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      • id1029
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      • abstract_of_study<p>\n <strong>PROTOCOL TITLE: A 3-ARM, RANDOMIZED, BLINDED, ACTIVE-CONTROLLED, PHASE II STUDY OF RO7121661, A PD1-TIM3 BISPECIFIC ANTIBODY AND RO7247669, A PD1-LAG3 BISPECIFIC ANTIBODY, COMPARED WITH NIVOLUMAB IN PARTICIPANTS WITH ADVANCED OR METASTATIC SQUAMOUS CELL CARCINOMA OF THE ESOPHAGUS</strong></p>\n<p>\n  </p>\n<p>\n <strong>PROTOCOL NUMBER: </strong>BP42772</p>\n<p>\n <strong>TEST PRODUCT: </strong>RO7121661, RO7247669, Nivolumab</p>\n<p>\n <strong>PHASE: </strong>II</p>\n<p>\n <strong>RATIONALE</strong></p>\n<p>\n Cancer remains a major cause of death worldwide despite several new agents providing survival</p>\n<p>\n benefits to patients. Many cancer indications have a poor prognosis and the management of</p>\n<p>\n most advanced solid tumors remains challenging because of the high rate of tumor recurrence or</p>\n<p>\n the development of distant metastases.</p>\n<p>\n Despite the effectiveness of PD1/L1 checkpoint inhibitor (CPI) therapy in various tumor types</p>\n<p>\n including esophageal squamous-cell carcinoma (ESCC), additional treatment options targeting</p>\n<p>\n immune checkpoints are needed, because the majority of patients eventually progress after an</p>\n<p>\n initial response or fail to respond to PD1/L1 checkpoint blockade.</p>\n<p>\n By targeting both PD1 and TIM3 or LAG3 on dysfunctional tumor-specific T lymphocytes, the</p>\n<p>\n PD1-TIM3 and PD1-LAG3 bispecific antibodies aim to restore an effective anti-tumor</p>\n<p>\n immune-response and provide survival benefit to more patients with cancer than currently</p>\n<p>\n available agents do. PDL1 expression in ESCC ranges from 15% to 83% in tumor cells and from</p>\n<p>\n 13% to 31% in tumor-infiltrated immune cells. Studies with nivolumab, pembrolizumab, and other</p>\n<p>\n PD1 inhibitors demonstrated benefit over chemotherapy in the second-line (2L) ESCC</p>\n<p>\n population leading to market authorizations in that setting (e.g. in the U.S., EU, Japan, South</p>\n<p>\n Korea, and other jurisdictions). Both TIM3 and LAG3 have been shown to be expressed on</p>\n<p>\n tumor-infiltrating lymphocytes in patients with ESCC. RO7121661 and RO7247669 may</p>\n<p>\n therefore have the potential to be a therapeutic option for patients with ESCC.</p>\n<p>\n The purpose of this study is to assess the efficacy of RO7121661 and RO7247669 compared</p>\n<p>\n with nivolumab to address a significant unmet medical need in patients with unresectable</p>\n<p>\n advanced or recurrent ESCC who are refractory or intolerant to one prior line of chemotherapy.</p>\n<p>\n <strong>OBJECTIVES AND ENDPOINTS</strong></p>\n<p>\n <strong>Primary Objective:</strong> To evaluate the efficacy of RO7121661 and RO7247669 compared with nivolumab.</p>\n<p>\n <strong>Primary Endpoint: </strong>OS, defined as the time from randomization to death from any cause</p>\n<p>\n Secondary Objectives:</p>\n<ul>\n <li>\n To evaluate the safety and tolerability of RO7121661and RO7247669 compared with nivolumab.</li>\n <li>\n To evaluate the efficacy of RO7121661 and RO7247669 compared with nivolumab.</li>\n <li>\n To investigate the pharmacokinetics (PK) of RO7121661, RO7247669, and nivolumab.</li>\n <li>\n To evaluate the immune response after administration of RO7121661, RO7247669, and nivolumab.</li>\n <li>\n To assess treatment-induced pharmacodynamic changes (PD Biomarkers) in peripheral blood and tumor microenvironment</li>\n <li>\n To assess baseline characteristics in the tumor microenvironment as predictive biomarkers of response</li>\n</ul>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n <strong>OVERALL DESIGN</strong></p>\n<p>\n <strong>Study Design</strong></p>\n<p>\n This is a Phase II, randomized, blinded, active-controlled, global, multicenter study designed to evaluate the safety and efficacy of RO7121661 and RO7247669, compared with nivolumab in patients with advanced or metastatic ESCC refractory or intolerant to fluoropyrimidine- or taxane- and platinum-based regimen. The study will enroll approximately 255 participants aged ³ 18 years with Eastern Cooperative Oncology Group Performance Status of 0 or 1. Participants will be randomized in a 1:1:1 ratio to receive RO7121661, RO7247669, or nivolumab. Participants will be stratified by previous (neo-)adjuvant chemotherapy, chemoradiotherapy or definitive chemoradiotherapy in curative intention (yes versus no), expression of PDL1 (< 1% versus ³ 1%), and geographic region of the enrolling site (Asia versus Rest of World). Randomization should occur on Day -1 or Day 1after the patient’s eligibility (i.e., inclusion/exclusion criteria) has been confirmed. In the experimental arms, participants will receive RO7121661 or RO7247669 at a fixed dose of 2100 mg administered by IV infusion every 2 weeks (Q2W) on Day 1 of each 14-day cycle. In the active comparator arm, participants will receive nivolumab at a fixed dose of 240 mg administered by IV infusion Q2W on Day 1 of each 14-day cycle. Treatment may be continued as long as participants are experiencing clinical benefit, as assessed by the Investigator, in the absence of unacceptable toxicity or symptomatic deterioration attributed to disease progression after an integrated assessment of radiographic data, biopsy results (if available), and clinical status for a maximum of 24 months. Participants who meet the criteria for disease progression per RECIST v1.1 will be permitted to continue study treatment if they meet all criteria for treatment beyond progression.