of_protocol22-03-2024
      • study_drugMeasles, Mumps and Rubella (MMR) Vaccine
      • disease_conditionMeasles, Mumps and Rubella
      • 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
      • comparatorYes
      • comparator_name WHO Prequalified GSK MMR Vaccine
      • comparator_registeredYes
      • comparator_countriesGermany. >100 countries outside US Including European countries, Canada, Australia, pre-qualified by WHO
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressi.omollo13@gmail.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_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 Walter Otieno
      • declaration_date105-05-2024
      • declaration_principal_investigatorDr Walter Otieno
      • declaration_date205-05-2024
      • placebo_presentNo
      • study_objectives<p>\n 1. Primary Objectives: Immunogenicity To demonstrate non-inferiority of SIBP MMR vaccine compared to GSK MMR vaccine when administered individually based on immunogenicity as measured at baseline and 42 days after vaccination.</p>\n<p>\n 2. Secondary Objectives:</p>\n<ul>\n <li>\n Safety: To assess the safety of SIBP MMR vaccine compared with the GSK MMR vaccine when administered alone in terms of immediate post-vaccination reactogenicity events, solicited adverse events, unsolicited adverse events and serious adverse events. To assess the safety of the SIBP MMR vaccine co-administered with YF vaccine compared with SIBP MMR vaccine when administered separately from YF vaccine in terms of immediate post- vaccination reactogenicity events, solicited adverse events, unsolicited adverse events, and serious adverse events.</li>\n <li>\n Immunogenicity: To evaluate the immunological interference of SIBP MMR vaccine and a licensed YF vaccine when co-administered compared to the immunogenicity when administered alone, in terms of seropositivity rate as measured at baseline and 42 days after vaccination in seronegative children, 9-11 months of age.</li>\n</ul>\n
      • principal_inclusion_criteria<p>\n 1. Healthy male and female child as established by medical history and clinical examination at enrollment.</p>\n<p>\n 2. Age: 9-11 months (inclusive) at the time of enrollment</p>\n<p>\n 3. Parent’s/legally acceptable representative’s (LAR) ability to read and willingness to provide written informed consent as per the ethical and regulatory requirements of the site.</p>\n<p>\n 4. Parent confirms intention to stay in the study area for the study duration, bring their child in for the required study visits or to accept a home visit by the study staff.</p>\n
      • principal_exclusion_criteria<div -webkit-text-stroke-width:=\"\" background-color:=\"\" class=\"OutlineElement Ltr SCXW251702351 BCX8\" font-size:=\"\" font-style:=\"\" font-variant-caps:=\"\" font-variant-ligatures:=\"\" font-weight:=\"\" letter-spacing:=\"\" orphans:=\"\" segoe=\"\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; clear: both; cursor: text; overflow: visible; position: relative; direction: ltr; color: rgb(0, 0, 0); font-family: \" text-align:=\"\" text-decoration-color:=\"\" text-decoration-style:=\"\" text-decoration-thickness:=\"\" text-indent:=\"\" text-transform:=\"\" ui=\"\" white-space:=\"\" widows:=\"\" word-spacing:=\"\">\n <p class=\"Paragraph SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px 0px 10.6667px; padding: 0px; user-select: text; overflow-wrap: break-word; white-space: pre-wrap; font-weight: normal; font-style: normal; vertical-align: baseline; font-kerning: none; background-color: transparent; color: windowtext; text-align: left; text-indent: 0px;\">\n <span class=\"TextRun SCXW251702351 BCX8\" data-contrast=\"auto\" lang=\"EN-GB\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; font-variant-ligatures: none !important; font-size: 12pt; line-height: 20.925px; font-family: Aptos, Aptos_EmbeddedFont, Aptos_MSFontService, sans-serif;\"><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">1. Presence of fever (defined as axillary temperature ≥ 37.5°C) (temporary exclusion until recovery)</span></span><span class=\"EOP SCXW251702351 BCX8\" data-ccp-props=\"{\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; font-size: 12pt; line-height: 20.925px; font-family: Aptos, Aptos_EmbeddedFont, Aptos_MSFontService, sans-serif;\"> </span></p>\n</div>\n<div -webkit-text-stroke-width:=\"\" background-color:=\"\" class=\"OutlineElement Ltr SCXW251702351 BCX8\" font-size:=\"\" font-style:=\"\" font-variant-caps:=\"\" font-variant-ligatures:=\"\" font-weight:=\"\" letter-spacing:=\"\" orphans:=\"\" segoe=\"\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; clear: both; cursor: text; overflow: visible; position: relative; direction: ltr; color: rgb(0, 0, 0); font-family: \" text-align:=\"\" text-decoration-color:=\"\" text-decoration-style:=\"\" text-decoration-thickness:=\"\" text-indent:=\"\" text-transform:=\"\" ui=\"\" white-space:=\"\" widows:=\"\" word-spacing:=\"\">\n <p class=\"Paragraph SCXW251702351 BCX8\" lang=\"EN-GB\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px 0px 10.6667px; padding: 0px; user-select: text; overflow-wrap: break-word; white-space: pre-wrap; font-weight: normal; font-style: normal; vertical-align: baseline; font-kerning: none; background-color: transparent; color: windowtext; text-align: left; text-indent: 0px;\">\n <span class=\"TextRun SCXW251702351 BCX8\" data-contrast=\"auto\" lang=\"EN-GB\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; font-variant-ligatures: none !important; font-size: 12pt; line-height: 20.925px; font-family: Aptos, Aptos_EmbeddedFont, Aptos_MSFontService, sans-serif;\"><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">2. Acute disease of moderate to severe intensity at the time of </span><span class=\"NormalTextRun SpellingErrorV2Themed SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; background-repeat: repeat-x; background-position: left bottom; background-image: var(--urlSpellingErrorV2, url(\'data:image/svg+xml;base64,PD94bWwgdmVyc2lvbj0iMS4wIiBlbmNvZGluZz0iVVRGLTgiPz4KPHN2ZyB3aWR0aD0iNXB4IiBoZWlnaHQ9IjRweCIgdmlld0JveD0iMCAwIDUgNCIgdmVyc2lvbj0iMS4xIiB4bWxucz0iaHR0cDovL3d3dy53My5vcmcvMjAwMC9zdmciIHhtbG5zOnhsaW5rPSJodHRwOi8vd3d3LnczLm9yZy8xOTk5L3hsaW5rIj4KICAgIDwhLS0gR2VuZXJhdG9yOiBTa2V0Y2ggNTYuMiAoODE2NzIpIC0gaHR0cHM6Ly9za2V0Y2guY29tIC0tPgogICAgPHRpdGxlPnNwZWxsaW5nX3NxdWlnZ2xlPC90aXRsZT4KICAgIDxkZXNjPkNyZWF0ZWQgd2l0aCBTa2V0Y2guPC9kZXNjPgogICAgPGcgaWQ9IkZsYWdzIiBzdHJva2U9Im5vbmUiIHN0cm9rZS13aWR0aD0iMSIgZmlsbD0ibm9uZSIgZmlsbC1ydWxlPSJldmVub2RkIj4KICAgICAgICA8ZyB0cmFuc2Zvcm09InRyYW5zbGF0ZSgtMTAxMC4wMDAwMDAsIC0yOTYuMDAwMDAwKSIgaWQ9InNwZWxsaW5nX3NxdWlnZ2xlIj4KICAgICAgICAgICAgPGcgdHJhbnNmb3JtPSJ0cmFuc2xhdGUoMTAxMC4wMDAwMDAsIDI5Ni4wMDAwMDApIj4KICAgICAgICAgICAgICAgIDxwYXRoIGQ9Ik0wLDMgQzEuMjUsMyAxLjI1LDEgMi41LDEgQzMuNzUsMSAzLjc1LDMgNSwzIiBpZD0iUGF0aCIgc3Ryb2tlPSIjRUIwMDAwIiBzdHJva2Utd2lkdGg9IjEiPjwvcGF0aD4KICAgICAgICAgICAgICAgIDxyZWN0IGlkPSJSZWN0YW5nbGUiIHg9IjAiIHk9IjAiIHdpZHRoPSI1IiBoZWlnaHQ9IjQiPjwvcmVjdD4KICAgICAgICAgICAgPC9nPgogICAgICAgIDwvZz4KICAgIDwvZz4KPC9zdmc+\')); border-bottom: 1px solid transparent;\">enrollment</span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\"> (temporary exclusion until recovery)</span></span><span class=\"EOP SCXW251702351 BCX8\" data-ccp-props=\"{\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; font-size: 12pt; line-height: 20.925px; font-family: Aptos, Aptos_EmbeddedFont, Aptos_MSFontService, sans-serif;\"> </span></p>\n</div>\n<div -webkit-text-stroke-width:=\"\" background-color:=\"\" class=\"OutlineElement Ltr SCXW251702351 BCX8\" font-size:=\"\" font-style:=\"\" font-variant-caps:=\"\" font-variant-ligatures:=\"\" font-weight:=\"\" letter-spacing:=\"\" orphans:=\"\" segoe=\"\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; clear: both; cursor: text; overflow: visible; position: relative; direction: ltr; color: rgb(0, 0, 0); font-family: \" text-align:=\"\" text-decoration-color:=\"\" text-decoration-style:=\"\" text-decoration-thickness:=\"\" text-indent:=\"\" text-transform:=\"\" ui=\"\" white-space:=\"\" widows:=\"\" word-spacing:=\"\">\n <p class=\"Paragraph SCXW251702351 BCX8\" lang=\"EN-GB\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px 0px 10.6667px; padding: 0px; user-select: text; overflow-wrap: break-word; white-space: pre-wrap; font-weight: normal; font-style: normal; vertical-align: baseline; font-kerning: none; background-color: transparent; color: windowtext; text-align: left; text-indent: 0px;\">\n <span class=\"TextRun SCXW251702351 BCX8\" data-contrast=\"auto\" lang=\"EN-GB\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; font-variant-ligatures: none !important; font-size: 12pt; line-height: 20.925px; font-family: Aptos, Aptos_EmbeddedFont, Aptos_MSFontService, sans-serif;\"><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">3. Use of antipyretics within the last 72 hours prior to enrolment (temporary exclusion until recovery)</span></span><span class=\"EOP SCXW251702351 BCX8\" data-ccp-props=\"{\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; font-size: 12pt; line-height: 20.925px; font-family: Aptos, Aptos_EmbeddedFont, Aptos_MSFontService, sans-serif;\"> </span></p>\n</div>\n<div -webkit-text-stroke-width:=\"\" background-color:=\"\" class=\"OutlineElement Ltr SCXW251702351 BCX8\" font-size:=\"\" font-style:=\"\" font-variant-caps:=\"\" font-variant-ligatures:=\"\" font-weight:=\"\" letter-spacing:=\"\" orphans:=\"\" segoe=\"\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; clear: