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      • abstract_of_study<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong><u>STUDY RATIONALE</u></strong></div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n The purpose of this study is to assess the efficacy and safety of astegolimab compared with placebo in participants with chronic obstructive pulmonary disease (COPD) who are former or current smokers and have a history of frequent exacerbations. </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <div>\n <strong><u>OBJECTIVES AND ENDPOINTS</u></strong></div>\n <div>\n Primary and selected secondary objectives for the study are expressed using the estimand framework in accordance with the International Conference on  harmonization E9 (R1) statistical principles for clinical trials (FDA 2020) in Section 3. The objectives include (but are not limited to) the evaluation of the efficacy and safety of astegolimab compared with placebo.</div>\n <div>\n  </div>\n</div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong><u>OVERALL DESIGN</u></strong></div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n This is a Phase III, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of astegolimab in combination with standard of care (SOC) compared with placebo in combination with SOC, in participants with COPD who are former or current smokers and have a history of frequent exacerbations.  Approximately 1290 participants with COPD are expected to be enrolled globally.</div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Following a screening period of at least 7 days and to up to 4 weeks, participants will be randomized in a 1:1:1 ratio to 1 of 3 treatment arms to receive blinded treatment with either astegolimab or placebo.  Randomization will be stratified by smoking status at screening (former smoker vs. current smoker) and region.</div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n The first dose of study drug (astegolimab or placebo) will be administered on Day 1; treatment will continue through Week 50, followed by a 12-week safety follow-up period.  The treatment regimens for each arm are as follows: </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Astegolimab 476 mg SC every 2 weeks (Q2W)</li>\n <li style=\"line-height: 20px;\">\n Astegolimab 476 mg SC every 4 weeks (Q4W) </li>\n </ul>\n <div>\n To ensure that all study participants undergo the same visit schedule, participants randomized to the Q4W dosing arm will alternate between injections of astegolimab and placebo Q2W (beginning with astegolimab on Day 1), thus receiving astegolimab Q4W.</div>\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Placebo SC Q2W </li>\n </ul>\n <div>\n Participants will return to the clinic Q2W through the treatment completion visit at Week 52.  The primary endpoint analyses will be conducted using the 52-week treatment period data for all participants. </div>\n <div>\n  </div>\n <div>\n <div>\n Several key aspects of the study design and study population are summarized below.  </div>\n <table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" style=\"max-width: 100%; border-collapse: collapse; border-spacing: 0px; width: 576px;\" width=\"576\">\n <tbody>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Phase:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>Phase </em><em>3</em></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 156px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Population Type:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 144px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>Adult patients of any gender</em></p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Control Method:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>Placebo</em></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 156px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Population Diagnosis or Condition:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 144px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>Chronic obstructive pulmonary disease</em></p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Interventional Model:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>Parallel group</em></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 156px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Population Age:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 144px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>40</em><em>-</em><em>80</em><em> years</em></p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Test Compound{s}:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>Astegolimab</em></p>\n <p style=\"margin: 0px 0px 10px;\">\n  </p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 156px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Site Distribution:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 144px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>Multi-site and multi-region</em></p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Active Comparator:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>Not applicable</em></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 156px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Study Intervention Assignment Method:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 144px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>Randomization and stratification</em></p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Number of Arms:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>3</em></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 156px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Number of Participants to Be Enrolled:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 144px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>Approximately 1290 participants</em></p>\n <div>\n  </div>\n </td>\n </tr>\n </tbody>\n </table>\n </div>\n</div>\n<p>\n  </p>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>STUDY TREATMENT</strong></div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Astegolimab and placebo will be supplied by the Sponsor as a sterile liquid in 2.25 mL pre-filled syringes with a needle safety device, providing 238 mg/1.7 mL of astegolimab or placebo. </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Study drug administration must occur after all other procedures have been completed at the visit, unless specifically indicated otherwise.  Study drug will be administered by trained medical personnel.</div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Each dose of study drug (astegolimab or placebo) will be administered as 2 SC injections (for a total of 3.4 mL), with each injection administered on a different side of the abdomen (i.e., right or left).  All participants will be observed for at least 30 minutes after each dose and longer (approximately 60 minutes) in the event of an injection-site reaction, as determined by the investigator.  If a participant develops any signs or symptoms to suggest a systemic hypersensitivity reaction or anaphylactic event, longer observation may be warranted as per the opinion of the investigator.</div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n There must be a minimum of 8 days between doses. In the event a dosing visit would occur within 8 days of a subsequent or previous dosing visit (e.g., due to an out-of-window visit), the study drug may not be administered. Instead, the next dose of study drug should be administered at the subsequent scheduled visit within the protocol-defined visit window to ensure that the 8-day minimum dosing interval is maintained.</div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>DURATION OF PARTICIPATION</strong></div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n The total duration of study participation for each individual is expected to be approximately 15 months. </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n ----</div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Q2W = every 2 weeks; Q4W =  every 4 weeks; SOC = Standard of Care; SC = Subcutaneous</div>\n
      • study_title<p>\n <span style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">A PHASE III, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ASTEGOLIMAB IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE</span></p>\n
      • laymans_summary<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Chronic obstructive pulmonary disease (COPD) is a respiratory disorder characterized by irreversible changes in air flow causing progressive obstruction. The prevalence of diagnosed COPD has dramatically increased over recent years and is among the leading causes of disabilities and mortality. The airflow obstruction among COPD patients is largely linked with long-term morbidity and comorbidities such as hypertension, diabetes, ischemic heart disease, stroke, and heart failures were reported in patients with exacerbated COPD cases. These comorbidities are often linked with smoking, systemic inflammation, airflow limitation, and aging.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n These comorbidities do not only negatively impact the patients’ quality of life but also lower their survival rate. Although cigarette smoking is traditionally known as the predominant cause of COPD, there have been increasing cases of non-smokers being diagnosed with the disease. COPD is more prevalent among the older population, with the rising prevalence and mortality among women than male, attributed from increased population of female smokers.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Other risk factors include occupational exposure to chemical fumes, air pollution, childhood infection, and genetic heredity. Spirometry is regarded as the gold standard diagnostic tool for COPD which can detect COPD at early, asymptomatic stages. There is no cure for COPD, however, there are availability of therapies that can improve symptoms and a patients’ quality of life. Despite the treatment advances, there is still an unmet need for improved pharmacological intervention against COPD, particularly in the reduction of exacerbations and modifying the disease progression.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Astegolimab is a drug that is under development for the treatment of patients with COPD. This study will focus on finding out if astegolimab is safe and if it works in comparison to placebo as a treatment for COPD patients who are current or former smokers with a history of frequent exacerbations.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n If found to be efficacious, participants will be given access to the study drug in an Open Label Extension study (GB43374) subject to approval by relevant health authorities.</p>\n
      • short_titleARNASA
      • protocol_noECCT/23/08/01
      • version_no4
      • date_of_protocol20-06-2023
      • study_drugAstegolimab (RO7187807)
      • disease_conditionChronic obstructive pulmonary disease (COPD)
      • 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_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)
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      • 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_applicantArinda Eloff
      • declaration_date107-08-2023
      • declaration_principal_investigatorDr Teresa Kinyari
      • declaration_date207-08-2023
      • placebo_presentYes
      • study_objectives<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n The study objectives are listed below:</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate the efficacy of astegolimab compared with placebo</li>\n <li style=\"line-height: 20px;\">\n To evaluate the safety of astegolimab compared with placebo</li>\n <li style=\"line-height: 20px;\">\n To characterize the astegolimab PK profile </li>\n <li style=\"line-height: 20px;\">\n To evaluate the immune response to astegolimab</li>\n <li style=\"line-height: 20px;\">\n To evaluate potential relationships between selected covariates and exposure to astegolimab</li>\n <li style=\"line-height: 20px;\">\n To evaluate the efficacy of astegolimab compared with placebo</li>\n <li style=\"line-height: 20px;\">\n To evaluate the safety of astegolimab compared with placebo</li>\n <li style=\"line-height: 20px;\">\n To evaluate potential relationships between drug exposure and the efficacy and safety of astegolimab</li>\n <li style=\"line-height: 20px;\">\n To evaluate potential effects of ADAs </li>\n <li style=\"line-height: 20px;\">\n To identify and/or evaluate biomarkers that are predictive of response to astegolimab (i.e., predictive biomarkers), are early surrogates of efficacy, are associated with progression to a more severe disease state (i.e., prognostic biomarkers), can provide evidence of astegolimab activity (i.e., PD  iomarkers), or can increase the knowledge and understanding of disease biology and drug safety or pharmacokinetics </li>\n <li style=\"line-height: 20px;\">\n To evaluate health status utility scores of participants treated with astegolimab compared with placebo</li>\n </ul>\n</div>\n<p>\n  </p>\n
      • principal_inclusion_criteria<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Able and willing to provide written informed consent and to comply with the study protocol</li>\n <li style=\"line-height: 20px;\">\n Age 40-80 years at Visit 1</li>\n <li style=\"line-height: 20px;\">\n Documented COPD diagnosis for <u>></u> 12 months prior to Visit 1</li>\n <li style=\"line-height: 20px;\">\n History of frequent exacerbations, defined as having had 2 or more moderate or severe COPD exacerbations within 12 months prior to Visit 1</li>\n</ol>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n A moderate COPD exacerbation is defined as new or increased COPD symptoms (e.g., dyspnoea, sputum volume, and sputum purulence) that lead to treatment with systemic corticosteroids (oral, IV, or intramuscular [IM]) and/or antibiotics.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Prior use of antibiotics alone does not qualify as a moderate exacerbation unless the use was specifically for the treatment of worsening symptoms of COPD.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n A severe COPD exacerbation is defined as new or increased COPD symptoms that lead to hospitalization (duration 24 hours) or lead to death.</p>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"5\">\n Post-bronchodilator FEV1 <u>></u>20% and <80% of predicted at Visit 1 or Visit 2</li>\n <li style=\"line-height: 20px;\" value=\"6\">\n Post-bronchodilator FEV1/FVC < 0.70 at Visit 1 or Visit 2</li>\n <li style=\"line-height: 20px;\" value=\"7\">\n mMRC score <u>></u>2 at screening</li>\n <li style=\"line-height: 20px;\" value=\"8\">\n Current tobacco smoker or former smoker (having stopped smoking for at least 6 months prior to Visit 1) with a history of smoking <u>></u> 10 pack-years (e.g., 20 cigarettes/day for 10 years) At Visit 1, participants who meet the protocol definition of current smoker will receive smoking cessation counselling</li>\n <li style=\"line-height: 20px;\" value=\"9\">\n On optimized COPD maintenance therapy as defined below for <u>></u> 12 months prior to Visit 1.</li>\n</ol>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n – Inhaled corticosteroid (ICS) plus long-acting beta-agonist (LABA)</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n – Long-acting muscarinic antagonist (LAMA) plus LABA</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n – ICS plus LAMA plus LABA Participants must be stable on current medications and doses for at least 4 weeks prior to Visit 1.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Initiation of new COPD therapy, including a methylxanthine preparation, maintenance macrolide therapy, and/or phosphodiesterase 4 (PDE4) inhibitor is not permitted within 4 weeks prior to Visit 1.</p>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"10\">\n Chest X-ray or computed tomography (CT) scan within 6 months prior to Visit 1 or chest X-ray during the screening period (prior to Visit 2) that confirms the absence of clinically significant lung disease besides COPD</li>\n <li style=\"line-height: 20px;\" value=\"11\">\n Demonstrated ability to use and comply with electronic diary (eDiary) requirements, defined as completion of all questions on at least 5 of 7 days prior to Visit 2 Participants unable to demonstrate compliance with the eDiary during the screening period will be screen failed. Participants will have the opportunity to demonstrate eDiary compliance if re-screened (see Protocol Version 2 dated 09 Nov 2022 Section 8.3.3.3).</li>\n <li style=\"line-height: 20px;\" value=\"12\">\n For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, as defined below: Female participants 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.</li>\n</ol>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n A female participant is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state ( 12 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., Müllerian agenesis). Per this definition, a female participant with a tubal ligation is considered to be of childbearing potential. The definition of childbearing potential may be adapted for alignment with local guidelines or regulations.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Examples of contraceptive methods with a failure rate of 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 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 individual. 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.</p>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"13\">\n For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm, as defined below:</li>\n</ol>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n With a female partner of childbearing potential or pregnant female partner, male participants must remain abstinent or use a condom during the treatment period and for 12 weeks after the final dose of astegolimab to avoid exposing the embryo. Male participants must refrain from donating sperm during this same period.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 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 individual. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of preventing drug exposure. If required per local guidelines or regulations, information about the reliability of abstinence will be described in the local Informed Consent Form.</p>\n