</p>\n<p>\n Participants will undergo tumor assessments at screening and every 6 weeks (± 7 days) for</p>\n<p>\n 48 weeks following Day 1 of Cycle 1 (D1C1), regardless of treatment delays. After completion of the Week 48 tumor assessment, tumor assessments will be required every 12 weeks (± 7 days) regardless of treatment delays until radiographic disease progression per RECIST v1.1, initiation of a new anti-cancer therapy, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Thus, tumor assessments are to continue according to the schedule in participants who discontinue treatment for reasons other than disease progression or loss of clinical benefit. For participants who continue treatment after progressive disease, tumor assessments are to continue according to schedule until study treatment is discontinued. At the Investigator’s discretion, tumor assessments may be repeated at any time if progressive disease is suspected. Response will be assessed according to RECIST v1.1 and modified RECIST v1.1 for immune-based therapeutics (iRECIST). Objective response at a single timepoint will be determined by the Investigator according to RECIST v1.1. Objective response per iRECIST will be calculated programmatically by the Sponsor based on Investigator assessments of individual lesions at each specified timepoint. All primary imaging data used for tumor assessments may</p>\n<p>\n be collected by the Sponsor; centralized, blinded independent review of response endpoints by an independent review facility may be conducted. The primary comparison of interest are the hazard ratio of OS of each experimental arm compared to nivolumab, assessing the superiority of the experimental arms over the active comparator treatment. The primary comparison of OS will be made regardless of whether participants withdraw from treatment or receive new anti-cancer therapy prior to disease progression. In order not to confound the OS endpoint, crossover from any of the treatment arms to another arm will not be allowed.</p>\n<p>\n  </p>\n<p>\n During the study, participants will be asked to complete patient-reported outcome (PRO) questionnaires at the beginning of the study, during study treatment, at treatment discontinuation, and during survival follow-up. These will assess disease and treatment-related symptoms, as well as functioning and overall health-related quality of life.</p>\n<p>\n During the study, serum samples will be collected to monitor RO7121661, RO7247669, and nivolumab pharmacokinetics (PK) and to detect the presence of antibodies to RO7121661, RO7247669, or nivolumab. Blood samples for PK analysis may be collected at the participant’s home. This specifically applies to days where no other hospital assessments are required—i.e., C1D8 and C5D8.</p>\n<p>\n Participant samples, including archival and fresh tumor tissue, serum, plasma, and blood samples, will also be collected for biomarker assessments. Safety assessments will include the incidence, nature, and severity of AEs, and other protocol-specified tests such as laboratory abnormalities that are deemed critical to the safety evaluation of the study.</p>\n<p>\n After study treatment discontinuation and disease progression per RECIST v1.1, survival follow-up information will be collected by means of telephone calls, participant medical records, and/or clinic visits approximately every 3 months until death, lost to follow-up, or study termination by the Sponsor, whichever occurs first. All participants will be periodically contacted for survival and new anti-cancer therapy information unless the participant requests to be withdrawn from follow-up (this request must be documented in the source documents and signed by the Investigator). If the participant withdraws from the study, study staff may use a public information source (e.g., county records) when permissible to obtain information about survival status.</p>\n<p>\n The IMPs are: RO7121661 (2100 mg Q2W IV), RO7247669 (2100 mg Q2W IV), and nivolumab (240 mg Q2W IV).</p>\n<p>\n <strong>Length of Study</strong></p>\n<p>\n The duration in each period of the study for each participant will be as follows:</p>\n<p>\n · Screening: Days -28 to -1.</p>\n<p>\n · Treatment Period: Cycle 1 Day 1 up to a maximum of 24 months.</p>\n<p>\n · Survival follow-up: 90 (± 7) days after last treatment with study drug; then every</p>\n<p>\n 3 months (± 14 days) until death, loss to follow-up, or study termination by the Sponsor.</p>\n<p>\n <strong>End of Study</strong></p>\n<p>\n The end of the study will occur when all of the following criteria have been met:</p>\n<p>\n · The required number of deaths for the primary analysis of OS has been observed.</p>\n<p>\n · The last participant, last visit has occurred.</p>\n<p>\n <strong>Data Monitoring Committee</strong></p>\n<p>\n A Joint Monitoring Committee (JMC) will review available safety data periodically and make</p>\n<p>\n recommendations regarding study conduct to ensure the safety of patients enrolled in the study.</p>\n<p>\n The JMC will consist of designated Sponsor personnel and independent clinical expert(s) (i.e., expert[s] independent from the Sponsor). The JMC Chair will be a medical oncologist who is neither the Medical Monitor nor associated with the study. Other JMC members will include, but not be limited to, a drug-safety scientist and biostatistician. The responsibility, membership, and communication flow of the JMC is further described in the JMC Charter.</p>\n<p>\n  </p>\n<p>\n <strong>PARTICIPANT POPULATION</strong></p>\n<p>\n The study population consists of male and female participants with advanced or metastatic</p>\n<p>\n ESCC who are not indicated for radical resection and who are refractory or intolerant to</p>\n<p>\n fluoropyrimidine- or taxane- and platinum-based regimen.