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• trial_statuses(array)
  • 1Recruiting
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• applications(array)
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    • Application(array)
      • id1479
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      • trial_status_id(null)
      • abstract_of_study<p class=\"SynchrogenixBodyText\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <span lang=\"EN-US\">Modeling suggests that the most effective contribution to TB control in high burden countries would be a vaccine that prevents pulmonary TB in adolescents and adults [</span><span lang=\"EN-US\" style=\"color: blue;\">WHO</span><span lang=\"EN-US\" style=\"color: blue;\">2021</span><span lang=\"EN-US\">]. In very high incidence geographies, the incidence rate of TB is highest in older adolescents and young adults (e.g., 15 to 44 years of age). In addition, pulmonary TB is the predominant form of TB in this age group (with the primary mode of TB transmission being via aerosol), and young adults are more likely to transmit to more contacts because they are active and mix extensively [</span><span lang=\"EN-US\" style=\"color: blue;\">Knight</span><span lang=\"EN-US\" style=\"color: blue;\">2014</span><span lang=\"EN-US\">].</span></p>\n<p class=\"SynchrogenixBodyText\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n The primary objective of this Phase 3 efficacy trial is to evaluate VE in the prevention of laboratory-confirmed pulmonary TB in IGRA-positive participants who do not have HIV. The rationale for focusing on IGRA-positive participants is based on Phase 3 trial simulations that evaluated the feasibility of demonstrating VE in an “all-comer” population (i.e., regardless of IGRA status) of young adults (15 to 44 years of age) in very high burden settings with an IGRA-positive prevalence of 67%. Based on these simulations, it appears feasible to demonstrate vaccine efficacy against tuberculosis disease (VE[D]) in an IGRA-positive, HIV-negative population, with a sample size of <span class=\"msoIns\"><ins cite=\"mailto:Debbie%20Daehnick%20(DT%20Medical%20Writing%20Corp)\" datetime=\"2024-01-08T12:19\">9</ins></span>,000 participants per arm, within 4 years from start of enrollment, whereas a trial in an all-comer population would have to be much larger, and the larger population would still be inadequate to demonstrate VE(D) in IGRA-negative participants.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Trial simulation assumptions included an annual IGRA conversion rate of 3% per person-year, and an incidence of active pulmonary TB of 0.4% per person-year. These simulations suggested that even with a 67% IGRA-positive prevalence at enrollment, more than 90% of laboratory-confirmed cases of TB would be observed in IGRA-positive participants, and less than 10% in IGRA-negative participants; such a trial would not be powered to demonstrate VE(D) in IGRA-negative participants as a subset.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n A confirmatory trial in IGRA-negative participants is not considered feasible (in a reasonable amount of time and with a reasonable population size), given the low rate of laboratory-confirmed cases expected in baseline IGRA-negative participants. Given the inability to demonstrate VE(D) in IGRA-negative participants as a subset in an ‘all-comer’ trial, this Phase 3 trial aims to demonstrate VE(D) in IGRA-positive participants only, and to generate descriptive safety, immunogenicity, and VE(D) data in a HIV-negative, IGRA-negative Cohort  (N=1,000) and in a cohort of PLHIV (N=1,000) of either positive or negative IGRA status.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n GlaxoSmithKline Biologicals, SA (GSK) developed M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span>, an investigational TB vaccine, to protect against the development of TB in <em>Mtb</em>-infected adolescents and adults. The GSK Phase 2b trial (TB-018) evaluated vaccine safety and efficacy in approximately 3500 IGRA-positive adults (1:1, M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4 </span>and placebo) [Van Der Meeren2018; Tait2019]. Most participants in the TB-018 trial had previously received the BCG vaccine as neonates. The observed VE against active pulmonary TB in the Phase 2b trial was 49.7% (95% CI: 2.1% to 74.2%) at 36 months and no safety signals that would prevent further development were observed [Tait2019].</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n In 2020, the Bill & Melinda Gates Medical Research Institute (Gates MRI) licensed the M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4 </span>investigational TB vaccine for continued development.</p>\n
      • study_title<p>\n <span style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">A Phase 3, randomized, double-blind, placebo-controlled, multicenter, clinical trial to assess the prophylactic efficacy, safety, and immunogenicity of the investigational M72/AS01</span><span style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span><span style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\"> Mycobacterium tuberculosis (Mtb) vaccine when administered intramuscularly on a 0,1-month schedule to adolescents and adults.</span></p>\n
      • laymans_summary<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Tuberculosis (TB) is caused by the bacterium Mycobacterium tuberculosis (Mtb); it typically affects the lungs but can also affect other sites. TB is spread from person to person via the respiratory route and is manifested by the presence of Mtb in sputum. TB is the second leading infectious killer after COVID-19 (above HIV/AIDS). It is present in all countries and age groups, but the larger number of new cases occur in countries of the South-East Asian Region and African Region.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Bacille Calmette-Guérin, known as BCG, is the only licensed TB vaccine to date; however, the impact of BCG on the transmission of Mtb in adults is limited, since it offers minimal or no protection against pulmonary TB in adults. TB treatment is lengthy, and compliance is often incomplete, resulting in an increasing incidence of multi-drug resistant (MDR)-TB and extensively drug resistant (XDR)-TB.</p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Given the substantial morbidity and mortality associated with TB, the challenges associated with TB treatment, and the limited options for prevention, a vaccine is urgently needed, both to protect against disease, including the progression from latent Mtb infection to active TB, and to accelerate the end of the TB epidemic.</p>\n
      • short_titleGates MRI TBV02-301
      • protocol_noECCT/24/10/02
      • version_no2.0
      • date_of_protocol08-01-2024
      • study_drugM72/AS01E-4 investigational vaccine
      • disease_conditionTuberculosis (TB)
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorNo
      • comparator_nameN/A
      • comparator_registeredN/A
      • comparator_countriesN/A
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressamina.salim@iqvia.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantMaureen Anyango Olwero
      • declaration_date111-10-2024
      • declaration_principal_investigatorDr Isaac Tsikhutsu- PI - Kenya Medical Research Institute/Walter Reed Project, Clinical Research Center
      • declaration_date211-10-2024
      • placebo_presentYes
      • study_objectives<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <div font-size:=\"\" trebuchet=\"\">\n <strong>Primary Efficacy Objective:</strong></div>\n <ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n To evaluate the vaccine efficacy (VE) of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> in the prevention of laboratory-confirmed pulmonary TB among IGRA-positive participants without HIV infection (IGRA-Positive Cohort) in the per-protocol (PP) analysis set</li>\n </ul>\n <p font-size:=\"\" style=\"margin: 0px 0px 10px;\" trebuchet=\"\">\n <strong font-size:=\"\" trebuchet=\"\">Secondary Efficacy Objectives:</strong></p>\n <ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n To evaluate the VE of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> in the prevention of <em>Mtb</em> infection among the IGRA-Negative Cohort in the PP analysis set</li>\n <li style=\"line-height: 20px;\">\n To evaluate the VE of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> in the prevention of laboratory-confirmed pulmonary TB among the IGRA-Negative Cohort in the PP analysis set</li>\n <li style=\"line-height: 20px;\">\n To evaluate the VE of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> in the prevention of laboratory-confirmed pulmonary TB among the HIV Cohort in the PP analysis set</li>\n <li style=\"line-height: 20px;\">\n To evaluate the VE of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> in the prevention of less stringently defined laboratory-confirmed pulmonary TB among the IGRA-Positive Cohort in the PP analysis set</li>\n </ul>\n <p font-size:=\"\" style=\"margin: 0px 0px 10px;\" trebuchet=\"\">\n <strong>Secondary Safety Objective:</strong></p>\n <ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n To evaluate the safety and reactogenicity following administration of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> vaccine or placebo</li>\n </ul>\n <p font-size:=\"\" style=\"margin: 0px 0px 10px;\" trebuchet=\"\">\n <strong>Secondary Immunogenicity Objective:</strong></p>\n <ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n To assess the humoral immunogenicity of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> vaccination</li>\n </ul>\n <p font-size:=\"\" style=\"margin: 0px 0px 10px;\" trebuchet=\"\">\n <strong>Exploratory Objectives:</strong></p>\n <ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n To further explore the VE of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> in the prevention of <strong>laboratory</strong>-confirmed pulmonary TB as defined for the primary endpoint, among the IGRA-Positive Cohort in the mITT analysis set</li>\n <li style=\"line-height: 20px;\">\n To explore the effect of potential covariates on the VE of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> in the prevention of <strong>laboratory</strong>-confirmed pulmonary TB as defined for the primary endpoint, among the IGRA-Positive Cohort in the PP analysis set</li>\n <li style=\"line-height: 20px;\">\n To explore the VE of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4 </span>in the prevention of <strong>laboratory-confirmed</strong> pulmonary TB, where sputum was collected up to 28 days after treatment initiation among IGRA-positive, IGRA-negative, and HIV Cohorts, respectively, in the mITT analysis set.</li>\n <li style=\"line-height: 20px;\">\n To explore the VE of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> in the prevention of <strong>clinical</strong> TB (including extrapulmonary TB) defined as a participant for whom a clinician has diagnosed TB, and has initiated TB treatment, in the absence of laboratory-confirmed pulmonary TB, among IGRA-positive, IGRA-negative, and HIV Cohorts, respectively, in the mITT analysis set. </li>\n <li style=\"line-height: 20px;\">\n To explore the VE of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4 </span>in the prevention of <strong>subclinical </strong>TB, defined as a participant with a positive result from Xpert Ultra or similar assay (excluding “trace positive”) from a single sputum sample at the EoT visit, in the absence of signs or symptoms of pulmonary TB, among IGRA-positive, IGRA-negative, and HIV Cohorts, respectively, in the mITT analysis set.</li>\n <li style=\"line-height: 20px;\">\n To assess the cellular immunogenicity of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> vaccination using M72-specific CD4+ and CD8+ T-cell responses measured by co-expression of 2 or more cytokines using intracellular cytokine staining (ICS)</li>\n <li style=\"line-height: 20px;\">\n To further explore the cellular immunogenicity of M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E-4</span> vaccination using M72-specific CD4+ and CD8+ T-cell responses measured by co-expression of multiple functional markers by ICS</li>\n <li style=\"line-height: 20px;\">\n To confirm candidate CoP and CoR if identified in the M72 Immune Correlates Program and to explore new candidate CoP and CoR</li>\n <li style=\"line-height: 20px;\">\n To explore characteristics of <em>Mtb </em>isolates, including drug susceptibility profiles and genetic diversity</li>\n </ul>\n</div>\n<p>\n  </p>\n
      • principal_inclusion_criteria<p class=\"SynchrogenixBodyText\" font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <span lang=\"EN-US\">Participants are eligible for randomization and trial intervention administration only if all of the following criteria apply.</span></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n    <strong>Age</strong></p>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Participant must be 15 to 44 years of age (inclusive), at the time of signing the consent or assent.</li>\n</ol>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Type of Participant and Disease Characteristics</strong></p>\n<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\" value=\"2\">\n Capable of giving informed consent or informed assent (as appropriate). For participants below the age of consent, the participant’s parent, or legally authorized representative (LAR) will be required to sign a statement of informed consent, in addition to the minor’s signed statement of assent.</li>\n <li style=\"line-height: 20px;\" value=\"3\">\n In the opinion of the investigator, can and will comply with the requirements of the protocol (e.g., completion of diary cards as applicable, and return for follow-up visits).</li>\n <li style=\"line-height: 20px;\" value=\"4\">\n Agree to actively stay in contact with the trial site for the duration of the trial for the participants own safety.</li>\n <li style=\"line-height: 20px;\" value=\"5\">\n Agree to provide updated contact information as necessary, and have no current plans to relocate from the trial area for the duration of the trial.</li>\n <li style=\"line-height: 20px;\" value=\"6\">\n Healthy, or with preexisting stable disease, as established by medical history and physical examination and as determined by the investigator. Preexisting stable disease is defined as not requiring significant change in therapy or hospitalization for worsening disease during the 28 days before enrollment.</li>\n <li style=\"line-height: 20px;\" value=\"7\">\n Negative sputum Xpert Ultra or similar assay result at screening </li>\n <li style=\"line-height: 20px;\" value=\"8\">\n Both males and females are included. Females are included with restrictions. Females must either be of non-childbearing potential, defined as pre-menarche, have a history of either current tubal ligation, hysterectomy, or ovariectomy, or post-menopause, <strong>or</strong>, if she is of childbearing potential, she has practiced abstinence from penile-vaginal intercourse or adequate contraception for 28 days prior to vaccination, has a negative pregnancy test on the day of screening and the day of first vaccination, and agrees to continue abstinence or adequate contraception until 2 months after the second dose of trial intervention.</li>\n <li style=\"line-height: 20px;\" value=\"9\">\n HIV-negative test result at screening (IGRA-Positive Cohort and IGRA-Negative Cohort only)</li>\n <li style=\"line-height: 20px;\" value=\"10\">\n HIV Cohort only: Participants with documented<ins cite=\"mailto:Debbie%20Daehnick%20(DT%20Medical%20Writing%20Corp)\" datetime=\"2024-01-08T12:19\">*</ins> HIV infection who fulfill all of the following criteria:</li>\n</ol>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n have reactive anti-HIV antibody at screening</li>\n <li style=\"line-height: 20px;\">\n have been on ART for at least 3 consecutive months at screening and agree to remain on ART throughout the trial</li>\n <li style=\"line-height: 20px;\">\n have documented HIV RNA <200 copies/mL at screening</li>\n <li style=\"line-height: 20px;\">\n have CD4+ cell count ≥200 cells/µL at screening</li>\n <li style=\"line-height: 20px;\">\n have had TPT in the past and are not receiving TPT at the time of screening, according to the judgment of the investigators</li>\n <li style=\"line-height: 20px;\">\n have an IGRA-positive or negative result at screening.</li>\n</ul>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <ins cite=\"mailto:Debbie%20Daehnick%20(DT%20Medical%20Writing%20Corp)\" datetime=\"2024-01-08T12:19\">*Note that ‘documented’ refers to documentation from the site personnel’s review of the participant’s medical records, medical examination, or medical history interview.</ins></p>\n
      • principal_exclusion_criteria<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Participants are excluded from the trial if any of the following criteria apply:</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Medical Conditions</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 1. Current TB, or history of TB or treatment for TB disease</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 2. Clinical suspicion of pulmonary TB at screening, defined as a participant presenting with one or more of the following signs or symptoms: unexplained cough, unexplained fever, night sweats, unintentional weight loss, hemoptysis, pleuritic chest pain</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 3. Any current medical, psychiatric, occupational, or substance abuse problems that, in the opinion of the investigator, will make it unlikely that the participant will comply with the protocol, or that will interfere with the assessments or the safety of the participant</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 4. Any confirmed or suspected immunosuppressive or immunodeficient condition resulting from disease (e.g., invasive, or malignant cancers), other than HIV infection in the HIV Cohort</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 5. Known bleeding disorder that is considered a contracindication to intramuscular injection or phlebotomy </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Prior/Concomitant Therapy</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 6. Any cytotoxic drugs or administration of medications known to have a major impact on the immune system, as determined by the investigator, within 90 days prior to Day 1. These include immune globulin, blood, or blood products, potent immunosuppressants and immunomodulators, and systemic corticosteroids (exceeding 20 mg/day prednisone equivalent). Inhaled, topical, and intra-articular corticosteroids are allowed.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Prior/Concurrent Clinical Trial Experience</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 7. Planned receipt of blood, or blood products during the trial period</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 8. Receipt or planned receipt of any vaccine in the period starting 28 days before, and ending 28 days after, each dose of the trial vaccine</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 9. History of previous administration of an experimental <em>Mtb</em> vaccine including M72/AS01<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">E </span>in a previous trial</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 10. History of allergy or hypersensitivity to the trial intervention, excipients, or related substances</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Diagnostic assessments</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 11. An indeterminate IGRA test result at screening</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 12. Female participants with any one of the following conditions: currently pregnant or lactating; having positive serum pregnancy test during the screening window, positive urine pregnancy test on Day 1, planning a pregnancy within 2 months after completion of the vaccination series</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 13. Only in the HIV Cohort: Safety laboratory values at screening that are of concern, based on investigator’s judgment. Note that preexisting stable chronic disease will not necessarily lead to exclusion, especially if laboratory values are graded as mild (Section 13).</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Other Exclusions</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 14. Participation in an interventional clinical trial in which the participant has been or will be exposed to an investigational product (pharmaceutical product or device), within 28 days prior to signing consent or assent, or during the trial period.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 15. Individuals who are acting as personnel for this trial, or who have immediate family members (brother, sister, child, parent, or the spouse/partner) who are acting as personnel for this trial.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 16. Child in Care, defined as a child who is under the care (control or protection) of an agency, organization, institution or entity by the courts, the government body, acting in accordance with powers conferred in them by law or regulations. The definition of a child in care can include a child who is cared for by foster parents or living in a care home or institution, provided that the arrangements fall within the definition above. The definition of a child in care <strong>does not include</strong> a child who is adopted or has an appointed LAR.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 17. Participants who had a Tuberculin Skin Test (TST) within 6 months prior to Day 1</p>\n