      • principal_exclusion_criteria<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Potential participants are excluded from the study if any of the following criteria apply:</p>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the study drug</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"2\">\n Any prior treatment with astegolimab</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"3\">\n Current documented diagnosis of asthma</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"4\">\n History of clinically significant pulmonary disease other than COPD</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"5\">\n Diagnosis of alpha-1-antitrypsin deficiency</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"6\">\n History of long-term treatment with oxygen at > 4.0 litres/minute While breathing supplemental oxygen, the participant should demonstrate an oxyhemoglobin saturation of <u>></u> 89%.</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"7\">\n Lung volume reduction surgery or procedure within 12 months prior to Visit 1</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"8\">\n Individuals participating in, or scheduled for, an intensive COPD rehabilitation program (participants who are in the maintenance phase of a rehabilitation program are eligible)</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"9\">\n History of lung transplant</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"10\">\n Any infection that resulted in hospital admission for <u>></u>24 hours and/or treatment with oral, IV, or IM antibiotics within 4 weeks prior to Visit 1 or during screening</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"11\">\n Upper or lower respiratory tract infection within 4 weeks prior to Visit 1 or during screening</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"12\">\n Treatment with oral, IV, or IM corticosteroids (>10 mg/day prednisolone or equivalent) within 4 weeks prior to initiation of study drug</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"13\">\n Treatment with investigational therapy within 3 months or 5 drug-elimination half-lives (whichever is longer) prior to screening</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"14\">\n Treatment with a licensed biologic agent (e.g., omalizumab, dupilumab, and/or anti-IL-5 therapies) within 3 months or 5 drug-elimination half-lives (whichever is longer) prior to screening</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"15\">\n Initiation of or change in non-biologic immunomodulatory or immunosuppressive therapy within 3 months prior to screening</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"16\">\n Treatment that is considered palliative (e.g., for life expectancy < 12 months)  </li>\n <li style=\"line-height: 20px;\" value=\"17\">\n Planned surgical intervention during the study</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"18\">\n Receipt of a live attenuated vaccine within 4 weeks prior to Visit 1 or during screening</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"19\">\n Known immunodeficiency, including but not limited to, HIV infection</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"20\">\n Known evidence of active or untreated latent tuberculosis</li>\n <li style=\"line-height: 20px;\" value=\"21\">\n AST, ALT, or total bilirubin elevation <u>></u> 2.0 X the upper limit of normal (ULN) during screening</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"22\">\n Substance abuse, as determined by the investigator, within 12 months prior to screening</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"23\">\n History of malignancy within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year overall survival rate > 90%), such as adequately treated carcinoma in situ of the cervix non-melanoma skin carcinoma, localized prostate cancer, or ductal carcinoma in situ</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"24\">\n Any other serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant’s safe participation in and completion of the study</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"25\">\n Unstable cardiac disease, myocardial infarction, or New York Heart Association Class III or IV heart failure within 12 months prior to screening</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"26\">\n History or presence of an abnormal ECG that is deemed clinically significant by the investigator, including complete left bundle branch block or second- or third-degree atrioventricular heart block</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"27\">\n QT interval corrected through use of Fridericia’s formula (QTcF) >450 ms if the participant is male or QTcF >470 ms if the participant is female for male or female participants with QRS > 120: QTcF > 480 ms.</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"28\">\n History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease (e.g., severe left ventricular systolic dysfunction, significant left ventricular hypertrophy with strain), or family history of sudden unexplained death or long QT syndrome</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"29\">\n Pregnant or breastfeeding, or intention of becoming pregnant during the study or within 12 weeks after the final dose of astegolimab</li>\n</ol>\n
      • primary_end_points<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Primary Endpoint</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n The primary efficacy objective for this study is to evaluate the efficacy of astegolimab compared with placebo in the mITT population on the basis of the following endpoint:</p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Annualized rate of moderate and severe COPD exacerbations over the 52-week treatment period</li>\n</ul>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n A moderate COPD exacerbation is defined as new or increased COPD symptoms (e.g., dyspnea, sputum volume, and sputum purulence) that lead to treatment (duration <u>></u> 3 days) with systemic corticosteroids (oral, IV, or IM) at a dose of > 10 mg/day prednisolone equivalent and/or antibiotics.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n A severe COPD exacerbation is defined as new or increased COPD symptoms that lead to hospitalization (duration > 24 hours) or lead to death.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <em>Primary Estimand</em></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n The <em>primary</em> estimand is defined <em>as follows</em>:</p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n <em><u>Population:  </u></em><em>Participants with COPD who are former or current smokers and have a history of frequent exacerbations, as defined by the inclusion and exclusion criteria (see Sections </em><em>5.1</em><em>and </em><em>5.2</em><em>, respectively)</em><em>, and received at least one </em><em>dose of study drug (mITT population)</em></li>\n <li style=\"line-height: 20px;\">\n <em><u>Variable:  </u></em><em>annualized rate of moderate and severe COPD exacerbations over the 52-week treatment period</em></li>\n <li style=\"line-height: 20px;\">\n <em><u>Treatments:</u></em></li>\n</ul>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 40px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n <em>Experimental: astegolimab Q2W</em></li>\n <li style=\"line-height: 20px;\">\n <em>Experimental: astegolimab Q4W</em></li>\n <li style=\"line-height: 20px;\">\n <em>Control: placebo</em></li>\n</ul>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n <em><u>Intercurrent events</u></em><em>:</em></li>\n</ul>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 40px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n <em>Early</em><em> discontinuation from study treatment</em></li>\n</ul>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n <em><u>Handling of intercurrent events</u></em><em>:  A treatment policy with regards to the intercurrent events listed above will be applied for the primary analysis</em></li>\n <li style=\"line-height: 20px;\">\n <em><u>Summary measure</u></em><em>:  rate ratio (RR) for annualized rate of moderate and severe COPD exacerbations</em></li>\n</ul>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Secondary Endpoints</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n The secondary efficacy objective for this study is to evaluate the efficacy of astegolimab compared with placebo in the mITT population on the basis of the following endpoints:</p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Time to first moderate or severe COPD exacerbation during the 52-week treatment period</li>\n <li style=\"line-height: 20px;\">\n Absolute change from baseline in HRQoL at Week 52, as assessed through the SGRQ-C total score</li>\n <li style=\"line-height: 20px;\">\n Absolute change from baseline in post-bronchodilator FEV<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">1</span> (liters) at Week 52</li>\n <li style=\"line-height: 20px;\">\n Absolute change from baseline in E‑RS:COPD total score at Week 52</li>\n <li style=\"line-height: 20px;\">\n Proportion of participants with improvement in HRQoL, defined as a decrease from baseline of <u>></u> 4 points in SGRQ-C total score, at Week 52</li>\n <li style=\"line-height: 20px;\">\n Annualized rate of severe COPD exacerbations over the 52-week treatment period</li>\n</ul>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n The secondary endpoints will be analyzed in the mITT population<em>.  Time-to-event endpoints will be analyzed using log-rank test and Cox proportional hazards regression models. Continous endponts will be summarized by treatment arm and timepoints, and analyzed using mixed models for repeated measures.  Improvement in HRQoL will be summarized as proportion of responders, i.e., patients achieving pre-specified improvement, and analyzed using logistic regression models.  </em></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Other Seconday and Exploratory Endpoints are the following:</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Objective: To evaluate the safety of astegolimab compared with placebo</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Endpoints: </p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Incidence and severity of all TEAEs, including SAEs, AESIs, and TEAEs leading to death or discontinuation</li>\n</ul>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n TEAEs severity will be 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 (see Appendix 8) </div>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Change from baseline in selected vital signs </li>\n <li style=\"line-height: 20px;\">\n Change from baseline in selected clinical laboratory test results and ECGs </li>\n</ul>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Objective: To characterize the astegolimab PK profile </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Endpoints: Serum concentration of astegolimab at specified timepoints</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Objective: To evaluate the immune response to astegolimab </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Endpoints: Prevalence of ADAs at baseline and incidence of ADAs during the study</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Objective: To evaluate the efficacy of astegolimab compared with placebo </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Endpoints: </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Change in COPD symptoms as measured by the E-RS:COPD total score at Week 24  </li>\n <li style=\"line-height: 20px;\">\n Change in E-RS:COPD individual domain scores (breathlessness, cough and sputum, and chest symptoms) from baseline at Week 24 and 52 </li>\n <li style=\"line-height: 20px;\">\n Change in EXACT individual domain scores (tired or weak, sleep disturbance, and scared or worried) from baseline at Week 24 and 52 </li>\n <li style=\"line-height: 20px;\">\n Proportion of participants with HRQoL improvement, defined as a decrease from baseline of <u>></u> 4 points in SGRQ-C total score, at Week 12 and Week 24 </li>\n <li style=\"line-height: 20px;\">\n Proportion of participants with symptom improvement, defined as a decrease of <u>></u> 2 points from baseline in E-RS:COPD total score, at Week 24 and Week 52 </li>\n <li style=\"line-height: 20px;\">\n bsolute change from baseline in post-bronchodilator</li>\n <li style=\"line-height: 20px;\">\n FEV1 (liters) at Weeks 12, 24, and 36 </li>\n <li style=\"line-height: 20px;\">\n Annualized rate of moderate COPD exacerbations over the 52-week treatment period </li>\n <li style=\"line-height: 20px;\">\n Duration of hospital stay for severe COPD exacerbations </li>\n <li style=\"line-height: 20px;\">\n Proportion of severe COPD exacerbations requiring hospital readmission within 30 days </li>\n <li style=\"line-height: 20px;\">\n Absolute change from baseline in daily step count at Weeks 12, 24, and 52 </li>\n <li style=\"line-height: 20px;\">\n Absolute change from baseline in time in moderate and vigorous physical activity at Weeks 12, 24, and 52 </li>\n </ul>\n</div>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Obective: To evaluate potential relationships between drug exposure and the efficacy and safety of astegolimab</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Endpoints:</p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Relationship between serum concentration or PK parameters for astegolimab and efficacy endpoints</li>\n <li style=\"line-height: 20px;\">\n Relationship between serum concentration or PK parameters for astegolimab and safety endpoints </li>\n</ul>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Objective: To evaluate potential relationships between selected covariates and exposure to astegolimab </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Endpoint: Relationship between selected covariates and serum concentration or PK parameters for astegolimab</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Objective: To evaluate potential effects of ADAs</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Endpoint: Relationship between ADA status and efficacy, safety, PK or biomarker endpoints</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Objective: To identify and/or evaluate biomarkers that are predictive of response to astegolimab (i.e., predictive biomarkers), are early surrogates of efficacy, are</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 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</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n increase the knowledge and understanding of disease biology and drug safety or pharmacokinetics </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Endpoint:  Relationship between biomarkers in blood, plasma, and serum and efficacy, safety, PK, immunogenicity, or other biomarker endpoints </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Objective: To evaluate health status utility scores of participants treated with astegolimab compared with placebo</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Endpoint: Change from baseline in EuroQol EQ-5D-5Lindex-based and VAS scores at Week 52</div>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic0
      • scope_pharmacogenomic1
      • 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 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.</p>\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. \n <div>\n  Clinical Research Nurses: Obtain Informed consents, Make CRF entries/resolve queries; Collect medical information; Vital 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. \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 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). \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. \n <div>\n  The ambulatory chest clinic also offers streamlined, efficient care by a multidisciplinary team of respiratory specialists. \n <div>\n This coordinated approach provides comprehensive care and support for patients with lung disease and their caregivers. \n <div>\n  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 </div>\n</div>\n<p>\n  </p>\n
      • other_details_explanation<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">Switzerland is the host country and Sponsor intends to submit study for approval in the host country</span></p>\n
      • other_details_regulatory_notapproved<table itemprop=\"copy-paste-table\">\n <tbody>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\"><strong>Country</strong></span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\"><strong>Status</strong></span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\"><strong>Submission Date</strong></span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Australia</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">19-May-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">China</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">25-May-2023</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">India</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">10-May-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">New Zealand</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">20-Apr-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Philippines</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">04-Apr-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Taiwan, Province of China</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">20-Apr-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Thailand</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">27-Apr-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Argentina</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Brazil</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted </span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">15-Mar-2023 / 20Mar2023</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Chile</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">23-May-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Mexico</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">02-May-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Switzerland</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">06-Apr-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Turkey</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">23-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">United Kingdom</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">13-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Austria</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Belgium</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Bulgaria</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Czech Republic</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Denmark</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">France</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Germany</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Greece</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Hungary</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Italy</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Latvia</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Netherlands</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Poland</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Romania</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Spain</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Sweden</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Submitted</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">07-Mar-23</span></p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\"> </span></p>\n
      • other_details_regulatory_approved<p>\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\"> </span></p>\n<table itemprop=\"copy-paste-table\">\n <tbody>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\"><strong>Country</strong></span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\"><strong>Name of Regulatory Authority</strong></span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\"><strong>Approval date</strong></span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\"><strong>Number of Sites</strong></span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">United States of America </span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">The United States Food and Drug Administration </span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">18 November 2022 </span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">74</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Canada </span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Health Canada </span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">19 April 2023</span></p>\n </td>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">10</span></p>\n </td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">South Africa</span></p>\n </td>\n <td>\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">SAHPRA</span></td>\n <td>\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">11 May 2023</span></td>\n <td>\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">8</span></td>\n </tr>\n <tr>\n <td>\n <p style=\"margin-bottom: 10px; margin-left: 0px;\">\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">Korea</span></p>\n </td>\n <td>\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">MFDA</span></td>\n <td>\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">18 April 2023</span></td>\n <td>\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\">10</span></td>\n </tr>\n </tbody>\n</table>\n<p>\n <span class=\"ui-provider fz b c d e f g h i j k l m n o p q r s t u v w x y z ab ac ae af ag ah ai aj ak\" dir=\"ltr\"> </span></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_durationThe total duration of study participation for each individual is expected to be approximately 15 months.
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states39
      • number_of_sitesApproximately 6 sites will participate in Kenya. As approvals from the Local Ethics Committees (LECs) are obtained to avoid delays in site-activation as each site submits to their LEC at different timepoints.
      • multi_country_listChin ; Hong Kong; India; Korea, Republic of; New Zealand; Philippines; Taiwan, Province of China; Thailand; Vietnam; Argentina; Brazil; Chile; Mexico; Canada; United States; Egypt; Israel; Kenya; South Africa; Switzerland; Turkey; United Kingdom; Austria; Belgium; Bulgaria; Czech Republic; Denmark; France; Germany; Greece; Hungary; Italy; Latvia; Netherlands; Poland; Romania; Spain; Sweden; Australia
      • data_monitoring_committeeYes
      • total_enrolment_per_siteNo maximum nor minimum enrolment per site as enrolment is competitive worldwide, but it is expected that approximately 2 - 3 participants will participate per site.
      • total_participants_worldwideApproximately 1290 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_nameProfessor Videlis
      • 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_participantsEnrolment is competitive worldwide. Approximately 12 participants will participate in Kenya.