</p>\n<p>\n  </p>\n<p>\n <strong>Key Inclusion Criteria</strong></p>\n<p>\n · Participants whose major lesion was histologically confirmed ESCC.</p>\n<p>\n · Patients who are not indicated for radical resection and have previously received 1 line of treatment in non-curative intention prior to randomization. The prior line must be either a fluoropyrimidine- and platinum- or a taxane- and platinum-based regimen and patients must have experienced progressive disease after at least 3 cycles or are intolerable to the treatment. Patients who received treatment with curative intent, i.e. patients who underwent a radical resection (R0 resection confirmed) in conjunction with chemotherapy with fluoropyrimidine-/taxane- and platinum-based drugs including neo-adjuvant/adjuvant therapy (± radiotherapy) or patients who were treated with chemo-radiation (including patients who underwent chemo-radiation followed by salvage surgery) are allowed.</p>\n<p>\n · If recurrence was confirmed by imaging or by pathological assessment of a biopsy within 24 weeks after the last dose of the treatment, patients are eligible and do not require an additional line of therapy in the non-curative setting.</p>\n<p>\n · If recurrence occurred later than 24 weeks after the last dose of the treatment, patients need to be exposed to an additional line of fluoropyrimidine-/taxane- and platinum-based drugs in the non-curative setting to be eligible for the study—unless the Investigator considers the patient not eligible for the re-exposure with fluoropyrimidine/taxane and platinum-based drugs.</p>\n<p>\n · The last dose of chemotherapy or the last radiation treatment (whichever occurs later) should be considered for the determination of the timepoint of recurrence after chemo-radiation.</p>\n<p>\n · Radiologically measurable disease according to RECIST v1.1. Previously irradiated lesions should not be counted as target lesions unless clearly progressed after the radiotherapy.</p>\n<p>\n · Eastern Cooperative Oncology Group Performance Status 0-1.</p>\n<p>\n · A life expectancy of ³ 12 weeks.</p>\n<p>\n · Tissue samples must be provided for analysis of PD-L1 tumor positivity using the PDL1 IHC 28-8 pharmDx assay. Testing will be done centrally and results must be obtained prior to stratification.</p>\n<p>\n · Adequate visceral organ functions</p>\n<p>\n · AEs from any prior radiotherapy, chemotherapy, or surgical procedure must have resolved to Grade £ 1, except alopecia (any grade), vitiligo, endocrinopathy managed with replacement therapy, and Grade 2 peripheral neuropathy.</p>\n<p>\n · Adequate contraception</p>\n<p>\n <strong>Key Exclusion Criteria</strong></p>\n<p>\n · Pregnancy, lactation, or breastfeeding.</p>\n<p>\n · Known hypersensitivity to any of the components of RO7121661, RO7247669, or nivolumab, including but not limited to, hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies.</p>\n<p>\n · Patients with significant malnutrition. Patients whose nutrition has been well controlled for ³ 28 days prior to randomization may be enrolled.</p>\n<p>\n · Evidence of complete esophageal obstruction not amenable to treatment.</p>\n<p>\n · Higher risk of bleeding or fistula caused by esophageal lesions invading adjacent organs (aorta or tracheobronchial tree).</p>\n<p>\n · Symptomatic central nervous system (CNS) metastases.</p>\n<p>\n · Spinal cord compression not definitively treated with surgery and/or radiation or without evidence that disease has been clinically stable for ³ 14 days prior to randomization.</p>\n<p>\n · Active or history of carcinomatous meningitis/leptomeningeal disease.</p>\n<p>\n Asymptomatic CNS primary tumors or metastases if they have requirement for steroids</p>\n<p>\n or enzyme-inducing anticonvulsants in the last 28 days prior to randomization.</p>\n<p>\n · Uncontrolled tumor-related pain.</p>\n<p>\n · Patients with an active second malignancy.</p>\n<p>\n · Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results.</p>\n<p>\n · Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent.</p>\n<p>\n · Significant cardiovascular/cerebrovascular disease within 6 months prior to randomization.</p>\n<p>\n · Known active or uncontrolled bacterial, viral, fungal, mycobacterial (including but not limited to tuberculosis [TB] and typical mycobacterial disease), parasitic, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics, except if for tumor fever) within 28 days prior to randomization.</p>\n<p>\n · Known clinically significant liver disease, including alcoholic hepatitis, cirrhosis, and inherited liver disease.</p>\n<p>\n · Major surgical procedure or significant traumatic injury (excluding biopsies) within 28 days prior to randomization, or anticipation of the need for major surgery during the course of the study.</p>\n<p>\n · Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high risk from treatment complications.</p>\n<p>\n · Dementia or altered mental status that would prohibit informed consent.</p>\n<p>\n · Uncontrolled pleural effusion (with the exception of participants with indwelling catheters, e.g., PleurXâ), pericardial effusion, or ascites requiring recurrent drainage procedures (expected to occur once monthly or more frequently).</p>\n<p>\n · Active or history of autoimmune disease or immune deficiency.</p>\n<p>\n · Positive HIV test at screening.</p>\n<p>\n · Positive hepatitis B surface antigen (HBsAg) or positive total hepatitis B core antibody (HBcAb) test at screening. Participants with a positive HBsAg or total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening are eligible.