      • primary_end_points<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n <strong>Primary Efficacy Endpoint:</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n Laboratory-confirmed pulmonary TB over a period starting 1 month post Dose 2 and lasting up to End of Trial (EoT) where a laboratory-confirmed pulmonary TB case is defined as a participant with:</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 21.6pt; color: rgb(51, 51, 51);\" trebuchet=\"\">\n ·       Suspected pulmonary TB as defined as a participant presenting with one or more of the following signs or symptoms:</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 39.7pt; color: rgb(51, 51, 51);\" trebuchet=\"\">\n o   unexplained cough, unintentional weight loss, hemoptysis, unexplained fever, night sweats, pleuritic chest pain</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n who has</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n At least 2 positive <em>Mtb</em> test results (positive <em>Mtb</em> culture and/or positive test result from Xpert Ultra or similar assay, excluding “trace positive”), from the same or from different sputum samples collected during 3 suspected TB visits, preferably within a 7-day time frame, before initiation of TB treatment</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n <strong>Secondary Efficacy Endpoints:</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n Sustained QuantiFERON®-TB Gold Plus assay (or similar) conversion (i.e., initial conversion and IGRA-positive test result at next attended scheduled visit) over a period starting 1 month post dose 2 and lasting up to EoT </p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n Laboratory-confirmed pulmonary TB over a period starting 1 month post Dose 2 and lasting up to EoT, where a laboratory-confirmed pulmonary TB case follows the same definition as the primary endpoint</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n Laboratory-confirmed pulmonary TB over a period starting 1 month post Dose 2 and lasting up to EoT, where a laboratory-confirmed pulmonary TB case follows the same definition as the primary endpoint</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n Laboratory-confirmed pulmonary TB over a period starting 1 month post Dose 2 and lasting up to EoT, where a laboratory-confirmed pulmonary TB case is defined less stringently as a participant with:</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 17.3pt; color: rgb(51, 51, 51);\" trebuchet=\"\">\n ·       Suspected pulmonary TB as defined for the primary efficacy endpoint, and</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n At least 1 positive <em>Mtb</em> culture or at least 1 positive result from Xpert Ultra or similar assay (excluding “trace positive”),from the same or from different sputum samples collected during the 3 suspected TB visits, preferably within a 7-day time frame, before initiation of TB treatment</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n <strong>Secondary Safety Endpoints:</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n Occurrence of solicited AEs during the 7 days following each vaccination (starting on day of vaccination and 6 subsequent days after each vaccine dose) Safety analysis set</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n Occurrence of unsolicited AEs during the 28 days following each vaccination (starting on day of vaccination and 27 subsequent days after each vaccine dose) Safety analysis set</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n Occurrence of all serious adverse events (SAEs) and potential immune-mediated diseases (pIMDs) from Day 1 through Month 13, Safety analysis set</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n Occurrence of SAEs related to trial participation through <ins cite=\"mailto:Debbie%20Daehnick%20(DT%20Medical%20Writing%20Corp)\" datetime=\"2024-01-08T12:19\">trial</ins> end, Safety analysis set</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n <strong>Secondary Immunogenicity Endpoint:</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n Geometric mean concentration (GMC) and seropositivity of M72-specific antibodies at Day 1, Month 1, Month 2, Month 7, Month 13, Month 37, and Month 49 among each of the IGRA-Positive Cohort, IGRA-Negative Cohort, and HIV Cohorts in the per-protocol for immunogenicity (PPI) analyses set</p>\n<p style=\"margin: 0px 0px 10px;\">\n  </p>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<div>\n  </div>\n<div>\n <div>\n The site has a long-standing experience in conducting several studies including clinical trials,</div>\n <div>\n ranging from therapeutics that included a study of the safety and impact of broadly neutralizing</div>\n <div>\n monoclonal antibody therapy with VRC01 on viremia in acute HIV infection, alone or in</div>\n <div>\n combination with antiretroviral therapy (ART), vaccines (HIV, Polio, Ebola, Shigella) and</div>\n <div>\n cohort studies. The clinical trials range from phase I to IV with age ranges from birth to the elderly,</div>\n <div>\n some of which are randomized double blind, placebo controlled and United States</div>\n <div>\n Investigational New Drug (IND)/ Food and Drug Administration (FDA)- regulated. </div>\n <div>\n Kericho County has a TB prevalence of 200 per 100,000 people with an HIV prevalence of 3.7%. </div>\n <div>\n Kericho also has a large youthful population in schools and colleges who are willing to participate</div>\n <div>\n in vaccine trials.</div>\n <div>\n  </div>\n <div>\n The Kericho CRC is equipped with two emergency rooms (one per floor) with equipment and medications to provide immediate emergency care in the event of emergencies during vaccinations such as anaphylaxis, convulsions, hypotension, and provisions (resuscitation equipment) are in place for immediate resuscitation on site. Additionally, the Kericho site has a standby, fully equipped ambulance for evacuation of participants for more specialized care when necessary. The</div>\n <div>\n Kericho County Referral Hospital, which sits in the same compound as the CRC is a COVID-19 treatment center and has an Intensive Care Unit (ICU) which will be utilized should need arise. The study staffs (clinicians/nurses) are trained on handling emergencies. All study procedures will be done at KEMRI/USAMRD-A Clinical Research Center, Kericho with additional satellite sites setup to cater for the anticipated large number of participants to be enrolled. The site uses UTK</div>\n <div>\n hospital as a satellite site for inpatient admissions of participants needing inpatient services. The hospital is located about two kilometers from the CRC and has both outpatient and inpatient services.</div>\n <div>\n  </div>\n <div>\n <div>\n The Kericho CRC pharmacy Infrastructure. The site has two pharmacies one located on the first floor of the Clinical Research Center (CRC) building and the other located in the USHMA building. Entry to the pharmacies is restricted through biometric access doors. The pharmacies are equipped with lockable filing cabinets, and granite-topped workstations and are designed with window/hatch access to adjacent examination rooms allowing direct passage for blinded vaccine studies. The pharmacies are connected to the main national electric power grid, with two automatic back-up generators.</div>\n <div>\n  </div>\n <div>\n <div>\n  </div>\n <div>\n Pharmacy equipment. For cold storage, each pharmacy is equipped with a -20°C freezers, a -80°C freezers, and a 2-8°C refrigerators. An additional set of cold chain equipment made up of a -20°C freezer, a -80°C freezer and a 2-8°C refrigerator is located in the freezer farm that is on the ground floor of the CRC building. This equipment in the freezer farm serves as back up to the main equipment in both pharmacies. The CRC pharmacy has a two-class II biological safety cabinet</div>\n <div>\n (BSC), a Type B2 and Type A, while the USHMA pharmacy has a class II Type A BSC. Temperature monitoring in both pharmacies is done by an Eltek temperature and Humidity monitoring system with built-in sensor phone that sends short text message alerts in the event of an excursion. In addition, both pharmacies have dual air conditioning system, temperature data loggers and a dehumidifier. The pharmacy equipment is annually calibrated.</div>\n <div>\n  </div>\n <div>\n <div>\n The pharmacies are staffed by 5 full time employees.2 pharmacists and 3 Pharmaceutical technologists. The pharmacy operations are governed by policies that include standard operating procedures, Study specific procedures, quality management plans, local pharmacy regulations and any sponsor specific pharmacy manuals. The pharmacy supports end to end supply chain  management for all vaccine conducted at the KEMRI/WRP Kericho site.  This entails IMP forecasting, ordering, importation, receipt, storage, accountability, preparation, inventory, dispensing, and disposal. The Kericho site laboratory was the first (2008) and to date, only CAP-accredited laboratory in Kenya and has since undergone six reaccreditation cycles. The Laboratory is also Certified by the Kenya Medical Laboratory Board as Class “G” – the highest class in the country. The laboratory consists of two main sections: HIV and Microbiology. The HIV laboratory is divided into</div>\n </div>\n <div>\n <div>\n subsections that encompass specimen-processing and associated freezer farm, clinical (hematology, chemistry and flow cytometry), serology and molecular diagnostics. All specimens are accessioned using either the Freezerworks (FW) or Laboratory Data Management Systems (LDMS). The laboratory has the capacity to process peripheral blood mononuclear cells (PBMCs), plasma, serum and mucosal specimens. The   laboratory is equipped with several class II biosafety cabinets (BSC), centrifuges, refrigerators and freezers (range: -20 degrees to -196 degrees)  and an on-site liquid nitrogen production facility. Temperature-sensitive storage is monitored through Eltek, a continuous, automatic, electronic temperature-monitoring system with in-built sensor phones and short text message capability and manual checks.  </div>\n <div>\n  </div>\n </div>\n </div>\n <div>\n  </div>\n </div>\n <div>\n <div>\n The hematology subsection performs complete blood counts (CBC) including five-part differentials, estimated sedimentation rate (ESR), reticulocyte counts and blood parasites including malaria. Additionally, this subsection performs Prothrombin Time/International Normalized Ratio (PT/INR), fibrinogen, and Activated Partial Thromboplastin Time (APTT) assays with a platform that has additional capacity including factor assays. The chemistry subsection uses Roche platforms (Cobas</div>\n <div>\n C311) and performs all chemistry analytes including liver function tests (LFTs), renal function tests (RFTs), electrolytes, and lipid profile. The flow cytometry subsection has a Beckman Coulter AQUIOS CL  and BD FACSCanto platforms that can stain for all lymphocyte subsets (CD4/8,NK, B lymphocytes) in addition to doing intracellular cytokine staining (ICS) research assays. The serology subsection has capacity to test for Cryptococcal antigen, hepatitis B surface antigen</div>\n <div>\n (HBsAg) screening and confirmatory, hepatitis C antibody (HCV Ab), pregnancy, syphilis and HIV1 using rapid , Enzyme-Linked Immuno-Sorbent Assay (ELISA)- both third abd fourth generation ELISAs, and Immunoblot assays.</div>\n </div>\n <div>\n  </div>\n <div>\n <div>\n The Molecular subsection has the Roche Taqman Ampliprep and Abbott m2000 and Alinity platforms for quantitative HIV viral load monitoring and the Hologic Aptima qualitative RNA assay for detection of acute HIV infection (AHI) and monitoring. HIV-Drug resistance testing is performed using the ThermoFisher HIV-1 Genotyping Kit with Integrase features. </div>\n <div>\n  </div>\n <div>\n <div>\n  All laboratory assays are monitored through several external proficiency testing (EPT) panels from CAP, United Kingdom National External Quality Assessment Service (UKNEQAS); Human Quality Assessment Services (HUQAS); and the Virology Quality Assurance (VQA) </div>\n <div>\n  </div>\n <div>\n <div>\n The microbiology section provides expertise and laboratory support for the detection and diagnosis of bacterial, parasitic and viral causes of acute diarrhea in Kenya. The laboratory provides support for outbreak response preparation and ongoing surveillance of microbial agents, including antimicrobial resistance patterns. The laboratory’s diagnostic focus includes blood and body fluid samples including cerebrospinal fluid (CSF). Automated Identification and Antimicrobial</div>\n <div>\n Susceptibility Testing (ID/AST) are performed using the MicroScan Walkaway system. Several platforms are available for polymerase chain reaction (PCR), allowing for rapid identification and subtyping of pathogens. Serotyping capabilities are being expanded and pulsed field gel electrophoresis (PFGE) is being implemented to further characterize isolated agents. The laboratory has also recently implemented the Matrix-Assisted Laser Desorption/Ionization (MALDI) Biotyper to improve identification time. In a collaborative partnership with HJF/MHRP, the microbiology facility is enrolling participants for several protocols. The laboratory also has capacity to perform Candida albicans and cryptococcal fungal cultures.</div>\n <div>\n  </div>\n <div>\n <div>\n KEMRI/WRP BSL-3 Laboratory is the first and only College of American Pathologist accredited and DAIDS GCLP Certified BSL-3 Laboratory in Kenya. The state-of-the-art Laboratory has enhanced BSL-3 capacities: engineering, physical, and administrative controls, and therefore, conforms to WHO biosafety and other international standards for performing TB testing. The laboratory has the technical capacity (including human resources, infrastructure and equipment) to perform AFB microscopy, culture, identification, and drug susceptibility testing (DST) of M. tuberculosis using phenotypic and molecular methods according to current WHO policy guidance. The Laboratory is officially recognized by Kenya Ministry of Health as one of the National Level TB Reference Laboratory, supporting a functional national laboratory as well as conducting cutting edge clinical research. </div>\n <div>\n  </div>\n <div>\n <div>\n The laboratory has a strong QA/QC department to ensure that the most current documents are in use. Internal semi-annual audits are done with alternating two-year accreditation cycles by by the United States National Institute of Health-DAIDS contracted auditor, the Pharmaceutical Product Development (PPD).and CAP. The laboratory supports inter-laboratory quality assurance (QA) programs with memoranda of understanding with the Centers for Disease Control and Prevention (CDC) lab, Kisumu, Kenya, that is South African National Accreditation System (SANAS)accredited and the Moi University/Academic Model Providing Access to Healthcare (AMPATH) Partnership., Eldoret, Kenya, that is Kenya Accrediation National Service (KENAS)- Accredited.</div>\n <div>\n  </div>\n <div>\n <div>\n The laboratory performance evaluations for shipping, export and storage by both ACTG and IMPAACT networks have been outstanding. The average performance for the last six months has been over 90%.  </div>\n <div>\n  </div>\n </div>\n <div>\n The Kericho site laboratory is good clinical laboratory practice (GCLP) compliant and all members of the technical staff are GCLP-certified. Total staff are 34 working in different sections as described above.</div>\n </div>\n </div>\n <div>\n  </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=\"\">This Phase 3 TB vaccine trial will be conducted in adolescents and adults in communities with a high burden of pulmonary tuberculosis (TB). The trial is being conducted in Kenya because TB is significantly more prevalent (>200 cases per 100,000 population) than the USA (<3 cases per 100,000 population). </span></p>\n
      • other_details_regulatory_notapproved<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"648\">\n <tbody>\n <tr>\n <td rowspan=\"2\" style=\"width:97px;height:19px;\">\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n <strong>C</strong><strong>o</strong><strong>u</strong><strong>ntry</strong></p>\n </td>\n <td rowspan=\"2\" style=\"width:213px;height:19px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n <strong>N</strong><strong>ame of Competent Authority</strong></p>\n </td>\n <td rowspan=\"2\" style=\"width:187px;height:19px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n <strong>Submission status</strong></p>\n </td>\n <td rowspan=\"2\" style=\"width:151px;height:19px;\">\n <p style=\"margin-left:4.85pt;\">\n <strong>C</strong><strong>ompetent</strong></p>\n <p style=\"margin-left:4.85pt;\">\n <strong>A</strong><strong>uthority decision</strong></p>\n </td>\n <td height=\"29\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td rowspan=\"2\" style=\"width:97px;height:19px;\">\n <p>\n <strong>Kenya</strong></p>\n </td>\n <td colspan=\"3\" style=\"width:551px;height:19px;\">\n <p style=\"margin-left:5.0pt;\">\n Kenya Pharmacy and Poison Board (KPPB):</p>\n </td>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:213px;height:23px;\">\n <p style=\"margin-left:5.0pt;\">\n Site 1206</p>\n <p>\n  </p>\n </td>\n <td style=\"width:187px;height:23px;\">\n <p>\n Current submission</p>\n </td>\n <td style=\"width:151px;height:23px;\">\n <p>\n Current submission</p>\n </td>\n <td height=\"35\" style=\"height:23px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:97px;height:81px;\">\n <p style=\"margin-left:4.85pt;\">\n <strong>V</strong><strong>ietnam</strong></p>\n </td>\n <td style=\"width:213px;height:81px;\">\n <p style=\"margin-left:5.0pt;\">\n Vietnam Ministry of Health</p>\n </td>\n <td style=\"width:187px;height:81px;\">\n <p style=\"margin-left:5.0pt;\">\n V1.0 Submitted 08 Jan 2024</p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n V2.0 submitted 11 June 2024</p>\n </td>\n <td style=\"width:151px;height:81px;\">\n <p style=\"margin-left:4.85pt;\">\n Pending</p>\n </td>\n <td height=\"122\" style=\"height:81px;\">\n  </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_regulatory_approved<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"648\">\n <tbody>\n <tr>\n <td rowspan=\"2\" style=\"width:97px;height:19px;\">\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n <strong>C</strong><strong>o</strong><strong>u</strong><strong>ntry</strong></p>\n </td>\n <td colspan=\"2\" rowspan=\"2\" style=\"width:213px;height:19px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n <strong>N</strong><strong>ame of Competent Authority</strong></p>\n </td>\n <td rowspan=\"2\" style=\"width:187px;height:19px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n <strong>Submission status</strong></p>\n </td>\n <td rowspan=\"2\" style=\"width:151px;height:19px;\">\n <p style=\"margin-left:4.85pt;\">\n <strong>C</strong><strong>ompetent</strong></p>\n <p style=\"margin-left:4.85pt;\">\n <strong>A</strong><strong>uthority decision</strong></p>\n </td>\n <td height=\"29\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td rowspan=\"9\" style=\"width:97px;height:19px;\">\n <p>\n <strong>Kenya</strong></p>\n </td>\n <td colspan=\"4\" style=\"width:551px;height:19px;\">\n <p style=\"margin-left:5.0pt;\">\n Kenya Pharmacy and Poison Board (KPPB):</p>\n </td>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:213px;height:19px;\">\n <p style=\"margin-left:5.0pt;\">\n Site 1201</p>\n <p>\n  </p>\n </td>\n <td style=\"width:187px;height:19px;\">\n <p style=\"margin-left:5.0pt;\">\n V2.0 Submitted 28 Mar 2024</p>\n <p>\n  </p>\n </td>\n <td style=\"width:151px;height:19px;\">\n <p>\n Approved: 25 Apr 2024</p>\n </td>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:213px;height:19px;\">\n <p style=\"margin-left:5.0pt;\">\n Site 1202</p>\n <p>\n  </p>\n </td>\n <td style=\"width:187px;height:19px;\">\n <p style=\"margin-left:5.0pt;\">\n V2.0 Submitted 08 May 2024</p>\n <p>\n  </p>\n </td>\n <td style=\"width:151px;height:19px;\">\n <p>\n Approved: 27 May 2024</p>\n </td>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:213px;height:50px;\">\n <p style=\"margin-left:5.0pt;\">\n Site 1203</p>\n <p>\n  </p>\n </td>\n <td style=\"width:187px;height:50px;\">\n <p>\n V2.0 Submitted 30 July 2024</p>\n </td>\n <td style=\"width:151px;height:50px;\">\n <p>\n Approved: 20 Aug 2024</p>\n </td>\n <td height=\"76\" style=\"height:50px;\">\n  </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:213px;height:41px;\">\n <p style=\"margin-left:5.0pt;\">\n Site 1204</p>\n <p>\n  </p>\n </td>\n <td style=\"width:187px;height:41px;\">\n <p>\n V2.0 Submitted 11 June 2024</p>\n </td>\n <td style=\"width:151px;height:41px;\">\n <p>\n Approved: 02 July 2024</p>\n </td>\n <td height=\"62\" style=\"height:41px;\">\n  </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:213px;height:19px;\">\n <p style=\"margin-left:5.0pt;\">\n Site 1205</p>\n <p>\n  </p>\n </td>\n <td style=\"width:187px;height:19px;\">\n <p>\n V2.0 Submitted_ 28 June 2024</p>\n </td>\n <td style=\"width:151px;height:19px;\">\n <p>\n Approved: 28 July 2024</p>\n </td>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:213px;height:19px;\">\n <p style=\"margin-left:5.0pt;\">\n Site 1207 </p>\n <p>\n  </p>\n </td>\n <td style=\"width:187px;height:19px;\">\n <p style=\"margin-left:5.0pt;\">\n V2.0 Submitted 30 Apr 2024</p>\n </td>\n <td style=\"width:151px;height:19px;\">\n <p>\n Approved: 08 May 2024</p>\n </td>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:213px;height:19px;\">\n <p style=\"margin-left:5.0pt;\">\n Site 1208</p>\n <p>\n  </p>\n </td>\n <td style=\"width:187px;height:19px;\">\n <p style=\"margin-left:5.0pt;\">\n V2.0 Submitted 03 May 2024</p>\n </td>\n <td style=\"width:151px;height:19px;\">\n <p>\n Approved: 08 May 2024</p>\n </td>\n <td height=\"28\" style=\"height:19px;\">\n  </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:213px;height:24px;\">\n <p>\n   Site 1209</p>\n </td>\n <td style=\"width:187px;height:24px;\">\n <p style=\"margin-left:5.0pt;\">\n V2.0 Submitted 02 May 2024</p>\n </td>\n <td style=\"width:151px;height:24px;\">\n <p>\n Approved: 08 May 2024</p>\n </td>\n <td height=\"36\" style=\"height:24px;\">\n  </td>\n </tr>\n <tr>\n <td rowspan=\"2\" style=\"width:97px;height:28px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.25pt;\">\n <strong>South Africa</strong></p>\n </td>\n <td colspan=\"2\" rowspan=\"2\" style=\"width:213px;height:28px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n South Africa Health Products</p>\n <p style=\"margin-left:5.0pt;\">\n Regulatory Authority (SAHPRA)</p>\n </td>\n <td style=\"width:187px;height:28px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n V1.0 Submitted – 11Aug 2023</p>\n </td>\n <td style=\"width:151px;height:28px;\">\n <p>\n Approved: 15 Nov 2023</p>\n <p>\n  </p>\n <p>\n  </p>\n </td>\n <td height=\"42\" style=\"height:28px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:187px;height:63px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n V2.0 Submitted – 19 Jan 2024</p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n </td>\n <td style=\"width:151px;height:63px;\">\n <p>\n  </p>\n <p>\n  </p>\n <p>\n Approved: 02 Feb 2024</p>\n </td>\n <td height=\"95\" style=\"height:63px;\">\n  </td>\n </tr>\n <tr>\n <td rowspan=\"2\" style=\"width:97px;height:33px;\">\n <p style=\"margin-left:2.6pt;\">\n <strong>I</strong><strong>ndonesia</strong></p>\n </td>\n <td colspan=\"2\" rowspan=\"2\" style=\"width:213px;height:33px;\">\n <p style=\"margin-left:5.0pt;\">\n Indonesian Food and Drug Authority</p>\n <p style=\"margin-left:5.0pt;\">\n (Indonesia NADFC-BPOM)</p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n </td>\n <td style=\"width:187px;height:33px;\">\n <p style=\"margin-left:5.0pt;\">\n V1.0 Submitted –07Sep2023</p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n </td>\n <td rowspan=\"2\" style=\"width:151px;height:33px;\">\n <p style=\"margin-left:4.85pt;\">\n V1.0 – N/A</p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <div style=\"margin-left:4.85pt;\">\n <p>\n V2.0 – Approved</p>\n <p>\n Site 2201: 06 May 2024</p>\n <p>\n Site 2202: 21 May 2024</p>\n <p>\n Site 2203: 19 Apr 2024</p>\n <p>\n Site 2204: 26 Apr 2024</p>\n <p>\n Site 2205: 06 May 2024</p>\n <p>\n  </p>\n <p>\n  </p>\n </div>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n </td>\n <td height=\"49\" style=\"height:33px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:187px;height:174px;\">\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n V2.0 – Submitted  19 Jan 2024</p>\n </td>\n <td height=\"260\" style=\"height:174px;\">\n  </td>\n </tr>\n <tr>\n <td rowspan=\"2\" style=\"width:97px;height:62px;\">\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n <strong>Z</strong><strong>a</strong><strong>mbia</strong></p>\n </td>\n <td style=\"width:15px;height:62px;\">\n <p style=\"margin-left:.05pt;\">\n §</p>\n </td>\n <td style=\"width:198px;height:62px;\">\n <p style=\"margin-left:6.1pt;\">\n Zambia Medicines Regulatory</p>\n <p style=\"margin-left:6.1pt;\">\n Authority (ZAMRA)</p>\n <p style=\"margin-left:6.1pt;\">\n  </p>\n <p style=\"margin-left:6.1pt;\">\n  </p>\n <p style=\"margin-left:6.1pt;\">\n  </p>\n <p style=\"margin-left:6.1pt;\">\n  </p>\n <p style=\"margin-left:6.1pt;\">\n  </p>\n </td>\n <td style=\"width:187px;height:62px;\">\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n V1.0 Submitted- 31 Oct 2023</p>\n <p style=\"margin-left:4.85pt;\">\n V2.0 Submitted: 04 Apr 2024</p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n </td>\n <td rowspan=\"2\" style=\"width:151px;height:62px;\">\n <p style=\"margin-left:4.85pt;\">\n V1.0 N/A</p>\n <p style=\"margin-left:4.85pt;\">\n V2.0 approved 10 May 2024</p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p style=\"margin-left:4.85pt;\">\n V2.0 19 June 2024</p>\n </td>\n <td height=\"94\" style=\"height:62px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:15px;height:42px;\">\n <p style=\"margin-left:.05pt;\">\n §</p>\n </td>\n <td style=\"width:198px;height:42px;\">\n <p style=\"margin-left:6.1pt;\">\n National Health Research</p>\n <p style=\"margin-left:6.1pt;\">\n Authority (NHRA)</p>\n </td>\n <td style=\"width:187px;height:42px;\">\n <p>\n V2.0 – Submitted  05 Apr 2024</p>\n </td>\n <td height=\"63\" style=\"height:42px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:97px;height:275px;\">\n <p style=\"margin-left:4.85pt;\">\n <strong>M</strong><strong>alawi</strong></p>\n </td>\n <td colspan=\"2\" style=\"width:213px;height:275px;\">\n <p style=\"margin-left:5.0pt;\">\n Pharmacy and Medicines Regulatory</p>\n <p style=\"margin-left:5.0pt;\">\n Authority (PMRA)</p>\n </td>\n <td style=\"width:187px;height:275px;\">\n <p style=\"margin-left:5.0pt;\">\n V1.0 Submitted – 08 Dec 2023</p>\n <p style=\"margin-left:5.0pt;\">\n  </p>\n <p style=\"margin-left:5.0pt;\">\n V2.0 Submitted – 15 Mar 2024</p>\n </td>\n <td style=\"width:151px;height:275px;\">\n <p style=\"margin-left:4.85pt;\">\n V1.0  approved 27 May 2024</p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p style=\"margin-left:4.85pt;\">\n Site 2401_ V2.0 Approved_ 11 July 2024, Cover letter _corrected 22 July 2024</p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p style=\"margin-left:4.85pt;\">\n Site 2402_V2.0 Approved_ 07 June 2024 corrected 11 July 2024 (Site 2402)</p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n <p style=\"margin-left:4.85pt;\">\n Site 2402_ V2.0_Final approval_16Sep2024</p>\n <p style=\"margin-left:4.85pt;\">\n  </p>\n </td>\n <td height=\"413\" style=\"height:275px;\">\n  </td>\n </tr>\n <tr>\n <td style=\"width:97px;height:69px;\">\n <p>\n  </p>\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n <strong>M</strong><strong>o</strong><strong>z</strong><strong>a</strong><strong>m</strong><strong>bi</strong><strong>que</strong></p>\n </td>\n <td colspan=\"2\" style=\"width:213px;height:69px;\">\n <p>\n  </p>\n <p>\n  </p>\n <p style=\"margin-left:2.7pt;\">\n National Medicines Regulatory</p>\n <p style=\"margin-left:.05pt;\">\n Authority (ANARME)</p>\n </td>\n <td style=\"width:187px;height:69px;\">\n <p>\n  </p>\n <p>\n  </p>\n <p style=\"margin-left:5.0pt;\">\n V2.0 Submitted – 04 June 2024</p>\n </td>\n <td style=\"width:151px;height:69px;\">\n <p>\n  </p>\n <p>\n  </p>\n <p style=\"margin-left:4.85pt;\">\n V2.0 Approved_19 Sep 2024</p>\n </td>\n <td height=\"104\" style=\"height:69px;\">\n  </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration4 Years
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states7
      • number_of_sites9
      • multi_country_listKenya, South Africa, Malawi, Zambia, Mozambique, Indonesia and Vietnam
      • data_monitoring_committeeYes
      • total_enrolment_per_siteCompetitive enrolment approximated at 500 per Site
      • total_participants_worldwide20,000
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameDr Videlis
      • investigator1_middle_name
      • investigator1_family_nameNduba
      • investigator1_qualificationMBChB, MPH,PhD
      • investigator1_professional_addressKEMRI Centre for Clinical Respiratory Diseases Research (KEMRI CRDR), KEMRI/ CRDR Clinical Research Annex, KNH Complex Behind Government Chemist and Off Raila Odinga Way, P.O Box 47855 - 00100,Nairobi Kenya
      • investigator1_telephone+254 724 522 474
      • investigator1_emailvnduba@gmail.com
      • organisations_transferred_Yes
      • number_participants4,500
      • notification
      • approval_date12-11-2024
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted11-10-2024
      • is_child0
      • unsubmitted1
      • initial_date_submitted11-10-2024
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonApproved as per the AVAREF Assessment report.\n
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-03-11 13:55:36
      • created2024-10-11 14:48:39
      • total_sites1
      • ecitizen_invoice322983
    • InvestigatorContact(array)
      • 0(array)
        • id1176
        • application_id1479
        • given_nameDr Isaac
        • middle_name
        • family_nameTsikhutsu
        • qualificationMBChB, MMED, FPCCM
        • professional_addressKenya Medical Research Institute/Walter Reed Project, Clinical Research Center, P.O Box 1357, 20200, Kericho, Kenya
        • telephone+254 729 110124
        • emailIsaac.tsikhutsu@usamru-k.org
        • created2024-10-11 14:57:37
        • modified2024-10-28 16:23:26
    • SiteDetail(array)
      • 0(array)
        • id1800
        • application_id1479
        • county_id35
        • site_nameKenya Medical Research Institute/Walter Reed Project, Clinical Research Center
        • physical_addressKenya Medical Research Institute/Walter Reed Project, Clinical Research Center, P.O Box 1357, 20200, Kericho, Kenya
        • contact_details+254 729 110124; P.O Box 1357, 20200, Kericho, Kenya
        • contact_personDr Isaac Tsikhutsu
        • site_capacity(null)
        • misc(null)
        • created2024-10-11 14:57:37
        • modified2024-10-28 16:23:27
        • County(array)
          • id35
          • county_nameKericho
          • created2012-06-15 10:26:16
          • modified2012-06-15 10:26:16
    • Sponsor(array)
      • 0(array)
        • id787
        • application_id1479
        • sponsorBill & Melinda Gates Medical Research Institute (Gates MRI)
        • sponsor_typeResearch Institution
        • contact_personKristen Mayer
        • addressOne Kendall Square, Building 600, Suite 6-301, Cambridge, MA 02139, USA
        • telephone_number+1 617-465-0089
        • fax_numberN/A
        • cell_number+1 617-465-0089
        • email_addressKristen.mayer@gatesmri.org
        • created2024-10-11 14:57:37
        • modified2024-10-28 16:23:26
  • 1(array)
    • Application(array)
      • id1312
      • user_id263
      • trial_status_id4
      • abstract_of_study<div style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Bifidobacteria are gram-positive, heterofermentative, anaerobic bacteria that colonize the newborn gut within the first days and weeks of life. They are often the most abundant bacterial genus in a breast-fed infant’s intestinal flora. B. infantis metabolizes Human milk oligosaccharides (HMOs) and produces short chain fatty acids (SCFA) that are thought to play an important role in nutrition and immune development, stimulating anti-inflammatory and inhibiting pro-inflammatory responses [Halloran 2019; Henrick 2021].</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 B. infantis Bi-26 strain is a nutritional probiotic intervention that will be evaluated in this trial for its ability to improve weight gain and health outcomes of underweight infants with WAZ <-2 who have been hospitalized with acute illness.</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 Clinical study data in the United States (US) have shown that B. infantis strain EVC001 colonizes the gut and is associated with significant changes to fecal microbiome composition in healthy breast-fed infants [Frese 2017; Henrick 2019]. Supplementation of B. infantis EVC001 has been associated with a reduction in pro-inflammatory cytokines [Henrick 2019]. Similar observations have been reported for preterm infants given B. infantis EVC001 [Nguyen 2021].</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 In a pilot trial evaluating B. infantis EVC001 supplementation in Bangladesh in hospitalized 2-to 6-month-old infants with SAM, i.e., weight-for-length z score [WLZ] <-3, researchers observed that daily supplementation with B. infantis for 4 weeks was associated with B. infantis colonization and an increase in WAZ [Barratt 2022].</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 A number of B. infantis strains, including Bi-26, have been designated as generally recognized as safe (GRAS) based on review by a panel of independent experts in the field. Furthermore, the US Food and Drug Administration (FDA) did not have questions about the GRAS determination of Bi-26 (GRN 985). In the US, the GRAS determination and the FDA no question letter allow the use of Bi-26 under its intended conditions of use (healthy term infants) in infant formula. The strain bearing the GRAS designation can also be used in dietary supplements, including those for infants.</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 In low-income countries, B. infantis strain Bi-26, evaluated in this study, could potentially be used as a dietary supplement in underweight infants if the safety and efficacy findings of the previous pilot study are confirmed.</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 3, randomized, double-blind, placebo-controlled study to evaluate the effect of Bi-26 (strain of Bifidobacterium longum, B. infantis) supplementation versus placebo on weight gain in underweight infants</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 Poor countries bear a greater burden of children who are born with a weight that is less than it should be for their age. Poor health in the digestive system (gut) can be caused by a poor balance of good bacteria that are thought to play a role in how nutrients are absorbed in the intestines. Good bacteria in a baby’s gut are important in helping the baby grow, develop normally, and be healthier. One of the bacteria, called <em>B. infantis</em>, that is normally found in babies’ guts makes it easier for the baby to digest their mother’s milk and help keep the baby healthy. Babies who have a weight that is less than it should be for their age have less of the <em>B. infantis</em> bacteria, compared to healthy babies. This may cause poor absorption of these nutrients and can lead to babies not being able to gain weight, leading to them becoming underweight and failing to thrive. Providing a dietary supplement with a specific strain of the bacteria known as EVC001 has been shown to boost the friendly bacteria living in the gut and cause significant changes in the composition of the friendly bacteria and its environment in the gut especially in healthy babies who are breastfed. </p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n A small study in Bangladesh tested this strain among babies who were aged between 2 and 6 months and had been admitted to hospital, who were also suffering from severe acute malnutrition. They were given the friendly <em>B. infantis</em> bacteria species as a dietary supplement daily for a period of four weeks. It was found out that this supplementation boosted the friendly bacteria and resulted in the children gaining weight and improving their nutritional weight-for-age Z score (WAZ). We want to study underweight babies who are between 1 and 4 months of age who are in the hospital, to see if they will also gain weight after taking the <em>B. infantis </em>supplement Bi-26. If the results in our study show that the dietary supplements with this friendly bacterial species of <em>B. infantis</em> improves weight gain among underweight children, then it can potentially be used in poor countries as a dietary supplement in babies who are underweight.</p>\n
      • short_titleCONSTELLATION
      • protocol_noECCT/23/09/03
      • version_no4.0
      • date_of_protocol12-09-2022
      • study_drugBi-26 (strain of Bifidobacterium longum, B. infantis)
      • disease_conditionInfant malnutrition
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals1
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorYes
      • comparator_namePlacebo
      • comparator_registeredN/A
      • comparator_countriesN/A
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressamina.salim@iqvia.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantFerial Israel
      • declaration_date114-09-2023
      • declaration_principal_investigatorDr Lucas Otieno Tina
      • declaration_date214-09-2023
      • placebo_presentYes
      • study_objectives<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Primary Objective</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n To evaluate the change in weight (standardized for age) of infants receiving Bi-26</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Key Secondary Objective</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n To evaluate the change in weight of infants receiving Bi-26</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Other Secondary Objectives</strong></p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n ​​To estimate the treatment response over time associated with Bi-26</li>\n <li style=\"line-height: 20px;\">\n To assess the proportion of infants who achieve a specified change in WAZ from baseline to Day 56</li>\n <li style=\"line-height: 20px;\">\n To assess the proportion of infants who achieve a specified WAZ at Day 56</li>\n <li style=\"line-height: 20px;\">\n To assess the re-hospitalization rate</li>\n <li style=\"line-height: 20px;\">\n To assess the safety of Bi-26 supplementation through End of Study (EoS, Day 90 visit)</li>\n <li style=\"line-height: 20px;\">\n To measure engraftment of B. infantis in participants</li>\n</ul>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Exploratory Objectives</strong></div>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n To describe stool biomarkers in response to Bi-26 supplementation in terms of stool composition (e.g., microbiome, pH)</li>\n <li style=\"line-height: 20px;\">\n To describe the blood biomarkers (e.g., inflammation, metabolomics), in response to Bi-26 supplementation</li>\n</ul>\n
      • principal_inclusion_criteria<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Age</strong></div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 1. Participant must be between 30 days and 120 days of age (inclusive), at the time of enrollment (study Day 1)</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 <strong>Type of Participant and Disease Characteristics</strong></div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 2. Hospitalized for acute non-surgical illness</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 3. Completed acute stabilization phase of treatment, including fluid rehydration and antibiotic course, prior to enrollment (study Day 1)</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 <strong>Weight</strong></div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 4. WAZ at enrollment (study Day 1) is less than negative 2 (<-2)</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 <strong>Sex</strong></div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 5. Any</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 <strong>Informed consent</strong></div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 6. Participant’s parent(s)/legal guardian is capable of giving informed consent which includes agreement to comply with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol</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 <div>\n <strong>Additional requirements</strong></div>\n <div>\n 7. Participant’s parent(s)/legal guardian agrees to stay in contact with the study site for the duration of the study, provide updated contact information as necessary, and have no current plans to relocate from the study area for the duration of the study</div>\n <div>\n 8. Participant’s parent(s)/legal guardian has easy access to reliable refrigeration (for storage of investigational product)</div>\n <div>\n 9. Participant receives some feedings from breastmilk and mother intends to continue breastfeeding.</div>\n</div>\n<p>\n  </p>\n
      • principal_exclusion_criteria<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 1. Congenital condition (suspected or confirmed) that the investigator considers likely to interfere with feeding or with normal growth and development</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 2. Infant has not been discharged from hospital since birth or has not been at home for at least one week since birth</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 3. Infant hospitalized with septic shock during current hospitalization</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 4. Infant required mechanical ventilation during current hospitalization</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 5. Infant with acute kidney injury on hospital admission</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 6. Infant with severe jaundice and suspected kernicterus</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 7. Infant receiving treatment for suspected or confirmed tuberculosis, or suspected or confirmed HIV infection</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 8. Ongoing infant antibiotic (e.g. as prophylaxis in sickle cell disease) and/or probiotic usage</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 9. Ongoing maternal antibiotic and/or probiotic usage for breast-feeding infants</div>\n<div font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 10. Inability of participant’s parent(s)/legal guardian to comply with protocol requirements, as per investigator assessment.</div>\n