      • notification<p>\n N/A</p>\n
      • approval_date06-12-2023
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted03-01-2024
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonApproved after satisfactory response to reviewer comments
      • 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 11:24:46
      • created2023-07-19 09:16:00
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id953
        • application_id1294
        • given_nameDr Teresa
        • middle_name
        • family_nameKinyari
        • qualificationMedical Doctor
        • professional_addressKenyatta National Hospital Respiratory Disease Unit Prof Mungai Road Off Wasawo Drive Off Riverside Drive Chiromo Campus University Of Nairobi P.O. Box 19676 00202 Nairobi Kenya
        • telephone+254 707028067
        • emailKinyari Teresa Mwendwa <tmwendwa@uonbi.ac.ke>
        • created2023-07-19 12:07:46
        • modified2024-01-03 14:21:03
    • SiteDetail(array)
      • 0(array)
        • id1564
        • application_id1294
        • 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)
        • created2023-07-19 12:07:46
        • modified2024-01-03 14:21:03
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 1(array)
        • id1565
        • application_id1294
        • 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)
        • created2023-07-19 13:02:58
        • modified2024-01-03 14:21:03
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 2(array)
        • id1566
        • application_id1294
        • 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)
        • created2023-07-19 14:32:46
        • modified2024-01-03 14:21:03
        • County(array)
          • id16
          • county_nameMachakos
          • created2012-06-15 10:23:55
          • modified2012-06-15 10:23:55
      • 3(array)
        • id1567
        • application_id1294
        • county_id41
        • site_nameKEMRI-CRDR Siaya Clinical Research Annex
        • physical_addressSiaya County Referral Hospital Grounds, P.O. BOX 40600-144, Siaya, Kenya
        • contact_details+254700111395 / +254731141831
        • contact_personProf. Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2023-07-19 14:32:46
        • modified2024-01-03 14:21:03
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
      • 4(array)
        • id1568
        • application_id1294
        • 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)
        • created2023-07-19 14:32:46
        • modified2024-01-03 14:21:03
        • County(array)
          • id3
          • county_nameKilifi
          • created2012-05-31 16:15:49
          • modified2012-05-31 16:15:49
      • 5(array)
        • id1569
        • application_id1294
        • 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)
        • created2023-07-19 14:32:46
        • modified2024-01-03 14:21:03
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
    • Sponsor(array)
      • 0(array)
        • id683
        • application_id1294
        • sponsorF. Hoffmann-La Roche Ltd
        • sponsor_typeIndustry
        • contact_personNadia Walli
        • addressClinical Research (PDG - CCO, North America),7070 Mississauga Road Mississauga, ON L5N 5M8 Canada
        • telephone_number+41 61 688 1111
        • fax_number
        • cell_number+416-930-1484
        • email_addressnadia.walli@roche.com
        • created2023-07-19 12:07:46
        • modified2024-01-03 14:21:03
  • 1(array)
    • Application(array)
      • id1284
      • user_id693
      • trial_status_id6
      • abstract_of_study<div>\n Background Information: </div>\n<div>\n Marburg virus (MARV) is one of the 6 genera in the family Filoviridae, which, along with Ebolavirus and Cuevavirus, are known to induce viral hemorrhagic fever. MARV is a large, negative-strand RNA virus composed of 7 genes encoding viral proteins, including a single GP. In humans, MARV is responsible for causing MVD, formerly known as Marburg hemorrhagic fever. It spreads through human-to-human transmission, with infection resulting from direct contact with blood, secretions, organs, or other bodily fluids of infected people and indirect contact with contaminated environments. MVD has an incubation period of 2 to 21 days followed by a rapid and abrupt onset of non-specific symptoms such as fever, extreme fatigue, gastrointestinal complaints, abdominal pain, anorexia, headache, myalgias,</div>\n<div>\n and/or arthralgias, and diarrhea can persist for a week. Many patients develop severe hemorrhagic manifestations, including hemorrhagic rash, epistaxis, mucosal bleeding, hematuria, hemoptysis, hematemesis, melena, conjunctival hemorrhage, tachypnea, confusion, somnolence, and hearing loss between 5 and 7 days after infection. Laboratory findings include low white blood cell and platelet counts and elevated liver enzymes (WHO 2021). In the last decades, MARV has been associated with large outbreaks of MVD in Africa; the average case fatality rate is around 50%, varying from 23% to 90% depending</div>\n<div>\n on virus strain and case management (CDC 2021).  The MARV is the etiologic agent of MVD and has been associated with 12 major outbreaks; the 2 largest occurring in Africa (Democratic Republic of Congo from 1998 to 2000 and Angola in 2005) that resulted in case fatality rates over 80%. The first recorded case of MVD in Guinea and West Africa occurred in August 2021 and resulted in 1 fatality. Recently 2 fatal cases of MVD were reported from Ashanti region, Ghana in June 2022 (WHO 2022). There is a continued potential threat of spread to other countries given the frequency of international travel (IB 2022). Sabin cAd3-Marburg vaccine is supplied as a single-dose vial that contains a recombinantcAd3 vector that expresses WT GP from the Angola strain of the MARV. The primary goal of</div>\n<div>\n the cAd3-Marburg vaccine is to induce rapid immunity followed by durable protection against MVD. </div>\n
      • study_title<div>\n A Phase 2, Randomized, Double-blind, Placebo-Controlled Trial to Evaluate Safety, Tolerability, and Immune Responses of an Investigational Monovalent Chimpanzee Adenoviral-Vectored Marburg Virus Vaccine in Healthy Adults </div>\n
      • laymans_summary<div>\n <span style=\"font-size:14px;\"><span style=\"color: rgb(27, 27, 27); font-family: Roboto, sans-serif;\">This is a multi-center, double-blinded, placebo-controlled, Phase II study to evaluate safety, tolerability, and immunogenicity of a single dose of cAd3-Marburg vaccine in healthy adults up to 70 years of age, in Uganda and Kenya. The study will enroll 125 eligible participants randomized 4:1 to receive the cAd3-Marburg vaccine at 1.0 × 10^11 PU dose or placebo (0.9% sodium chloride (NaCl) solution) at Day 1, intramuscularly in deltoid muscle. Participants will be screened for eligibility up to 28 days before enrollment. Enrollment will be staggered, starting with healthy adults 18 to 50 years of age (inclusive). Upon enrollment of minimum 25 younger adult participants (sentinel), the safety data up to 7 days post vaccination of these 25 sentinel participants will be reviewed by the independent DSMB. Progression to enrollment of the older adults (>50 to 70 years of age) will be dependent on the unblinded review of the Data Safety Monitoring Board (DSMB). Safety and immunogenicity will be assessed at Days 1, 8, 15, 29, 85, 169, and will conclude at the end of study visit on Day 366.</span></span></div>\n<p>\n  </p>\n
      • short_titleSabin
      • protocol_noECCT/23/07/05
      • version_noOriginal; Version 1.0
      • date_of_protocol06-12-2022
      • study_drugMarburg Virus Vaccine
      • disease_conditionMarburg Virus
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorNo
      • comparator_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_date126-07-2023
      • declaration_principal_investigatorProf. Videlis Nduba
      • declaration_date226-07-2023
      • placebo_presentYes
      • study_objectives<div>\n Primary Objective </div>\n<div>\n To evaluate the safety and tolerability of cAd3-Marburg vaccine</div>\n<div>\n  </div>\n<div>\n Secondary objective</div>\n<div>\n <div>\n To evaluate the antibody response (IgG) to cAd3-Marburg vaccine at Day 29 post-vaccination.</div>\n <div>\n  </div>\n <div>\n Other secondary objective</div>\n <div>\n <div>\n To determine the antibody (IgG) response  to cAd3-Marburg vaccine across additional timepoints post-vaccination. </div>\n <div>\n  </div>\n <div>\n Exploratory Objective</div>\n <div>\n <div>\n To describe the antibody response (IgM) to cAd3-Marburg vaccine.</div>\n <div>\n To describe the neutralizing antibody response to cAd3-Marburg vaccine. </div>\n </div>\n </div>\n <div>\n  </div>\n</div>\n<p>\n  </p>\n
      • principal_inclusion_criteria<ol style=\"box-sizing: border-box; color: rgb(27, 27, 27); font-family: Roboto, sans-serif; font-size: 15.84px;\">\n <li style=\"box-sizing: border-box;\">\n <p style=\"box-sizing: border-box; margin-block: 0px 8px;\">\n <span style=\"font-size:12px;\">Able and willing to complete and provide written informed consent prior to any study procedure; including injection site photograph consent, completing an Assessment of Understanding (AoU) prior to enrollment by answering 9 out of 10 questions correctly at least once in 3 attempts, and including optional consent for retention of blood samples for potential future testing and assay development.</span></p>\n <p style=\"box-sizing: border-box; margin-block: 0px;\">\n <span style=\"font-size:12px;\">Note: Participants can be enrolled even if they do not provide optional consent for retention of blood samples for potential future testing and assay development.</span></p>\n </li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Able to read and write the language used in diary card.</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Male or non-pregnant female 18 to 70 years of age (inclusive) at time of informed consent.</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Is capable of understanding and agrees to comply with planned study procedures and to be available for all clinic follow-up for all planned study visits.</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Has a means to be contacted and to contact the investigator during the study.</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Agree not to receive any vaccine within 28 days from study vaccination (prior and after), with the exception of an emergency use authorization or authorized non-adenoviral vectored coronavirus disease 2019 (COVID-19) vaccine, which may be given within 14 days of study vaccination.</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Agree not to donate bone marrow, blood, or blood products until 3 months after the study vaccination.</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">In good general health without clinically significant medical conditions, based on medical history, physical examination, vital signs, and clinical laboratory results as deemed acceptable by the principal investigator.</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Clinical laboratory results within 28 days prior to vaccination within the site's laboratory reference ranges (or deemed not clinically significant by the principal investigator) for the following parameters: hematology (complete blood count (CBC) including hemoglobin, white blood cell (WBC), red blood cell (RBC), total lymphocyte count); coagulation tests (prothrombin time, international normalized ratio (INR), fibrinogen); chemistry (C-reactive protein, d-dimer, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum creatinine). A laboratory result that is outside the reference range and is deemed not clinically significant by the principal investigator will not exclude the participant.</span></li>\n <li style=\"box-sizing: border-box;\">\n <p style=\"box-sizing: border-box; margin-block: 0px 8px;\">\n <span style=\"font-size:12px;\">Has a body mass index (BMI) >17 and ≤37 at screening.</span></p>\n <p style=\"box-sizing: border-box; margin-block: 0px;\">\n <span style=\"font-size:12px;\">Female participant specific criteria:</span></p>\n </li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Negative pregnancy serum test at screening, and negative urine pregnancy test before vaccination, if of reproductive potential.</span></li>\n <li style=\"box-sizing: border-box;\">\n <p style=\"box-sizing: border-box; margin-block: 0px 8px;\">\n <span style=\"font-size:12px;\">Agrees to use an effective means of birth control from at least 21 days prior to enrollment through 24 weeks after study vaccination if assessed to be woman of childbearing potential UNLESS they fulfill one of the following criteria:</span></p>\n <ul style=\"box-sizing: border-box;\">\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">At least 1 year postmenopausal.</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Surgically sterile.</span></li>\n </ul>\n <p style=\"box-sizing: border-box; margin-block: 0px;\">\n <span style=\"font-size:12px;\">Male participants must agree:</span></p>\n </li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Not to father a child or donate sperm through study end.</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">To use a barrier (condom) means of birth control from vaccination through study end, if assessed to be of reproductive potential.</span></li>\n</ol>\n
      • principal_exclusion_criteria<ol style=\"box-sizing: border-box; color: rgb(27, 27, 27); font-family: Roboto, sans-serif; font-size: 15.84px;\">\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Pregnant or lactating female or plans to become pregnant or breastfeed starting from study vaccination through to study end.</span></li>\n <li style=\"box-sizing: border-box;\">\n <p style=\"box-sizing: border-box; margin-block: 0px 8px;\">\n <span style=\"font-size:12px;\">Has any medical disease or condition that, in the opinion of the investigator, precludes study participation. This includes any acute, subacute, intermittent, or chronic medical disease or condition that</span></p>\n <ul style=\"box-sizing: border-box;\">\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">would place the participant at an unacceptable risk of injury,</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">render the participant unable to comply with the requirements of the protocol,</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">or may interfere with the evaluation of responses or the participant's successful completion of the trial; (chronic conditions that are well-controlled and medically stable, ie, no change in treatment for medical reasons occurred in the last 6 months, are allowed at the discretion of the principal investigator, eg, hypertension, asthma, thyroid disease).</span></li>\n </ul>\n <p style=\"box-sizing: border-box; margin-block: 0px;\">\n <span style=\"font-size:12px;\">The medical disease or condition also includes any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (eg, malignancy, HIV infection) or immunosuppressive/cytotoxic therapy (eg, medications used during cancer chemotherapy, organ transplantation or to treat autoimmune disorders).</span></p>\n </li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Serology screen positive for infectious diseases (hepatitis B, hepatitis C, HIV 1 and 2, syphilis).</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Known prior exposure to MARV or prior diagnosis of Marburg virus disease (MVD).</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Current diagnosis of COVID-19 by reverse transcription polymerase chain reaction (RT-PCR) or antigenic testing or current signs and symptoms of COVID-19. Participants may be enrolled 14 days post resolution of all signs and symptoms of COVID-19 or of testing positive for COVID-19 in asymptomatic participants.</span></li>\n <li style=\"box-sizing: border-box;\">\n <p style=\"box-sizing: border-box; margin-block: 0px 8px;\">\n <span style=\"font-size:12px;\">History of or active status of any of the following clinically significant conditions:</span></p>\n <ul style=\"box-sizing: border-box;\">\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Serious adverse reactions to vaccines such as anaphylaxis, urticaria (hives), respiratory difficulty, angioedema, or abdominal pain.</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Allergic reaction to excipients in the study vaccine including gentamycin, neomycin or streptomycin or any other aminoglycoside.</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">History of Diabetes mellitus Type I or Type II.</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Active Tuberculosis.</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema.</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Idiopathic urticaria within the last year.</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Bleeding disorder diagnosed by a doctor or use of anticoagulant medications such as, warfarin, apixaban, dabigatran (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws.</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Major thrombotic event or heparin-induced thrombocytopenia or vaccine-induced thrombotic thrombocytopenia (VITT).</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">History of malignancy of any organ system, treated or untreated, within the past 5 years from screening. (If diagnosed malignancy is 5 or more years prior to enrollment and cured with no ongoing treatment it will NOT be considered an exclusion).</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Seizure in the past 3 years or treatment for seizure disorder in the past 3 years.</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Asplenia or functional asplenia.</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Autoimmune disease/autoinflammatory condition.</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Any medical, psychiatric, social condition, occupational reason, or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a participant's ability to give informed consent.</span></li>\n </ul>\n </li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Has a clinically significant acute illness (this does not include minor illnesses) or temperature ≥38.0°Celsius (≥100.4° Fahrenheit) within 24 hours of the planned dose of study vaccine, re-evaluation of eligibility may be performed at resolution of all signs and symptoms, and randomization at a later date is permitted at the discretion of the investigator and after consultation with the sponsor (as appropriate).</span></li>\n <li style=\"box-sizing: border-box;\">\n <p style=\"box-sizing: border-box; margin-block: 0px 8px;\">\n <span style=\"font-size:12px;\">Receipt of any of the following substances:</span></p>\n <ul style=\"box-sizing: border-box;\">\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">COVID-19 vaccine that has not received emergency use authorization or approval per local regulatory agency.</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Prior receipt of Ebola or Marburg vaccine.</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Prior receipt of any adenoviral-vectored vaccine, adenovirus-based or adeno-associated viruses (AAV)-based gene therapies or treatments, including adenoviral COVID-19 vaccines or boosters.</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Participant received an investigational drug (including investigational drugs for prophylaxis of COVID-19) within 28 days of dosing or within washout period (5 half-lives) of such drug or has used an invasive investigational medical device within 28 days of dosing.</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Received investigational Ig or monoclonal antibodies within 3 months.</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Received convalescent serum for COVID-19 treatment within 3 months.</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Received an investigational vaccine within 3 months before the planned administration of the first dose of study vaccine.</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Is currently enrolled or plans to participate in another investigational or interventional study during this study (observational/registry studies are allowed).</span></li>\n </ul>\n </li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Use of immunomodulators or systemic glucocorticoids in daily doses of glucocorticoid equivalence >20 mg of prednisolone in the last 90 days, and for periods exceeding 10 days. NSAIDS are permitted.</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Receipt of blood products within 3 months prior to enrollment.</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Current anti-tuberculosis prophylaxis or therapy.</span></li>\n <li style=\"box-sizing: border-box;\">\n <span style=\"font-size:12px;\">Abnormality or permanent body art (such as tattoo) in deltoid region that would interfere with ability to observe or assess injection site reactions.</span></li>\n</ol>\n