</p>\n<p>\n · Positive hepatitis C virus (HCV) antibody test at screening. Participants with a positive</p>\n<p>\n HCV antibody test followed by a negative HCV RNA test at screening are eligible.</p>\n<p>\n · Prior cancer therapy with any immunomodulatory agents including CPIs (such as anti-PDL1/PD1, anti-CTLA-4, anti-LAG3, anti-TIM3).</p>\n<p>\n · Vaccination with live vaccines within 28 days prior to randomization, or anticipation that a live attenuated vaccine will be required during the study.</p>\n<p>\n · Treatment with therapeutic oral or IV antibiotics within 14 days prior to randomization.</p>\n<p>\n · Concurrent therapy with any other investigational drug (defined as treatment for which there is currently no regulatory authority-approved indication) < 28 days or 5 half-lives of the drug, whichever is shorter, prior to randomization.</p>\n<p>\n · Treatment with immune-modulating and immune suppressive agents/medication</p>\n<p>\n < 5 half-lives or 28 days (whichever is shorter) prior to randomization.</p>\n<p>\n · Regular immunosuppressive therapy (i.e., for organ transplantation, chronic rheumatologic disease).</p>\n<p>\n · Radiotherapy within the last 28 days before start of study drug treatment is not allowed, with the exception of limited palliative radiotherapy.</p>\n<p>\n · Prior treatment with adoptive cell therapies, such as CAR-T therapies.</p>\n<p>\n  </p>\n<p>\n <strong>NUMBER OF PARTICIPANTS</strong></p>\n<p>\n The planned number of enrolled participants is 255, randomized 1:1:1 into 3 arms.</p>\n<p>\n <strong>CONCOMITANT MEDICATIONS</strong></p>\n<p>\n As a general rule, no concomitant medication will be permitted, with the exception of medications to treat AEs, unless the rationale for exception is discussed and clearly documented between the Investigator and the Sponsor. Use of the following therapies is prohibited during the study and for at least 28 days or</p>\n<p>\n 5 half-lives of the drug, whichever is shorter, prior to randomization and during study treatment, unless otherwise specified below:</p>\n<p>\n · Investigational or unlicensed/unapproved agents.</p>\n<p>\n · Therapy intended for the treatment of cancer (including, but not limited to, chemotherapy, hormonal therapy, immunotherapy, and radiotherapy [with the exception of limited palliative radiotherapy], as well as herbal therapy or traditional Chinese medicines with anti-cancer activity in the label), whether Health Authority approved or experimental.</p>\n<p>\n · Chronic use of steroids (inhaled and topical steroids are permitted) at baseline of > 10 mg of prednisone/day (or equivalent). Concurrent high doses of systemic corticosteroids.</p>\n<p>\n · Administration of a live, attenuated vaccine or anticipation that such a live attenuated vaccine will be required during the study.</p>\n<p>\n · Systemic immunostimulatory agents (including, but not limited to, interferons and IL-2) because these agents could potentially increase the risk for autoimmune conditions when given in combination with CPIs.</p>\n<p>\n · Systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, and thalidomide) because these agents could potentially alter the efficacy and safety of the study drug.</p>\n<p>\n · Adoptive cell therapies, such as CAR-T therapies.</p>\n<p>\n  </p>\n
      • study_title<div>\n A 3-ARM, RANDOMIZED, BLINDED, ACTIVE-CONTROLLED, PHASE II STUDY OF RO7121661, A PD1-TIM3 BISPECIFIC ANTIBODY AND RO7247669, A PD1-LAG3 BISPECIFIC ANTIBODY, COMPARED WITH NIVOLUMAB IN PARTICIPANTS WITH ADVANCED OR METASTATIC SQUAMOUS CELL CARCINOMA OF THE ESOPHAGUS</div>\n
      • laymans_summary<p>\n This is a Phase II, randomized, blinded, active-controlled, global, multicenter study designed to evaluate the safety and efficacy of RO7121661 and RO7247669, compared with nivolumab, in patients with advanced or metastatic esophageal squamous-cell carcinoma (ESCC) refractory or intolerant to fluoropyrimidine- or taxane- and platinum-based regimen.</p>\n<p>\n The purpose of this study is to find out what effects, good or bad, RO7121661 and RO7247669, have on ESCC patients as compared to nivolumab.</p>\n<p>\n RO7121661, RO7247669, and nivolumab belong to a group of medicines called cancer immunotherapeutics. They are designed to recognize and kill tumor cells in the body by activating the body’s own immune system, in particular, T-cells (a type of immune cell) against the tumor.</p>\n<p>\n More precisely<strong>, </strong>RO7121661, RO7247669, and nivolumab are antibodies, which block proteins on T-cells, which help keep the body’s immune responses in check. These proteins are called PD1, TIM3, and LAG3. PD1, TIM3, and LAG3 are involved in regulating the body's natural immune response. Tumors can take advantage of this regulation to partially resist or evade the immune system. RO7121661 blocks PD1 and TIM3, RO7247669 blocks PD1 and LAG3, and nivolumab blocks PD1. By blocking these proteins, RO7121661, RO7247669, and nivolumab may help your immune system stop or reverse the growth of tumors.</p>\n<p>\n RO7121661 and RO7247669 are experimental drugs, which means Health Authorities have not approved RO7121661 and RO7247669 for the treatment of esophageal cancer. Nivolumab is approved in some countries for the treatment of cancer including esophageal cancer.</p>\n<p>\n Approximately 255 participants will take part in this study. The participants will be divided into three groups, receiving either RO7121661, RO7247669, or nivolumab. Each group will consist of 85 participants.</p>\n<p>\n The primary study objective is To evaluate the efficacy of RO7121661 and RO7247669 compared with nivolumab and the primary endpoint is overall survival (OS) defined as the time from randomization to death from any cause.</p>\n<p>\n The duration in each period of the study for each participant will be as follows:</p>\n<ul>\n <li>\n Screening: Days -28 to -1.</li>\n <li>\n Treatment Period: Cycle 1 Day 1 up to a maximum of 24 months.</li>\n <li>\n Survival follow-up: 90 (±7) days after last treatment with study drug; then every 3 months (± 14 days) until death, loss to follow-up, or study termination by the Sponsor.</li>\n</ul>\n<p>\n The end of the study will occur when all of the following criteria have been met:</p>\n<ul>\n <li>\n The required number of deaths for the primary analysis of OS has been observed.</li>\n <li>\n The last participant, last visit has occurred.</li>\n</ul>\n<p>\n  </p>\n