both; cursor: text; overflow: visible; position: relative; direction: ltr; color: rgb(0, 0, 0); font-family: \" text-align:=\"\" text-decoration-color:=\"\" text-decoration-style:=\"\" text-decoration-thickness:=\"\" text-indent:=\"\" text-transform:=\"\" ui=\"\" white-space:=\"\" widows:=\"\" word-spacing:=\"\">\n <p class=\"Paragraph SCXW251702351 BCX8\" lang=\"EN-GB\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px 0px 10.6667px; padding: 0px; user-select: text; overflow-wrap: break-word; white-space: pre-wrap; font-weight: normal; font-style: normal; vertical-align: baseline; font-kerning: none; background-color: transparent; color: windowtext; text-align: left; text-indent: 0px;\">\n <span class=\"TextRun SCXW251702351 BCX8\" data-contrast=\"auto\" lang=\"EN-GB\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; font-variant-ligatures: none !important; font-size: 12pt; line-height: 20.925px; font-family: Aptos, Aptos_EmbeddedFont, Aptos_MSFontService, sans-serif;\"><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">4. Prior (within 6 months) or concurrent participation in another interventional clinical trial during the study</span></span><span class=\"EOP SCXW251702351 BCX8\" data-ccp-props=\"{\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; font-size: 12pt; line-height: 20.925px; font-family: Aptos, Aptos_EmbeddedFont, Aptos_MSFontService, sans-serif;\"> </span></p>\n</div>\n<div -webkit-text-stroke-width:=\"\" background-color:=\"\" class=\"OutlineElement Ltr SCXW251702351 BCX8\" font-size:=\"\" font-style:=\"\" font-variant-caps:=\"\" font-variant-ligatures:=\"\" font-weight:=\"\" letter-spacing:=\"\" orphans:=\"\" segoe=\"\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; clear: both; cursor: text; overflow: visible; position: relative; direction: ltr; color: rgb(0, 0, 0); font-family: \" text-align:=\"\" text-decoration-color:=\"\" text-decoration-style:=\"\" text-decoration-thickness:=\"\" text-indent:=\"\" text-transform:=\"\" ui=\"\" white-space:=\"\" widows:=\"\" word-spacing:=\"\">\n <p class=\"Paragraph SCXW251702351 BCX8\" lang=\"EN-GB\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px 0px 10.6667px; padding: 0px; user-select: text; overflow-wrap: break-word; white-space: pre-wrap; font-weight: normal; font-style: normal; vertical-align: baseline; font-kerning: none; background-color: transparent; color: windowtext; text-align: left; text-indent: 0px;\">\n <span class=\"TextRun SCXW251702351 BCX8\" data-contrast=\"auto\" lang=\"EN-GB\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; font-variant-ligatures: none !important; font-size: 12pt; line-height: 20.925px; font-family: Aptos, Aptos_EmbeddedFont, Aptos_MSFontService, sans-serif;\"><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">5. Presence of severe malnutrition (weight-for-height z-score < -3SD median)</span></span><span class=\"EOP SCXW251702351 BCX8\" data-ccp-props=\"{\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; font-size: 12pt; line-height: 20.925px; font-family: Aptos, Aptos_EmbeddedFont, Aptos_MSFontService, sans-serif;\"> </span></p>\n</div>\n<div -webkit-text-stroke-width:=\"\" background-color:=\"\" class=\"OutlineElement Ltr SCXW251702351 BCX8\" font-size:=\"\" font-style:=\"\" font-variant-caps:=\"\" font-variant-ligatures:=\"\" font-weight:=\"\" letter-spacing:=\"\" orphans:=\"\" segoe=\"\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; clear: both; cursor: text; overflow: visible; position: relative; direction: ltr; color: rgb(0, 0, 0); font-family: \" text-align:=\"\" text-decoration-color:=\"\" text-decoration-style:=\"\" text-decoration-thickness:=\"\" text-indent:=\"\" text-transform:=\"\" ui=\"\" white-space:=\"\" widows:=\"\" word-spacing:=\"\">\n <p class=\"Paragraph SCXW251702351 BCX8\" lang=\"EN-GB\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px 0px 10.6667px; padding: 0px; user-select: text; overflow-wrap: break-word; white-space: pre-wrap; font-weight: normal; font-style: normal; vertical-align: baseline; font-kerning: none; background-color: transparent; color: windowtext; text-align: left; text-indent: 0px;\">\n <span class=\"TextRun SCXW251702351 BCX8\" data-contrast=\"auto\" lang=\"EN-GB\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; font-variant-ligatures: none !important; font-size: 12pt; line-height: 20.925px; font-family: Aptos, Aptos_EmbeddedFont, Aptos_MSFontService, sans-serif;\"><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">6. Positive test for any of the following: HIV, hepatitis B, hepatitis C and syphilis</span></span><span class=\"EOP SCXW251702351 BCX8\" data-ccp-props=\"{\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; font-size: 12pt; line-height: 20.925px; font-family: Aptos, Aptos_EmbeddedFont, Aptos_MSFontService, sans-serif;\"> </span></p>\n</div>\n<div -webkit-text-stroke-width:=\"\" background-color:=\"\" class=\"OutlineElement Ltr SCXW251702351 BCX8\" font-size:=\"\" font-style:=\"\" font-variant-caps:=\"\" font-variant-ligatures:=\"\" font-weight:=\"\" letter-spacing:=\"\" orphans:=\"\" segoe=\"\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; clear: both; cursor: text; overflow: visible; position: relative; direction: ltr; color: rgb(0, 0, 0); font-family: \" text-align:=\"\" text-decoration-color:=\"\" text-decoration-style:=\"\" text-decoration-thickness:=\"\" text-indent:=\"\" text-transform:=\"\" ui=\"\" white-space:=\"\" widows:=\"\" word-spacing:=\"\">\n <p class=\"Paragraph SCXW251702351 BCX8\" lang=\"EN-GB\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px 0px 10.6667px; padding: 0px; user-select: text; overflow-wrap: break-word; white-space: pre-wrap; font-weight: normal; font-style: normal; vertical-align: baseline; font-kerning: none; background-color: transparent; color: windowtext; text-align: left; text-indent: 0px;\">\n <span class=\"TextRun SCXW251702351 BCX8\" data-contrast=\"auto\" lang=\"EN-GB\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; font-variant-ligatures: none !important; font-size: 12pt; line-height: 20.925px; font-family: Aptos, Aptos_EmbeddedFont, Aptos_MSFontService, sans-serif;\"><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">7. Presence of any systemic disorder (cardiovascular, pulmonary, hepatic, renal, gastrointestinal, </span><span class=\"NormalTextRun SpellingErrorV2Themed SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; background-repeat: repeat-x; background-position: left bottom; background-image: var(--urlSpellingErrorV2, url(\'data:image/svg+xml;base64,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\')); border-bottom: 1px solid transparent;\">hematological</span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\"> (including severe </span><span class=\"NormalTextRun SpellingErrorV2Themed SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; background-repeat: repeat-x; background-position: left bottom; background-image: var(--urlSpellingErrorV2, url(\'data:image/svg+xml;base64,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\')); border-bottom: 1px solid transparent;\">anemia</span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">), endocrine, immunological, dermatological, neurological, cancer, or autoimmune disease) as </span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">determined</span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\"> by medical history</span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\"> </span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">and / or physical examination which would compromise the</span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\"> </span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">participant’s health or is likely to result in nonconformance to the</span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\"> </span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">protocol.</span></span><span class=\"EOP SCXW251702351 BCX8\" data-ccp-props=\"{\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; font-size: 12pt; line-height: 20.925px; font-family: Aptos, Aptos_EmbeddedFont, Aptos_MSFontService, sans-serif;\"> </span></p>\n</div>\n<div -webkit-text-stroke-width:=\"\" background-color:=\"\" class=\"OutlineElement Ltr SCXW251702351 BCX8\" font-size:=\"\" font-style:=\"\" font-variant-caps:=\"\" font-variant-ligatures:=\"\" font-weight:=\"\" letter-spacing:=\"\" orphans:=\"\" segoe=\"\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; clear: both; cursor: text; overflow: visible; position: relative; direction: ltr; color: rgb(0, 0, 0); font-family: \" text-align:=\"\" text-decoration-color:=\"\" text-decoration-style:=\"\" text-decoration-thickness:=\"\" text-indent:=\"\" text-transform:=\"\" ui=\"\" white-space:=\"\" widows:=\"\" word-spacing:=\"\">\n <p class=\"Paragraph SCXW251702351 BCX8\" lang=\"EN-GB\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px 0px 10.6667px; padding: 0px; user-select: text; overflow-wrap: break-word; white-space: pre-wrap; font-weight: normal; font-style: normal; vertical-align: baseline; font-kerning: none; background-color: transparent; color: windowtext; text-align: left; text-indent: 0px;\">\n <span class=\"TextRun SCXW251702351 BCX8\" data-contrast=\"auto\" lang=\"EN-GB\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; font-variant-ligatures: none !important; font-size: 12pt; line-height: 20.925px; font-family: Aptos, Aptos_EmbeddedFont, Aptos_MSFontService, sans-serif;\"><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\"> 8. Known or suspected impairment of immunological function based</span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\"> </span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">on medical history and physical examination.