      • primary_end_points<div>\n Primary Endpoint: Count and percentage of</div>\n<div>\n vaccinated participants who develop: </div>\n<div>\n ï‚· SAEs, </div>\n<div>\n ï‚· solicited AEs, </div>\n<div>\n ï‚· unsolicited AEs, </div>\n<div>\n ï‚· AESI, </div>\n<div>\n ï‚· MAAE,</div>\n<div>\n ï‚· AE at each intensity level.</div>\n<div>\n Estimand 1a (Primary): Count and percentage of</div>\n<div>\n vaccinated participants who would develop SAEs,</div>\n<div>\n solicited AEs, unsolicited AEs, AESI, MAAE, and</div>\n<div>\n AE at each intensity level will be evaluated with each</div>\n<div>\n treatment group. A treatment policy strategy is used</div>\n<div>\n for assessing safety irrespective of a current (or prior)</div>\n<div>\n infection at time of the vaccination. Infections and</div>\n<div>\n death (if they meet the AE and time window criteria)</div>\n<div>\n are included in the endpoint (composite strategy). </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_others1
      • scope_others_specifyTolerability, and Immune Responses
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n Site activities will be located in Siaya County at the Siaya County Referral Hospital grounds at the Clinical Research Annex. Siaya site is a modern research facility, well equipped with capacity to conduct this vaccine trial. All the study activities will be conducted at the Clinical Research Site. After community mobilization, recruitment, screening and enrollment, IP storage and dispensation (vaccinations) will occur at the Siaya Research Annex. The site has conducted more than 20 clinical trials since establishment.</p>\n<p>\n  The site lab is well equipped with the necessary equipment and capacity to collect, process, store and manage the collected study samples. The equipments are well maintained with regular calibration. The site laboratory staff are qualified by education, training and experience. In addition, they are GCLP and Laboratory IATA trained and Certified. The Site pharmacy is equipped with fridges and temperature monitoring devices for IP management.</p>\n<p>\n The site is ICH/GCP compliant with all staff undertaking the GCP and ethics training prior to conducting the delegated duties. In addition, the community team is GPP compliant with good recruitment and retention plan that is goal oriented.</p>\n<p>\n Site Personnel responsible for day to day running of the project include a Principal Investigator, 2 Medical Officers, 2 Pharmacists, 2 Pharmaceutical Technologists, 6 Nurses, 6 QA/QC officers, 4 Clinical Officers,4 Laboratory Technologists, 2 Administrative Officers, 4 Data personnel and 7 Community Interviewers. This clinical research team is well trained and experienced in data collection including eligibility assessment and participant care during follow up.</p>\n
      • other_details_explanation<p>\n <em>Two prior studies for this IP have been conducted in the United States (?in a predominantly Caucasian population):</em></p>\n<ol>\n <li>\n <em>RV 507,  a Phase I open-label dose escalation clinical trial of 40 40 recipients of the cAd3-Marburg vaccine at a single dose of 1 x 10¹⁰ or 1 x 10¹¹PU/mL, with one or more unsolicited AEs being reported by 24 of 40 subjects (60.0%) with most events reported as mild in severity. </em></li>\n <li>\n <em>Sabin-001, a Phase 1b,  clinical trial evaluating the safety, tolerability and immune responses of two cAd3-vectored IP (Ebola Sudan and Marburg) where a total of 16 participants received a 1 x 10¹¹ PU dose of cAd3-Marburg vaccine by IM route. The IP overall was generally well tolerated, with all reported reactogenicity being mild to moderate in severity.</em></li>\n</ol>\n<p>\n <em>Sabin-002 is a phase 2 study, building on the study results above, intended to evaluate the safety, tolerability, and immunogenicity of the same product, for generalizable study data in an African population, that is likely to have markedly different prior exposure to the cAd3 vector (and other pathogens that may impact on immunogencity); as well as potential for further  differences in immunogenicity due to different genetics.</em></p>\n<p>\n <em>As defined in the Site-specific addendums, both countries are at risk of a Marburg outbreaks, and assessing the safety, tolerability and immune responses of this study in this population is pertinent to this population</em>.</p>\n<p>\n  </p>\n<p>\n  </p>\n
      • other_details_regulatory_notapproved<p>\n Uganda National Drug Authority. Application done on 15June 2023. </p>\n
      • other_details_regulatory_approved<p>\n None </p>\n
      • other_details_regulatory_rejected<p>\n None </p>\n
      • other_details_regulatory_halted<p>\n None. </p>\n
      • estimated_duration18months
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo _Normal Saline
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKEMRI / CRDR, KEMRI Clinical Research Annex, Siaya County Referral Hospital Ground. P.O BOX 144-40600 ,Siaya, Kenya
      • single_site_physical_addressP.O BOX 144-40600 ,Siaya, Kenya
      • single_site_contact_personDr. Videlis Nduba
      • single_site_telephone+254724522474
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states2
      • number_of_sites
      • multi_country_listKenya and Uganda
      • data_monitoring_committeeYes
      • total_enrolment_per_siteApproximately 80 participants
      • total_participants_worldwide125
      • 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_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsNo
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameDr. Videlis Nduba
      • investigator1_middle_nameNduba
      • investigator1_family_nameNzioka
      • investigator1_qualificationGeneral Practice
      • investigator1_professional_addressKEMRI / CRDR, KEMRI Clinical Research Annex, Siaya County Referral Hospital Ground. P.O BOX 144-40600 ,Siaya, Kenya
      • investigator1_telephone+254724522474
      • investigator1_emailvnduba@kemri.org
      • organisations_transferred_Yes
      • number_participantsApproximately 80 participants
      • notification
      • approval_date11-09-2023
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted26-07-2023
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-04-01 15:50:01
      • created2023-06-22 08:11:01
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id941
        • application_id1284
        • given_nameProf. Videlis Nduba
        • middle_nameNduba
        • family_nameNzioka
        • qualificationGeneral Practice
        • professional_addressKEMRI / CRDR, KEMRI Clinical Research Annex, Siaya County Referral Hospital Ground. P.O BOX 144-40600 ,Siaya, Kenya
        • telephone+254724522474
        • emailvnduba@kemri.org
        • created2023-06-22 08:23:35
        • modified2023-07-26 19:09:22
    • SiteDetail(array)
      • 0(array)
        • id1531
        • application_id1284
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2023-06-22 08:23:35
        • modified2023-07-26 19:09:22
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id674
        • application_id1284
        • sponsorSabin Vaccine Institute
        • sponsor_typeResearch Institution
        • contact_personEkaterinaVert-Wong
        • address2175 K Street, NW, Suite 400 Washington DC 20037
        • telephone_number+1 202-621-1682
        • fax_number
        • cell_number+1 202-621-1682
        • email_addressKatya.Vert-Wong@Sabin.org
        • created2023-06-22 08:23:35
        • modified2023-07-26 19:09:22
  • 2(array)
    • Application(array)
      • id1295
      • user_id796
      • trial_status_id2
      • abstract_of_study<p>\n Sickle cell disease is a chronic hemolytic anemia caused by inheritance of a mutated form of hemoglobin (Hb), sickle Hb (HbS). The disease is characterized by polymerization of HbS in RBCs when in the deoxygenated state, resulting in a sickle-shaped deformation of RBCs. Sickled cells aggregate in capillaries precipitating vaso-occlusive events that generally present as acute and painful crises (VOC) resulting in tissue ischemia, infarction, and long-term tissue damage, that underlies the significant morbidity and increased mortality associated with this disease. Red blood cells in SCD patients tend to be fragile due to sickling and other factors, and the mechanical trauma of circulation causes hemolysis and chronic anemia. Sickle cell disease is the most common inherited hemolytic anemia, affecting approximately 100,000 individuals in the United States (US) (CDC 2020), approximately 35,000 to 164,000 individuals in Europe, and millions more worldwide (Hassell, 2010; Lobitz et al, 2018). In Kenya, Ministry of Heath estimates that at least 6000 children are born annually with SCD. The paediatric to adult ratio stands at 3:1 and Sickle Cell disease has been found to be more prevalent in areas with high prevalence of Malaria in Kenya (Williams et al., 2005). Kombewa lies in the area with high prevalence of Malaria. Therapeutic treatment of SCD remains inadequate. Potentially curative therapies, such as bone marrow transplant or gene therapies are invasive and such high-risk procedures are available to only a limited number of patients. For most patients, treatment involves supportive care for management of vaso-occlusive crisis (VOC) or the use of hydroxyurea (HU), to stimulate production of fetal Hb (HbF) and reduce Hb polymerization. However, the myelosuppressive and teratogen effects of HU limit its effectiveness. More recently other therapies have been approved; L-Glutamine to reduce the acute complications of SCD, Volexotor, indicated to reduce hemolysis and improve hemoglobin levels, and Crizanlizumab to reduce the incidence of VOCs. None of these therapies results in both improvement of anemia and a reduction in the frequency of VOCs. Additional therapies that target the underlying physiology are needed. Pyruvate kinase R (PKR) is the isoform of Pyruvate kinase expressed in RBCs and its activation is proposed to directly target both sickling by reducing deoxy-HbS and Hemolysis by improving RBC membrane integrity. The study drug, Etavopivat (FT-4202) is a potent selective activator of PKR. This is a randomized, placebo-controlled, double-blind, multicenter Phase 2/3 study among SCD patients, aged 12 to 65 years. The primary objective is to assess the efficacy of FT- 4202 in adolescents and adults with SCD as compared to placebo as measured by improvement in hemoglobin (Hb) and annualized vaso-occlusive crisis (VOC) rate. The Phase 2, is the dose determination portion and the selected dose will be assessed in Phase 3, the efficacy portion against placebo. Following a double blind period of 52 weeks, all patients may enter a 52-week open-label extension period. The study will enroll approximately 344 adult and adolescent patients with SCD, who fulfill the eligibility criteria (60 to 90 patients in the Dose Determination Group and approximately 274 patients in the Efficacy Continuation Group). The Kombewa Clinical Research Centre targets to enroll about 25 Subjects in the dose determination group and about 40 subjects in the efficacy continuation group. Study activities during visits will include but not limited to a physical, vital signs, randomization, 12-Lead ECG, and various laboratory assessments at screening and as part of efficacy and safety assessments at time points as per the protocol Schedule. Patients will be evaluated for safety by collection of adverse events (AEs)/serious adverse events (SAEs), laboratory tests and vital signs. Serious adverse events will be collected from the time of signature of informed consent throughout the dosingperiod and including the follow-up period. Ethical approvals will be sought from the relevant authorities prior to study implementation. Results from the overall study will inform the potential usefulness of FT-4202 in the treatment of patients with SCD.</p>\n
      • study_title<p>\n An Adaptive, Randomized, Placebo-controlled, Double-blind, Multi-center Study of Oral FT-4202, a Pyruvate Kinase Activator in Patients with Sickle Cell Disease (PRAISE)</p>\n
      • laymans_summary<p>\n Sickle cell disease (SCD) is an blood disease that causes the Red blood cells in blood to (RBCs) to change to sickle shape. Sickled cells do not flow easily through small blood vessels and may cause obstruction resulting in recurrent episodes of pain. These episodes are referred to as vaso-occlusive events (VOC). The sickled cells have a shorter life span than the non sickled cells and this results in low blood levels (anaemia). SCD affects about 100,000 patients in the United States, up to 164,000 patients in Europe, and millions more in the rest of the world. In Kenya, the Ministry of Health estimates that at least 6000 children are born with SCD every year. Sickle Cell disease patients are found in larger numbers in areas with where Malaria common than in areas where malaria is less common in Kenya (Williams et al., 2005). Kombewa lies in an area where Malaria is common. Cure for SCD can be achieved by procedures called bone marrow transplant or gene therapies, but these are not available or possible for all patients and are also expensive. For most patients treatment is mainly supportive; pain control, blood transfusions or the use of hydroxyurea (HU). Newer treatments have been developed that increase blood level or reduce frequency of VOCs but none of the treatments does both. The search for other treatmentsis on going. The study drug, Etavopivat (FT- 4202) is a potent activator of a protein called Pyruvate kinase R (PKR), which is key in the process of generating energy in the body. It is that PKR activation will reduce the rate of RBC sickling and RBC destruction leading to less frequent episodes of pain(VOC) and increased blood levels. This study is designed to take place in phases among patients with SCD, aged 12 to 65 years. The phase 2 is the dose determination portion when patients will receive one of two dose levels of study drug or placebo (a placebo is a substance that looks like the study drug but has no effects on the body). The selected dose will be assessed for efficacy (effectiveness) in Phase 3, for increasing blood level and reducing episodes of VOC, over 52 weeks, when compared to a placebo (). After the 52 week follow up period the patients may enter 52 weeks period in which all patients receive the study drug. This study will enroll up to about 344 patients with SCD (60 to 90 patients in the Dose Determination Group and 274 patients in the Phase 3). The Kombewa Clinical Research Centre targets to enroll about 25 Subjects in the dose determination group and about 40 subjects in the efficacy continuation group. At study pre-determined time points, the participants will undergo heath assessments; physical examinations, taking of vital signs (e.g. temperature, Blood pressure, heart rate, respiratory rate), recording heart activity using an electrocardiogram (ECG), and various laboratory assessments as part of follow up safety assessments. All the information will be recorded and then analyzed. Ethical approvals will be sought from the relevant authorities prior to study start. Results from the overall study will inform on the potential usefulness of the study drug (FT-4202) in the treatment of patients with SCD</p>\n
      • short_titlePRAISE
      • protocol_noECCT/23/07/04
      • version_no2.0
      • date_of_protocol15-10-2020
      • study_drugFT-4202
      • disease_conditionSickle Cell
      • 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_nameFT-4202
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressmctafrica.regarchive@mct-cro.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_applicant0721996988
      • declaration_date121-07-2023
      • declaration_principal_investigatorNA
      • declaration_date221-07-2023
      • placebo_presentYes
      • study_objectives<p>\n 1. To assess the efficacy of FT-4202 in adolescents and adults with SCD as compared to placebo as measured by improvement in hemoglobin (Hb)</p>\n<p>\n 2.To assess the efficacy of FT-4202 as compared to placebo on the annualized vaso-occlusive crisis (VOC) rate.</p>\n<p>\n <strong>Secondary Efficacy Objectives ·</strong></p>\n<p>\n To measure the effects of FT-4202 on clinical measures and sequelae of hemolysis ·</p>\n<p>\n To evaluate the effects of FT-4202 on the sequelae of VOC ·</p>\n<p>\n To assess changes in fatigue of sickle cell patients taking FT-4202</p>\n
      • principal_inclusion_criteria<p>\n Eligibility for inclusion will be determined on the basis of diagnosis SCD genetic type, age of 12 to 65 years and at least 2 VOCs in the last12 months prior to providing informed assent/consent. For the itemized list of Inclusion criteria please refer to the main study protocol, Section 5.1 titled “Inclusion Criteria”.</p>\n<p>\n  </p>\n<p>\n Inclusion Criteria Participants are eligible to be included in the study only if all the following criteria apply:</p>\n<p>\n Informed Consent</p>\n<p>\n 1. Patient has provided documented informed consent or assent (the informed consent form [ICF] must be reviewed and signed by each patient; in the case of adolescent patients, both the consent of the patient’s legal representative or legal guardian, and the patient’s assent must be obtained)</p>\n<p>\n Age 2. Age 12 to 65 years, inclusive, at time of randomization Type of Participant and Disease Characteristics</p>\n<p>\n 3. Patient has a confirmed diagnosis of sickle cell disease • Documentation of SCD genotype (HbSS, HbSβ0 -thalassemia or other sickle cell syndrome variants) based on prior history of laboratory testing; if unavailable, must be confirmed by laboratory testing during screening</p>\n<p>\n 4. Patient has had at least 2 episodes of VOC in the past 12 months • For study eligibility, VOC is defined as a previously documented episode of ACS or acute painful crisis (for which there was no explanation other than VOC) which required prescription or healthcare professional-instructed use of analgesics for moderate to severe pain (documentation must exist in the patient medical record prior to Screening)</p>\n<p>\n 5. Hemoglobin ≥ 5.5 and ≤ 10 g/dL (≥ 55 and ≤ 100 g/L) during screening</p>\n<p>\n 6. For participants taking HU, the dose of HU (mg/kg) must be stable (no more than a 20% change in dosing) for at least 90 days prior to start of study treatment with no anticipated need for dose adjustments during the study, in the opinion of the Investigator Sex and Contraceptive/Barrier Requirements</p>\n<p>\n 7. Patients, who if female and of child bearing potential, are using highly effective methods of contraception and agree not to donate ova from study start to 90 days after the last dose of study drug, and who if male are willing to use barrier methods of contraception and agree not to donate sperm, from study start to 90 days after the last dose of study drug.</p>\n