      • short_titleTALIOS
      • protocol_noECCT/21/07/02
      • version_no1
      • date_of_protocol08-12-2020
      • study_drugRO7121661, RO7247669, Nivolumab
      • disease_conditionAdvanced or Metastatic Esophageal Squamous Cell Carcinoma
      • 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_nameNivolumab
      • comparator_registeredyes
      • comparator_countriesCanada, the United States, the European Union, Japan, Taiwan, Israel, Turkey, Australia, Hong Kong, Brazil, South Korea, Mexico, China, Singapore
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addresshuwaida.bulhan@roche.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
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      • 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
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      • applicant_signed_checklist1
      • statistical_analysis_plan1
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      • declaration_applicantDr. Huwaida Bulhan - Roche Kenya Ltd.
      • declaration_date107-07-2021
      • declaration_principal_investigatorProf. Mansoor Saleh - AgaKhan University Hostpital Nairobi
      • declaration_date207-07-2021
      • placebo_presentNo
      • study_objectives<div class=\"ct-body3\" color:=\"\" font-size:=\"\" helvetica=\"\" line-height:=\"\" sans=\"\" source=\"\" style=\"box-sizing: border-box; font-family: \">\n <p>\n <strong>Primary Objective:</strong></p>\n <p>\n To evaluate the efficacy of RO7121661 and RO7247669 compared with nivolumab.</p>\n <span style=\"font-size:14px;\"><strong><span style=\"color: rgb(34, 34, 34); font-family: Arial, Verdana, sans-serif;\">Secondary Objectives:</span></strong></span></div>\n<ul>\n <li>\n <span style=\"font-size:14px;\">To evaluate the safety and tolerability of RO7121661and RO7247669 compared with nivolumab.</span></li>\n <li>\n <span style=\"font-size:14px;\">To evaluate the efficacy of RO7121661 and RO7247669 compared with nivolumab.</span></li>\n <li>\n <span style=\"font-size:14px;\">To investigate the pharmacokinetics (PK) of RO7121661, RO7247669, and nivolumab.</span></li>\n <li>\n <span style=\"font-size:14px;\">To evaluate the immune response after administration of RO7121661, RO7247669, and nivolumab.</span></li>\n <li>\n <span style=\"font-size:14px;\">To assess treatment-induced pharmacodynamic changes (PD Biomarkers) in peripheral blood and tumor microenvironment</span></li>\n <li>\n <span style=\"font-size:14px;\">To assess baseline characteristics in the tumor microenvironment as predictive biomarkers of response</span></li>\n</ul>\n<div class=\"ct-body3\" color:=\"\" font-size:=\"\" helvetica=\"\" line-height:=\"\" margin-right:=\"\" sans=\"\" source=\"\" style=\"box-sizing: border-box; font-family: \">\n <p style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n  </p>\n</div>\n<p>\n  </p>\n
      • principal_inclusion_criteria<ul font-size:=\"\" helvetica=\"\" margin-bottom:=\"\" sans=\"\" source=\"\" style=\"box-sizing: border-box; margin-top: 1ex; margin-left: 0px; padding-left: 24px; color: rgb(0, 0, 0); font-family: \">\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Major lesion was histologically confirmed esophageal squamous-cell carcinoma (ESCC)</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Patients who have previously received 1 line of treatment with either a fluoropyrimidine- and platinum- or a taxane- and platinum-based regimen in non-curative intention prior to randomization; or patients who received treatment with a fluoropyrimidine-/taxane- and platinum-based regimen in curative intention and had recurrence within 24 weeks after the last dose of the treatment</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Radiologically measurable disease according to RECIST v1.1. Previously irradiated lesions should not be counted as target lesions unless clearly progressed after the radiotherapy</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n A life expectancy of at least (≥)12 weeks</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Tissue samples must be provided for analysis of anti-programmed death ligand-1 (PD-L1) tumor positivity</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Adverse events from any prior radiotherapy, chemotherapy, or surgical procedure must have resolved to Grade ≤1, except alopecia (any grade), vitiligo, endocrinopathy managed with replacement therapy, and Grade 2 peripheral neuropathy</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Adequate cardiovascular, hematological, liver, and renal function</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Serum albumin ≥25 grams per liter (g/L),</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n For participants not receiving therapeutic anticoagulation: prothrombin time (PT) and activated partial thromboplastin time ≤1.5 times (×) the upper limit of normal (ULN); for participants receiving therapeutic anticoagulation: stable anticoagulant regimen</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n A female participant is eligible to participate if she is not pregnant, not breastfeeding, not a woman of childbearing potential (WOCBP), or a WOCBP who agrees to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods during the treatment period and for at least 5 months after the final dose of study drug and have a negative pregnancy test (blood) within the 7 days prior to randomization.</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n A male participant must remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures such as a condom plus an additional contraceptive method and refrain from donating sperm during the treatment period and for at least 5 months after the final dose of study drug</li>\n</ul>\n