      • primary_end_points<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Primary Endpoints</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n WAZ change from baseline (Day 1) to the Day 56 visit in Bi-26 group</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Key Secondary Endpoints</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Change in weight (in grams) from baseline (Day 1) to the Day 56 visit in the Bi-26 group</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Other Secondary Endpoints</strong></p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n WAZ change from baseline (Day 1) over time through the Day 90 visit (longitudinal assessment) by duration of dosing</li>\n <li style=\"line-height: 20px;\">\n Proportion of infants with a ≥ 0.3, ≥ 0.4, and ≥ 0.5 change in WAZ from baseline (Day 1) to Day 56 visit</li>\n <li style=\"line-height: 20px;\">\n Proportion of infants who achieve a WAZ > -2 at Day 56 visit</li>\n <li style=\"line-height: 20px;\">\n Number of re-hospitalizations for acute non-surgical illness through the Day 56 visit</li>\n <li style=\"line-height: 20px;\">\n Number of adverse events (AEs) and serious adverse events (SAEs) through Day 90</li>\n <li style=\"line-height: 20px;\">\n Presence of B. infantis in stool on Days 1, 28, 56, and 90</li>\n</ul>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Exploratory Endpoints</strong></p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Stool biomarkers on Days 1, 28, and 56</li>\n <li style=\"line-height: 20px;\">\n Blood biomarkers on Days 1 and 28</li>\n</ul>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n The study will be conducted in Homa Bay County, western Kenya. The main site will be Homa Bay County Teaching and Referral Hospital, with the surrounding sub-county hospitals (Marindi, Makongeni, Rangwe Ndhiwa and Mbita), health centres (Nyalkinyi), dispensaries (Otaro, Ogande, Wiga, Koduogo, Nyamasi, Pedo, Imbo, Kijawa, Miniambo, Pala Masogo and Orego) and private health facilities (St. Paul, Samarimed and St. Lawrence) referring cases to the main hospital. </p>\n<p>\n  </p>\n<p>\n <strong>Simon Kariuki, PhD,</strong> is Chief Research Officer and the Malaria Branch Chief at KEMRI, CDC and LSTM Collaborative Program in Kisumu, Kenya. He is the PI of this study and will facilitate project procedures in Kenya and act as the main liaison between the investigators and KEMRI and the local regulator and other relevant authorities.  He will also be responsible for the overseeing the development of the site-specific protocol, standard operating procedures (SOPs), training of personnel, recruitment of study participants. He will provide all the onsite oversight during study conduct, data collection, interpretation and manuscript preparation.</p>\n<p>\n  </p>\n<p>\n <strong>Prof. Stephen Allen, (MB, ChB; DTM&H; MD; FRCPCH) </strong>is a paediatric gastroenterologist undertaking clinical practice in the Gambia.  As a co-investigator, he will provide technical advice on various aspects of the study in collaboration with other co-investigators involved<strong>.</strong></p>\n<p>\n  </p>\n<p>\n <strong>Iwaret Otiti, MBChB, MSc</strong>, is a medical doctor with training in epidemiology. She will participate in managing the clinical trial in close consultation with the Principal Investigator and other Co-Investigators. She will be responsible for amendments to the study protocol, obtaining ethics and regulatory clearances and standard operating procedures, and coordinating the fieldwork in Kenya. She will also be responsible for overseeing any centralised functions including the coordination of data management and laboratory testing and oversee provision of clinical care to study participants and supervision of clinical officers and other study staff. She will also participate in reporting of SAEs, data collection and preparation of manuscripts.</p>\n<p>\n  </p>\n<p>\n <strong>Kephas Otieno, MSc</strong>, is the head of the Malaria laboratory of the KEMRI, CDC and LSTM Collaborative Program in Kisumu, Kenya. He will be responsible for training and supervision of staff involved in collection of laboratory samples. He will also provide oversight over the processing, storage/archiving and shipment of all samples. He will coordinate the quality assurance/quality control aspects of the study.</p>\n<p>\n  </p>\n<p>\n <strong>Ruth Njoroge, BPharm,</strong> is the KEMRI/CGHR pharmacist. She will participate in the implementation of the study, oversee handling of investigational product, training of staff on data collection on pharmacovigilance and reporting to the Kenya Pharmacy and Poisons Board (KPPB). She will also participate in the interpretation of data and the preparation of manuscripts.</p>\n<p>\n  </p>\n<p>\n <strong>Micah June, BSc,</strong> will participate in planning the study, recruitment, training and supervision of clinic and field staff, data collection, reporting of SAEs, quality control and assurance including oversee other regulatory roles, and manuscript preparation.</p>\n<p>\n  </p>\n
      • other_details_explanation<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">This study focuses on infants in low- and middle-income countries as these are the regions where the burden of disease is greatest as noted in the protocol and the IB. Approximately 90% of underweight children are found in Southeast Asia and Sub-Saharan Africa (</span><a aria-label=\"Link Food Sci Nutr.\" class=\"fui-Link ___1qmgydl f3rmtva f1ewtqcl fyind8e f1k6fduh f1w7gpdv fk6fouc fjoy568 figsok6 f1hu3pq6 f11qmguv f19f4twv f1tyq0we f1g0x7ka fhxju0i f1qch9an f1cnd47f fqv5qza f1vmzxwi f1o700av f13mvf36 f1cmlufx f9n3di6 f1ids18y f1tx3yz7 f1deo86v f1eh06m1 f1iescvh ftqa4ok f2hkw1w fhgqx19 f1olyrje f1p93eir f1h8hb77 f1x7u7e9 f10aw75t fsle3fq\" font-size:=\"\" href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9007294/\" overflow-wrap:=\"\" rel=\"noreferrer noopener\" style=\"color: rgb(51, 51, 51); text-decoration-line: none; font-family: \" target=\"_blank\" title=\"https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9007294/\" trebuchet=\"\">Food Sci Nutr.</a><span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\"> 2022 Apr; 10(4): 1167–1174. </span><a aria-label=\"Link Published online 2022 Jan 18. doi: 10.1002/fsn3.2748\" class=\"fui-Link ___1qmgydl f3rmtva f1ewtqcl fyind8e f1k6fduh f1w7gpdv fk6fouc fjoy568 figsok6 f1hu3pq6 f11qmguv f19f4twv f1tyq0we f1g0x7ka fhxju0i f1qch9an f1cnd47f fqv5qza f1vmzxwi f1o700av f13mvf36 f1cmlufx f9n3di6 f1ids18y f1tx3yz7 f1deo86v f1eh06m1 f1iescvh ftqa4ok f2hkw1w fhgqx19 f1olyrje f1p93eir f1h8hb77 f1x7u7e9 f10aw75t fsle3fq\" font-size:=\"\" href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9007294/\" overflow-wrap:=\"\" rel=\"noreferrer noopener\" style=\"color: rgb(51, 51, 51); text-decoration-line: none; font-family: \" target=\"_blank\" title=\"https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9007294/\" trebuchet=\"\">Published online 2022 Jan 18. doi: 10.1002/fsn3.2748</a><span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">). Thus, countries in these regions were selected for participation in this study, including Kenya, as there is an unmet medical need for management of underweight infants in those regions.</span></p>\n
      • other_details_regulatory_notapproved<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Pakistan - 28 Dec 2022</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Tanzania - 30 Dec 2022</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Bangladesh - planned for mid-July 2023</p>\n
      • other_details_regulatory_approved<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">All approvals are pending</span></p>\n
      • other_details_regulatory_rejected<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">Not applicable</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 study duration for each participant is approximately 3 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_comparatorpotato maltodextrin
      • 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_states4
      • number_of_sites8
      • multi_country_listKenya, Tanzania, Pakistan and Bangladesh
      • data_monitoring_committeeYes
      • total_enrolment_per_siteMinimum per site = 5, maximum per site = 30
      • total_participants_worldwide396
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerYes
      • population_childrenNo
      • population_adolescentNo
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyMalnourished infants
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameDr Lucas
      • investigator1_middle_nameOtieno
      • investigator1_family_nameTina
      • investigator1_qualificationMBChB, MPH DLSHTM
      • investigator1_professional_addressVictoria Biomedical Research Institute, Kisumu County Referral Hospital Off Ang\'awa Road, P.O. Box 7180, Postal Code 40100, Kisumu, Kenya
      • investigator1_telephone+254708358451
      • investigator1_emailltina@vibriafrica.org
      • organisations_transferred_Yes
      • number_participants160
      • notification<p>\n The study has already been reviewed and approved by KPPB on 31 July 2023. This included the site of Dr Lucas Tina. This application is the submission of an additional site of Dr Simon Kariuki.</p>\n
      • approval_date19-12-2023
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted14-09-2023
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonAll reviewer comments have been addressed.
      • final_report
      • implication_results
      • quantity_imported
      • quantity_dispensed
      • quantity_destroyed
      • quantity_exported
      • balance_site
      • final_date0000-00-00
      • modified2025-04-24 16:21:11
      • created2023-09-05 14:26:18
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id961
        • application_id1312
        • given_nameDr Simon
        • middle_name
        • family_nameKariuki
        • qualificationBsc. Mphil, PhD, Post-Doc
        • professional_address.or 8088, Eldoret, Kenya
        • telephoneTel: +254 (0) 57 2022902, 2022929,
        • emailskkariuki@kemri.org
        • created2023-09-05 14:32:11
        • modified2023-09-14 16:38:40
    • SiteDetail(array)
      • 0(array)
        • id1587
        • application_id1312
        • county_id42
        • site_nameKenya Medical Research Institute- Centre for Global Health Research
        • physical_addressKisian Campus, Off Kisumu-Busia Highway, P.O.Box 1578-40100, Kisumu, Kenya
        • contact_details+254 725 389 246
        • contact_personDr Simon Kariuki
        • site_capacity(null)
        • misc(null)
        • created2023-09-05 14:32:11
        • modified2023-09-14 16:38:40
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id689
        • application_id1312
        • sponsorBill & Melinda Gates Medical Research Institute
        • sponsor_typeResearch Institution
        • contact_personJanie Parrino
        • addressOne Kendall Square Building 600,Cambridge, Massachusetts, 02139, United States
        • telephone_number+12155397606
        • fax_number
        • cell_numberN/A
        • email_addressjanie.parrino@gatesmri.org
        • created2023-09-05 14:32:11
        • modified2023-09-14 16:38:40
  • 2(array)
    • Application(array)
      • id1344
      • user_id263
      • trial_status_id6
      • abstract_of_study<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 <strong>Protocol Title:</strong></p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n A Phase 2a, Multicenter, Open-label, Dose-finding, Dose escalation Study of Meplazumab in Adult Patients diagnosed with Uncomplicated <em>Plasmodium falciparum</em> Malaria.</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 <strong>Rationale</strong><strong>:</strong></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 Meplazumab, an erythrocytic stage-macromolecular antibody drug, has the potential to control clinical occurrence of falciparum malaria. Meplazumab is a humanized anti-CD147 immunoglobulin G subclass 2 (IgG2) monoclonal antibody with strong affinity to CD147. CD147 is expressed on erythrocyte lineage cells throughout erythroid development, including mature erythrocytes and is the target for Plasmodium merozoites to allow reorientation and subsequent invasion of the erythrocytes. Nonclinical studies have demonstrated that meplazumab binding to CD147 interferes with the receptor‑ligand interaction between CD147 and rhoptry-associated protein 2 (RAP2) of the <em>P. falciparum</em> merozoite and inhibits the formation of parasitophorous vacuoles of <em>P. falciparum</em> thus preventing the invasion of <em>P. falciparum</em> into human erythrocytes. Furthermore, the therapeutic and prophylactic effects of meplazumab were demonstrated in vivo using a human erythrocyte chimeric NOG mouse model, which is considered as an optimal choice for in vivo inhibition efficacy study for human-hosted <em>P. falciparum</em>.</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 Meplazumab has previously been studied in healthy participants in two Phase 1 studies and has also been evaluated for activity in 2 completed clinical trials in patients diagnosed with coronavirus disease 2019 (COVID‑19). In the safety, tolerability, and pharmacokinetics study in healthy participants, MPZ‑I-01, results demonstrated a high and prolonged receptor occupancy (RO%) of meplazumab at CD147.</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 This Phase 2a study is designed as a dose escalation trial to assess safety of meplazumab in the target population and to evaluate whether meplazumab is efficacious in treating malaria. The data obtained in this study will be used to determine a recommended meplazumab dose for future Phase 2b and 3 efficacy trials.</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 <strong>Protocol Title:</strong></p>\n<p style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n A Phase 2a, Multicenter, Open-label, Dose-finding, Dose escalation Study of Meplazumab in Adult Patients diagnosed with Uncomplicated <em>Plasmodium falciparum</em> Malaria.</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 <strong>Rationale</strong><strong>:</strong></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 Meplazumab, an erythrocytic stage-macromolecular antibody drug, has the potential to control clinical occurrence of falciparum malaria. Meplazumab is a humanized anti-CD147 immunoglobulin G subclass 2 (IgG2) monoclonal antibody with strong affinity to CD147. CD147 is expressed on erythrocyte lineage cells throughout erythroid development, including mature erythrocytes and is the target for Plasmodium merozoites to allow reorientation and subsequent invasion of the erythrocytes. Nonclinical studies have demonstrated that meplazumab binding to CD147 interferes with the receptor‑ligand interaction between CD147 and rhoptry-associated protein 2 (RAP2) of the <em>P. falciparum</em> merozoite and inhibits the formation of parasitophorous vacuoles of <em>P. falciparum</em> thus preventing the invasion of <em>P. falciparum</em> into human erythrocytes. Furthermore, the therapeutic and prophylactic effects of meplazumab were demonstrated in vivo using a human erythrocyte chimeric NOG mouse model, which is considered as an optimal choice for in vivo inhibition efficacy study for human-hosted <em>P. falciparum</em>.</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 Meplazumab has previously been studied in healthy participants in two Phase 1 studies and has also been evaluated for activity in 2 completed clinical trials in patients diagnosed with coronavirus disease 2019 (COVID‑19). In the safety, tolerability, and pharmacokinetics study in healthy participants, MPZ‑I-01, results demonstrated a high and prolonged receptor occupancy (RO%) of meplazumab at CD147.</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 This Phase 2a study is designed as a dose escalation trial to assess safety of meplazumab in the target population and to evaluate whether meplazumab is efficacious in treating malaria. The data obtained in this study will be used to determine a recommended meplazumab dose for future Phase 2b and 3 efficacy trials.</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 <strong>Objectives and Endpoints</strong><strong>:</strong></p>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" style=\"max-width: 100%; border-collapse: collapse; border-spacing: 0px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\" title=\"Synopsis\">\n <thead>\n <tr>\n <th style=\"padding: 4px 5px; line-height: 20px; text-align: left; vertical-align: bottom; border-top: 0px; width: 264px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Objectives</strong></p>\n </th>\n <th style=\"padding: 4px 5px; line-height: 20px; text-align: left; vertical-align: bottom; border-top: 0px; width: 342px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Endpoints</strong></p>\n </th>\n </tr>\n </thead>\n <tbody>\n <tr>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 606px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Primary</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: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate the safety of meplazumab in an adult population with uncomplicated, symptomatic <em>P. falciparum</em> infection</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Incidence and severity of AE</li>\n <li style=\"line-height: 20px;\">\n Incidence of (number of participants with):\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 0px 25px;\">\n <li style=\"line-height: 20px;\">\n Drug-related SAE</li>\n <li style=\"line-height: 20px;\">\n All-cause SAE</li>\n <li style=\"line-height: 20px;\">\n Drug-related AESI</li>\n <li style=\"line-height: 20px;\">\n All-cause AESI</li>\n <li style=\"line-height: 20px;\">\n Participants discontinuation/ withdrawals due to AE</li>\n </ul>\n </li>\n </ul>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 606px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Secondary</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: 264px; height: 50px;\">\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 meplazumab as defined by:\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 0px 25px;\">\n <li style=\"line-height: 20px;\">\n Early treatment failure</li>\n <li style=\"line-height: 20px;\">\n Late clinical failure</li>\n <li style=\"line-height: 20px;\">\n Late parasitological failure</li>\n <li style=\"line-height: 20px;\">\n Uncorrected ACPR</li>\n </ul>\n </li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px; height: 50px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Incidence (number of participants with) of early treatment failure</li>\n <li style=\"line-height: 20px;\">\n Incidence of late clinical failure</li>\n <li style=\"line-height: 20px;\">\n Incidence of late parasitological failure</li>\n <li style=\"line-height: 20px;\">\n Incidence of uncorrected ACPR at Day 28</li>\n </ul>\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: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate PRR</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n PRR at 72h</li>\n </ul>\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: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To determine the recrudescence (see Section 9.3.7) and re-infection (see Section 9.3.7)</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Incidence of (number of participants with) recrudescence and re-infection at Week 4</li>\n <li style=\"line-height: 20px;\">\n Time to recrudescence and re-infection at Week 4</li>\n </ul>\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: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To determine the time to relief of fever</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n FCT at 72h</li>\n </ul>\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: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To determine the dose-response trend relationship between 3 dose  levels of meplazumab by evaluation of safety, efficacy and ACPR outcomes</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Dose-response trend relationship between the 3 dose levels of meplazumab, based on change from baseline in the summary of the safety and efficacy outcomes to Week 4</li>\n </ul>\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: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate the pharmacokinetics of meplazumab in serum</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Meplazumab serum concentration-time profiles and PK parameters including but not limited to C<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">max</span>, t<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">max</span>, AUC<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">(0-last)</span>, AUC<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">(0-inf)</span>, t<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">½</span>, CL, V<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">z</span>, and V<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">ss</span></li>\n </ul>\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: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate immunogenicity following meplazumab administration</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Frequency of confirmed anti-drug antibody (ADA) response, ADA titers, and neutralizing activity</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 606px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Exploratory</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: 264px; height: 45px;\">\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 meplazumab by PCR-corrected ACPR</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px; height: 45px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Incidence of (number of participants with) PCR‑corrected ACPR at Week 4</li>\n </ul>\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: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate RO (%) of meplazumab in red blood cells following single dose administration</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Meplazumab RO%-time profiles, pharmacodynamic parameters determined for RO including but not limited to maximum RO% and duration RO% (RO% half-life)</li>\n </ul>\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: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To quantify the levels of complement regulatory proteins, the deposition of complement on  erythrocytes, and serum complement activation in human subjects treated with meplazumab.</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Cell-surface expression of complement regulatory proteins and presence of complement products measured by flow cytometry; and complement activation measured by ELISA kit</li>\n </ul>\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: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate the relationship between exposure to meplazumab and key efficacy and/or safety parameters</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Graphical (and statistical, if appropriate) display of exposure versus response</li>\n </ul>\n </td>\n </tr>\n </tbody>\n</table>\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 Abbreviations: ACPR=adequate clinical & parasitological response; ADA=anti-drug antibodies; AE=adverse event; AESI =adverse event of special interest; AUC<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">(0‑inf)</span>=area under the concentration‑time curve extrapolated to infinity; AUC<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">(0‑last)</span>=area under the concentration‑time curve to the last quantifiable concentration; CL=systemic clearance; C<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">max</span>=maximum concentration; FCT=fever clearance time; polymerase chain reaction PCR=polymerase chain reaction; <em>P. falciparum</em>=<em>Plasmodium falciparum</em>; PRR=parasite reduction rate; RO=receptor occupancy; SAE=serious adverse event; t<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">½</span>=elimination half‑life; t<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">max</span>=time to C<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">max</span>; V<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">z</span>=volume of distribution; V<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">ss</span>=volume at steady state.</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 <strong>Overall Design:</strong></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 This is a Phase 2a multicenter, open-label, dose-finding, dose escalation study. The study will recruit participants with confirmed <em>P. falciparum</em> infection. Up to 60 participants will be enrolled into 1 of 3 meplazumab dose levels (20 participants /dose level).</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 <strong>Number of Participants:</strong></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 Up to 60 participants will be enrolled into 1 of 3 meplazumab dose levels (20 participants/dose level).</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 <strong>Intervention Groups and Duration</strong><strong>:</strong></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 Participants will be administered a single intravenous (IV) infusion dose of meplazumab 120±5 minutes on Day 0 and hospitalized for 72 hours after dosing (up to Day 3) to monitor for safety and tolerability of therapy, and to ensure treatment response. During hospitalization, blood sampling for safety, pharmacokinetic (PK), and RO pharmacodynamic (PD) testing at predefined times will be collected as specified per the Schedule of Assessment (SoA). Furthermore, in a subset of first 10 participants/dose level, additional (serial) PK and PD samples will be collected at 1, 2, 4 and 8 hours post end-of-infusion. Up to 3 additional samples may be added to the Day 0-3 serial sample collection period.</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 clinically well, participants may be discharged from the clinical unit on Day 3 at the Investigator’s discretion. Participants will return to the study center for follow-up visits on Days 28±2, 56±7, 84±7 and 182±7 (End of Study) for safety, tolerability, PK, PD (RO rate), and immunogenicity assessments as per the SoA (Weeks 4, 8, 12 and 26).</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 <strong>Data Monitoring/Other Committee: </strong>Yes</p>\n