      • principal_exclusion_criteria<p>\n Exclusion Criteria Patients are excluded from the study if they meet any of the following criteria:</p>\n<p>\n Medical Conditions</p>\n<p>\n 1. More than 10 VOCs (as defined in Inclusion Criterion 4) within the past 12 months</p>\n<p>\n 2. Hospitalized for sickle cell crisis or other vaso-occlusive event within 14 days of signing the ICF</p>\n<p>\n 3. Female who is breast feeding or pregnant</p>\n<p>\n 4. Hepatic dysfunction characterized by: • Alanine aminotransferase (ALT) > 4.0 × upper limit of normal (ULN) • Direct bilirubin > 3.0 × ULN</p>\n<p>\n 5. Patients with clinically significant bacterial, fungal, parasitic, or viral infection requiring systemic therapy • Patients with acute bacterial, fungal, parasitic, or viral infection requiring systemic therapy should delay screening/enrollment until active therapy has been completed Note: Infection prophylaxis is allowed (see concomitant medication restrictions)</p>\n<p>\n 6. Known human immunodeficiency virus (HIV) positivity</p>\n<p>\n 7. Active infection with hepatitis B virus (hepatitis B surface antigen [HepBsAg] and hepatitis B core antibody [HepBcAb] positive)</p>\n<p>\n 8. Active hepatitis C infection</p>\n<p>\n 9. Severe renal dysfunction (estimated glomerular filtration rate at the Screening visit; calculated by the central laboratory < 30 mL/min/1.73 m2 ) or on chronic dialysis</p>\n<p>\n 10. History of malignancy within the past 2 years prior to treatment Day 1 requiring systemic chemotherapy and/or radiation • Patients with malignancy considered surgically cured are eligible (eg, nonmelanoma skin cancer, cancer of the cervix in-situ, ductal carcinoma in situ [stage 1], grade 1 endometrial cancer)</p>\n<p>\n 11. History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including but not limited to the following: • Unstable angina pectoris or myocardial infarction or elective coronary intervention • Congestive heart failure requiring hospitalization • Uncontrolled clinically significant arrhythmias • Symptomatic pulmonary hypertension</p>\n<p>\n 12. History of overt clinical stroke within previous 2 years or any history of an intracranial hemorrhage</p>\n<p>\n 13. Any condition affecting drug absorption, such as major surgery involving the stomach or small intestine (prior cholecystectomy is acceptable)</p>\n<p>\n 14. Patients with iron deficiency (eg, serum iron less than the lower limit of normal [LLN] or ferritin <10 µg/L) who are not taking or are unable to take iron supplements at the time of consent and during the study</p>\n<p>\n 15. Patients with folate (or folic acid or Vitamin B9) or Vitamin B12 deficiency (eg, folate or Vitamin B12 levels less than the LLN) who are not taking or are unable to take supplements before the first dose of study drug and during the study</p>\n<p>\n 16. Patients who are not taking or are unable to take antimalarial prophylaxis at the time of consent and during the study if they live in areas of endemic malaria where prophylaxis is recommended</p>\n
      • primary_end_points<p>\n Hb response rate at Week 24 (increase of > 1 g/dL [> 10 g/L] from baseline) during the blinded treatment period Annualized VOC rate during the 52-week blinded treatment period based on adjudicated VOC review</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specifyTherapeutic exploratory and Confirmatory
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n Kombewa Clinical Research Centre Site Capacity 25 Mar 2023 There are 35 health facilities within the Kombewa Clinical Research Centre catchment area out of which 6 can hospitalize. Kombewa County Hospital is the referral point for all the facilities in Seme sub-County, while Chulaimbo is the referral facility in Kisumu West County. The patients are referred to Jaramogi Oginga Odinga Teaching and referral hospital, Avenue Hospital, and other private facilities within Kisumu city in case of an emergency. The unit has the following staff to support research studies; 2 paedricians, 3 medical offices, 5 clinical offices, 1 regulatory officer, 6 study coordinators,7 laboratory technologist, 9 nurses, 1 pharmacist, 2 pharmaceutical technologist, 8 data clerks and 38 filed workers. The unit has two storey building consisting of office space, laboratory which includes clinical, immunology and microbiology labs, clinical rooms, emergency room, observation room, pharmacy, records storage area and archives.</p>\n
      • other_details_explanation<p>\n NA</p>\n
      • other_details_regulatory_notapproved<p>\n NONE</p>\n
      • other_details_regulatory_approved<p>\n Oman: Turkey: KSA: Nigeria, USA</p>\n
      • other_details_regulatory_rejected<p>\n NONE</p>\n
      • other_details_regulatory_halted<p>\n NA</p>\n
      • estimated_duration104 Weeks
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overYes
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo Controlled
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states10
      • number_of_sites4
      • multi_country_listNigeria, Ghana, Egypt, Turkey, Kenya, USA, KSA, Spain, Oman, Russia
      • data_monitoring_committeeYes
      • total_enrolment_per_site30
      • total_participants_worldwide344
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentYes
      • population_above_18Yes
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyParticipant under the age of 18
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameJanet
      • investigator1_middle_nameN
      • investigator1_family_nameOyieko
      • investigator1_qualificationMedical Officer
      • investigator1_professional_addressP.o Box Kombewa
      • investigator1_telephone0721996988
      • investigator1_emailjanet.oyieko@usamru-k.org
      • organisations_transferred_Yes
      • number_participants30
      • notification<p>\n None</p>\n
      • approval_date28-08-2023
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted21-07-2023
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewers have provided approval for the protocol.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-01-14 22:20:12
      • created2023-07-21 10:46:54
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id954
        • application_id1295
        • given_nameDr. Janet
        • middle_name
        • family_nameOyieko
        • qualificationMedical Officer
        • professional_addressP.O Box 54 Kisumu
        • telephone0721996988
        • emailjanet.oyieko@usamru-k.org
        • created2023-07-21 10:59:42
        • modified2023-07-21 20:38:31
    • SiteDetail(array)
      • 0(array)
        • id1570
        • application_id1295
        • county_id42
        • site_nameKondele Children\'s Hospital Center for Clinical Research (CCR),
        • physical_addressJaramogi Oginga Odinga Teaching and Referral Hospital
        • contact_detailsP.O Box Jaramogi Oginga Odinga Teaching and Referral Hospital
        • contact_personDr. Ogutu
        • site_capacity(null)
        • misc(null)
        • created2023-07-21 10:59:42
        • modified2023-07-21 20:38:31
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 1(array)
        • id1571
        • application_id1295
        • county_id47
        • site_nameGertrude\'s Children Hospital
        • physical_address34 MUTHAIGA ROAD,
        • contact_detailsNAIROBI P.O. BOX 42325 - 00100 NAIROBI, KENYA
        • contact_personProf. J. Githanga
        • site_capacity(null)
        • misc(null)
        • created2023-07-21 12:35:56
        • modified2023-07-21 20:38:31
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 2(array)
        • id1572
        • application_id1295
        • county_id41
        • site_nameKEMRI/CRDR Kemri Clinical Research Annex
        • physical_addressSiaya County Referral Hospital Grounds, Siaya
        • contact_details0724522474
        • contact_personDr. Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2023-07-21 12:35:56
        • modified2023-07-21 20:38:31
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
    • Sponsor(array)
      • 0(array)
        • id684
        • application_id1295
        • sponsorForma Therapeutics
        • sponsor_typeIndustry
        • contact_personDanish Khan
        • address500 Arsenal Street, Suite 100 Watertown, MA 02742
        • telephone_number617-679-1970
        • fax_number
        • cell_number617-880-9574
        • email_addressmedicalmonitor@formatherapeutics.com
        • created2023-07-21 10:59:42
        • modified2023-07-21 20:38:31
  • 3(array)
    • Application(array)
      • id1293
      • user_id693
      • trial_status_id6
      • abstract_of_study<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong><u>STUDY RATIONALE</u></strong></div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n The purpose of this study is to assess the efficacy and safety of astegolimab compared with placebo in participants with chronic obstructive pulmonary disease (COPD) who are former or current smokers and have a history of frequent exacerbations. </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <div>\n <strong><u>OBJECTIVES AND ENDPOINTS</u></strong></div>\n <div>\n Primary and selected secondary objectives for the study are expressed using the estimand framework in accordance with the International Conference on  harmonization E9 (R1) statistical principles for clinical trials (FDA 2020) in Section 3. The objectives include (but are not limited to) the evaluation of the efficacy and safety of astegolimab compared with placebo.</div>\n <div>\n  </div>\n</div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong><u>OVERALL DESIGN</u></strong></div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n This is a Phase III, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of astegolimab in combination with standard of care (SOC) compared with placebo in combination with SOC, in participants with COPD who are former or current smokers and have a history of frequent exacerbations.  Approximately 1290 participants with COPD are expected to be enrolled globally.</div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Following a screening period of at least 7 days and to up to 4 weeks, participants will be randomized in a 1:1:1 ratio to 1 of 3 treatment arms to receive blinded treatment with either astegolimab or placebo.  Randomization will be stratified by smoking status at screening (former smoker vs. current smoker) and region.</div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n The first dose of study drug (astegolimab or placebo) will be administered on Day 1; treatment will continue through Week 50, followed by a 12-week safety follow-up period.  The treatment regimens for each arm are as follows: </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Astegolimab 476 mg SC every 2 weeks (Q2W)</li>\n <li style=\"line-height: 20px;\">\n Astegolimab 476 mg SC every 4 weeks (Q4W) </li>\n </ul>\n <div>\n To ensure that all study participants undergo the same visit schedule, participants randomized to the Q4W dosing arm will alternate between injections of astegolimab and placebo Q2W (beginning with astegolimab on Day 1), thus receiving astegolimab Q4W.</div>\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Placebo SC Q2W </li>\n </ul>\n <div>\n Participants will return to the clinic Q2W through the treatment completion visit at Week 52.  The primary endpoint analyses will be conducted using the 52-week treatment period data for all participants. </div>\n <div>\n  </div>\n <div>\n <div>\n Several key aspects of the study design and study population are summarized below.  </div>\n <table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" style=\"max-width: 100%; border-collapse: collapse; border-spacing: 0px; width: 576px;\" width=\"576\">\n <tbody>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Phase:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>Phase </em><em>3</em></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 156px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Population Type:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 144px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>Adult patients of any gender</em></p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Control Method:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>Placebo</em></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 156px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Population Diagnosis or Condition:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 144px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>Chronic obstructive pulmonary disease</em></p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Interventional Model:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>Parallel group</em></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 156px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Population Age:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 144px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>40</em><em>-</em><em>80</em><em> years</em></p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Test Compound{s}:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>Astegolimab</em></p>\n <p style=\"margin: 0px 0px 10px;\">\n  </p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 156px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Site Distribution:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 144px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>Multi-site and multi-region</em></p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Active Comparator:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>Not applicable</em></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 156px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Study Intervention Assignment Method:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 144px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>Randomization and stratification</em></p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Number of Arms:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 138px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>3</em></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 156px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong><em>Number of Participants to Be Enrolled:</em></strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 144px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <em>Approximately 1290 participants</em></p>\n <div>\n  </div>\n </td>\n </tr>\n </tbody>\n </table>\n </div>\n</div>\n<p>\n  </p>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>STUDY TREATMENT</strong></div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Astegolimab and placebo will be supplied by the Sponsor as a sterile liquid in 2.25 mL pre-filled syringes with a needle safety device, providing 238 mg/1.7 mL of astegolimab or placebo. </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Study drug administration must occur after all other procedures have been completed at the visit, unless specifically indicated otherwise.  Study drug will be administered by trained medical personnel.</div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Each dose of study drug (astegolimab or placebo) will be administered as 2 SC injections (for a total of 3.4 mL), with each injection administered on a different side of the abdomen (i.e., right or left).  All participants will be observed for at least 30 minutes after each dose and longer (approximately 60 minutes) in the event of an injection-site reaction, as determined by the investigator.  If a participant develops any signs or symptoms to suggest a systemic hypersensitivity reaction or anaphylactic event, longer observation may be warranted as per the opinion of the investigator.</div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n There must be a minimum of 8 days between doses. In the event a dosing visit would occur within 8 days of a subsequent or previous dosing visit (e.g., due to an out-of-window visit), the study drug may not be administered. Instead, the next dose of study drug should be administered at the subsequent scheduled visit within the protocol-defined visit window to ensure that the 8-day minimum dosing interval is maintained.</div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>DURATION OF PARTICIPATION</strong></div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n The total duration of study participation for each individual is expected to be approximately 15 months. </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n  </div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n ----</div>\n<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Q2W = every 2 weeks; Q4W =  every 4 weeks; SOC = Standard of Care; SC = Subcutaneous</div>\n
      • study_title<p>\n <span style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">A PHASE III, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MULTICENTER STUDY TO EVALUATE THE EFFICACY AND SAFETY OF ASTEGOLIMAB IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE</span></p>\n
      • laymans_summary<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Chronic obstructive pulmonary disease (COPD) is a respiratory disorder characterized by irreversible changes in air flow causing progressive obstruction. The prevalence of diagnosed COPD has dramatically increased over recent years and is among the leading causes of disabilities and mortality. The airflow obstruction among COPD patients is largely linked with long-term morbidity and comorbidities such as hypertension, diabetes, ischemic heart disease, stroke, and heart failures were reported in patients with exacerbated COPD cases. These comorbidities are often linked with smoking, systemic inflammation, airflow limitation, and aging.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n These comorbidities do not only negatively impact the patients’ quality of life but also lower their survival rate. Although cigarette smoking is traditionally known as the predominant cause of COPD, there have been increasing cases of non-smokers being diagnosed with the disease. COPD is more prevalent among the older population, with the rising prevalence and mortality among women than male, attributed from increased population of female smokers.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Other risk factors include occupational exposure to chemical fumes, air pollution, childhood infection, and genetic heredity. Spirometry is regarded as the gold standard diagnostic tool for COPD which can detect COPD at early, asymptomatic stages. There is no cure for COPD, however, there are availability of therapies that can improve symptoms and a patients’ quality of life. Despite the treatment advances, there is still an unmet need for improved pharmacological intervention against COPD, particularly in the reduction of exacerbations and modifying the disease progression.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Astegolimab is a drug that is under development for the treatment of patients with COPD. This study will focus on finding out if astegolimab is safe and if it works in comparison to placebo as a treatment for COPD patients who are current or former smokers with a history of frequent exacerbations.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n If found to be efficacious, participants will be given access to the study drug in an Open Label Extension study (GB43374) subject to approval by relevant health authorities.</p>\n
      • short_titleARNASA
      • protocol_noECCT/23/07/03
      • version_no2
      • date_of_protocol09-11-2022
      • study_drugAstegolimab (RO7187807)
      • disease_conditionChronic obstructive pulmonary disease (COPD)
      • 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_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_applicantArinda Eloff
      • declaration_date121-07-2023
      • declaration_principal_investigatorProf. Videlia Nduba (National Co-Ordinator)
      • declaration_date220-07-2023
      • placebo_presentYes
      • study_objectives<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n The study objectives are listed below:</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate the efficacy of astegolimab compared with placebo</li>\n <li style=\"line-height: 20px;\">\n To evaluate the safety of astegolimab compared with placebo</li>\n <li style=\"line-height: 20px;\">\n To characterize the astegolimab PK profile </li>\n <li style=\"line-height: 20px;\">\n To evaluate the immune response to astegolimab</li>\n <li style=\"line-height: 20px;\">\n To evaluate potential relationships between selected covariates and exposure to astegolimab</li>\n <li style=\"line-height: 20px;\">\n To evaluate the efficacy of astegolimab compared with placebo</li>\n <li style=\"line-height: 20px;\">\n To evaluate the safety of astegolimab compared with placebo</li>\n <li style=\"line-height: 20px;\">\n To evaluate potential relationships between drug exposure and the efficacy and safety of astegolimab</li>\n <li style=\"line-height: 20px;\">\n To evaluate potential effects of ADAs </li>\n <li style=\"line-height: 20px;\">\n To identify and/or evaluate biomarkers that are predictive of response to astegolimab (i.e., predictive biomarkers), are early surrogates of efficacy, are associated with progression to a more severe disease state (i.e., prognostic biomarkers), can provide evidence of astegolimab activity (i.e., PD  iomarkers), or can increase the knowledge and understanding of disease biology and drug safety or pharmacokinetics </li>\n <li style=\"line-height: 20px;\">\n To evaluate health status utility scores of participants treated with astegolimab compared with placebo</li>\n </ul>\n</div>\n<p>\n  </p>\n