      • principal_exclusion_criteria<ul font-size:=\"\" helvetica=\"\" margin-bottom:=\"\" sans=\"\" source=\"\" style=\"box-sizing: border-box; margin-top: 1ex; margin-left: 0px; padding-left: 24px; color: rgb(0, 0, 0); font-family: \">\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Pregnancy, lactation, or breastfeeding</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Known hypersensitivity to any of the components of RO7121661, RO7247669, or nivolumab, including but not limited to, hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Patients with significant malnutrition. Patients whose nutrition has been well controlled for ≥28 days prior to randomization may be enrolled</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Evidence of complete esophageal obstruction not amenable to treatment</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Higher risk of bleeding or fistula caused by esophageal lesions invading adjacent organs (aorta or tracheobronchial tree)</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Symptomatic central nervous system (CNS) metastases</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Spinal cord compression not definitively treated with surgery and/or radiation or without evidence that disease has been clinically stable for ≥14 days prior to randomization</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Active or history of carcinomatous meningitis/leptomeningeal disease</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Asymptomatic CNS primary tumors or metastases if they have requirement for steroids or enzyme inducing anticonvulsants in the last 28 days prior to randomization</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Uncontrolled tumor-related pain. Participants requiring pain medication must be on a stable regimen at study entry</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Active second malignancy (with some exceptions)</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders, known autoimmune diseases or immune deficiency, or other diseases with ongoing fibrosis (such as scleroderma, pulmonary fibrosis, emphysema, neurofibromatosis, palmar/plantar fibromatosis, etc.).</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Significant cardiovascular/cerebrovascular disease within 6 months prior to randomization</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Known active or uncontrolled bacterial, viral, fungal, mycobacterial (including but not limited to tuberculosis [TB] and typical mycobacterial disease), parasitic, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with intravenous (IV) antibiotics or hospitalization (relating to the completion of the course of antibiotics, except if for tumor fever) within 28 days prior to randomization</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Known clinically significant liver disease, including alcoholic hepatitis, cirrhosis, and inherited liver disease.</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Major surgical procedure or significant traumatic injury (excluding biopsies) within 28 days prior to randomization, or anticipation of the need for major surgery during the course of the study</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high risk from treatment complications</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Dementia or altered mental status that would prohibit informed consent</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (expected to occur once monthly or more frequently)</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Active or history of autoimmune disease or immune deficiency</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Positive human immunodeficiency virus (HIV) test at screening</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Positive hepatitis B surface antigen (HBsAg) or positive total hepatitis B core antibody (HBcAb) test at screening</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Positive hepatitis C virus (HCV) antibody test at screening</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Prior cancer therapy with any immunomodulatory agents including checkpoint inhibitors (CPIs; such as anti-PDL1/PD1, anti-CTLA-4, anti-LAG3, anti-TIM3)</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Vaccination with live vaccines within 28 days prior to randomization, or anticipation that a live attenuated vaccine will be required during the study</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Treatment with therapeutic oral or IV antibiotics within 14 days prior to randomization</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Concurrent therapy with any other investigational drug (defined as treatment for which there is currently no regulatory authority approved indication) 28 days or 5 half-lives of the drug (whichever is shorter) prior to randomization</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Treatment with immune-modulating and immune suppressive agents/medication 5 half-lives or 28 days (whichever is shorter) prior to randomization</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Regular immunosuppressive therapy (i.e., for organ transplantation, chronic rheumatologic disease)</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Radiotherapy within the last 28 days before start of study drug treatment is not allowed, with the exception of limited palliative radiotherapy</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Prior treatment with adoptive cell therapies, such as chimeric antigen receptor T cells (CAR-T) therapies</li>\n</ul>\n