</span></span><span class=\"EOP SCXW251702351 BCX8\" data-ccp-props=\"{\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; font-size: 12pt; line-height: 20.925px; font-family: Aptos, Aptos_EmbeddedFont, Aptos_MSFontService, sans-serif;\"> </span></p>\n</div>\n<div -webkit-text-stroke-width:=\"\" background-color:=\"\" class=\"OutlineElement Ltr SCXW251702351 BCX8\" font-size:=\"\" font-style:=\"\" font-variant-caps:=\"\" font-variant-ligatures:=\"\" font-weight:=\"\" letter-spacing:=\"\" orphans:=\"\" segoe=\"\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; clear: both; cursor: text; overflow: visible; position: relative; direction: ltr; color: rgb(0, 0, 0); font-family: \" text-align:=\"\" text-decoration-color:=\"\" text-decoration-style:=\"\" text-decoration-thickness:=\"\" text-indent:=\"\" text-transform:=\"\" ui=\"\" white-space:=\"\" widows:=\"\" word-spacing:=\"\">\n <p class=\"Paragraph SCXW251702351 BCX8\" lang=\"EN-GB\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px 0px 10.6667px; padding: 0px; user-select: text; overflow-wrap: break-word; white-space: pre-wrap; font-weight: normal; font-style: normal; vertical-align: baseline; font-kerning: none; background-color: transparent; color: windowtext; text-align: left; text-indent: 0px;\">\n <span class=\"TextRun SCXW251702351 BCX8\" data-contrast=\"auto\" lang=\"EN-GB\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; font-variant-ligatures: none !important; font-size: 12pt; line-height: 20.925px; font-family: Aptos, Aptos_EmbeddedFont, Aptos_MSFontService, sans-serif;\"><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\"> 9. Prior receipt or intent to receive measles, mumps, rubella, or </span><span class=\"NormalTextRun SpellingErrorV2Themed SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; background-repeat: repeat-x; background-position: left bottom; background-image: var(--urlSpellingErrorV2, url(\'data:image/svg+xml;base64,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\')); border-bottom: 1px solid transparent;\">yellow</span><span class=\"NormalTextRun SpellingErrorV2Themed SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; background-repeat: repeat-x; background-position: left bottom; background-image: var(--urlSpellingErrorV2, url(\'data:image/svg+xml;base64,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\')); border-bottom: 1px solid transparent;\">fever</span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">-containing vaccine during the study vaccination and follow up</span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\"> </span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">period up to Day 85 outside the study </span><span class=\"NormalTextRun SpellingErrorV2Themed SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; background-repeat: repeat-x; background-position: left bottom; background-image: var(--urlSpellingErrorV2, url(\'data:image/svg+xml;base64,PD94bWwgdmVyc2lvbj0iMS4wIiBlbmNvZGluZz0iVVRGLTgiPz4KPHN2ZyB3aWR0aD0iNXB4IiBoZWlnaHQ9IjRweCIgdmlld0JveD0iMCAwIDUgNCIgdmVyc2lvbj0iMS4xIiB4bWxucz0iaHR0cDovL3d3dy53My5vcmcvMjAwMC9zdmciIHhtbG5zOnhsaW5rPSJodHRwOi8vd3d3LnczLm9yZy8xOTk5L3hsaW5rIj4KICAgIDwhLS0gR2VuZXJhdG9yOiBTa2V0Y2ggNTYuMiAoODE2NzIpIC0gaHR0cHM6Ly9za2V0Y2guY29tIC0tPgogICAgPHRpdGxlPnNwZWxsaW5nX3NxdWlnZ2xlPC90aXRsZT4KICAgIDxkZXNjPkNyZWF0ZWQgd2l0aCBTa2V0Y2guPC9kZXNjPgogICAgPGcgaWQ9IkZsYWdzIiBzdHJva2U9Im5vbmUiIHN0cm9rZS13aWR0aD0iMSIgZmlsbD0ibm9uZSIgZmlsbC1ydWxlPSJldmVub2RkIj4KICAgICAgICA8ZyB0cmFuc2Zvcm09InRyYW5zbGF0ZSgtMTAxMC4wMDAwMDAsIC0yOTYuMDAwMDAwKSIgaWQ9InNwZWxsaW5nX3NxdWlnZ2xlIj4KICAgICAgICAgICAgPGcgdHJhbnNmb3JtPSJ0cmFuc2xhdGUoMTAxMC4wMDAwMDAsIDI5Ni4wMDAwMDApIj4KICAgICAgICAgICAgICAgIDxwYXRoIGQ9Ik0wLDMgQzEuMjUsMyAxLjI1LDEgMi41LDEgQzMuNzUsMSAzLjc1LDMgNSwzIiBpZD0iUGF0aCIgc3Ryb2tlPSIjRUIwMDAwIiBzdHJva2Utd2lkdGg9IjEiPjwvcGF0aD4KICAgICAgICAgICAgICAgIDxyZWN0IGlkPSJSZWN0YW5nbGUiIHg9IjAiIHk9IjAiIHdpZHRoPSI1IiBoZWlnaHQ9IjQiPjwvcmVjdD4KICAgICAgICAgICAgPC9nPgogICAgICAgIDwvZz4KICAgIDwvZz4KPC9zdmc+\')); border-bottom: 1px solid transparent;\">center</span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">. </span></span><span class=\"EOP SCXW251702351 BCX8\" data-ccp-props=\"{\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; font-size: 12pt; line-height: 20.925px; font-family: Aptos, Aptos_EmbeddedFont, Aptos_MSFontService, sans-serif;\"> </span></p>\n</div>\n<div -webkit-text-stroke-width:=\"\" background-color:=\"\" class=\"OutlineElement Ltr SCXW251702351 BCX8\" font-size:=\"\" font-style:=\"\" font-variant-caps:=\"\" font-variant-ligatures:=\"\" font-weight:=\"\" letter-spacing:=\"\" orphans:=\"\" segoe=\"\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; clear: both; cursor: text; overflow: visible; position: relative; direction: ltr; color: rgb(0, 0, 0); font-family: \" text-align:=\"\" text-decoration-color:=\"\" text-decoration-style:=\"\" text-decoration-thickness:=\"\" text-indent:=\"\" text-transform:=\"\" ui=\"\" white-space:=\"\" widows:=\"\" word-spacing:=\"\">\n <p class=\"Paragraph SCXW251702351 BCX8\" lang=\"EN-GB\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px 0px 10.6667px; padding: 0px; user-select: text; overflow-wrap: break-word; white-space: pre-wrap; font-weight: normal; font-style: normal; vertical-align: baseline; font-kerning: none; background-color: transparent; color: windowtext; text-align: left; text-indent: 0px;\">\n <span class=\"TextRun SCXW251702351 BCX8\" data-contrast=\"auto\" lang=\"EN-GB\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; font-variant-ligatures: none !important; font-size: 12pt; line-height: 20.925px; font-family: Aptos, Aptos_EmbeddedFont, Aptos_MSFontService, sans-serif;\"><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">10. Receipt of any vaccine (except OPV and inactivated influenza)</span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\"> </span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">within 4 weeks of the day of study vaccination or intent to receive</span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\"> </span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">any within 6 weeks after study vaccination. 11. Receipt of immunoglobulin therapy and / or blood products in the</span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\"> </span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">past 9 months or planned administration during the study period</span></span><span class=\"EOP SCXW251702351 BCX8\" data-ccp-props=\"{\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; font-size: 12pt; line-height: 20.925px; font-family: Aptos, Aptos_EmbeddedFont, Aptos_MSFontService, sans-serif;\"> </span></p>\n</div>\n<div -webkit-text-stroke-width:=\"\" background-color:=\"\" class=\"OutlineElement Ltr SCXW251702351 BCX8\" font-size:=\"\" font-style:=\"\" font-variant-caps:=\"\" font-variant-ligatures:=\"\" font-weight:=\"\" letter-spacing:=\"\" orphans:=\"\" segoe=\"\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; clear: both; cursor: text; overflow: visible; position: relative; direction: ltr; color: rgb(0, 0, 0); font-family: \" text-align:=\"\" text-decoration-color:=\"\" text-decoration-style:=\"\" text-decoration-thickness:=\"\" text-indent:=\"\" text-transform:=\"\" ui=\"\" white-space:=\"\" widows:=\"\" word-spacing:=\"\">\n <p class=\"Paragraph SCXW251702351 BCX8\" lang=\"EN-GB\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px 0px 10.6667px; padding: 0px; user-select: text; overflow-wrap: break-word; white-space: pre-wrap; font-weight: normal; font-style: normal; vertical-align: baseline; font-kerning: none; background-color: transparent; color: windowtext; text-align: left; text-indent: 0px;\">\n <span class=\"TextRun SCXW251702351 BCX8\" data-contrast=\"auto\" lang=\"EN-GB\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; font-variant-ligatures: none !important; font-size: 12pt; line-height: 20.925px; font-family: Aptos, Aptos_EmbeddedFont, Aptos_MSFontService, sans-serif;\"><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">12. Receipt of any immune-modifying or immunosuppressant drugs</span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\"> </span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">prior to the first study vaccine dose or planned use during the study. A chronic oral or parenteral use (defined as more than 14 days) of</span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\"> </span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">high dose corticosteroids (defined as ≥2 mg/kg of body weight or</span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\"> </span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">≥20 mg/day of prednisone or equivalent for persons who weigh >10</span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\"> </span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">kg) will be exclusionary for the study. Children on inhaled or topical</span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\"> </span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">steroids may be </span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">permitted</span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\"> to </span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">participate</span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\"> in the study. 