      • study_title<p>\n <span style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">A Phase 2a, Multicenter, Open-label, Dose-finding, Dose Escalation Study of Meplazumab in Adult Patients Diagnosed with Uncomplicated </span><em style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">Plasmodium falciparum</em><span style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\"> Malaria</span></p>\n
      • laymans_summary<p>\n <span style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">Open-Label Study to evaluate the safety of meplazumab in an adult population with uncomplicated, symptomatic P. falciparum infection. Malaria is caused by Plasmodium, a parasite which is transmitted to humans by infected female anopheles mosquitoes (malaria vector). When infected anopheles bites a human, Plasmodium sporozoites in the mosquito’s saliva enter the bloodstream and migrate to the liver, followed by the merozoites reproduction within the hepatocytes. This stage is known as exoerythrocytic phase. Merozoites reproduce and form schizonts, which contain several thousands of merozoites. After the schizonts mature and rupture, merozoites are released into the blood and invade erythrocytes, hence initiating the merozoites reproduction in the erythrocytic phase. Current methods toward malaria elimination usually involve the combination of prevention and treatment. Artemisinin-based combination therapies (ACTs) are currently recommended by the World Health Organization for the treatment of malaria. Antimalarial drugs mainly include drugs to eliminate Plasmodium during the erythrocytic or exoerythrocytic phase. From the 1950s, falciparum malaria has developed general resistance to antimalarial drugs such as chloroquine, and sulfadoxine-pyrimethamine, leading to ineffective malaria control. Plasmodium developed higher resistance to the drugs used in combination in ACTs. Therefore, new antimalarial therapies and drugs are imperative due to the recurrent drug resistance of Plasmodium. Meplazumab, an erythrocytic stage-macromolecular antibody drug, has the potential to control clinical occurrence of falciparum malaria. Meplazumab is a humanized anti-CD147 immunoglobulin G subclass 2 (IgG2) monoclonal antibody with strong affinity to CD147. CD147 is expressed on erythrocyte lineage cells throughout erythroid development, including mature erythrocytes and is the target for Plasmodium merozoites to allow reorientation and subsequent invasion of the erythrocytes.</span></p>\n
      • short_titleMPZ-MAL-01
      • protocol_noECCT/23/11/06
      • version_noAmendment 1
      • date_of_protocol27-07-2023
      • study_drugMeplazumab
      • disease_conditionUncomplicated Plasmodium falciparum Malaria
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals1
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressamina.salim@iqvia.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantQuinter Atieno
      • declaration_date129-11-2023
      • declaration_principal_investigatorDr Bernhards Ogutu
      • declaration_date229-11-2023
      • placebo_presentNo
      • study_objectives<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: \" title=\"Synopsis\" trebuchet=\"\">\n <thead>\n <tr>\n <th style=\"padding: 4px 5px; line-height: 20px; text-align: left; vertical-align: bottom; border-top: 0px; width: 264px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Objectives</strong></p>\n </th>\n <th style=\"padding: 4px 5px; line-height: 20px; text-align: left; vertical-align: bottom; border-top: 0px; width: 342px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Endpoints</strong></p>\n </th>\n </tr>\n </thead>\n <tbody>\n <tr>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 606px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Primary</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: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate the safety of meplazumab in an adult population with uncomplicated, symptomatic <em>P. falciparum</em> infection</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Incidence and severity of AE</li>\n <li style=\"line-height: 20px;\">\n Incidence of (number of participants with):\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 0px 25px;\">\n <li style=\"line-height: 20px;\">\n Drug-related SAE</li>\n <li style=\"line-height: 20px;\">\n All-cause SAE</li>\n <li style=\"line-height: 20px;\">\n Drug-related AESI</li>\n <li style=\"line-height: 20px;\">\n All-cause AESI</li>\n <li style=\"line-height: 20px;\">\n Participants discontinuation/ withdrawals due to AE</li>\n </ul>\n </li>\n </ul>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 606px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Secondary</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: 264px; height: 50px;\">\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 meplazumab as defined by\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 0px 25px;\">\n <li style=\"line-height: 20px;\">\n Early treatment failure</li>\n <li style=\"line-height: 20px;\">\n Late clinical failure</li>\n <li style=\"line-height: 20px;\">\n Late parasitological failure</li>\n <li style=\"line-height: 20px;\">\n Uncorrected ACPR</li>\n </ul>\n </li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px; height: 50px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Incidence (number of participants with) of early treatment failure</li>\n <li style=\"line-height: 20px;\">\n Incidence of late clinical failure</li>\n <li style=\"line-height: 20px;\">\n Incidence of late parasitological failure</li>\n <li style=\"line-height: 20px;\">\n Incidence of uncorrected ACPR at Day 28</li>\n </ul>\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: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate PRR</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n PRR at 72h</li>\n </ul>\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: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To determine the recrudescence (see Section 9.3.7) and re-infection (see Section 9.3.7)</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Incidence of (number of participants with) recrudescence and re-infection at Week 4</li>\n <li style=\"line-height: 20px;\">\n Time to recrudescence and re-infection at Week 4</li>\n </ul>\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: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To determine the time to relief of fever</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n FCT at 72h</li>\n </ul>\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: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To determine the dose-response trend relationship between 3 dose levels of meplazumab by evaluation of safety, efficacy and ACPR outcomes</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Dose-response trend relationship between the 3 dose levels of meplazumab, based on change from baseline in the summary of the safety and efficacy outcomes to Week 4</li>\n </ul>\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: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate the pharmacokinetics of meplazumab in serum</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Meplazumab serum concentration-time profiles and PK parameters including but not limited to C<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">max</span>, t<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">max</span>, AUC<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">(0-last)</span>, AUC<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">(0-inf)</span>, t<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">½</span>, CL, V<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">z</span>, and V<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">ss</span></li>\n </ul>\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: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate immunogenicity following meplazumab administration</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Frequency of confirmed ADA response, ADA titers, and neutralizing activity</li>\n </ul>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 606px;\">\n <p style=\"margin: 0px 0px 10px;\">\n <strong>Exploratory</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: 264px; height: 45px;\">\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 meplazumab by PCR-corrected ACPR</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px; height: 45px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Incidence of (number of participants with) PCR‑corrected ACPR at Week 4</li>\n </ul>\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: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate RO (%) of meplazumab in red blood cells following single dose administration</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Meplazumab RO%-time profiles, pharmacodynamic parameters determined for RO including but not limited to maximum RO% and duration RO% (RO% half-life)</li>\n </ul>\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: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To quantify the levels of complement regulatory proteins, the deposition of complement on  erythrocytes, and serum complement activation in human subjects treated with meplazumab.</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Cell-surface expression of complement regulatory proteins and presence of complement products measured by flow cytometry; and complement activation measured by ELISA kit</li>\n </ul>\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: 264px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n To evaluate the relationship between exposure to meplazumab and key efficacy and/or safety parameters</li>\n </ul>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top: 1px solid rgb(221, 221, 221); width: 342px;\">\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px;\">\n <li style=\"line-height: 20px;\">\n Graphical (and statistical, if appropriate) display of exposure versus response</li>\n </ul>\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 Abbreviations: ACPR=adequate clinical & parasitological response; ADA=anti-drug antibodies; AE=adverse event; AESI=adverse event of special interest; AUC<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">(0‑inf)</span>=area under the concentration‑time curve extrapolated to infinity; AUC<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">(0‑last)</span>=area under the concentration‑time curve to the last quantifiable concentration; CL=systemic clearance; C<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">max</span>=maximum concentration; FCT=fever clearance time; polymerase chain reaction PCR=polymerase chain reaction; <em>P. falciparum</em>=<em>Plasmodium falciparum</em>; PRR=parasite reduction rate; RO=receptor occupancy; SAE=serious adverse event; t<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">½</span>=elimination half‑life; t<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">max</span>=time to C<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">max</span>; V<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">z</span>=volume of distribution; V<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; bottom: -0.25em;\">ss</span>=volume at steady state.</p>\n
      • principal_inclusion_criteria<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Participants are eligible to be included in the study only if all 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 Ability to provide informed consent signed by the study participant or legally authorized representative</li>\n <li style=\"line-height: 20px;\">\n Adults 18 to 55 years at the time of signing the informed consent form (ICF)</li>\n <li style=\"line-height: 20px;\">\n Female participants are eligible to participate if they do not qualify as a woman of childbearing potential (WOCBP), as defined in Section 10.4.</li>\n <li style=\"line-height: 20px;\">\n Male participants who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception as described in Section 10.4.</li>\n <li style=\"line-height: 20px;\">\n BMI ≥18 to ≤30 kg/m<span style=\"position: relative; font-size: 9.375px; line-height: 0; vertical-align: baseline; top: -0.5em;\">2</span></li>\n <li style=\"line-height: 20px;\">\n Mono-infection with <em>P. falciparum</em> documented by:</li>\n</ol>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Microscopically confirmed parasite infection using Giemsa-stained thick film (refer to the laboratory manual for details) consisting of 1000 – 100,000 asexual parasites /µL of blood <strong><u>and</u></strong></li>\n <li style=\"line-height: 20px;\">\n Documented fever (≥38.0°C oral, rectal or tympanic; ≥37.5°C axillary) or documented history of fever in previous 24 hours</li>\n</ul>\n
      • principal_exclusion_criteria<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Participants are NOT eligible to be included in the study if any of the following exclusion 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 Presence of severe malaria (as defined by World Health Organization Guidelines for Malaria 16 February 2021).</li>\n</ol>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Severe falciparum malaria is defined as one or more of the following, occurring in the absence of an identified alternative cause and in the presence of <em>P. falciparum</em> asexual parasitemia.\n <ul style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 0px 25px;\">\n <li style=\"line-height: 20px;\">\n Impaired consciousness: A Glasgow coma score <11 in adults</li>\n <li style=\"line-height: 20px;\">\n Prostration: Generalized weakness so that the person is unable to sit, stand or walk without assistance</li>\n <li style=\"line-height: 20px;\">\n Multiple convulsions: More than 2 episodes within 24 h</li>\n <li style=\"line-height: 20px;\">\n Acidosis: A base deficit of >8 mEq/L or, if not available, a plasma bicarbonate level of <15 mmol/L or venous plasma lactate ≥5 mmol/L. Severe acidosis manifests clinically as respiratory distress (rapid, deep, labored breathing).</li>\n <li style=\"line-height: 20px;\">\n Hypoglycemia: Blood or plasma glucose <2.2 mmol/L (<40 mg/dL)</li>\n <li style=\"line-height: 20px;\">\n Severe malarial anemia: Hemoglobin concentration ≤7 g/dL or a hematocrit of ≤20% in adults with a parasite count >10,000/μL</li>\n <li style=\"line-height: 20px;\">\n Renal impairment: Plasma or serum creatinine >265 μmol/L (3 mg/dL) or blood urea >20 mmol/L</li>\n <li style=\"line-height: 20px;\">\n Jaundice: Plasma or serum bilirubin >50 μmol/L (3 mg/dL) with a parasite count >100,000/ μL</li>\n <li style=\"line-height: 20px;\">\n Pulmonary edema: Radiologically confirmed or oxygen saturation <92% on room air with a respiratory rate >30/min, often with chest indrawing and crepitations on auscultation</li>\n <li style=\"line-height: 20px;\">\n Significant bleeding: Including recurrent or prolonged bleeding from the nose, gums or venepuncture sites; hematemesis or melena</li>\n <li style=\"line-height: 20px;\">\n Shock: Compensated shock is defined as capillary refill ≥3 s or temperature gradient on leg (mid to proximal limb), but no hypotension. Decompensated shock is defined as systolic blood pressure <80 mmHg in adults, with evidence of impaired perfusion (cool peripheries or prolonged capillary refill).</li>\n <li style=\"line-height: 20px;\">\n Hyperparasitemia: <em>P. falciparum</em> parasitemia >10%</li>\n </ul>\n </li>\n</ul>\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 Antimalarial treatment (alone or in combination) during the following periods before Screening:</li>\n</ol>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Piperaquine, mefloquine, naphthoquine or sulfadoxine-pyrimethamine within 6 weeks prior to Screening.</li>\n <li style=\"line-height: 20px;\">\n Amodiaquine, chloroquine within 4 weeks prior to Screening.</li>\n <li style=\"line-height: 20px;\">\n Any artemisinin derivative (artesunate, artemether or dihydroartemisinin), quinine, lumefantrine or any other antimalarial treatment or antibiotic with antimalarial activity (including cotrimoxazole, tetracyclines, quinolones and fluoroquinolones and azithromycin) within 14 days prior to Screening.</li>\n <li style=\"line-height: 20px;\">\n Any herbal products or traditional medicines, within the past 7 days.</li>\n</ul>\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 Previous participation in any malaria vaccine study or received malaria vaccine within 3 months of Screening Visit.</li>\n <li style=\"line-height: 20px;\" value=\"4\">\n Known allergy to any study medication, including allergy to any component of protocol prescribed rescue treatment i.e., country-specific ACT regimen.</li>\n <li style=\"line-height: 20px;\" value=\"5\">\n Any clinically important illness as judged by the investigator, including but not limited to a history of clinically significant chronic respiratory disease (eg, chronic obstructive pulmonary disease [COPD] or asthma), medical/surgical procedure, or trauma within 4 weeks of the first administration of investigational product.</li>\n <li style=\"line-height: 20px;\" value=\"6\">\n Participants participate in another clinical study. There will be a need for washout with 5 half-lives depending on the study treatment or 30 days, whichever is longer.</li>\n <li style=\"line-height: 20px;\" value=\"7\">\n Use of anti-cancer, anti-transplant rejection, or immunomodulatory biological drug or kinase inhibitor (e.g., tocilizumab, sarilumab) or Janus kinase inhibitors (within 30 days of enrollment or 5 times the half-life [whichever is longer]).</li>\n <li style=\"line-height: 20px;\" value=\"8\">\n  Systemic administration of corticosteroids (PO/IV/IM) at a dose of ≥20 mg/day of prednisone or equivalent for more than 14 consecutive days within 90 days prior to informed consent. Topical, inhaled, and intranasal corticosteroids are permitted. Intermittent use (one dose in 30 days) of intra-articular corticosteroids are also permitted.</li>\n <li style=\"line-height: 20px;\" value=\"9\">\n Live (live-attenuated) vaccines are not permitted within 2 weeks prior to study treatment or during the study treatment and safety follow-up periods.</li>\n <li style=\"line-height: 20px;\" value=\"10\">\n Presence of Hepatitis A IgM, Hepatitis B surface antigen, or Hepatitis C antibody, or Anti-HIV1 and/or HIV2 antibody , or Rapid Plasma Reagin test positive for syphilis..</li>\n <li style=\"line-height: 20px;\" value=\"11\">\n TBL >1.5 × ULN, ALT >2 × ULN, or AST >2 × ULN.</li>\n <li style=\"line-height: 20px;\" value=\"12\">\n Hematocrit <20%, hemoglobin <70 g/L (<7 g/dL), or white blood count >15,000/μL.</li>\n <li style=\"line-height: 20px;\" value=\"13\">\n Creatinine >1.5 × ULN.</li>\n</ol>\n