      • principal_inclusion_criteria<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Able and willing to provide written informed consent and to comply with the study protocol</li>\n <li style=\"line-height: 20px;\">\n Age 40-80 years at Visit 1</li>\n <li style=\"line-height: 20px;\">\n Documented COPD diagnosis for <u>></u> 12 months prior to Visit 1</li>\n <li style=\"line-height: 20px;\">\n History of frequent exacerbations, defined as having had 2 or more moderate or severe COPD exacerbations within 12 months prior to Visit 1</li>\n</ol>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n A moderate COPD exacerbation is defined as new or increased COPD symptoms (e.g., dyspnoea, sputum volume, and sputum purulence) that lead to treatment with systemic corticosteroids (oral, IV, or intramuscular [IM]) and/or antibiotics.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Prior use of antibiotics alone does not qualify as a moderate exacerbation unless the use was specifically for the treatment of worsening symptoms of COPD.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n A severe COPD exacerbation is defined as new or increased COPD symptoms that lead to hospitalization (duration 24 hours) or lead to death.</p>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"5\">\n Post-bronchodilator FEV1 <u>></u>20% and <80% of predicted at Visit 1 or Visit 2</li>\n <li style=\"line-height: 20px;\" value=\"6\">\n Post-bronchodilator FEV1/FVC < 0.70 at Visit 1 or Visit 2</li>\n <li style=\"line-height: 20px;\" value=\"7\">\n mMRC score <u>></u>2 at screening</li>\n <li style=\"line-height: 20px;\" value=\"8\">\n Current tobacco smoker or former smoker (having stopped smoking for at least 6 months prior to Visit 1) with a history of smoking <u>></u> 10 pack-years (e.g., 20 cigarettes/day for 10 years) At Visit 1, participants who meet the protocol definition of current smoker will receive smoking cessation counselling</li>\n <li style=\"line-height: 20px;\" value=\"9\">\n On optimized COPD maintenance therapy as defined below for <u>></u> 12 months prior to Visit 1.</li>\n</ol>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n – Inhaled corticosteroid (ICS) plus long-acting beta-agonist (LABA)</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n – Long-acting muscarinic antagonist (LAMA) plus LABA</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n – ICS plus LAMA plus LABA Participants must be stable on current medications and doses for at least 4 weeks prior to Visit 1.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Initiation of new COPD therapy, including a methylxanthine preparation, maintenance macrolide therapy, and/or phosphodiesterase 4 (PDE4) inhibitor is not permitted within 4 weeks prior to Visit 1.</p>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"10\">\n Chest X-ray or computed tomography (CT) scan within 6 months prior to Visit 1 or chest X-ray during the screening period (prior to Visit 2) that confirms the absence of clinically significant lung disease besides COPD</li>\n <li style=\"line-height: 20px;\" value=\"11\">\n Demonstrated ability to use and comply with electronic diary (eDiary) requirements, defined as completion of all questions on at least 5 of 7 days prior to Visit 2 Participants unable to demonstrate compliance with the eDiary during the screening period will be screen failed. Participants will have the opportunity to demonstrate eDiary compliance if re-screened (see Protocol Version 2 dated 09 Nov 2022 Section 8.3.3.3).</li>\n <li style=\"line-height: 20px;\" value=\"12\">\n For female participants of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraception, as defined below: Female participants 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.</li>\n</ol>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n A female participant is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state ( 12 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., Müllerian agenesis). Per this definition, a female participant with a tubal ligation is considered to be of childbearing potential. The definition of childbearing potential may be adapted for alignment with local guidelines or regulations.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Examples of contraceptive methods with a failure rate of 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 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 individual. 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.</p>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"13\">\n For male participants: agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agree to refrain from donating sperm, as defined below:</li>\n</ol>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n With a female partner of childbearing potential or pregnant female partner, male participants must remain abstinent or use a condom during the treatment period and for 12 weeks after the final dose of astegolimab to avoid exposing the embryo. Male participants must refrain from donating sperm during this same period.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 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 individual. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not adequate methods of preventing drug exposure. If required per local guidelines or regulations, information about the reliability of abstinence will be described in the local Informed Consent Form.</p>\n
      • principal_exclusion_criteria<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Potential participants are excluded from the study if any of the following criteria apply:</p>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n History of a severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the study drug</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"2\">\n Any prior treatment with astegolimab</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"3\">\n Current documented diagnosis of asthma</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"4\">\n History of clinically significant pulmonary disease other than COPD</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"5\">\n Diagnosis of alpha-1-antitrypsin deficiency</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"6\">\n History of long-term treatment with oxygen at > 4.0 litres/minute While breathing supplemental oxygen, the participant should demonstrate an oxyhemoglobin saturation of <u>></u> 89%.</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"7\">\n Lung volume reduction surgery or procedure within 12 months prior to Visit 1</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"8\">\n Individuals participating in, or scheduled for, an intensive COPD rehabilitation program (participants who are in the maintenance phase of a rehabilitation program are eligible)</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"9\">\n History of lung transplant</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"10\">\n Any infection that resulted in hospital admission for <u>></u>24 hours and/or treatment with oral, IV, or IM antibiotics within 4 weeks prior to Visit 1 or during screening</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"11\">\n Upper or lower respiratory tract infection within 4 weeks prior to Visit 1 or during screening</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"12\">\n Treatment with oral, IV, or IM corticosteroids (>10 mg/day prednisolone or equivalent) within 4 weeks prior to initiation of study drug</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"13\">\n Treatment with investigational therapy within 3 months or 5 drug-elimination half-lives (whichever is longer) prior to screening</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"14\">\n Treatment with a licensed biologic agent (e.g., omalizumab, dupilumab, and/or anti-IL-5 therapies) within 3 months or 5 drug-elimination half-lives (whichever is longer) prior to screening</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"15\">\n Initiation of or change in non-biologic immunomodulatory or immunosuppressive therapy within 3 months prior to screening</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"16\">\n Treatment that is considered palliative (e.g., for life expectancy < 12 months)  </li>\n <li style=\"line-height: 20px;\" value=\"17\">\n Planned surgical intervention during the study</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"18\">\n Receipt of a live attenuated vaccine within 4 weeks prior to Visit 1 or during screening</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"19\">\n Known immunodeficiency, including but not limited to, HIV infection</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"20\">\n Known evidence of active or untreated latent tuberculosis</li>\n <li style=\"line-height: 20px;\" value=\"21\">\n AST, ALT, or total bilirubin elevation <u>></u> 2.0 X the upper limit of normal (ULN) during screening</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"22\">\n Substance abuse, as determined by the investigator, within 12 months prior to screening</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"23\">\n History of malignancy within 5 years prior to screening, with the exception of malignancies with a negligible risk of metastasis or death (e.g., 5-year overall survival rate > 90%), such as adequately treated carcinoma in situ of the cervix non-melanoma skin carcinoma, localized prostate cancer, or ductal carcinoma in situ</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"24\">\n Any other serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the participant’s safe participation in and completion of the study</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"25\">\n Unstable cardiac disease, myocardial infarction, or New York Heart Association Class III or IV heart failure within 12 months prior to screening</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"26\">\n History or presence of an abnormal ECG that is deemed clinically significant by the investigator, including complete left bundle branch block or second- or third-degree atrioventricular heart block</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"27\">\n QT interval corrected through use of Fridericia’s formula (QTcF) >450 ms if the participant is male or QTcF >470 ms if the participant is female for male or female participants with QRS > 120: QTcF > 480 ms.</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"28\">\n History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease (e.g., severe left ventricular systolic dysfunction, significant left ventricular hypertrophy with strain), or family history of sudden unexplained death or long QT syndrome</li>\n</ol>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"29\">\n Pregnant or breastfeeding, or intention of becoming pregnant during the study or within 12 weeks after the final dose of astegolimab</li>\n</ol>\n
      • primary_end_points<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Primary Endpoint</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n The primary efficacy objective for this study is to evaluate the efficacy of astegolimab compared with placebo in the mITT population on the basis of the following endpoint:</p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Annualized rate of moderate and severe COPD exacerbations over the 52-week treatment period</li>\n</ul>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n A moderate COPD exacerbation is defined as new or increased COPD symptoms (e.g., dyspnea, sputum volume, and sputum purulence) that lead to treatment (duration <u>></u> 3 days) with systemic corticosteroids (oral, IV, or IM) at a dose of > 10 mg/day prednisolone equivalent and/or antibiotics.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n A severe COPD exacerbation is defined as new or increased COPD symptoms that lead to hospitalization (duration > 24 hours) or lead to death.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <em>Primary Estimand</em></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n The <em>primary</em> estimand is defined <em>as follows</em>:</p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n <em><u>Population:  </u></em><em>Participants with COPD who are former or current smokers and have a history of frequent exacerbations, as defined by the inclusion and exclusion criteria (see Sections </em><em>5.1</em><em>and </em><em>5.2</em><em>, respectively)</em><em>, and received at least one </em><em>dose of study drug (mITT population)</em></li>\n <li style=\"line-height: 20px;\">\n <em><u>Variable:  </u></em><em>annualized rate of moderate and severe COPD exacerbations over the 52-week treatment period</em></li>\n <li style=\"line-height: 20px;\">\n <em><u>Treatments:</u></em></li>\n</ul>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 40px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n <em>Experimental: astegolimab Q2W</em></li>\n <li style=\"line-height: 20px;\">\n <em>Experimental: astegolimab Q4W</em></li>\n <li style=\"line-height: 20px;\">\n <em>Control: placebo</em></li>\n</ul>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n <em><u>Intercurrent events</u></em><em>:</em></li>\n</ul>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 40px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n <em>Early</em><em> discontinuation from study treatment</em></li>\n</ul>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n <em><u>Handling of intercurrent events</u></em><em>:  A treatment policy with regards to the intercurrent events listed above will be applied for the primary analysis</em></li>\n <li style=\"line-height: 20px;\">\n <em><u>Summary measure</u></em><em>:  rate ratio (RR) for annualized rate of moderate and severe COPD exacerbations</em></li>\n</ul>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Secondary Endpoints</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n The secondary efficacy objective for this study is to evaluate the efficacy of astegolimab compared with placebo in the mITT population on the basis of the following endpoints:</p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Time to first moderate or severe COPD exacerbation during the 52-week treatment period</li>\n <li style=\"line-height: 20px;\">\n Absolute change from baseline in HRQoL at Week 52, as assessed through the SGRQ-C total score</li>\n <li style=\"line-height: 20px;\">\n Absolute change from baseline in post-bronchodilator FEV<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">1</span> (liters) at Week 52</li>\n <li style=\"line-height: 20px;\">\n Absolute change from baseline in E‑RS:COPD total score at Week 52</li>\n <li style=\"line-height: 20px;\">\n Proportion of participants with improvement in HRQoL, defined as a decrease from baseline of <u>></u> 4 points in SGRQ-C total score, at Week 52</li>\n <li style=\"line-height: 20px;\">\n Annualized rate of severe COPD exacerbations over the 52-week treatment period</li>\n</ul>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n The secondary endpoints will be analyzed in the mITT population<em>.  Time-to-event endpoints will be analyzed using log-rank test and Cox proportional hazards regression models. Continous endponts will be summarized by treatment arm and timepoints, and analyzed using mixed models for repeated measures.  Improvement in HRQoL will be summarized as proportion of responders, i.e., patients achieving pre-specified improvement, and analyzed using logistic regression models.  </em></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Other Seconday and Exploratory Endpoints are the following:</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Objective: To evaluate the safety of astegolimab compared with placebo</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Endpoints: </p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Incidence and severity of all TEAEs, including SAEs, AESIs, and TEAEs leading to death or discontinuation</li>\n</ul>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n TEAEs severity will be 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 (see Appendix 8) </div>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Change from baseline in selected vital signs </li>\n <li style=\"line-height: 20px;\">\n Change from baseline in selected clinical laboratory test results and ECGs </li>\n</ul>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Objective: To characterize the astegolimab PK profile </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Endpoints: Serum concentration of astegolimab at specified timepoints</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Objective: To evaluate the immune response to astegolimab </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Endpoints: Prevalence of ADAs at baseline and incidence of ADAs during the study</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Objective: To evaluate the efficacy of astegolimab compared with placebo </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Endpoints: </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Change in COPD symptoms as measured by the E-RS:COPD total score at Week 24  </li>\n <li style=\"line-height: 20px;\">\n Change in E-RS:COPD individual domain scores (breathlessness, cough and sputum, and chest symptoms) from baseline at Week 24 and 52 </li>\n <li style=\"line-height: 20px;\">\n Change in EXACT individual domain scores (tired or weak, sleep disturbance, and scared or worried) from baseline at Week 24 and 52 </li>\n <li style=\"line-height: 20px;\">\n Proportion of participants with HRQoL improvement, defined as a decrease from baseline of <u>></u> 4 points in SGRQ-C total score, at Week 12 and Week 24 </li>\n <li style=\"line-height: 20px;\">\n Proportion of participants with symptom improvement, defined as a decrease of <u>></u> 2 points from baseline in E-RS:COPD total score, at Week 24 and Week 52 </li>\n <li style=\"line-height: 20px;\">\n bsolute change from baseline in post-bronchodilator</li>\n <li style=\"line-height: 20px;\">\n FEV1 (liters) at Weeks 12, 24, and 36 </li>\n <li style=\"line-height: 20px;\">\n Annualized rate of moderate COPD exacerbations over the 52-week treatment period </li>\n <li style=\"line-height: 20px;\">\n Duration of hospital stay for severe COPD exacerbations </li>\n <li style=\"line-height: 20px;\">\n Proportion of severe COPD exacerbations requiring hospital readmission within 30 days </li>\n <li style=\"line-height: 20px;\">\n Absolute change from baseline in daily step count at Weeks 12, 24, and 52 </li>\n <li style=\"line-height: 20px;\">\n Absolute change from baseline in time in moderate and vigorous physical activity at Weeks 12, 24, and 52 </li>\n </ul>\n</div>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Obective: To evaluate potential relationships between drug exposure and the efficacy and safety of astegolimab</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Endpoints:</p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Relationship between serum concentration or PK parameters for astegolimab and efficacy endpoints</li>\n <li style=\"line-height: 20px;\">\n Relationship between serum concentration or PK parameters for astegolimab and safety endpoints </li>\n</ul>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Objective: To evaluate potential relationships between selected covariates and exposure to astegolimab </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Endpoint: Relationship between selected covariates and serum concentration or PK parameters for astegolimab</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Objective: To evaluate potential effects of ADAs</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Endpoint: Relationship between ADA status and efficacy, safety, PK or biomarker endpoints</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Objective: To identify and/or evaluate biomarkers that are predictive of response to astegolimab (i.e., predictive biomarkers), are early surrogates of efficacy, are</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 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</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n increase the knowledge and understanding of disease biology and drug safety or pharmacokinetics </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Endpoint:  Relationship between biomarkers in blood, plasma, and serum and efficacy, safety, PK, immunogenicity, or other biomarker endpoints </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Objective: To evaluate health status utility scores of participants treated with astegolimab compared with placebo</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Endpoint: Change from baseline in EuroQol EQ-5D-5Lindex-based and VAS scores at Week 52 </div>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic0