13. Evidence of a clinically significant major congenital anomaly or</span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\"> </span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">genetic defect as judged by the investigator. 14. Any known or suspected bleeding disorder in the participant that</span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\"> </span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">would pose a risk to venipuncture or intramuscular injection. 15. History of any neurologic disorders including encephalopathy, epilepsy, and other progressive neurological diseases</span></span><span class=\"EOP SCXW251702351 BCX8\" data-ccp-props=\"{\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; font-size: 12pt; line-height: 20.925px; font-family: Aptos, Aptos_EmbeddedFont, Aptos_MSFontService, sans-serif;\"> </span></p>\n</div>\n<div -webkit-text-stroke-width:=\"\" background-color:=\"\" class=\"OutlineElement Ltr SCXW251702351 BCX8\" font-size:=\"\" font-style:=\"\" font-variant-caps:=\"\" font-variant-ligatures:=\"\" font-weight:=\"\" letter-spacing:=\"\" orphans:=\"\" segoe=\"\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; clear: both; cursor: text; overflow: visible; position: relative; direction: ltr; color: rgb(0, 0, 0); font-family: \" text-align:=\"\" text-decoration-color:=\"\" text-decoration-style:=\"\" text-decoration-thickness:=\"\" text-indent:=\"\" text-transform:=\"\" ui=\"\" white-space:=\"\" widows:=\"\" word-spacing:=\"\">\n <p class=\"Paragraph SCXW251702351 BCX8\" lang=\"EN-GB\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px 0px 10.6667px; padding: 0px; user-select: text; overflow-wrap: break-word; white-space: pre-wrap; font-weight: normal; font-style: normal; vertical-align: baseline; font-kerning: none; background-color: transparent; color: windowtext; text-align: left; text-indent: 0px;\">\n <span class=\"TextRun SCXW251702351 BCX8\" data-contrast=\"auto\" lang=\"EN-GB\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; font-variant-ligatures: none !important; font-size: 12pt; line-height: 20.925px; font-family: Aptos, Aptos_EmbeddedFont, Aptos_MSFontService, sans-serif;\"><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">16. A known or suspected sensitivity or allergy to any components of</span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\"> </span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">the investigational product including egg, chicken protein and the</span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\"> </span><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">antibiotic gentamycin. </span></span><span class=\"EOP SCXW251702351 BCX8\" data-ccp-props=\"{\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; font-size: 12pt; line-height: 20.925px; font-family: Aptos, Aptos_EmbeddedFont, Aptos_MSFontService, sans-serif;\"> </span></p>\n</div>\n<div -webkit-text-stroke-width:=\"\" background-color:=\"\" class=\"OutlineElement Ltr SCXW251702351 BCX8\" font-size:=\"\" font-style:=\"\" font-variant-caps:=\"\" font-variant-ligatures:=\"\" font-weight:=\"\" letter-spacing:=\"\" orphans:=\"\" segoe=\"\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; clear: both; cursor: text; overflow: visible; position: relative; direction: ltr; color: rgb(0, 0, 0); font-family: \" text-align:=\"\" text-decoration-color:=\"\" text-decoration-style:=\"\" text-decoration-thickness:=\"\" text-indent:=\"\" text-transform:=\"\" ui=\"\" white-space:=\"\" widows:=\"\" word-spacing:=\"\">\n <p class=\"Paragraph SCXW251702351 BCX8\" lang=\"EN-GB\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px 0px 10.6667px; padding: 0px; user-select: text; overflow-wrap: break-word; white-space: pre-wrap; font-weight: normal; font-style: normal; vertical-align: baseline; font-kerning: none; background-color: transparent; color: windowtext; text-align: left; text-indent: 0px;\">\n <span class=\"TextRun SCXW251702351 BCX8\" data-contrast=\"auto\" lang=\"EN-GB\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; font-variant-ligatures: none !important; font-size: 12pt; line-height: 20.925px; font-family: Aptos, Aptos_EmbeddedFont, Aptos_MSFontService, sans-serif;\"><span class=\"NormalTextRun SCXW251702351 BCX8\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text;\">17. History of severe allergic reaction with generalized urticaria, angioedema, or anaphylaxis. Any medical condition in the parent/LAR or child which, in the judgment of the Investigator, would interfere with or serves as a contraindication to protocol adherence or a participant’s parent’s/LAR’s ability to give informed consent</span></span><span class=\"EOP SCXW251702351 BCX8\" data-ccp-props=\"{\" style=\"-webkit-user-drag: none; -webkit-tap-highlight-color: transparent; margin: 0px; padding: 0px; user-select: text; font-size: 12pt; line-height: 20.925px; font-family: Aptos, Aptos_EmbeddedFont, Aptos_MSFontService, sans-serif;\"> </span></p>\n</div>\n<p>\n  </p>\n
      • primary_end_points<p>\n <strong>Primary Endpoints</strong></p>\n<p>\n <strong>Immunogenicity </strong></p>\n<p>\n An evaluation of seropositivity rate to Measles, Mumps and Rubella viruses of SIBP MMR vaccine when compared GSK MMR vaccine will be measured 42 days after vaccination in seronegative children at baseline. Seropositivity rate is defined as the proportion of participants with antibody response above the cut-off point for seropositivity. The seropositivity for the antibody titers is defined as:</p>\n<ul>\n <li>\n Anti-measles immunoglobulin G (IgG) antibody concentrations by enzyme-linked immunosorbent assay (ELISA) of > 200 mIU/mL</li>\n <li>\n Anti-mumps IgG antibody concentrations by ELISA of > 100 U/mL</li>\n <li>\n Anti-rubella IgG antibody concentrations by ELISA of > 20 IU/mL</li>\n</ul>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • scope_therapy0
      • scope_safety1
      • scope_efficacy0
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others1
      • scope_others_specifyImmunigenicity
      • 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 The sites have adequate staffing including investigators, study coordinators and all other roles needed for study conduct who are experienced and well trained. The facilities are well equiped including emergency facilities. There is robust infrastructure to support clinical trials.</p>\n<p>\n Kisumu County, Kenya, has a population of about 1,155,574 (Kenya National Bureau of Statistics, 2019 Census). The land area of Kisumu County totals 2085.9 km2 . The county has a shoreline on Lake Victoria, occupying northern, western and a part of the southern shores of the Winam Gulf. Several institutions that are either private or government funded provide health services in Kisumu County. There is one teaching and referral hospital, 5 County referral hospitals, 14 sub-county hospitals, 74 dispensaries and 18 health centers in the county . The Kisumu County Referral Hospital (KCRH) is a level 4 facility designed to provide preventive and curative care for patients and has the capacity for regulated clinical trials. It has a clinical laboratory including hematology, chemistry and microbiology capability. The site has a pharmacy, study drug administration area, clinical assessment area, data entry area, internal quality control and registration area and adequate space where monitoring can be done. The hospital will serve as a clinical research site and primary storage facility for both vaccines and biological samples. Kakamega County, is located in western Kenya. It has a population of 1,867,579 and an area of 3,033.8 km2 (Kenya National Bureau of Statistics, 2019 Census). Butere is the one of largest sub- counties in Kakamega county. The population in the study area is primarily black African, and the languages spoken are Luhya (predominant ethnic group), Kiswahili and English. The Butere County Hospital (BCH) is designed to provide preventive and curative care for patients and has the capacity for regulated clinical trials. It has a clinical laboratory including hematology, chemistry and microbiology capability. The site has a pharmacy, study drug administration area, clinical assessment area, data entry area, internal quality control and registration area and adequate space where monitoring can be done. The hospital will serve as a clinical research site. Homabay County, is located in the former Nyanza Province in Kenya. Its capital and largest town is Homa Bay. The county has a population of 1,131,950 (Kenya National Bureau of Statistics, 2019 Census) and an area of 3,154.7 km2. Lake Victoria is a major source of livelihood for Homa Bay County. The population in the study area is primarily black African, and the languages spoken are Luo (predominant ethnic group), Kiswahili and English. The Rachuonyo County Hospital (RCH) is designed as a primary care facility to provide preventive and curative care for patients. It has a clinical laboratory including hematology, and chemistry capability. The site has a pharmacy, study drug administration area, clinical assessment area, data entry area, internal quality control and registration area and adequate space where monitoring can be done. The hospital will serve as a satellite clinical research site for the Kisumu site. The site will be used for recruitment, screening, vaccination and follow up activities. Given that VIBRI has access to a well-developed health system coupled with a strong collaborative network with the county ministries of health as well as easy accessibility of patients through the hospital networks in Kisumu County, Homabay County, Kakamega County among others, it is anticipated that the study will be able to screen and enroll participants into the study with minimal challenges. The research team will work closely with personnel working in the Ministry of Health facilities within the study area. Trained study staff will assist with study activities conducted in the field including follow up of study participants using demographic and locator information obtained at the</p>\n