      • primary_end_points<p font-size:=\"\" style=\"margin: 0px 0px 10px 18pt; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n ·       Incidence and severity of AE</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 18pt; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n ·       Incidence of (number of participants with):</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 54pt; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n o   Drug-related SAE</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 54pt; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n o   All-cause SAE</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 54pt; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n o   Drug-related AESI</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 54pt; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n o   All-cause AESI</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 54pt; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n o  Participants discontinuation/ withdrawals due to AE</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • 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_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p>\n                                                                     <strong><u>AHERO CLINICAL TRIALS UNIT</u></strong></p>\n<p>\n                                                    <strong><u>INFORMATION ON   SITE CAPACITY</u></strong></p>\n<p>\n Ahero Clinical Trials Unit site is located within the Ahero county hospital in Nyando Sub- County, Kisumu County. Ahero County Hospital is level 4 hospital, with a bed capacity of 40, which receives referral from surrounding peripheral health facilities within Nyando Sub County, and is able to accommodate both outpatient and in-patient adults and pediatric patients for several days.     </p>\n<p>\n  </p>\n<p>\n <strong><u>Staffing [ Human Workforce</u></strong>]</p>\n<p>\n The hospital has a total staff of over 100 health workers including, 2 Medical Officers,15 Clinical Officers,1 Pharmacist, 6 pharmaceutical technologists, Laboratory technologists and 40 Nurses.</p>\n<p>\n The Study Site in addition has: 2 Pediatricians,1 Medical Officer,4 Clinical officers,6 nurses,</p>\n<p>\n 2Study Coordinators,2 Pharmacist ,1 Pharmaceutical technologist ,1 Pharmaceutical technician, 1Field Coordinator, 2 Field Supervisors, 22 Community health workers, 1Data Manager,4 Data Clerks, 5 Laboratory technologist ,1 laboratory technician and microscopists with certificate for malaria microscopy proficiency testing (PT), regulatory officers, quality assurance officers and administrative officer. Some of our investigators are also part of Ethical Committee at SERU.</p>\n<p>\n  </p>\n<p>\n <strong><u>Institutional facilities</u></strong></p>\n<p>\n Ahero Clinical Trials Unit which is within the Ahero County Hospital is mainly used for research related activities including clinical trials. It holds clinical rooms, emergency room with a fully equipped crash cart, temperature controlled pharmacy and laboratory, data room with stable internet connectivity for 24hours, Active Archival storage space and monitoring room.</p>\n<p>\n There are also several facilities within the hospital, which complement research activities. These include:</p>\n<ul>\n <li>\n An ISO 15189:2012 accredited laboratory which is well-equipped and that handles both routine and specialized tests including, biochemistry, hematology and microbiology.</li>\n <li>\n Adult and Pediatric wards that can accommodate any admission referral from the study</li>\n <li>\n Vital signs equipment is available in both the out-patient and in-patient departments and at the Ahero Clinical Trials Unit site. The study site has also 1 ECG machine as well.</li>\n <li>\n Continuous supply of oxygen from commercial supply from bulk oxygen cylinder.</li>\n</ul>\n<p>\n <strong><u>Waste Management and Handling.</u></strong></p>\n<p>\n The site has established protocols for waste handling and disposal. This is based on sorting the waste according to the different biohazard level. The waste is then disposed according to protocol. There is an incinerator at the hospital to assist in the proper destruction and disposal of the waste.</p>\n<p>\n <strong><u>Quality assurance policies and protocols.</u></strong></p>\n<p>\n The site has quality assurance SOPs that it follows for all its procedures. The staff are well trained and refresher courses are offered on a regular basis. Quality control / quality assurance checks and source data verification happens on the three major levels: </p>\n<p>\n Level 1 – Self Quality Check: Done on completion of study procedures while still seated with the participant</p>\n<p>\n Level 2 – Quality Control Check: Which entails QC checks that will be performed by the clinic QA officer/MO/SSC on a real-time basis and any errors picked will be addressed there and then.</p>\n<p>\n Level 3 – Quality Assurance Check: Done level are done at the data entry center by the data entry team during the receiving of the data from the field, clinics and during entry into the data base system to assure completeness and legibility.</p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n
      • other_details_explanation<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">No</span></p>\n
      • other_details_regulatory_notapproved<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Rwanda Food and Drug Authority-3 November 2023</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Ghana Food and Drug Authority-17 October 2023</p>\n
      • other_details_regulatory_approved<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">No Approvals received yet.</span></p>\n
      • other_details_regulatory_rejected<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">Not Applicable</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_duration2 years
      • design_controlled_randomised
      • design_controlled_open
      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
      • design_controlled_cross_over
      • design_controlled_other
      • design_controlled_specify
      • design_controlled_comparator
      • design_controlled_other_medicinal
      • design_controlled_placebo
      • design_controlled_medicinal_other
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states4
      • number_of_sites3
      • multi_country_listRwanda \nGhana \nGabon
      • data_monitoring_committeeYes
      • total_enrolment_per_siteRecruitment is competitive between sites and countries. There are no minimum or maximum number per site.
      • total_participants_worldwide60
      • 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_elderlyNo
      • 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_nameBernhards
      • investigator1_middle_name
      • investigator1_family_nameOgutu
      • investigator1_qualificationMedical Doctor
      • investigator1_professional_addressAHERO CLINICAL TRIALS UNIT, Ahero County Hospital, Nairobi, Kenya
      • investigator1_telephone+254733812613
      • investigator1_emailOgutu6@gmail.com
      • organisations_transferred_Yes
      • number_participants9 participants
      • notification
      • approval_date05-02-2024
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted29-11-2023
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-03-14 19:59:03
      • created2023-11-07 15:22:30
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id994
        • application_id1344
        • given_nameBernhards
        • middle_name
        • family_nameOgutu
        • qualificationMedical Doctor
        • professional_addressAHERO CLINICAL TRIALS UNIT, Ahero County Hospital, Nairobi, Kenya
        • telephone+254733812613
        • emailOgutu6@gmail.com
        • created2023-11-07 15:30:26
        • modified2023-11-29 16:46:03
    • SiteDetail(array)
      • 0(array)
        • id1622
        • application_id1344
        • county_id42
        • site_nameAHERO CLINICAL TRIALS UNIT
        • physical_addressHOUSED WITHIN AHERO COUNTY HOSPITAL, PO BOX 54,40100 KISUMU, ALONG KISUMU NAIROBI HIGHWAY FIELD SITE FOR CENTRE FOR RESEARCH IN THERAPEUATIC SCIENCES
        • contact_details+254733812613
        • contact_personDr. Bernhards Ogutu
        • site_capacity(null)
        • misc(null)
        • created2023-11-07 15:30:26
        • modified2023-11-29 16:46:03
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 1(array)
        • id1623
        • application_id1344
        • county_id42
        • site_nameVictoria Biomedical Research Institute (VIBRI)
        • physical_addressKisumu County Referral Hospital, off Ang’awa Avenue, P O Box 7180-40100, Kisumu, Kenya
        • contact_details+254 720 597654
        • contact_personDr Lucas Otieno Tina
        • site_capacity(null)
        • misc(null)
        • created2023-11-07 15:46:06
        • modified2023-11-29 16:46:03
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 2(array)
        • id1624
        • application_id1344
        • county_id41
        • site_nameKenya Medical Research Institute(KEMRI):Siaya Clinical Research Annex
        • physical_addressKEMRI Clinical Research Annex, Within Siaya County Referral Hospital Ground. P.O BOX 144-40600 ,Siaya, Kenya
        • contact_details+254724522474
        • contact_personDr Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2023-11-07 15:46:06
        • modified2023-11-29 16:46:03
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
    • Sponsor(array)
      • 0(array)
        • id706
        • application_id1344
        • sponsorJiangsu Pacific Meinuoke Biopharmaceutical Co. Ltd.(PMBP)
        • sponsor_typeIndustry
        • contact_personXiaochun Chen
        • addressNo. 128 Hehai West Road, Xinbei District, Changzhou, 213022, Jiangsu People’s Republic of China
        • telephone_number+86 15851999825
        • fax_number
        • cell_number0519-68889888
        • email_addresscxc@pmbp.cn
        • created2023-11-07 15:30:26
        • modified2023-11-29 16:46:03
  • 3(array)
    • Application(array)
      • id1178
      • user_id693
      • trial_status_id6
      • abstract_of_study<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>B</strong><strong>a</strong><strong>c</strong><strong>k</strong><strong>g</strong><strong>r</strong><strong>o</strong><strong>und</strong><strong>:</strong></p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Sickle cell disease (SCD) is a serious and life-threatening inherited hemoglobin (Hb) disorder caused by a single amino acid substitution in the beta (β)-globin gene (β s c.20A>T; rs334). Sickle cell disease affects millions of people worldwide. The homozygous form (HbSS) occurs in most cases and represents approximately 88% to 96% in certain areas of Africa. Preliminary data indicate that mitapivat may reduce Hemoglobin S polymerization, sickling, and hemolysis. Therefore, in this study mitapivat is a therapeutic candidate for the treatment of adult patients with SCD with the potential to provide clinical benefit by both improvement of anemia and reduction in sickle cell pain crises (SCPCs).</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n The only current curative treatment approach for some patients with SCD is bone marrow transplant. However, a lack of histocompatible donors, concerns about transplantrelated morbidity and mortality, and pre-existing conditions (organ dysfunction or alloimmunization) often preclude patients from pursuing this treatment option. For decades, hydroxyurea was the only disease-modifying therapy available for patients with SCD. Hydroxyurea is indicated to reduce the frequency of painful crises; however, its use  is limited by its safety profile, which includes myelosuppression (neutropenia and thrombocytopenia) and gastrointestinal toxicity. Reduced fertility has been reported as a longterm adverse effect.</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>J</strong><strong>u</strong><strong>s</strong><strong>t</strong><strong>i</strong><strong>f</strong><strong>i</strong><strong>c</strong><strong>a</strong><strong>t</strong><strong>i</strong><strong>o</strong><strong>n</strong><strong>/</strong><strong>R</strong><strong>a</strong><strong>t</strong><strong>i</strong><strong>o</strong><strong>n</strong><strong>a</strong><strong>l</strong><strong>e</strong><strong>:</strong></p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n The use  of curative options for SCD is currently limited to a small subgroup of patients who are deemed fit for bone marrow transplantation and have available donors. The treatment options for SCD are not universally effective or globally available, tend to address only a single component of the disease, or are limited by their safety profile. Therefore, a significant unmet medical need exists for safe and effective therapies for the treatment of SCD that result in both an improvement in anemia and reduction in sickle cell–related crises.</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Mitapivat is a small molecule, oral activator of wild-type (WT) and mutant forms of the RBC-specific form of pyruvate kinase (PKR). Activation of PKR has potential application in the treatment of hemolytic anemias, including SCD, which are characterized by increased metabolic demands or by defects in glycolysis that contribute to the shortened life span of the RBC. Decreases in PKR function, exemplified in patients with pyruvate kinase deficiency, leads to dysfunctional RBCs that are characterized by defective glycolysis, including a build-up of 2,3-DPG and PEP with decreased levels of ATP. However, there is evidence that the activation of the normal (WT) PKR enzyme can play a role in other hemolytic anemias such  as SCD.</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>Main Objectives: Phase 2:</strong></p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n 1. To determine the recommended Phase 3 dose of mitapivat by evaluating the effect of 2 dose levels of mitapivat versus placebo on:</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n • Anemia in subjects with sickle cell disease (SCD)</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n • Safety</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Phase 3: 1. To determine the effect of mitapivat versus placebo on:</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n • Anemia in subjects with sickle cell disease (SCD)</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n • Sickle cell pain crises (SCPCs) in subjects with SCD</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>Secondary objectives:</strong></p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>Pha</strong><strong>se </strong><strong>2</strong><strong>:</strong></p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n 1. To evaluate the effect of 2 doses of mitapivat versus placebo on:</p>\n<ul>\n <li style=\"margin: 0px 0px 10px 29.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <img height=\"4\" src=\"file:///C:/Users/kimettjc/AppData/Local/Temp/msohtmlclip1/01/clip_image001.gif\" style=\"height: auto; max-width: 100%; vertical-align: middle; border: 0px;\" width=\"4\" />Anemia</li>\n <li style=\"margin: 0px 0px 10px 29.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <img height=\"4\" src=\"file:///C:/Users/kimettjc/AppData/Local/Temp/msohtmlclip1/01/clip_image002.gif\" style=\"height: auto; max-width: 100%; vertical-align: middle; border: 0px;\" width=\"4\" />Markers of hemolysis and erythropoiesis</li>\n <li style=\"margin: 0px 0px 10px 29.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <img height=\"4\" src=\"file:///C:/Users/kimettjc/AppData/Local/Temp/msohtmlclip1/01/clip_image003.gif\" style=\"height: auto; max-width: 100%; vertical-align: middle; border: 0px;\" width=\"4\" />Patient-reported fatigue</li>\n <li style=\"margin: 0px 0px 10px 29.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <img height=\"4\" src=\"file:///C:/Users/kimettjc/AppData/Local/Temp/msohtmlclip1/01/clip_image004.gif\" style=\"height: auto; max-width: 100%; vertical-align: middle; border: 0px;\" width=\"4\" />Sickle cell pain crises (SCPCs)</li>\n</ul>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n 2. To evaluate the pharmacokinetic and pharmacodynamic effects of mitapivat.</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>Pha</strong><strong>se </strong><strong>3</strong><strong>:</strong></p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n 1. To evaluate the effect of mitapivat versus placebo on:</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n • Anemia in subjects with SCD</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n • Markers of hemolysis</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n • Markers of erythropoiesis</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n • Patient-reported fatigue</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n • Additional clinical efficacy measures related to SCPC</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>Methods:</strong></p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>Ove</strong><strong>rall Study </strong><strong>d</strong><strong>e</strong><strong>s</strong><strong>i</strong><strong>g</strong><strong>n</strong></p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n This is a Phase 2/3, double-blind, randomized, placebo-controlled, global, multicenter study evaluating the efficacy and safety of mitapivat versus placebo in subjects with SCD using an operationally seamless design. The Phase 2 portion is a double-blind, randomized, placebo-controlled, dose-finding study evaluating 2 dose levels of mitapivat (50 mg BID and 100 mg BID) versus placebo to select the dose of mitapivat to be evaluated in the Phase 3 portion. The Phase 3 portion is a double-blind, randomized, placebo-controlled study evaluating the efficacy and safety of mitapivat at the selected Phase 3 dose versus placebo. Subjects who complete the Double-blind Period in eitherthe Phase 2 or Phase 3 portion will have the option to receive mitapivat in the Open-label Extension Period. A total of 267 subjects (69 in Phase 2 and 198 in Phase 3)</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n will be randomized in this study. The initiation of the Phase 3 portion will be based on prespecified go/no-go criteria and dose selection criteria. Subjects who participate in the</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n Phase 2 portion of the study are not eligible to participate in the Phase 3 portion of the study.</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>Study outcomes:</strong></p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n The primary outcome, or endpoint, for the phase 2 study is hemoglobin (Hb) response, defined as a ≥1.0 g/dL increase in average Hb concentration from Week 10 through Week 12 compared with baseline and safety defined as adverse events (AEs) and serious adverse events (SAEs). The primary outcome for the phase 3 study is Hemoglobin (Hb) response, defined as a ≥1.0 g/dL increase in average Hb concentration from Week 24 through Week 52 compared with baseline and annualized rate of sickle cell pain crises (SCPCs) in subjects with SCD.</p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <strong>S</strong><strong>tudy </strong><strong>du</strong><strong>r</strong><strong>a</strong><strong>t</strong><strong>i</strong><strong>o</strong><strong>n</strong><strong>:</strong></p>\n<p style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n The duration of participation of a subject in the Phase 2 portion is up to 4.5 years (236 weeks). The duration of participation of a subject in the Phase 3 portion is up to 5.3 years (276 weeks). The end of the study is defined as the time at which all subjects complete all study visits, are lost to follow-up, have withdrawn consent for further participation in the study, or when the Sponsor terminates the study.</p>\n
      • study_title<p>\n <span style=\"color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">A Phase 2/3, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Mitapivat in Subjects With Sickle Cell Disease. Mitapivat - AG348-C-020</span></p>\n
      • laymans_summary<table class=\"table table-condensed\" style=\"max-width: 100%; border-collapse: collapse; border-spacing: 0px; width: 915.271px; margin-bottom: 20px; color: rgb(51, 51, 51); font-family: "Trebuchet MS", Tahoma, Verdana, Arial, sans-serif; font-size: 12.5px;\">\n <thead>\n <tr>\n <th class=\"table-label required\" style=\"padding: 4px 15px 4px 5px; line-height: 20px; text-align: left; vertical-align: bottom; border-top: 0px; color: rgb(0, 112, 0); width: 895.271px;\">\n <h5 style=\"margin: 10px 0px; font-family: inherit; line-height: 20px; color: inherit; text-rendering: optimizelegibility; font-size: 14px; text-align: center;\">\n Laymans Summary: <span class=\"sterix\" style=\"color: red;\">*</span></h5>\n </th>\n </tr>\n </thead>\n <tbody>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221);\">\n <p style=\"margin: 0px 0px 10px;\">\n Sickle cell disease (SCD) is an inherited blood disorder where the red blood cells, which carry oxygen around the body, develop abnormally and become rigid and shaped like a crescent (sickle shape). Sickle cell disease affects millions of people worldwide and is very common in certain areas of Africa. This study will look at a possible drug for treatment of Sickle cell disease called Mitapivat. Results from earlier studies with mitapivat shows that it may reduce the change of shape in red blood cells which makes them look like a sickle and causes the red blood cells to be destroyed resulting in a person with sickle cell disease getting low blood level (anemia). Therefore, in this study mitapivat is a drug candidate for the treatment of adult patients with sickle cell disease with the potential to provide clinical benefit by both improvement of anemia and reduction in sickle cell pain crisis.</p>\n <p style=\"margin: 0px 0px 10px;\">\n  </p>\n <p style=\"margin: 0px 0px 10px;\">\n This study has both a Phase 2 and a Phase 3. The main aim of the Phase 2 portion of the study is to define how mitapivat works in the short term, how safe it is and the right dose which will be selected for the Phase 3 portion of the study. The aim of the Phase 3 portion of the study is to assess the how well the selected dose of mitapivat works for treatment and how safe it when used in patients with sickle cell disease. This portion of the study is intended to show the extent to which mitapivat treatment reduces painful crisis because of blocked blood vessels and reduces anemia in sickle cell disease. In this Phase2/3 study, both the participant and most study staff including the doctors don’t know which treatment has been given to the participant (referred to as doubleblind). One group of study participants called the treatment group will receive the mitapivat and another group called the control group will receive a study treatment with no active ingredient called a placebo.</p>\n <p style=\"margin: 0px 0px 10px;\">\n  </p>\n <p style=\"margin: 0px 0px 10px;\">\n The study is being done in different countries around the world, in multiple study centers in participants with SCD. The Phase 2 portion dose-finding study will assess 2 dose levels of mitapivat (50 mg twice a day and 100 mg twice a day) versus placebo to select the dose of mitapivat to be evaluated in the Phase 3 portion. The Phase 3 portion is a double-blind, randomized, placebo-controlled study evaluating how effective and safe mitapivat is at the selected Phase 3 dose versus placebo. Participants who complete the Double-blind Period in the Phase 2/3 portion will have the option to receive mitapivat in the non-blinded (Open label) Extension Period. Approximately 267 participants (69 in Phase 2 and 198 in Phase 3) are planned to be enrolled in this study worldwide. In Kenya there are 7 sites ,3 sites in Nairobi,1 in western and 3 in Nyanza. Enrollment is competitive world wide.</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • short_titleAgios Study