      • scope_pharmacogenomic1
      • 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 <strong>Nairobi Site</strong></p>\n<p>\n KEMRI/CRDR Nairobi clinical research annex is located within the KNH complex. This facility has several clinical rooms available for consenting, nursing procedures, clinical exams, and dosing. There are also additional facilities that include 3 bed male and female inpatient ward for admission when required, staff work areas, a monitoring space, a pharmacy, a conference board room, a laboratory, and kitchen for preparing participant meals. Site staff include the principal investigator, 5 medical officers, 3 pharmacists, 1 pharm tech, 8 nurses, 9 lab personnel, 5 quality assurance officers, 10 clinical officers, 3 administrators and 13 community health workers.</p>\n<p>\n  </p>\n<p>\n <strong>Siaya Site</strong></p>\n<p>\n KEMRI has a modern research annex at the Siaya County Referral Hospital with capacity to conduct all phases of studies. Site staff responsible for day to day running of the project include: 2 Medical Officer, 2 Pharmacist, 2 Pharmacy technicians, 6 Nurses, 6 Quality Assurance & Quality Control officers, 3 Clinical Officers, and 7 Community Interviewers, 4 lab personnel, 2 data personnel and 2 administration personnel.</p>\n<p>\n  </p>\n<p>\n ---</p>\n<ul>\n <li>\n All the site staff will be trained on all trial documents (Protocol, ICFs, Lab Manual, Source Doc and SOPs) before the study commencement.</li>\n <li>\n Stakeholders Sensitization and Mobilization about the study: This will involve the County Health Management Team (CHMT), Sub County Health Management Team (SCHMT), Community Advisory Board (CAB) and specific health referral Facilities.</li>\n <li>\n Assign full time contact persons in the referring facilities (Lab personnel, EPI Nurse and CHV) for identification of eligible participants. </li>\n</ul>\n<p>\n  </p>\n
      • other_details_explanation<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">Switzerland is the host country and Sponsor intends to submit study for approval in the host country.</span></p>\n
      • other_details_regulatory_notapproved<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" font-size:=\"\" style=\"max-width: 100%; border-collapse: collapse; border-spacing: 0px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\" width=\"413\" width:=\"\">\n <tbody>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 107px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Country</strong><strong>​</strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 100px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Status</strong><strong>​</strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 206px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Submission</strong><strong>​ Date</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 107px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Australia​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 100px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submitted​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 206px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 19-May-23​</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 107px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n China​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 100px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submitted​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 206px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 25-May-2023</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 107px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n India​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 100px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submitted​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 206px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 10-May-23​</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 107px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n New Zealand​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 100px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submitted​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 206px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 20-Apr-23​</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 107px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Philippines​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 100px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submitted​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 206px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 04-Apr-23​</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 107px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Taiwan, Province of China​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 100px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submitted​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 206px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 20-Apr-23​</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 107px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Thailand​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 100px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submitted​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 206px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 27-Apr-23​</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 107px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Argentina​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 100px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submitted​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 206px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 07-Mar-23​</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 107px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Brazil​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 100px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submitted â€‹</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 206px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 15-Mar-2023 / 20Mar2023​</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 107px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Chile​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 100px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submitted​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 206px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 23-May-23​</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 107px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Mexico​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 100px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submitted​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 206px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 02-May-23​</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 107px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Switzerland​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 100px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submitted​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 206px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 06-Apr-23​</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 107px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Turkey​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 100px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submitted​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 206px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 23-Mar-23​</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 107px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n United Kingdom​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 100px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submitted​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 206px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 13-Mar-23​</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 107px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Austria​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 100px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submitted​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 206px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 07-Mar-23​</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 107px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Belgium​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 100px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submitted​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 206px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 07-Mar-23​</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 107px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Bulgaria​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 100px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submitted​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 206px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 07-Mar-23​</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 107px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Czech Republic​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 100px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submitted​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 206px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 07-Mar-23​</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 107px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Denmark​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 100px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submitted​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 206px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 07-Mar-23​</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 107px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n France​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 100px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submitted​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 206px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 07-Mar-23​</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 107px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Germany​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 100px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submitted​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 206px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 07-Mar-23​</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 107px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Greece​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 100px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submitted​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 206px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 07-Mar-23​</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 107px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Hungary​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 100px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submitted​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 206px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 07-Mar-23​</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 107px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Italy​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 100px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submitted​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 206px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 07-Mar-23​</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 107px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Latvia​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 100px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submitted​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 206px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 07-Mar-23​</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 107px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Netherlands​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 100px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submitted​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 206px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 07-Mar-23​</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 107px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Poland​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 100px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submitted​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 206px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 07-Mar-23​</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 107px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Romania​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 100px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submitted​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 206px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 07-Mar-23​</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 107px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Spain​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 100px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submitted​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 206px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 07-Mar-23​</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 107px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Sweden​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 100px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Submitted​</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 206px; height: 28px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 07-Mar-23​</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_regulatory_approved<p>\n  </p>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" font-size:=\"\" style=\"max-width: 100%; border-collapse: collapse; border-spacing: 0px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\" width=\"100%\" width:=\"\">\n <tbody>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 231.516px; height: 20px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Country</strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 229.531px; height: 20px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Name of Regulatory Authority</strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 174px; height: 20px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Approval date</strong></p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 225.219px; height: 20px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Number of Sites</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 231.516px; height: 20px;\">\n <p style=\"margin: 0px 0px 10px;\">\n United States of America </p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 229.531px; height: 20px;\">\n <p style=\"margin: 0px 0px 10px;\">\n The United States Food and Drug Administration </p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 174px; height: 20px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 18 November 2022 </p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 225.219px; height: 20px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 74</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 231.516px; height: 27px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Canada </p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 229.531px; height: 27px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Health Canada </p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 174px; height: 27px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 19 April 2023</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 225.219px; height: 27px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 10</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 231.516px; height: 20px;\">\n <p style=\"margin: 0px 0px 10px;\">\n South Africa</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 229.531px; height: 20px;\">\n SAHPRA</td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 174px; height: 20px;\">\n 11 May 2023</td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 225.219px; height: 20px;\">\n 8</td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 231.516px; height: 20px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Korea</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 229.531px; height: 20px;\">\n MFDA</td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 174px; height: 20px;\">\n 18 April 2023</td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 225.219px; height: 20px;\">\n 10</td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 231.516px; height: 20px;\">\n <p style=\"margin: 0px 0px 10px;\">\n  </p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 229.531px; height: 20px;\">\n  </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 174px; height: 20px;\">\n  </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 225.219px; height: 20px;\">\n  </td>\n </tr>\n </tbody>\n</table>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n
      • other_details_regulatory_rejected<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">Not applicable.  None of the Regulatory Authorities or Ethics Committees have rejected this trial.</span></p>\n
      • other_details_regulatory_halted<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">Not applicable.</span></p>\n
      • estimated_durationThe total duration of study participation for each individual is expected to be approximately 15 months.
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states39
      • number_of_sitesApproximately 6 sites will participate in Kenya. As approvals from the Local Ethics Committees (LECs) are obtained to avoid delays in site-activation as each site submits to their LEC at different timepoints.
      • multi_country_listChin; Hong Kong; India; Korea, Republic of; New Zealand; Philippines; Taiwan, Province of China; Thailand; Vietnam; Argentina; Brazil; Chile; Mexico; Canada; United States; Egypt; Israel; Kenya; South Africa; Switzerland; Turkey; United Kingdom; Austria; Belgium; Bulgaria; Czech Republic; Denmark; France; Germany; Greece; Hungary; Italy; Latvia; Netherlands; Poland; Romania; Spain; Sweden; Australia
      • data_monitoring_committeeYes
      • total_enrolment_per_siteNo maximum nor minimum enrolment per site as enrolment is competitive worldwide, but it is expected that approximately 2 - 3 participants will participate per site.
      • total_participants_worldwideApproximately 1290 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_nameProfessor Videlis
      • 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 +254724522474
      • investigator1_emailvnduba@gmail.com
      • organisations_transferred_Yes
      • number_participantsEnrolment is competitive worldwide. Approximately 12 participants will participate in Kenya.