      • other_details_explanation<p>\n The vaccine is already registered in the host country and the study is being conducted in Kenya to enable WHO prequalification given the dfisease burden in the country. Additionally Kenyan investigators are very experienced including experienced and established clinical trial sites.</p>\n
      • other_details_regulatory_notapproved<p>\n N/A</p>\n
      • other_details_regulatory_approved<p>\n N/A</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration2 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_comparatorGSK MMR Vaccine
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherYes
      • design_controlled_medicinal_specifyYellow Fever Vaccine
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites3
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_site400-1200
      • total_participants_worldwideN/A
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerYes
      • population_childrenNo
      • population_adolescentNo
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyInfants aged between 9-11 months
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameDr Walter
      • investigator1_middle_name
      • investigator1_family_nameOtieno
      • investigator1_qualificationMBChB, MMED, PhD
      • investigator1_professional_addressVictoria Biomedical Research Institute, P.O. Box 7180, Postal Code 40100, Kisumu, Kenya
      • investigator1_telephone+254714481488
      • investigator1_emailwotieno@vibriafrica.org
      • organisations_transferred_Yes
      • number_participants1200
      • notification
      • approval_date27-05-2024
      • submitted1
      • deleted0
      • deleted_date2024-05-21 18:15:59
      • deactivated0
      • date_submitted21-05-2024
      • is_child0
      • unsubmitted1
      • initial_date_submitted15-05-2024
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer has provided approval
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-04-23 15:50:15
      • created2024-04-14 18:39:29
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id1064
        • application_id1396
        • given_nameDr Walter
        • middle_name
        • family_nameOtieno
        • qualificationMBChB, MMED, PhD
        • professional_addressVictoria Biomedical Research Institute, P.O. Box 7180, Postal Code 40100, Kisumu, Kenya
        • telephone+254714481488
        • emailwotieno@vibriafrica.org
        • created2024-04-22 19:37:03
        • modified2024-05-21 20:52:55
      • 1(array)
        • id1065
        • application_id1396
        • given_nameDr. Diana
        • middle_name
        • family_nameOdhiambo
        • qualificationMBChB MBA MPH
        • professional_addressVictoria Biomedical Research Institute, P.O. Box 7180, Postal Code 40100, Kisumu, Kenya
        • telephone+254722243110
        • emaildodhiambo@vibriafrica.org
        • created2024-04-22 19:53:53
        • modified2024-05-21 20:52:55
    • SiteDetail(array)
      • 0(array)
        • id1698
        • application_id1396
        • county_id42
        • site_nameVictoria Biomedical Research Institute
        • physical_addressKisumu County Hospital, P.O. Box 7180, Postal Code 40100
        • contact_details+254714481488, P.O. Box 7180, Postal Code 40100
        • contact_personDr Walter Otieno
        • site_capacity(null)
        • misc(null)
        • created2024-04-22 19:37:03
        • modified2024-05-21 20:52:55
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 1(array)
        • id1699
        • application_id1396
        • county_id42
        • site_nameVictoria Biomedical Research Institute
        • physical_addressRachuonyo County Hospital Clinical Research Site, P.O. Box 7180, Postal Code 40100
        • contact_details+254714481488, P.O. Box 7180, Postal Code 40100
        • contact_personDr Walter Otieno
        • site_capacity(null)
        • misc(null)
        • created2024-04-22 20:38:26
        • modified2024-05-21 20:52:55
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 2(array)
        • id1700
        • application_id1396
        • county_id42
        • site_nameVictoria Biomedical Research Institute
        • physical_addressButere County Hospital Site, P.O. Box 7180, Postal Code 40100
        • contact_details+254722243110
        • contact_personDr. Diana Odhiambo
        • site_capacity(null)
        • misc(null)
        • created2024-04-22 20:38:26
        • modified2024-05-21 20:52:55
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id742
        • application_id1396
        • sponsorShanghai Institute of Biological Products Co
        • sponsor_typeIndustry
        • contact_personChen Zhewen
        • address 758 Guangfeng Road, Shanghai, China
        • telephone_number +86-21-67130022
        • fax_number +86-21-67130022
        • cell_number +86-21-67130022
        • email_addresschenzhewen@sinopharm.com
        • created2024-04-22 19:37:03
        • modified2024-05-21 20:52:55
  • 4(array)
    • Application(array)
      • id200
      • user_id67
      • trial_status_id8
      • abstract_of_study<p>\n Oral candidiasis (OC) is among the most common opportunistic infections observed in HIV infected individuals. OC tends to occur in about 60%of patients with a CD4+T-cell count of <200cells/mm³and of these, more than half experience recurrence. Current criteria in the choice of treatment for OC is determined by availability and affordability of medications within a particular clinical setting or based on specified institutional or national guidelines. Kenya’s Ministry of Health guideline on management of OC recommends use of Gentian violet (0.5-1%), nystatin oral suspension, and clotrimazole cream while fluconazole and ketoconazole is recommended for systemic therapy when there is no improvement with topical preparations.   Gentian violet (GV) 0.5-1% has been used; though rarely due to stigma of discoloration of the oral cavity despite GV being cheaper, easy to use and store.  This study compares the safety and efficacy of topical GV (0.00165%) to that of oral nystatin suspension. HIV-1 positive participants’ ≥ 18 years of age will be randomized to receive either topical GV solution (5 mL swish and gargle for 2 minutes and spit BID) or nystatin oral suspension (5 mL swish for 2 minutes and swallow QID) for 14 days. Therapy will be considered as failed if participants have no clinical improvement (assessed by severity of pseudomembranous candidiasis) during either treatment regimen. Evaluation of signs and symptoms of OC will be done by an evaluator who is blinded to the treatment assignment. Participants who are failing treatment after the study-defined 14-day treatment regimen will be referred to their primary physician for care and treatment outside of the study, but will continue to be followed on study. Quantification of Colony Forming Units (CFUs) of <em>Candida </em>species (ssp.) and assessment of the emergence of resistance will be performed using an oropharyngeal swab and a second specimen from oral rinse will be collected and stored for future testing.The Kericho site will recruit about 40-80  participants who present with OC as evidenced by pseudomembranous candidiasis. Recruitment will be primarily done through Kericho District Hospital HIV clinic. All enrolled participants will be followed up for 13 weeks. The site accrual rate is estimated to be 10 participants per month; hence estimated duration of accrual is 4-8months. If GV is shown to be superior to nystatin in the treatment of OC, an effective low-cost therapy would then be readily available to patients who cannot afford more expensive therapy. This may be particularly relevant in resource-limited settings where the cost of therapy poses a serious challenge for patients as well as for treating physicians.</p>\n
      • study_title<p>\n A Phase III, Open-Label, Randomized, Assessment-Blinded Clinical Trial to Compare the Safety and Efficacy of Topical Gentian Violet to that of Nystatin Oral Suspension for the Treatment of Oropharyngeal Candidiasis in HIV-1 Infected Participants in Non-U.S. Settings</p>\n