      • protocol_noECCT/22/10/05
      • version_noAmendment 1 (V1.0)
      • date_of_protocol09-03-2022
      • study_drugMitavpivat Dr Nduba Siaya and Nairobi site
      • disease_conditionSickle Cell Disease
      • 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_nameMitapivat
      • 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_applicantMillicent.Aketch
      • declaration_date128-10-2022
      • declaration_principal_investigatorDr Ogutu Bernhards
      • declaration_date228-10-2022
      • placebo_presentYes
      • study_objectives<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Main objective:</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Phase 2:</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 1. To determine the recommended Phase 3 dose of mitapivat by evaluating the effect of 2 dose levels of mitapivat versus placebo on</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n : • Anemia in subjects with sickle cell disease (SCD). and</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 Safety </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 <strong>Safety Phase 3:</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 1. To determine the effect of mitapivat versus placebo on</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n : • Anemia in subjects with sickle cell disease (SCD)</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n • Sickle cell pain crises (SCPCs) in subjects with SCD</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Secondary objectives:</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Phase 2</strong>:</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 1. To evaluate the effect of 2 doses of mitapivat versus placebo on:</p>\n<ul>\n <li font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n Anemia</li>\n <li font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n Markers of hemolysis and erythropoiesis</li>\n <li font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n Patient-reported fatigue</li>\n <li font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n Sickle cell pain crises (SCPCs)</li>\n</ul>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 2. To evaluate the pharmacokinetic and pharmacodynamic effects of mitapivat.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Phase 3</strong>:</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 1. To evaluate the effect of mitapivat versus placebo on:</p>\n<ul>\n <li font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n Anemia in subjects with SCD</li>\n <li font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n Markers of hemolysis Markers of erythropoiesis</li>\n <li font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n Patient-reported fatigue</li>\n <li font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n Additional clinical efficacy measures related to SCPC</li>\n</ul>\n
      • principal_inclusion_criteria<p font-size:=\"\" style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 1. Age ≥16 years; subjects age 16 or 17 years must physically have completed puberty.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 2. Documented diagnosis of SCD (HbSS, HbSC, HbS/β0-thalassemia, HbS/β+ thalassemia, or other sickle cell syndrome variants).</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  3. At least 2 sickle cell pain crises (SCPCs) and no more than 10 SCPCs in the past 12 months.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  4. Hemoglobin ≥5.5 and ≤10.5 g/dL.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  5. If taking hydroxyurea, the hydroxyurea dose must be stable for at least 90 days before starting study drug.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  6. Women capable of becoming pregnant and men with partners who are women that are capable of becoming pregnant must agree to use  2 forms of contraception.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 7. Other protocol-defined inclusion criteria may apply</p>\n
      • principal_exclusion_criteria<p font-size:=\"\" style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 1. Pregnant or breastfeeding.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px 5.9pt; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 2. Receiving regularly scheduled transfusions.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  3. Hepatobiliary disorders including but not limited to significant liver disease or gallbladder disease.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  4. Severe kidney disease.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  5. Prior exposure to gene therapy or prior bone marrow or stem cell transplantation.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  6. Currently receiving treatment for SCD (eg, voxelotor, crizanlizumab, L glutamine), with the exception of hydroxyurea. The last dose of such  therapies must have been administered at least 90 days before starting study drug.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  7. Currently receiving treatment with hematopoietic stimulating agents; the last dose must have been administered at least 90 days before starting study drug.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  8. Received treatment on another investigational trial within 90 days prior to start of study drug or plans to participate in another investigational drug trial.</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n  9. Taking medications that are strong inhibitors of CYP3A4/5 or strong inducers of CYP3A4 that cannot be stopped in an acceptable timeframe before starting study drug (timeframe will be discussed with your doctor).</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 10. Other protocol defined exclusion criteria may apply</p>\n
      • primary_end_points<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Phase 2 Primary Endpoints</strong>:</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 1. Percentage of participants with hemoglobin (Hb) response</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 2. Percentage of participants with treatment emergent adverse events (AEs) and treatment emergent serious adverse events (SAEs)</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Timepoint(s) of evaluation of this end point:</strong></p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Phase 2 primary endpoint of percentage of participants with Hb response: Week 12</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Phase 2 primary endpoint of percentage of participants with treatment emergent AEs and treatment emergent SAEs: Up to Week 12</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Phase 3 Primary Endpoints</strong>:</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 1. Percentage of participants with hemoglobin (Hb) response</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n 2. Annualized rate of Sickle Cell Pain Crises (SCPCs)</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <strong>Timepoint(s) of evaluation of this end point</strong>:</p>\n<ul font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Phase 3 primary endpoint of percentage of participants with Hb response: Week 52</li>\n <li style=\"line-height: 20px;\">\n Phase 3 primary endpoint of annualized rate of sickle cell pain crises:Up to Week 52</li>\n</ul>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • 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_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n <strong>KEMRI/CRDR clinical research Site</strong></p>\n<p>\n Site activities will take place within the KEMRI/CRDR clinical research annex. This facility has several clinical rooms available for consenting, nursing procedures, clinical exams and dosing. There are also additional facilities that include an inpatient ward, staff work areas and a monitoring space, a pharmacy, laboratory and kitchen for preparing participant meals.</p>\n<p>\n Site staff include the principal investigator, 4 medical officers, 2 pharmacists, 1 pharmtech, 5 nurses, 5 quality assurance officers, 3 clinical officers and 6 community health workers.</p>\n<p>\n <strong>Kisumu/SiayaSite</strong></p>\n<p>\n Site activities are located in Kisumu/Siaya and Nairobi Counties. Kisumu hosts the main IP storage site, administrative offices of the PI and co-investigators, procurement and Human Resource functions are housed at theKEMRI Kisian Campus. Recruitment, follow-up of study participants will occur in Siaya. KEMRI has a modern research annex at the Siaya county hospital with capacity to conduct phase I to Phase III studies. After community mobilization, screening and enrollment, IP dispensation will occur at the Siaya Clinical Research Annexe.</p>\n<p>\n Site investigators responsible for day to day running of the project include: Medical Officer 2, Pharmacist 1, Pharm tech 2, Nurses 5, Quality Assurance Officer 2, Quality Control 1, Clinical Officer 2, Community Interviewers 4.</p>\n<p>\n N/A</p>\n<p>\n All the 5 sites have been submitted.</p>\n
      • other_details_explanation<p>\n <strong font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">N/A</strong><span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">, trial is being conducted in the USA</span></p>\n
      • other_details_regulatory_notapproved<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" font-size:=\"\" style=\"max-width: 100%; border-collapse: collapse; border-spacing: 0px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <tbody>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 186px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px;\">\n  </p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 153px; height: 13px;\">\n <table border=\"1\" cellpadding=\"1\" cellspacing=\"1\" style=\"width:500px;\">\n <tbody>\n <tr>\n <td>\n Country </td>\n <td>\n Date submited </td>\n <td>\n status </td>\n <td>\n  </td>\n </tr>\n <tr>\n <td>\n kenya </td>\n <td>\n 01 Sep 2022_ 2 sites </td>\n <td>\n Pending approval </td>\n <td>\n  </td>\n </tr>\n <tr>\n <td>\n Kenya </td>\n <td>\n 14 Oct  2022 _ 1 site </td>\n <td>\n Pending Apprval</td>\n <td>\n  </td>\n </tr>\n <tr>\n <td>\n Egypt </td>\n <td>\n 13 Jun 2022</td>\n <td>\n Pending  Approval</td>\n <td>\n  </td>\n </tr>\n </tbody>\n </table>\n <p>\n  </p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 61px; height: 13px;\">\n  </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_regulatory_approved<p>\n  </p>\n<table class=\"table table-condensed\" font-size:=\"\" style=\"max-width: 100%; border-collapse: collapse; border-spacing: 0px; width: 915.271px; margin-bottom: 20px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n <tbody>\n <tr>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221);\">\n <table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" style=\"max-width: 100%; background-color: transparent; border-collapse: collapse; border-spacing: 0px;\">\n <tbody>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 110px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n Regualtory</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 103px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n Approval Date</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 186px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n Number of site per Country</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 110px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n Canada</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 103px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 16 Nov  2021</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 186px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 4</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 110px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n United Kingdom</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 103px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 13 Sep 2021</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 186px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 7</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 110px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n Belgium</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 103px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 16 Feb 2022</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 186px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 8</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 110px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n France</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 103px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 27 Jan 2022</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 186px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 6</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 110px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n Germany</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 103px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 07 Apr 2022</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 186px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 4</p>\n </td>\n </tr>\n <tr>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 110px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n Italy</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 103px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 23 Feb 2022</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 186px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 8</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 148px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n Regulatory Authority</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 90px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n Approved Date</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 161px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n Number of site per country</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 148px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n Netherlands</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 90px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 23 Dec 2021</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 161px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 1</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 148px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n Brazil</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 90px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 21 Jan 2022</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 161px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 8</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 148px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n Israel</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 90px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 09 Aug 2021</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 161px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 4</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 148px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n United States of America</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 90px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 26 May 2022</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 161px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px 0.55pt;\">\n 23</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 148px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Turkey</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 90px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 04 Jul 2022 </p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 161px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 5</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 148px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px;\">\n Saudia Arabia</p>\n </td>\n <td colspan=\"2\" style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 90px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 06Sep 2022</p>\n </td>\n <td style=\"vertical-align: top; padding: 4px 5px; line-height: 20px; border-top-style: solid; border-top-color: rgb(221, 221, 221); width: 161px; height: 13px;\">\n <p style=\"margin: 0px 0px 10px;\">\n 3</p>\n </td>\n </tr>\n </tbody>\n </table>\n <p style=\"margin: 0px 0px 10px;\">\n Nigeria _ 22 Aug 2022 - sites _6 </p>\n <p style=\"margin: 0px 0px 10px;\">\n Kenya _ 06 Sep  2022 _ sites approved 2 out of 7 .</p>\n <div>\n  </div>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_regulatory_rejected<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">No Regulatory authority nor Ethics Committee has rejected this trial</span></p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration9 years 10 months 0 days
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherYes
      • design_controlled_specifyThere is an open label extension period following completion of the double blind period.
      • 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_states17
      • number_of_sites7
      • multi_country_listBelgium Brazil Canada Egypt France Germany Israel Italy Kenya Lebanon Netherlands Nigeria Oman Saudi Arabia Turkey\nUnited Kingdom United States
      • data_monitoring_committeeYes
      • total_enrolment_per_siteNo maximum nor minimum enrolment per site as enrolment is competitive world wide
      • total_participants_worldwide267 for both phases(69 in Phase 2 and 198 in Phase 3)
      • 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_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_consentYes
      • subjects_specifyFor subjects under 18 Years of age written informed assent/consent will be obtained from parents and child assent. It must be obtained before any study-related procedures are conducted
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameBernhards
      • investigator1_middle_nameRagama
      • investigator1_family_nameOgutu
      • investigator1_qualificationMedical Doctor
      • investigator1_professional_addressStrathmore University Medical Centre_CREATES Madaraka Estate, Ole Sangale Road P.O Box 59857-00200 Nairobi
      • investigator1_telephone+254 733812613
      • investigator1_emailogutu6@gmail.com
      • organisations_transferred_Yes
      • number_participantsEnrolment is competitive world wide
      • notification
      • approval_date26-02-2023
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted16-12-2022
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonThe Approval is based on review of a similar study ECCT/22/10/02, alongside response of PI to reviewer comments.\n
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-04-29 21:47:03
      • created2022-10-14 11:33:51
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id853
        • application_id1178
        • given_nameVidelis
        • middle_nameN
        • family_nameNduba
        • qualificationMedical Doctor
        • professional_addressKEMRI-CRDR , Kenyata National Hospital
        • telephone+254724522474
        • emailvnduba@gmail.com
        • created2022-10-14 11:35:08
        • modified2022-12-16 22:48:30
    • SiteDetail(array)
      • 0(array)
        • id1322
        • application_id1178
        • county_id47
        • site_nameKEMRI/CRDR
        • physical_addressKenyatta National Hospital Off Hospital Road, CRDR
        • contact_detailsTel:+254790484654, P.O Box 47855-00100
        • contact_personProf. Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2022-10-14 11:35:08
        • modified2022-12-16 22:48:30
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 1(array)
        • id1324
        • application_id1178
        • county_id41
        • site_nameKEMRI Siaya Clinical Research Annex
        • physical_addressKEMRI Clinical research Annex,Siaya County Hospital,
        • contact_detailsTel: +254722205901, P.O Box 144-40600
        • contact_personProf. Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2022-10-31 08:28:02
        • modified2022-12-16 22:48:30
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
    • Sponsor(array)
      • 0(array)
        • id607
        • application_id1178
        • sponsorAgios Pharmaceuticals, Inc.