      • notification
      • approval_date19-11-2023
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted06-11-2023
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonAll reviewer 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 11:29:45
      • created2023-07-17 16:33:59
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id951
        • application_id1293
        • given_nameProfessor Videlis
        • middle_name
        • family_nameNduba
        • qualificationMedical Doctor
        • professional_addressKENYA MEDICAL RESEARCH INSTITUTE-CENTRE FOR RESPIRATORY DISEASE RESEARCH (CRDR), Research Annex, Kenyatta National Hospital Grounds, Behind Government Chemist, P.O. BOX 47855, Nairobi, 00100
        • telephone +254724522474
        • emailvnduba@gmail.com
        • created2023-07-17 16:43:54
        • modified2023-11-06 08:52:48
      • 1(array)
        • id952
        • application_id1293
        • given_nameProfessor Videlis
        • middle_name
        • family_nameNduba
        • qualificationMedical Doctor
        • professional_addressKEMRI/CRDR, Siaya Clinical Research Annex, Within Siaya Country Referral Hospital Grounds, Siaya, Nyanza, 40600
        • telephone +254724522474
        • emailvnduba@gmail.com
        • created2023-07-17 16:46:38
        • modified2023-11-06 08:52:48
    • SiteDetail(array)
      • 0(array)
        • id1557
        • application_id1293
        • county_id47
        • site_nameKENYA MEDICAL RESEARCH INSTITUTE-CENTRE FOR RESPIRATORY DISEASE RESEARCH (CRDR)
        • physical_addressResearch Annex, Kenyatta National Hospital Grounds, Behind Government Chemist, P.O. BOX 47855, Nairobi, 00100
        • contact_details+254724522474
        • contact_personProf. Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2023-07-17 16:43:54
        • modified2023-11-06 08:52:48
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 1(array)
        • id1558
        • application_id1293
        • county_id41
        • site_nameKEMRI/CRDR, Siaya Clinical Research Annex
        • physical_addressWithin Siaya Country Referral Hospital Grounds, Siaya, Nyanza, 40600
        • contact_details+254724522474
        • contact_personProf. Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2023-07-17 16:53:06
        • modified2023-11-06 08:52:48
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
      • 2(array)
        • id1559
        • application_id1293
        • 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)
        • created2023-07-17 16:53:06
        • modified2023-11-06 08:52:48
        • County(array)
          • id16
          • county_nameMachakos
          • created2012-06-15 10:23:55
          • modified2012-06-15 10:23:55
      • 3(array)
        • id1560
        • application_id1293
        • 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)
        • created2023-07-17 16:53:06
        • modified2023-11-06 08:52:48
        • County(array)
          • id3
          • county_nameKilifi
          • created2012-05-31 16:15:49
          • modified2012-05-31 16:15:49
      • 4(array)
        • id1561
        • application_id1293
        • 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)
        • created2023-07-17 16:53:06
        • modified2023-11-06 08:52:48
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 5(array)
        • id1562
        • application_id1293
        • 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)
        • created2023-07-17 16:53:06
        • modified2023-11-06 08:52:48
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 6(array)
        • id1563
        • application_id1293
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        • 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)
        • created2023-07-17 16:53:06
        • modified2023-11-06 08:52:48
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
    • Sponsor(array)
      • 0(array)
        • id682
        • application_id1293
        • sponsorF. Hoffmann-La Roche Ltd
        • sponsor_typeIndustry
        • contact_personNadia Walli
        • addressClinical Research (PDG - CCO, North America),7070 Mississauga Road Mississauga, ON L5N 5M8 Canada
        • telephone_number+41 61 688 1111
        • fax_number
        • cell_number+416-930-1484
        • email_addressnadia.walli@roche.com
        • created2023-07-17 16:43:54
        • modified2023-11-06 08:52:48
  • 4(array)
    • Application(array)
      • id1289
      • user_id365
      • trial_status_id(null)
      • abstract_of_study<p>\n In western Kenya, HIV prevalence is 16% among women in the general population, and 29% among the most economically constrained women. The HIV/STI epidemic overlaps with broader reproductive health concerns. Menstrual hygiene management (MHM) is a pervasive problem across low- and middle-income countries. In Phillips-Howards’ survey of over 3,400 women in rural Kenya, two-thirds of women in impoverished settings state they depend on their sexual partners to provide branded products. Economically vulnerable women at high risk for HIV and STI are uniquely challenged because many continue to have sex during menses, and engage in harmful MHM practices, such as vaginal insertion of sponges and cotton to maintain dryness. Led by co-investigator Phillips-Howard, a cluster-randomized study of 644 girls aged 14-16 years old in western Kenya compared reusable menstrual cups to usual menstrual practice and counseling; after 9 months, menstrual cup use resulted in 35% reduction (p=0.034) in Bacterial vaginosis (BV) prevalence and 56% reduction (p=0.001) in STI prevalence compared to other materials. Among 431 Kenyan secondary schoolgirls aged 14-21, we observed cloth use for menses was associated with a 1.72-fold increased odds of non-optimal vaginal microbiome (CST-IV vs. CST-I: aOR=1.90; 95% CI: 1.03–2.86). Over 18 months of observation prior to COVID-19, girls using menstrual cups to manage menses had 20% higher occurrence of <em>Lactobacillus crispatus </em>dominated CST-I (aRR=1.29; 95% CI: 1.08–1.53, controlling for age, and baseline STI and sexual activity). Menstrual cups designed for use during intercourse may help women prevent BV and STIs through hygienic menstrual practices and avoidance of harmful practices to maintain vaginal dryness during menses. <strong>Objective: </strong>This single-arm interventional trial seeks to evaluate the preliminary efficacy of menstrual cups on non-optimal vaginal microbiome (VMB), BV, and STIs of economically vulnerable women at high risk for STIs and HIV, assess safety profile, and understand implementation needs. In <strong>Aim 1, </strong>we will evaluate the impact of menstrual cups on VMB, BV, and STIs among 402 economically vulnerable women in semi-urban Kisumu, Kenya. Each woman will be engaged in study protocol for 2 years. In <strong>Aim 2</strong>, we will conduct integrated surveillance for enhanced detection of safety endpoints, risk of cup contamination, and mitigating or facilitating water, sanitation, hygiene (WASH) factors. In <strong>Aim 3</strong>, we will identify constructs for successful MHM program implementation using an implementation science framework. <strong>Analytic Approaches: </strong>In Aim 1, we will apply linear mixed models with binomial distribution and log link function, with fixed effect for intervention period, to analyze baseline to 12 month cumulative incidence of BV in the control phase, and 12- to 24-month cumulative incidence in the intervention phase. We employ similar approach for secondary outcome of STI (binary composite of infection with CT, NG, or TV). Analyses for Aim 2 are descriptive, comparing frequency distribution of occurrence and type of SAE and AE before and after initiation of menstrual cup use, and will make use of pairwise statistical approaches (before-and-after), such as McNemar’s test (for paired categorical data), paired t-test (for normally distributed continuous data), or Mann Whitney test (for paired, non-normally distributed continuous or count data). In Aim 3, transcripts will undergo thematic content analysis, using inductive and deductive approaches for coding. The codes will be assigned under relevant themes and subthemes with a narrative written reflecting the assigned themes and illustrated with verbatim quotes. While the study period for each participant is 2 years, the entire study timeline is 5 years. This includes time for startup (procurement and training), participant accrual and follow-up, processing of biological specimens, and complex statistical analyses and manuscript writing. Participant recruitment and follow-up will take approximately 2.5-3 years to complete, as screening and enrollment of participants is expected to take place over 6 months.</p>\n<p>\n <strong>Future Directions: </strong>The biological protection suggested in a randomized setting, and our findings that unhygienic cloth use is associated with non-optimal VMB, while menstrual cup use increases optimal VMB composition, together provide rational justification for this trial, of relevance to economically challenged women globally. Assessing preliminary efficacy signal in conjunction with implementation characteristics and adverse events, will generate a comprehensive and necessary foundation for definitive assessment of effectiveness of menstrual cups as a multipurpose intervention for MHM, and to reduce BV and STIs.</p>\n
      • study_title<p>\n <strong>Single arm trial of menstrual cups among economically vulnerable women to </strong><strong>reduce Bacterial vaginosis and STIs through reduced harmful sexual and menstrual practices (POWWeR Health Study): A Phase 2 Trial</strong></p>\n
      • laymans_summary<p>\n This study is seeking to evaluate the preliminary efficacy of menstrual cups on non-optimal vaginal microbiome (VMB), Bacterial Vaginos, and Sexually Transmitted Infections among 402 economically vulnerable women in semi-urban Kisumu, Kenya at high risk for STIs and HIV. The study also seeks to assess safety profile of the menstrual cups, and understand implementation needs.</p>\n
      • short_titlePOWWeR Health Study
      • protocol_noECCT/23/07/01
      • version_no2.1
      • date_of_protocol30-08-2023
      • study_drugNone
      • disease_conditionBacterial Vaginosis and Sexually Transmitted Infections
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device1
      • product_type_chemical_name
      • product_type_medical_device_nameMenstrual Cups
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressfotieno@nrhskenya.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_addendum0
      • 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_applicantFredrick Odhiambo Otieno
      • declaration_date130-08-2023
      • declaration_principal_investigatorFredrick Odhiambo Otieno
      • declaration_date230-08-2023
      • placebo_presentNo
      • study_objectives<h2>\n Broad Objective</h2>\n<p>\n This single-arm interventional trial seeks to evaluate the preliminary efficacy of menstrual cups on non-optimal vaginal microbiome (VMB), BV, and STIs of economically vulnerable women at high risk for STIs and HIV, assess safety profile, and understand implementation needs.</p>\n<h2>\n Aims</h2>\n<h2>\n <strong style=\"font-size: 12px;\">Aim 1:</strong><span style=\"font-size: 12px;\">   Evaluate the impact of menstrual cups on VMB, BV, and STIs among economically vulnerable women at high risk for STIs.</span></h2>\n<h2>\n <strong style=\"font-size: 12px;\">Aim 2:</strong><span style=\"font-size: 12px;\">   Conduct integrated surveillance for safety, pharmacovigilance, and water, sanitation, hygiene.</span></h2>\n<h2>\n <strong style=\"font-size: 12px;\">Aim 3:   </strong><span style=\"font-size: 12px;\">Conduct qualitative study for integrative analysis with our diverse data (biological, behavioral), and to identify constructs for successful MHM program implementation.</span></h2>\n<p>\n  </p>\n
      • principal_inclusion_criteria<p>\n Adolescent girls and women aged 15 to 35 years:</p>\n<p>\n -       Menstruation in the past 2 months</p>\n<p>\n -       Having exchanged sex for money or items of value within the past 2 months</p>\n<p>\n -       Living and/or working in Kisumu area</p>\n<p>\n -      Consent to participate</p>\n
      • principal_exclusion_criteria<p>\n Participation exclusion criteria are as follows:</p>\n<ul>\n <li>\n Outside of eligible age range (<15 years or >35 years)</li>\n <li>\n Last menstrual period more than 2 months ago</li>\n <li>\n Current pregnancy (as determined by urine HCG)</li>\n <li>\n Pregnancy within the past 6 months</li>\n <li>\n Presently having an IUD</li>\n <li>\n Not living or working in study area</li>\n <li>\n Refused consent</li>\n</ul>\n<p>\n  </p>\n
      • primary_end_points<p>\n For primary outcome BV (binary, 7-10 vs. 0-6) the measures will be baseline to 12 month cumulative incidence control/pre-menstrual cup intervention and 12- to 24-month cumulative incidence in the intervention phase.</p>\n<p>\n  </p>\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_pharmacoecomomic1
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n This study is a prospective study to be conducted in Kisumu, Kenya, carried out by Nyanza Reproductive Health Society (NRHS). All subject enrollment and data collection will be conducted at NRHS UNIM Clinic under the supervision of the Director and Co-Investigator to this study, Dr. Frederick Otieno. Dr. Otieno has led field activities with clinical oversight of our other studies of menstrual cups, VMB, and STIs and has participated in the development of this study. He will oversee hiring, training, and management of all study staff (supported by Dr. Mehta and Prof Phillips-Howard). Study staff and nurses will include female staff who have extensive research experience in sexual and reproductive health, STIs, HIV, and working with key populations. The laboratory technicians who supported our current and prior menstrual cup, BV, VMB, and STI studies will continue to provide laboratory support for this new study. UNIM Clinic is located within Lumumba sub County Hospital which is a level 4 hospital that has requisite emergency and admission faciities.</p>\n<p>\n Additionally, the NRHS has a Community Advisory Board (CAB) comprised of representation from various stakeholder groups including religious, law enforcement, legal, judicial, transport, LGBTI, sex workers and research groups within Kisumu. This CAB provides community representation and safeguarding for the participants in the various studies within NHRS and this study protocol has also been discussed with the CAB and their input incorporated. As the study continues, the CAB will also be asked to continue with its review of study activities and participation to ensure community representation and safeguarding.</p>\n
      • other_details_explanation<p>\n <strong>Economically constrained women face a disproportionate burden of STIs and HIV. </strong>As reported by UNAIDS, 6 in 7 new HIV infections in sub-Saharan Africa are in adolescent girls and women, and HIV risk is 26 times higher for women engaged in transactional sex. In western Kenya, HIV prevalence is 12% among women in the general population and 29% among women who engage in transactional sex. HSV-2 prevalence increases from 27% among 15-19 year-old females to 73% among 20-24 year-olds in western Kenya. Bacterial vaginosis (BV) affects 20-50% of general population women in sub-Saharan Africa, and doubles the risk of HIV acquisition and transmission, increases risk of adverse pregnancy outcomes, and increases risk of <em>T. vaginalis </em>[15], HSV-2, <em>N. gonorrhoeae</em> and <em>C. trachomatis</em> , and HPV. HIV and BV are syndemic with STIs, with high prevalences in Kenya, especially among women who engage in transactional sex. Multipurpose interventions that can effectively address multiple contributing factors to STI and HIV risk are critically needed for improved health.</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n Rush University Medical Centre Institutional Review Board ORA Number: 22040505-IRB01-AM01 Date of Approval 4/8/2022</p>\n<p>\n LSTM REC Research Protocol (22-076) Date 2nd November 2022</p>\n<p>\n UIC ORPS Study 2023-0053 Date January 18, 2023</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration5 years
      • design_controlled_randomisedNo
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overYes
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorYear one before crossover
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaNyanza Reproductive Health Society
      • single_site_physical_addressUNIM Research and Training Centre, inside Lumumba sub County Hospital, Ondiek Avenue
      • single_site_contact_personFredrick Otieno
      • single_site_telephone+254 721 759867
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_site402 women
      • total_participants_worldwide402 women
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male0
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameFredrick
      • investigator1_middle_name
      • investigator1_family_nameOtieno
      • investigator1_qualificationPhD
      • investigator1_professional_addressNyanza Reproductive Health Society, P. O. Box 1764, Kisumu 40100
      • investigator1_telephone+254 721759867
      • investigator1_emailfotieno@nrhskenya.org
      • organisations_transferred_No
      • number_participants402 women
      • notification
      • approval_date20-12-2023
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted23-10-2023
      • is_child0
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      • initial_date_submitted(null)
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      • admin_stopped_reason(null)
      • approved2
      • approved_reasonAll reviewer comments have been addressed.
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      • balance_site(null)
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      • modified2023-12-20 12:23:43
      • created2023-07-03 13:22:55
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      • ecitizen_invoice(null)
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        • professional_addressNyanza Reproductive Health Society, P. O. Box 1764, Kisumu 40100
        • telephone+254 721759867
        • emailfotieno@nrhskenya.org
        • created2023-07-03 13:46:52
        • modified2023-10-23 09:03:19
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        • given_nameSupriya
        • middle_nameDinesh
        • family_nameMehta
        • qualificationPhD
        • professional_addressRush University School of Medicine 1750 W. Harrison Street, Jelke 1121
        • telephone+13124137485
        • emailSupriya_Mehta@rush.edu
        • created2023-07-03 13:57:53
        • modified2023-10-23 09:03:19
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        • id1541
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        • county_id(null)
        • site_name
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        • misc(null)
        • created2023-07-03 13:46:52
        • modified2023-10-23 09:03:19
        • County(empty)
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        • id680
        • application_id1289
        • sponsorRush University Medical Center
        • sponsor_typeResearch Institution
        • contact_personJennifer Garcia
        • addressRush University School of Medicine 1750 W. Harrison Street, Jelke 1121
        • telephone_number (312) 942-3554
        • fax_number
        • cell_number (312) 942-3554
        • email_addressjennifer_garcia@rush.edu
        • created2023-07-03 13:46:52
        • modified2023-10-23 09:03:19
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