      • laymans_summary<p>\n Oral candidiasis (OC) is among the most common opportunistic infections observed in HIV infected individuals. This study compares the safety and efficacy of topical GV (0.00165%) to that of oral nystatin suspension. HIV-1 positive participants’ ≥ 18 years of age will be randomly assigned to receive either topical GV solution (5 mL swish and gargle for 2 minutes and spit BID) or nystatin oral suspension (5 mL swish for 2 minutes and swallow QID) for 14 days. Therapy will be considered as failed if participants have no clinical improvement (assessed by severity of  candidiasis) during either treatment regimen.</p>\n
      • short_titleCompare the Efficacy and Safety of Gentian Violet to that of Nystatin
      • protocol_noECCT/11/08/03
      • version_noversion 1.0
      • date_of_protocol19-03-2010
      • study_drugTopical Gentian Violet
      • disease_conditionOropharyngeal Candidiasis
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameGentian Violet
      • product_type_medical_device_name
      • comparatorYes
      • comparator_namenystatin
      • comparator_registeredyes
      • comparator_countriesKenya
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressdeborah.langat@usamru-k.org
      • 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_countries0
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data0
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi0
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantDeborah C. Langat
      • declaration_date130-07-2013
      • declaration_principal_investigatorSamuel K. Sinei
      • declaration_date230-07-2013
      • placebo_presentNo
      • study_objectives<p>\n Primary Objective</p>\n<p>\n 1. To evaluate the clinical efficacy of topical GV solution compared to nystatin oral suspension in the treatment of OC, as evidenced by pseudomembranous candidiasis, in HIV-infected adult participants.</p>\n<p>\n Secondary Objectives</p>\n<p>\n 1.       To evaluate symptoms associated with OC at entry, end of treatment, and at clinical relapse.</p>\n<p>\n 2.       To evaluate quantitative yeast colony counts at entry, end of treatment, week 6, and at clinical relapse.</p>\n<p>\n 3.       To evaluate the effect of strata (baseline CD4+ T-cell count and ART) on clinical efficacy.</p>\n<p>\n 4.       To assess the emergence, if any, of fungal resistance in the treatment arms.</p>\n<p>\n 5.       To evaluate the safety of GV and nystatin in the treatment of OC.</p>\n<p>\n 6.       To evaluate participant tolerance, adherence, health self-assessment, and acceptability of GV and nystatin.</p>\n<p>\n 7.       To perform a cost analysis comparing the strategies of no treatment, treatment with nystatin, and treatment with GV for OC based on clinical efficacy as established by the trial and country-specific cost data.</p>\n<p>\n 8.       To create a specimen repository of oral rinse, serum, plasma, and Candida isolates that can be a resource for other AIDS Clinical Trials Group (ACTG) and Oral HIV/AIDS Research Alliance (OHARA) investigators.</p>\n<p>\n To compare clinical and mycological outcomes (clinical efficacy, quantitative yeast counts, and emergence of fungal resistance) in those with Karnofsky score ≥ 60 and those <60.</p>\n
      • principal_inclusion_criteria<p>\n 1.      HIV-1 infection, documented by any licensed rapid HIV test or HIV   enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to study entry and confirmed by licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, plasma HIV-1 RNA viral load.</p>\n<p>\n 2.      Pseudomembranous candidiasis documented by a complete oral exam (i.e., white or yellow spots or plaques with an underlying erythematous base that may be located in any part of the oral cavity) at the screening visit.</p>\n<p>\n NOTE: Participants with documented angular chelitis and/or erythematous candidiasis without pseudomembranous candidiasis are not eligible to enroll in the study.</p>\n<p>\n 3.      Direct microscopic examination (KOH or Gram-stained smear) consistent with <em>Candida</em> spp. at screening and evidence of pseudomembranous candidiasis within 21 days prior to study entry.</p>\n<ol>\n <li value=\"4\">\n If currently being treated with an ART regimen, initiation of regimen at least 12 weeks prior to study entry, and willingness of participant to remain on current ART regimen until the study-defined 14-day treatment period is complete.</li>\n</ol>\n<p>\n             NOTE: Participants who are not ART-naïve and not on ART are eligible to participate in</p>\n<p>\n             the study if they do not intend to initiate ART during the Study- defined 14-day treatment    </p>\n<p>\n             period.</p>\n<p>\n 5.      CD4+ cell count obtained within 30 days prior to study entry at a DAIDS- approved laboratory.</p>\n<p>\n 6.      Laboratory values obtained within 7 days prior to study entry:</p>\n<p style=\"margin-left:1in;\">\n Absolute neutrophil count (ANC) ³ 750/mm³</p>\n<p style=\"margin-left:1in;\">\n Hemoglobin ³ 7.0 g/dL</p>\n<p style=\"margin-left:1in;\">\n Platelet count ³ 50,000/mm³</p>\n<p style=\"margin-left:1in;\">\n Creatinine £ 3 ´ upper limit normal (ULN)</p>\n<p style=\"margin-left:1in;\">\n Aspartate aminotransferase (AST [SGOT]), alanine aminotransferase (ALT [SGPT]), and alkaline phosphatase £ 5 ´ ULN</p>\n<p style=\"margin-left:1in;\">\n Total bilirubin £ 2.5 ´ ULN</p>\n<p style=\"margin-left:1in;\">\n Serum glucose < 200 mg/dL (fasting not required)</p>\n<p>\n 7.      Female study volunteers of reproductive potential (defined as women who have not been post-menopausal for at least 24 consecutive months [i.e., who have had menses within the preceding 24 months], or have not undergone surgical sterilization [e.g., hysterectomy, bilateral oophorectomy, or salpingotomy]) must have a negative serum or urine pregnancy test (a sensitivity of at least 50mIU/mL) performed within 48 hours prior to study entry.</p>\n<p>\n 8.      If participating in sexual activity that could lead to pregnancy, the female study volunteer must use at least one form of contraceptive while receiving protocol-specified medication(s) and for 1 month after stopping the medications:</p>\n<p style=\"margin-left:1in;\">\n Condoms (male or female) with or without a spermicidal agent. Condoms are recommended because their appropriate use is the only contraception method effective for preventing HIV transmission.</p>\n<p style=\"margin-left:1in;\">\n Diaphragm or cervical cap with spermicide</p>\n<p style=\"margin-left:1in;\">\n Intrauterine device (IUD)</p>\n<p style=\"margin-left:1in;\">\n Hormone-based contraceptive</p>\n<p>\n If the female volunteer is not of reproductive potential (women who have been post-menopausal for at least 24 consecutive months or women who have undergone surgical sterilization [e.g., hysterectomy, bilateraloophorectomy, or salpingotomy]), she is eligible without requiring the use of a contraceptive. Acceptable documentation of sterilization, other contraceptive methods, and menopause is participant-reported history.</p>\n<p>\n 9.      Karnofsky performance score ≥ 30 at study screening.</p>\n<p style=\"margin-left:38.15pt;\">\n NOTE: Subject must be able to take the medication with or without assistance.  Subject  must be able to swish, gargle, and expectorate or swish and swallow as instructed.</p>\n<p>\n 10.  Men and women age ³ 18 years.</p>\n<p>\n 11.  Ability and willingness of participant to provide informed consent and to attend all planned study visits.</p>\n
      • principal_exclusion_criteria<p>\n 1.      Documented or presumptive signs or symptoms of esophageal candidiasis (e.g., dysphagia) during the screening period unless endoscopic examination of the esophagus was performed and fungal esophagitis were excluded.</p>\n<p>\n 2.      Use of any investigational drug currently or within 30 days prior to study entry.</p>\n<p>\n NOTE: For purposes of this study, drugs available under an FDA-authorized expanded access program will NOT be considered investigational.</p>\n<p>\n 3.      Concurrent vaginal candidiasis within 21 days prior to study entry.</p>\n<p>\n NOTE: Participant complaints and pelvic exam, if needed, will be used to</p>\n<p>\n             determine vaginal candidiasis. If vaginal candidiasis is detected,</p>\n<p>\n             participants will be referred for care accordingly.</p>\n<p>\n 4.      Use of inhaled or systemic corticosteroids within 14 days prior to study entry.</p>\n<p>\n 5.      Use of any antifungal agents within 14 days prior to study entry.</p>\n<p>\n NOTE: Antibacterials, antivirals (non-ART), and antimycobacterials for treatment or prophylaxis of other conditions/opportunistic infections are permitted.</p>\n<p>\n 6.      Anticipate need for systemic or oral/topical antifungal agents for other diagnoses within the study-defined 14-day treatment period.</p>\n<p>\n 7.      Intend to initiate ART during the screening period, at study entry, or within the study-defined 14-day treatment period.</p>\n<p>\n 8.      Intend to use any additional oral topical treatments within the study-defined 14-day   treatment period.</p>\n<p>\n 9.      Known allergy/sensitivity or any hypersensitivity to components of study              drugs or their formulation.</p>\n<p>\n 10.  Active drug or alcohol use or dependence that, in the opinion of the site      investigator, would interfere with adherence to study requirements.                   </p>\n<p>\n 11.  Serious illness, in the opinion of the site investigator, requiring systemic    treatment.</p>\n<p>\n 12.  Previous or current history of porphyria.</p>\n<p>\n 13.  Presence of oral warts during the screening period or the day of study entry before randomization.</p>\n<p>\n 14.  Current wearing of full dentures or a maxillary partial denture at study entry.</p>\n