        • sponsor_typeIndustry
        • contact_personJamie Cohen
        • address88 Sidney Street Cambridge, MA 02139-4169 USA
        • telephone_number+1 617-844-6657
        • fax_number+1 617-588-0455
        • cell_number+1 617-844-6657
        • email_addressJamie.cohen@agios.com
        • created2022-10-14 11:35:08
        • modified2022-12-16 22:48:30
  • 4(array)
    • Application(array)
      • id1141
      • user_id745
      • trial_status_id1
      • abstract_of_study<p>\n <strong>Introduction:</strong></p>\n<p>\n Anemia among women of reproductive age is a stubborn problem in resource-poor countries.  Approximately 38% and 41% of non-pregnant women in Africa and SE Asia, respectively, are anemic (1).  In the two regions combined, this sums to approximately 270 million cases.  At least half of anemia cases are due to iron deficiency.  Iron deficiency is estimated to be the cause of 18% of maternal deaths worldwide (2); a 10g/L increase in hemoglobin reduces maternal mortality by 29% (3).  Ministries of Health in many resource-poor countries have established programs such as iron supplementation, improving diets, and preventing infectious and communicable diseases that lead to anemia.  Still, the labor-intensive programs and interventions have limited reach and are thus ineffective for hundreds of millions of women.  Multi-prong approaches are needed (4).</p>\n<p>\n The proposed study will take place in Nairobi, Kenya, which is a metropolis with more than three million inhabitants.  Nairobi has large slum areas with poor health conditions that are typical of many large capital cities in sub-Saharan Africa (5).  The national prevalence of anemia, iron-deficiency (corrected for inflammation), and iron-deficiency anemia among non-pregnant women in Kenya is 21.9%, 21.3%. and 14.0%, respectively (6).  In the lowest wealth quintiles of Kenyan society, characteristic of slum areas, the levels are 34.6%, 27.5%, and 20.8%, respectively.</p>\n<p>\n The scientific premise for the proposed work is that a contraceptive technology (the levonorgestrel intrauterine system- LNG IUS) has been shown to reduce menstrual blood loss and consequently, increase hemoglobin and serum ferritin levels in broad populations of non-anemic women (7).  Given what is known about the delicate balance between intake of dietary iron, iron absorption, and iron losses from menstruation, it is highly plausible that retention of iron from using the LNG IUS can become another prong in the strategies to help alleviate anemia.  Both the US Centers for Disease Control and Prevention and the World Health Organization confirm that women with iron deficiency anemia can safely use the LNG IUS (Category 1 on Medical Eligibility Criteria) (8, 9). </p>\n<p>\n <strong>Objectives:</strong></p>\n<p>\n The primary objective is t<span style=\"color: rgb(0, 0, 0); font-family: Calibri, sans-serif;\">o compare hemoglobin changes over time in the randomized arms: LNG IUS versus a </span><span style=\"color: rgb(0, 0, 0); font-family: Calibri, sans-serif; font-size: 11pt;\">Combined oral contraceptives (</span><span style=\"color: rgb(0, 0, 0); font-family: Calibri, sans-serif;\">COC) with ferrous fumarate tablets. </span><span style=\"color: rgb(0, 0, 0); font-family: Calibri, sans-serif;\">The secondary objectives are (1) </span>To compare serum ferritin changes over time in the randomized arms (2) <span style=\"color: rgb(0, 0, 0); font-family: Calibri, sans-serif; text-align: justify;\">To correlate changes in hemoglobin and serum ferritin to reported changes in menstrual blood loss (3) </span><span style=\"color: rgb(0, 0, 0); font-family: Calibri, sans-serif; text-align: justify;\">To assess and compare participants’ satisfaction with the two contraceptive products and (4) </span><span style=\"color: rgb(0, 0, 0); font-family: Calibri, sans-serif; text-align: justify;\">To monitor incidence of progression to severe anemia and compare randomized arms</span></p>\n<p class=\"TableParagraph\" style=\"margin: 0cm; font-size: 11pt; font-family: Calibri, sans-serif; color: rgb(0, 0, 0); text-align: justify; line-height: 12.45pt;\">\n  </p>\n<p class=\"TableParagraph\" style=\"margin: 0cm; font-size: 11pt; font-family: Calibri, sans-serif; color: rgb(0, 0, 0); text-align: justify; line-height: 12.45pt;\">\n <span lang=\"EN-US\"><o:p></o:p></span></p>\n<p class=\"TableParagraph\" style=\"margin: 0cm; font-size: 11pt; font-family: Calibri, sans-serif; color: rgb(0, 0, 0); text-align: justify;\">\n <span lang=\"EN-US\"><o:p></o:p></span></p>\n<p>\n <strong>Methods:</strong></p>\n<p>\n  </p>\n<p>\n This randomized controlled trial will examine and compare changes in hemoglobin among anemic women randomized to either the LNG IUS or an LNG/EE/ferrous fumarate COC.  The equal-allocation, open label study will be conducted at a single site in Nairobi, Kenya.  The primary hypothesis that the mean change in hemoglobin in the group assigned to the LNG IUS will be superior to the COC/ferrous fumarate (control) group by at least 4 g/L after 18-months of product use.  The study products are approved for use only as contraceptives and are available in Kenya; this study is not seeking regulatory approval for a new indication. </p>\n<p>\n Clinic staff will recruit approximately 600 anemic women aged 18-50 who are seeking contraception and have regular menses.  Participation will require two low hemoglobin values (87 to 126 g/L, inclusive) taken approximately 2-4 weeks apart.  After randomization, each participant will be followed for 18 months; blood samples will be collected at enrollment and every six months for measuring hemoglobin, serum ferritin and other markers.  Intention-to-treat principles and per protocol analyses will be used to measure and compare mean change in hemoglobin (primary endpoint) and serum ferritin (secondary endpoint) in the randomized groups.  All results will be examined in relation to incidence of acute inflammation, changes in menstruation, and any non-study use of supplemental iron.</p>\n<p>\n <strong>Utility: </strong></p>\n<p>\n <span style=\"color: rgb(0, 0, 0); font-family: Calibri, sans-serif;\">This study aims to determine whether the LNG IUS can raise hemoglobin and serum ferritin levels in a marginalized, anemic population</span></p>\n<p>\n  </p>\n<p>\n  </p>\n
      • study_title<p>\n <span lang=\"EN-US\" style=\"color: rgb(0, 0, 0); font-size: 16pt; font-family: Calibri, sans-serif;\">Levonorgestrel intrauterine system effects on hemoglobin and serum ferritin among anemic women in Kenya: An open label randomized trial to compare with an oral contraceptive regimen that provides supplemental ferrous fumarate tablets</span></p>\n
      • laymans_summary<p>\n <span style=\"color: rgb(0, 0, 0); font-family: Calibri, sans-serif; font-size: 21.3333px;\">Levonorgestrel intrauterine system effects on hemoglobin and serum ferritin among anemic women in Kenya</span></p>\n
      • short_titleLISA Trial
      • protocol_noECCT/22/09/02
      • version_no3.0
      • date_of_protocol03-03-2022
      • study_druglevonorgestrel, ethinyl estradiol and ferrous fumarate
      • disease_conditionAnemia
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device1
      • product_type_chemical_namelevonorgestrel, ethinyl estradiol and ferrous fumarate
      • product_type_medical_device_namelevonorgestrel-releasing intrauterine system
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressfthuita@uonbi.ac.ke
      • 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_applicantDr Faith Thuita
      • declaration_date101-09-2022
      • declaration_principal_investigatorDr Faith Thuita
      • declaration_date201-09-2022
      • placebo_presentNo
      • study_objectives<p class=\"TableParagraph\" style=\"margin: 0cm; font-size: 11pt; font-family: Calibri, sans-serif; color: rgb(0, 0, 0); line-height: 12.45pt;\">\n <strong><span lang=\"EN-US\">Primary Objective:</span></strong><span lang=\"EN-US\"><o:p></o:p></span></p>\n<p class=\"TableParagraph\" style=\"margin: 0cm; font-size: 11pt; font-family: Calibri, sans-serif; color: rgb(0, 0, 0); line-height: 12.45pt;\">\n <span lang=\"EN-US\">To compare hemoglobin changes over time in the randomized arms: LNG IUS versus COCs</span></p>\n<p class=\"TableParagraph\" style=\"margin: 0cm; font-size: 11pt; font-family: Calibri, sans-serif; color: rgb(0, 0, 0); line-height: 12.45pt;\">\n <span lang=\"EN-US\"><o:p></o:p></span></p>\n<p class=\"TableParagraph\" style=\"margin: 0cm; font-size: 11pt; font-family: Calibri, sans-serif; color: rgb(0, 0, 0); line-height: 12.45pt;\">\n  </p>\n<p class=\"TableParagraph\" style=\"margin: 0cm; font-size: 11pt; font-family: Calibri, sans-serif; color: rgb(0, 0, 0); line-height: 12.45pt;\">\n <strong><span lang=\"EN-US\">Secondary Objectives:</span></strong><span lang=\"EN-US\"><o:p></o:p></span></p>\n<p class=\"TableParagraph\" style=\"margin: 0cm 0cm 0cm 36pt; font-size: 11pt; font-family: Calibri, sans-serif; color: rgb(0, 0, 0); text-indent: -18pt; line-height: 12.45pt;\">\n <span lang=\"EN-US\" style=\"font-family: Symbol;\">·<span new=\"\" style=\"font-variant-numeric: normal; font-variant-east-asian: normal; font-stretch: normal; font-size: 7pt; line-height: normal; font-family: \" times=\"\">       </span></span><span lang=\"EN-US\">To compare serum ferritin changes over time in the randomized arms<o:p></o:p></span></p>\n<p class=\"TableParagraph\" style=\"margin: 0cm 0cm 0cm 36pt; font-size: 11pt; font-family: Calibri, sans-serif; color: rgb(0, 0, 0); text-indent: -18pt; line-height: 12.45pt;\">\n <span lang=\"EN-US\" style=\"font-family: Symbol;\">·<span new=\"\" style=\"font-variant-numeric: normal; font-variant-east-asian: normal; font-stretch: normal; font-size: 7pt; line-height: normal; font-family: \" times=\"\">       </span></span><span lang=\"EN-US\">To </span><span lang=\"EN-US\">correlate changes in hemoglobin and serum ferritin to changes in self-reported menstrual blood loss<o:p></o:p></span></p>\n<p class=\"TableParagraph\" style=\"margin: 0cm 0cm 0cm 36pt; font-size: 11pt; font-family: Calibri, sans-serif; color: rgb(0, 0, 0); text-indent: -18pt; line-height: 12.45pt;\">\n <span lang=\"EN-US\" style=\"font-family: Symbol;\">·<span new=\"\" style=\"font-variant-numeric: normal; font-variant-east-asian: normal; font-stretch: normal; font-size: 7pt; line-height: normal; font-family: \" times=\"\">       </span></span><span lang=\"EN-US\">To </span><span lang=\"EN-US\">assess and compare participants’ satisfaction with the two contraceptive products<o:p></o:p></span></p>\n<p class=\"TableParagraph\" style=\"margin: 0cm 0cm 0cm 36pt; font-size: 11pt; font-family: Calibri, sans-serif; color: rgb(0, 0, 0); text-indent: -18pt; line-height: 12.45pt;\">\n <span lang=\"EN-US\" style=\"font-family: Symbol;\">·<span new=\"\" style=\"font-variant-numeric: normal; font-variant-east-asian: normal; font-stretch: normal; font-size: 7pt; line-height: normal; font-family: \" times=\"\">       </span></span><span lang=\"EN-US\">To monitor incidence of progression to severe anemia and compare randomized arms<o:p></o:p></span></p>\n
      • principal_inclusion_criteria<p>\n Prospective participants must meet the following main criteria:</p>\n<ol>\n <li>\n Provide sequential oral and written consents to screen for eligibility and enroll</li>\n <li>\n Female, aged 18-50</li>\n <li>\n Desire to use contraception or possibly switch methods</li>\n <li>\n Initial hemoglobin of <u><</u> 126 g/L</li>\n <li>\n Possession of a cell phone and willingness to be contacted</li>\n <li>\n Confirmatory low hemoglobin (minimum of 87 g/L and maximum of 126 g/L) taken 1 to 4 weeks after the initial test</li>\n <li>\n Regularly menstruating (at least once every 35 days)</li>\n <li>\n At least 6 weeks postpartum</li>\n <li>\n Willingness to agree to study procedures</li>\n <li>\n Willingness to be randomized to treatment</li>\n <li>\n Willingness to use assigned hormonal contraceptive for 18 months</li>\n</ol>\n
      • principal_exclusion_criteria<p>\n An individual who has any of the following will be excluded from participation in this study:</p>\n<ol>\n <li style=\"margin-left: 69pt;\">\n Severe anemia (hemoglobin <u><</u> 86 g/L), based on the second rapid test</li>\n <li style=\"margin-left: 69pt;\">\n Currently pregnant based on urine pregnancy test and failure to rule out possible pregnancy according to WHO guidelines</li>\n <li style=\"margin-left: 69pt;\">\n Surgically sterilized or had a hysterectomy</li>\n <li style=\"margin-left: 69pt;\">\n Participated previously in this study by being randomized to contraceptive</li>\n <li style=\"margin-left: 69pt;\">\n Currently using a subdermal contraceptive implant and does not wish to have it removed</li>\n <li style=\"margin-left: 69pt;\">\n Currently using an LNG IUS</li>\n <li style=\"margin-left: 69pt;\">\n Currently receiving treatment for anemia</li>\n <li style=\"margin-left: 69pt;\">\n Any of the following previously diagnosed disorders: hemosiderosis, hemochromatosis, hemolytic anemia</li>\n <li style=\"margin-left: 69pt;\">\n Known allergic reactions to oral contraceptives or LNG IUS</li>\n <li style=\"margin-left: 69pt;\">\n Currently receiving an investigational (unapproved) drug in another study</li>\n <li style=\"margin-left: 69pt;\">\n Any condition (social or medical) which in the opinion of the investigator would make study participation unsafe</li>\n <li style=\"margin-left: 69pt;\">\n ntending to become pregnant in the next 18 months</li>\n <li style=\"margin-left: 69pt;\">\n Mucopurulent cervicitis</li>\n <li style=\"margin-left: 69pt;\">\n Pelvic inflammatory disease</li>\n <li style=\"margin-left: 69pt;\">\n Other medical contraindications to treatment, according to WHO Medical Eligibility Criteria (categories 3 or 4)</li>\n</ol>\n
      • primary_end_points<p>\n <span lang=\"EN-US\" style=\"color: rgb(0, 0, 0); font-size: 11pt; font-family: Calibri, sans-serif;\">Hemoglobin levels of participants measured at 6, 12, and 18 months</span></p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_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_confirmatory0
      • trial_therapeutic_use1
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n <strong>Facilities</strong></p>\n<p>\n 1. A customized fully equiped fabricated project container installed within field site at Kangemi health centre comprising of:</p>\n<ul style=\"margin-left: 40px;\">\n <li>\n Reception area with lockable cabinets, shelves and necessary materials for record keeping and receiving study participants</li>\n <li>\n Laboratory room with a fridge for storage of samples pending transportation to UNITID-UoN main laboratory</li>\n <li>\n Procedure room equiped with a nursing station, examination couch, sink and relevant equipment for counselling and dispensing study products to eligible study particoipants by the study nurse.</li>\n <li>\n Data room equipped with a working desk for the data entry clerk, photocopie/scanner and lockable cabinets for filing hard copies of study tools</li>\n <li>\n Study coordinators room - lockable cabinet</li>\n <li>\n Reception area - Comfortable seating are for study participants</li>\n</ul>\n<p>\n 2. Health facility Pharmacy - Spacious well stocked pharmacy manned by a Pharmacy Tecnologist. Study products will be stored at this pharmacy with product records, handling and overall conditions monitored by the study pharmacist.</p>\n<p>\n 3. Incinerator for disposal of clinical waste</p>\n<p>\n 4. Generator accesible from KAVI-UoN through internal collaborative arrangements</p>\n<p>\n <strong>Project Staff </strong></p>\n<p style=\"margin-left: 40px;\">\n 1. Study cordinator: Shortlisting on-going to recruit an individual with academic background in a health related course at degree level & strong experience cordinating research activities preferably in a health related grant project.</p>\n<p style=\"margin-left: 40px;\">\n 2. Study Nurse; Jeremiah Kagongo, Registered Community Health Nurse, 8 years expeience in clinical and reserach clinic settings</p>\n<p style=\"margin-left: 40px;\">\n 3. Assistant Lab tecnician: Beryl Masinde, Lab tecnologist, over 8 years experience in reserach and linical labs</p>\n<p style=\"margin-left: 40px;\">\n 4.Data Manager - Agnes Ndirangu, Bsc Statistics & Posgraduate training in Monitoring and Evaluation, over 7years experience as a data manager in large health related reserach projects incuding KEMRI</p>\n<p style=\"margin-left: 40px;\">\n 5. Study Admin/Accountant: Dennis Wanyonyi, B.com, Accounting: Experienced, Former Finance and Fiscal Manager, KEMRI, Thika Project</p>\n<p style=\"margin-left: 40px;\">\n 6. Data entry clerk: In process of recuitment</p>\n<p>\n  </p>\n
      • other_details_explanation<p>\n <span font-size:=\"\" style=\"caret-color: rgb(51, 51, 51); color: rgb(51, 51, 51); font-family: \" text-size-adjust:=\"\" trebuchet=\"\">This is a single country trial where FHI 360 is the trial sponsor</span></p>\n
      • other_details_regulatory_notapproved<p>\n None</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 Not Applicable</p>\n
      • estimated_duration5 years - Overall duration inclusive of time for all preparatory activities and report writting. Actual follow-up of participants is 18 months.
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorStandard intervention
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKangemi Health Centre
      • single_site_physical_addressKangemi - Waiyaki Way, Nairobi
      • single_site_contact_personSarah Wachuka
      • single_site_telephone0726105764
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_site600 - Kangemi Health Centre and surrounding community
      • total_participants_worldwide600
      • 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_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_womenYes
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameDavid
      • investigator1_middle_name
      • investigator1_family_nameHubacher
      • investigator1_qualificationPhD, Senior Epidemiologist
      • investigator1_professional_addressFHI 360, 359 Blackwell Street, Suite 200 | Durham, NC 27701
      • investigator1_telephone+19193213459
      • investigator1_emailDHubacher@fhi360.org
      • organisations_transferred_Yes
      • number_participants600
      • notification
      • approval_date23-02-2023
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted14-02-2023
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonThe PI has responded to the Reviewer comments and proposed amendment done.
      • 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 15:09:13
      • created2022-05-06 14:55:29
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id820
        • application_id1141
        • given_nameFaith
        • middle_nameMugure
        • family_nameThuita
        • qualificationPhD, Senior Nutrition and Public health Lecturer and researcher
        • professional_addressP. O. BOX 19676 – 00202, Department of Public and Global Health, Kenyatta National Hospital Campus, Nairobi, Kenya
        • telephone+254722639719
        • emailfthuita@uonbi.ac.ke
        • created2022-05-09 09:04:00
        • modified2023-02-14 14:31:55
    • SiteDetail(array)
      • 0(array)
        • id1276
        • application_id1141
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2022-05-09 09:04:00
        • modified2023-02-14 14:31:55
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id590
        • application_id1141
        • sponsorFHI 360
        • sponsor_typeOthers
        • contact_personDavid Hubacher
        • addressFHI 360, 359 Blackwell Street, Suite 200 | Durham, NC 27701
        • telephone_number+19193213459
        • fax_number +19195447261
        • cell_number+19193213459
        • email_addressDHubacher@fhi360.org
        • created2022-05-09 09:04:00
        • modified2023-02-14 14:31:55
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App Constants

CakePHP Constants

PHP Environment

Included Files

Include Paths

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• 1/var/www/html/ctr/lib
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• 4-> /var/www/html/ctr/lib/Cake/

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