      • primary_end_points<p>\n 1. Clinical efficacy</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic1
      • 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 <strong>A) Site Principal Investigator</strong></p>\n<p>\n  Prof Samuel Sinei, MBChB, MMED</p>\n<p>\n Deputy Director Program Operations</p>\n<p>\n Kenya Medical Research Institute/Walter Reed Project</p>\n<p>\n HIV Program</p>\n<p>\n P.O Box 1357 – 20200,</p>\n<p>\n Hospital Road, Kericho, Kenya</p>\n<p>\n Tel: (+254 52 30686 / +254 52 30388</p>\n<p>\n Mobile: +254 727 531396</p>\n<p>\n Fax: +254 52 30662 / +254 52 30546</p>\n<p>\n Email: <a href=\"mailto:ssinei@wrp-kch.org\">samuel.sinei@usamru-k.org</a></p>\n<p>\n <strong>B) Co- Principal Investigator,</strong></p>\n<p>\n Dr Fredrick Sawe, MBChB, MMED</p>\n<p>\n Deputy Director, HIV Research and Treatment</p>\n<p>\n Kenya Medical Research Institute/Walter Reed Project</p>\n<p>\n HIV Program</p>\n<p>\n P.O Box 1357 – 20200,</p>\n<p>\n Hospital Road, Kericho, Kenya</p>\n<p>\n Tel: +254 52 30686 / +254 52 30388</p>\n<p>\n Mobile: +254 724 255623</p>\n<p>\n Fax: +254 52 30662 / +254 52 30546</p>\n<p>\n Email: <a href=\"mailto:fsawe@wrp-kch.org\">fredrick.sawe@usamru-k.org</a></p>\n<p>\n C) <strong>Associate Investigator,</strong></p>\n<p>\n Dr Deborah Langat, MBChB</p>\n<p>\n Kenya Medical Research Institute/Walter Reed Project</p>\n<p>\n HIV Program</p>\n<p>\n P.O Box 1357 – 20200,</p>\n<p>\n Hospital Road, Kericho, Kenya</p>\n<p>\n Tel: +254 52 30686 / +254 52 30388</p>\n<p>\n Mobile: +254 714 059596</p>\n<p>\n Fax: +254 52 30662 / +254 52 30546</p>\n<p>\n Email: <a href=\"mailto:dchepngeno@wrp-kch.org\">Deborah.langat@usamru-k.org</a></p>\n<p>\n  </p>\n<p>\n Dr Fredrick Kirui, MBChB, MMED</p>\n<p>\n Kenya Medical Research Institute/Walter Reed Project</p>\n<p>\n HIV Program</p>\n<p>\n  P.O. Box 1357 - 20200,</p>\n<p>\n Hospital Road, Kericho, Kenya</p>\n<p>\n Tel +254-52 30686/+254 52 30388</p>\n<p>\n Mobile: +254 727 531373</p>\n<p>\n Fax: + 254 52 30662/+254 52 30546.</p>\n<p>\n Email: <a href=\"mailto:fkkirui@wrp-kch.org\">fredrick.kirui@usamru-k.org</a>.</p>\n<p>\n Dr Josphat Kosgei, MBChB</p>\n<p>\n Kenya Medical Research Institute/Walter Reed Project</p>\n<p>\n HIV Program</p>\n<p>\n P.O Box 1357 - 20200,</p>\n<p>\n Hospital Road, Kericho, Kenya</p>\n<p>\n Tel: +254 52 30686/+254 52 30388</p>\n<p>\n Mobile: +254 729 110122</p>\n<p>\n Fax: +254 52 30662/+254 52 30546.</p>\n<p>\n Email: <a href=\"mailto:jkosgei@wrp-kch.org\">Josphat.kosgei@usamru-k.org</a>.</p>\n<p>\n  </p>\n<p>\n Dr Kathleen Rono, MBchB, MPH & TM</p>\n<p>\n Kenya Medical Research Institute/Walter Reed Project</p>\n<p>\n HIV Program</p>\n<p>\n P.O. Box 1357 – 20200,</p>\n<p>\n Hospital Road, Kericho, Kenya</p>\n<p>\n Tel: +254 52 30686/+254 52 30388</p>\n<p>\n Mobile: +254 716 555535</p>\n<p>\n Fax: +254 52 30662/+254 52 30546.</p>\n<p>\n Email: <a href=\"mailto:jkosgei@wrp-kch.org\">Kathleen.rono@usamru-k.org</a>.</p>\n<p>\n  </p>\n<p>\n Dr Lilian Apadet Osamong, Bachelor of Dental Surgery</p>\n<p>\n Kenya Medical Research Institute</p>\n<p>\n P.O. Box 60309 - 00200,</p>\n<p>\n Nairobi, Kenya</p>\n<p>\n Mobile: +254 721 513477</p>\n<p>\n Email: <a href=\"mailto:apadet@yahoo.com\">apadet@yahoo.com</a></p>\n<p>\n Ignatius Kiptoo, BSc, MS</p>\n<p>\n Kenya Medical Research Institute/Walter Reed</p>\n<p>\n Project HIV Program Information Technology</p>\n<p>\n Department Head,</p>\n<p>\n P.O. Box 1357 - 20200</p>\n<p>\n Hospital Road, Kericho, Kenya</p>\n<p>\n Tel: +254 52 30686 / +254 52 30388</p>\n<p>\n Mobile phone: +254 727 531375</p>\n<p>\n  Fax: +254 52 30662 / +254 52 30546</p>\n<p>\n E-mail: <a href=\"mailto:Ignatius.kiptoo@usamru-k.org\">Ignatius.kiptoo@usamru-k.org</a></p>\n<p>\n <strong>D) Head of Microbiology</strong>,</p>\n<p>\n Sheila Chebore, MSc</p>\n<p>\n P.O Box 1357 – 20200,</p>\n<p>\n Hospital Road, Kericho, Kenya</p>\n<p>\n Tel: +254 52 30686 / +254 52 30388</p>\n<p>\n Mobile: +254 714 058603</p>\n<p>\n Fax: +254 52 30662 / +254 52 30546</p>\n<p>\n Email: <a href=\"mailto:schebore@wrp-kch.org\">Sheilla.chebore@usamru-k.org</a></p>\n<p>\n <strong>E) Pharmacist,</strong></p>\n<p>\n Dr. Noah Tarus, B Pharm</p>\n<p>\n P.O Box 1357 – 20200,</p>\n<p>\n Hospital Road, Kericho, Kenya</p>\n<p>\n Tel: +254 52 30686 / +254 30388</p>\n<p>\n Mobile: +254 713 603222</p>\n<p>\n Fax: +254 52 30662 / +254 52 30546</p>\n<p>\n Email: <a href=\"mailto:ntarus@wrp-kch.org\">Noah.tarus@usamru-k.org</a></p>\n<p>\n <strong>F) Study Coordinator,</strong></p>\n<p>\n Beatrice Korir, KRCHN, Diploma</p>\n<p>\n P.O Box 1357 – 20200,</p>\n<p>\n Hospital Road, Kericho, Kenya</p>\n<p>\n Tel: +254 52 30686 / +254 52 30388</p>\n<p>\n Mobile: +254 702 119191Fax: +254 52 30662 / +254 52 30546</p>\n<p>\n Email: <a href=\"mailto:bkorir@wrp-kch.org\">Beatrice.korir@usamru-k.org</a></p>\n<p>\n <strong>G) Local Medical Monitors</strong></p>\n<p>\n Dr. Jonah Maswai, MBChB, MPH</p>\n<p>\n Kenya Medical Research Institute/Walter Reed Project</p>\n<p>\n HIV Program</p>\n<p>\n P.O Box 1357 – 20200,</p>\n<p>\n Hospital Road, Kericho, Kenya</p>\n<p>\n Tel: +254 52 30686 / +254 52 30388</p>\n<p>\n Mobile: +254 727531373</p>\n<p>\n Fax: +254 52 30662 / +254 52 30546</p>\n<p>\n Email: <a href=\"mailto:jmaswai@wrp-kch.org\">Jonah.maswai@usamru-k.org</a></p>\n<p>\n  </p>\n<p>\n Dr. Appolonia Aoko, MBChB</p>\n<p>\n Kenya Medical Research Institute/Walter Reed Project</p>\n<p>\n HIV Program</p>\n<p>\n P.O Box 1357 – 20200,</p>\n<p>\n Hospital Road, Kericho, Kenya</p>\n<p>\n Tel: +254 52 30686 / +254 52 30388</p>\n<p>\n Mobile: +254 715551234</p>\n<p>\n Fax: +254 52 30662 / +254 52 30546</p>\n<p>\n Email: <a href=\"mailto:aaoko@wrp-kch.org\">Appolonia.aoko@usamru-k.org</a></p>\n<div>\n Please see also page 85 of the Site Specific Addendum Apendix II, KEMRI/WRP Roles of Study</div>\n<div>\n Personnel</div>\n<p>\n  </p>\n
      • other_details_explanation<p>\n It is a multicentre study being conducted in non US setting. The drug being investigated is GV which is mainly used in the resource limitted  setting.</p>\n
      • other_details_regulatory_notapproved<p>\n N/A</p>\n
      • other_details_regulatory_approved<p>\n KEMRI ERC -  12 Jul 2012</p>\n<p>\n WRAIR IRB - 22 Aug 2012</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n The National Institute of Allergy and Infectious Diseases (NIAID) Division of AIDS Co-Infections and Complications Data and Safety Monitoring Board (DSMB) met on September 27, 2012, to review interim data for A5265 through July 19, 2012. They recommended that enrollment to the study be immediately halted to allow redesigning of the protocol. See attached memo.</p>\n
      • estimated_durationThe estimated duration of accrual is 10- 12 months
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherYes
      • design_controlled_specifyAssessment Blinded
      • design_controlled_comparatorNystatin oral suspension
      • design_controlled_other_medicinalYes
      • design_controlled_placeboNo
      • 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_sites2
      • multi_country_listBotswana, Kenya, Uganda, South Africa, India, Malawi, Zimbabwe
      • data_monitoring_committeeYes
      • total_enrolment_per_site40-80
      • total_participants_worldwide494
      • 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_nameBeatrice
      • investigator1_middle_nameM
      • investigator1_family_nameKorir
      • investigator1_qualificationKRCHN, Diploma
      • investigator1_professional_addressKEMRI/ WRP P.O BOX 1357 - 20200 Kericho
      • investigator1_telephone+254 702 119191
      • investigator1_emailBeatrice.korir@usamru-k.org
      • organisations_transferred_Yes
      • number_participants80
      • notification
      • approval_date22-11-2012
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted02-03-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<ol>\n <li>\n <strong>INTRODUCTION:</strong></li>\n</ol>\n<p style=\"margin-left:.5in;\">\n This was a phase III, randomized, open-label, assessment-blinded clinical trial in non-U.S. sites to compare the safety and efficacy of topical GV (0.00165%)  to that of oral nystatin suspension. Male and female HIV-1 positive participants ≥ 18 years of age were randomized with equal probability and stratified by CD4+ T-cell counts (> 200 cells/mm3 or ≤ 200 cells/mm3) to receive either topical GV solution (5 mL swish and gargle for 2 minutes and spit BID) or nystatin oral suspension (5 mL swish for 2 minutes and swallow QID) for 14 days. Therapy was considered as failed if participants had no clinical improvement (assessed by severity of pseudomembranous candidiasis) during either treatment regimen. Evaluation of signs and symptoms of OC was done by an evaluator who was blinded to the treatment assignment. In Kericho, the protocol was started in Dec 20, 2011, 43 participants were screened and of those screened 29 participants were eligible and were enrolled while 14 were ineligible. The last participant to be enrolled in our site was on Sep 26, 2012. The enrollment to the study was halted, on 01 Oct 2012 in order to address several DSMB recommendations in a new protocol version before restarting enrollment again. The issues, in part, related to their concern about not allowing ART for the 2 weeks of antifungal therapy in light of recent changes in guidelines with higher CD4 thresholds for ART initiation. In addition, there was concern raised about whether subjects enrolled were more ill than the protocol allowed. A notification memo was sent to KEMRI ERC on 01 Nov 2012.The last participant completed follow up in our site on Dec 17, 2012 and internationally the last participant completed follow up on Dec 20, 2012.</p>\n<p style=\"margin-left:.5in;\">\n The study was closed to follow up on 08 Jan 2014 after receiving a memo from protocol team on Study Closure to Patient Follow-up because the sponsor decided not to re-open the study due to study feasibility of the proposed re-design. </p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<p>\n  </p>\n<p>\n <strong>2. RESEARCH OBJECTIVES: </strong></p>\n<p>\n  </p>\n<p style=\"margin-left:.25in;\">\n <strong><em><u>Hypothesis</u></em></strong></p>\n<p style=\"margin-left:.25in;\">\n  </p>\n<p style=\"margin-left:.25in;\">\n Topical application of gentian violet (GV) for 14 days is superior to nystatin oral suspension in the treatment of oral candidiasis (OC) in HIV-1 infected participants.</p>\n<p style=\"margin-left:.25in;\">\n  </p>\n<p style=\"margin-left:.25in;\">\n <strong><em><u>Primary Objective</u></em></strong></p>\n<p style=\"margin-left:.25in;\">\n  </p>\n<p style=\"margin-left:.25in;\">\n To evaluate the clinical efficacy of topical GV solution compared to nystatin oral suspension in the treatment of OC, as evidenced by pseudomembranous candidiasis, in HIV-infected adult participants.</p>\n<p style=\"margin-left:.25in;\">\n  </p>\n<p style=\"margin-left:.25in;\">\n <strong><em><u>Secondary</u></em></strong><strong><em><u> Objectives</u></em></strong></p>\n<ol>\n <li>\n To evaluate symptoms associated with OC at entry, end of treatment, and at clinical relapse.</li>\n</ol>\n<p style=\"margin-left:.25in;\">\n  </p>\n<ol>\n <li value=\"2\">\n To evaluate quantitative yeast colony counts at entry, end of treatment, week 6, and at clinical relapse.</li>\n <li value=\"3\">\n To evaluate the effect of strata (baseline CD4+ T-cell count and ART) on clinical efficacy.</li>\n</ol>\n<p style=\"margin-left:.25in;\">\n  </p>\n<ol>\n <li value=\"4\">\n To assess the emergence, if any, of fungal resistance in the treatment arms.</li>\n</ol>\n<p style=\"margin-left:.25in;\">\n  </p>\n<ol>\n <li value=\"5\">\n To evaluate the safety of GV and nystatin in the treatment of OC.</li>\n</ol>\n<p style=\"margin-left:.25in;\">\n  </p>\n<ol>\n <li value=\"6\">\n To evaluate participant tolerance, adherence, self-reported quality of life, and acceptability of GV and nystatin.</li>\n</ol>\n<p style=\"margin-left:.25in;\">\n  </p>\n<ol>\n <li value=\"7\">\n To perform a cost analysis comparing the strategies of no treatment, treatment with nystatin, and treatment with GV for OC based on clinical efficacy as established by the trial and country-specific cost data.</li>\n</ol>\n<p style=\"margin-left:.25in;\">\n  </p>\n<ol>\n <li value=\"8\">\n To create a specimen repository of oral rinse, serum, plasma, and <em>Candida</em> isolates that can be a resource for other AIDS Clinical Trials Group (ACTG) and Oral HIV/AIDS Research Alliance (OHARA) investigators</li>\n</ol>\n<p style=\"margin-left:.25in;\">\n  </p>\n<p>\n <strong>3. SUMMARY OF STUDY RESULTS: </strong></p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n The study was closed early per Data Safety Monitoring Board after enrolling 221 participants (target 494) in all international sites. Among the 182 participants eligible for efficacy analysis, 63 (68.5%) in the gentian violet arm had cure or improvement of oropharyngeal candidiasis versus 61 (67.8%) in the NYS arm, resulting in a non-sizable difference of 0.007 (95% confidence interval: 0.129, 0.143). There was no sizable difference in cure rates between the two arms (0.0007; 95% confidence interval: 0.146, 0.131). No gentian violet–related adverse events were noted. No sizable differences were identified in tolerance, adherence, quality of life, or acceptability of study drugs. In gentian violet arm, 61 and 39% of participants reported ‘no’ and ‘mild to-moderate’ staining, respectively. Cost for medication procurement was significantly lower for gentian violet versus NYS (median $2.51 and 19.42, respectively, P=0.01).The Study concluded that efficacy of gentian violet was not statistically different than Nystatin (NYS), was well tolerated, and its procurement cost was substantially less than NYS.</p>\n<p>\n  </p>\n<p>\n <strong>4. List publications arising from study (attach copies of the manuscript(s).</strong></p>\n<p>\n  </p>\n<p style=\"margin-left:17.1pt;\">\n Mukherjee PK, Chen H, Patton LL, Evans S, Lee A, Kumwenda J, Hakim J, Masheto  G, Sawe F, Pho MT, Freedberg KA, Shiboski CH, Ghannoum MA, Salata RA; Oral HIVAIDS Research Alliance (OHARA) AIDS Clinical Trials Group (ACTG) 5265 Team. Topical gentian violet compared with nystatin oral suspension for the treatment of oropharyngeal candidiasis in HIV-1-infected participants. AIDS. 2017 Jan 2;31(1):81-88.</p>\n<p style=\"margin-left:17.1pt;\">\n  </p>\n<p style=\"margin-left:17.1pt;\">\n  </p>\n<p style=\"margin-left:13.5pt;\">\n <strong>5. Confirm destruction of each study participant’s identifiers and provide an assurance/evidence that the destruction has occurred (send copies of the blacked out books).</strong></p>\n<p style=\"margin-left:17.1pt;\">\n  </p>\n<p>\n At the Kericho site, each study participant was provided an identification number for study purposes. These study identification numbers were assigned centrally by the Statistical and Data Analysis Center (SDAC) / Data Management Centre (DMC) after the screening log had been entered through the DMC subject enrollment system. The subject ID does not contain any identifiable information or any information which can be used to identify a study participant either directly or indirectly. These identification numbers were used for all laboratory tests or samples collected and participants study medical records. The study participants’ study documents were stored in Clinical Research Center (CRC) archive room. The CRC archive room is access controlled and secured by triple lock.</p>\n<p>\n  </p>\n<p>\n The study documents have now been transferred to a safe, secured, long-term archive room within the Kericho CRC that is only accessible to regulatory personnel. All other research staff do not have access to this archive room. Access to study documents is controlled and restricted and the site is responsible for ensuring that any access is accurately recorded and any documents accessed/removed and returned are recorded. Destruction approval will be obtained from the sponsor and the IRBs will be notified when this is done.</p>\n<p style=\"margin-left:17.1pt;\">\n  </p>\n<ol>\n <li value=\"5\">\n <strong>Destruction of each study participant’s identifiers and provide an assurance/evidence that the destruction has occurred (send copies of the blacked out books).</strong></li>\n</ol>\n<p>\n Study documents have been transferred to a safe, secured, long-term archive room that is only accessible to two regulatory personnel. All other research staff do not have access to this archive room. Access to study documents is controlled and restricted and the site is responsible for ensuring that any access is accurately recorded and any documents accessed/removed and returned are recorded. Destruction approval will be obtained from the sponsor and the IRBs and ECCT will be notified when this is done.</p>\n<p>\n  </p>\n<ol>\n <li value=\"6\">\n <strong>Plan for future use of data from the study (if applicable)</strong></li>\n</ol>\n<p>\n  </p>\n<p>\n Data obtained from the conduct of this study are housed in a secure database maintained by the AIDS Clinical Trials Group Data Management Centre (ACTG DMC). ACTG DMC serves as the central data management facility for ACTG research protocols. Data managed by DMC are entered into and maintained in a password-protected database accessible only to participating A5265 sites, ACTG DMC and Information Technology staff authorized to work on the protocol. The database is located at New York and is protected by a firewall.</p>\n<p>\n This data does not contain participant names or national identification number, but is referenced only by the study identification number. The clinical database is currently locked, and DMC will maintain it indefinitely or until there is a regulatory requirement or sponsor instructions to destroy it.</p>\n<p>\n All work for this study is complete. Future use of individually coded data will have to be approved by the IRB.</p>\n<p>\n  </p>\n<ol>\n <li value=\"7\">\n <strong>Confirm destruction of surplus investigational agents and provide an assurance/evidence that the destruction has occurred (if applicable).</strong></li>\n</ol>\n<p>\n This was a non-IND study and study treatment was procured locally. Attached is A5265 Drug Accountability logs.</p>\n<p>\n  </p>\n<p>\n  </p>\n<ol>\n <li value=\"8\">\n <strong>Detail the plan for the destruction, storage, or future use of biological specimens obtained as part of this study (include number of samples being destroyed or stored).</strong></li>\n</ol>\n<p>\n All the samples that were not for safety testing were shipped out with the approval of KEMRI ERC for analysis.</p>\n
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