      • primary_end_points<div class=\"ct-body3\" color:=\"\" font-size:=\"\" helvetica=\"\" line-height:=\"\" sans=\"\" source=\"\" style=\"box-sizing: border-box; font-family: \">\n <span class=\"term\" data-term=\"primary outcome measure\" style=\"box-sizing: border-box; background-position: left bottom; background-size: 4px 1px; background-repeat: repeat-x; transition: background-color 0s ease 0s, all 0.2s ease 0s, box-shadow 0s ease 0s, all 0.2s ease 0s, color 0s ease 0s, all 0.2s ease 0s; border-bottom: 1px dotted; color: rgb(17, 46, 81); cursor: pointer; display: inline;\" tabindex=\"0\" title=\"Show definition\">Primary Outcome Measures </span> :\n <ol style=\"box-sizing: border-box; margin-top: 1ex; margin-bottom: 1ex;\">\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Overall Survival, Defined as the Time from Randomization to Death from Any Cause [ Time Frame: Up to 3 years, 4 months ]</li>\n </ol>\n</div>\n<div class=\"ct-body3\" color:=\"\" font-size:=\"\" helvetica=\"\" line-height:=\"\" margin-right:=\"\" sans=\"\" source=\"\" style=\"box-sizing: border-box; font-family: \">\n <span class=\"term\" data-term=\"secondary outcome measure\" style=\"box-sizing: border-box; background-position: left bottom; background-size: 4px 1px; background-repeat: repeat-x; transition: background-color 0s ease 0s, all 0.2s ease 0s, box-shadow 0s ease 0s, all 0.2s ease 0s, color 0s ease 0s, all 0.2s ease 0s; border-bottom: 1px dotted; color: rgb(17, 46, 81); cursor: pointer; display: inline;\" tabindex=\"0\" title=\"Show definition\">Secondary Outcome Measures </span> :\n <ol style=\"box-sizing: border-box; margin-top: 1ex; margin-bottom: 1ex;\">\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Number of Participants with Adverse Events, Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI-CTCAE v5.0) [ Time Frame: Up to 3 years, 4 months ]</li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Objective Response Rate (ORR), Defined as the Percentage of Participants with a Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) [ Time Frame: Up to 3 years, 4 months ]</li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Disease Control Rate (DCR), Defined as the Percentage of Participants with an Objective Response or Stable Disease According to RECIST v1.1 [ Time Frame: Up to 3 years, 4 months ]</li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Duration of Response for Participants with ORR, Defined as the Time from the First Occurrence of a Documented Objective Response to Disease Progression According to RECIST v1.1 or Death from any Cause, Whichever Occurs First [ Time Frame: Up to 3 years, 4 months ]</li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Progression-Free Survival (PFS), Defined as the Time from Randomization to the First Occurrence of Progression as Determined According to RECIST v1.1 or Death from any Cause, Whichever Occurs First [ Time Frame: Up to 3 years, 4 months ]</li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Percentage of Participants Reporting Clinically Meaningful Improvement in Global Health Status/Quality of Life (GHS/QoL), and Emotional and Social Functioning, Defined as a ≥10-Point Increase from Baseline as Measured by the EORTC QLQ-C30 [ Time Frame: Baseline (Day 1 of Cycle 1) and Day 1 of Cycles 4, 7, and 10 (each cycle is 14 days); then every 3 months until treatment discontinuation; and every 3 months during the first year of post-treatment follow-up (up to 3 years) ]\n <div class=\"tr-indent2\" style=\"box-sizing: border-box; line-height: 1.6; clear: both; margin-left: 1em; margin-top: 1ex;\">\n EORTC QLQ-C30 = European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30</div>\n </li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Percentage of Participants Reporting a Clinically Meaningful Improvement in GHS/QoL, and Emotional and Social Functioning, Defined as a ≥10-Point Increase from Baseline as Measured by the EORTC IL97 Questionnaire [ Time Frame: Baseline (Cycle 1 Day 1) and Day 1 of Cycles 2, 3, 5, 6, 8, and 9 (each cycle is 14 days) ]\n <div class=\"tr-indent2\" style=\"box-sizing: border-box; line-height: 1.6; clear: both; margin-left: 1em; margin-top: 1ex;\">\n EORTC IL97 = European Organisation for Research and Treatment of Cancer - Item Library 97</div>\n </li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Percentage of Participants Reporting a Clinically Meaningful Improvement in Dysphagia, Defined as a ≥10-Point Increase from Baseline as Measured by the EORTC QLQ-OES18 [ Time Frame: Baseline (Cycle 1 Day 1) and Day 1 of each subsequent treatment cycle (each cycle is 14 days) until treatment discontinuation; and every 3 months during the first year of post-treatment follow-up (up to 3 years) ]\n <div class=\"tr-indent2\" style=\"box-sizing: border-box; line-height: 1.6; clear: both; margin-left: 1em; margin-top: 1ex;\">\n EORTC QLQ-OES18 = European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire for Esophageal Cancer</div>\n </li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Serum Concentrations of RO7121661, RO7247669, and Nivolumab [ Time Frame: Predose and at end of infusion on Day 1 of every treatment cycle and on Day 8 of Cycles 1 and 5 (each cycle is 14 days); and at treatment discontinuation (up to 2 years) ]</li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Area Under the Time-Serum Concentration Curve (AUC) of RO7121661, RO7247669, and Nivolumab [ Time Frame: Predose and at end of infusion on Day 1 of every treatment cycle and on Day 8 of Cycles 1 and 5 (each cycle is 14 days); and at treatment discontinuation (up to 2 years) ]</li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Maximum Serum Concentrations of RO7121661, RO7247669, and Nivolumab [ Time Frame: Predose and at end of infusion on Day 1 of every treatment cycle and on Day 8 of Cycles 1 and 5 (each cycle is 14 days); and at treatment discontinuation (up to 2 years) ]</li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Total Clearance of RO7121661, RO7247669, and Nivolumab [ Time Frame: Predose and at end of infusion on Day 1 of every treatment cycle and on Day 8 of Cycles 1 and 5 (each cycle is 14 days); and at treatment discontinuation (up to 2 years) ]</li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Volume of Distribution at Steady State of RO7121661, RO7247669, and Nivolumab [ Time Frame: Predose and at end of infusion on Day 1 of every treatment cycle and on Day 8 of Cycles 1 and 5 (each cycle is 14 days); and at treatment discontinuation (up to 2 years) ]</li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Terminal Half-Life of RO7121661, RO7247669, and Nivolumab [ Time Frame: Predose and at end of infusion on Day 1 of every treatment cycle and on Day 8 of Cycles 1 and 5 (each cycle is 14 days); and at treatment discontinuation (up to 2 years) ]</li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Number of Participants with Anti-Drug Antibodies (ADAs) to RO7121661, RO7247669, or Nivolumab at Baseline and During the Study [ Time Frame: Predose at Baseline (Day 1 of Cycle 1) and on Day 1 of Cycles 2, 3, 4, 5, and 7, and then every 3 cycles thereafter (each cycle is 14 days); and at treatment discontinuation (up to 2 years) ]</li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Change from Baseline in the Number of T-cell Subsets by Phenotype and Activation Status (CD4/CD8 HLA-DR+Ki67+) in the Peripheral Blood [ Time Frame: Predose at Baseline (Day 1 of Cycle 1) and on Day 1 of Cycles 2, 3, 5, and 7, and then every 3 cycles thereafter (each cycle is 14 days); and at treatment discontinuation (up to 2 years) ]</li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Change from Baseline in the Number of CD8+ T-cells Infiltrating the Tumor Microenvironment [ Time Frame: Baseline and Day 1 of Cycle 3 (each cycle is 14 days) ]</li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Change from Baseline in the Number of CD8+ T-cells Proliferating (CD8+Ki67+) in the Tumor Microenvironment [ Time Frame: Baseline and Day 1 of Cycle 3 (each cycle is 14 days) ]</li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Baseline PDL1, CD8+PD1+, CD8+TIM3+, and CD8+LAG3+ Expression in the Tumor Microenvironment [ Time Frame: At Baseline ]</li>\n </ol>\n</div>\n<p>\n  </p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • 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_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n <strong><u>Aga Khan University, Nairobi</u></strong></p>\n<p>\n The study will be conducted at the Aga Khan University, Clinical Research Unit (CRU) which</p>\n<p>\n occupies a newly renovated space located on the 9th Floor of the Doctor’s Park Building, adjacent to the Aga Khan University Hospital, Nairobi and Aga Khan University Centre along 3rd Parklands Avenue Nairobi. </p>\n<p>\n The 4000sq.ft clinical research unit has been designed and equipped for the conduct of Phase 1-3 Clinical trials. The facility comprises of; phlebotomy and triage suites, examination rooms, informed consent booths, investigational product (IP) treatment suite, clinical research pharmacy, clinical research laboratory, research medical records facility and administrative offices. </p>\n<p>\n The CRU conducts ICH-GCP/FDA compliant Clinical Research. The CRU is well- staffed by trained personnel with expertise in the following research related tasks</p>\n<ul>\n <li>\n Clinical Research Nursing: Make CRF entries/resolve queries; Collect medical information; Vital signs; Collect adverse events; Administer IP; Collect lab samples; Participant recruitment and retention.</li>\n <li>\n Pharmacist and Pharmacy Technologist: Investigational Drug Services: Manage IP receipt/return; Prepare and dispense IP; Unblinding procedures.</li>\n <li>\n Regulatory Affairs: Manage submissions to ethics and regulatory authorities. Maintain essential documents.</li>\n <li>\n Contracts and Budgets: Maintain legal and financial documents; Ensure appropriate invoicing to the sponsor; Ensure appropriate processes for research covered procedures versus patients’ standard of care</li>\n <li>\n Data Management: Make CRF entries/resolve queries; Maintain the patients’ research documents</li>\n <li>\n Clinical Research operations: Oversight of AKU’s Clinical Research Unit’s studies and staff; support all research staff with their tasks</li>\n <li>\n Investigators: Obtain Informed Consent; Assess eligibility; Make CRF entries/resolve Queries; Medical decisions/review; Collect medical information; Vital signs; Assess Ordinal Scale; Collect/Assess Adverse Events; Administer IP; Conduct Physical Exam; Collect Lab Samples; Maintain Essential Documents; IP processes</li>\n</ul>\n<p>\n AKUH, N has Outpatient Cancer Care (OCC) as part of our larger Comprehensive Oncology Program. The facility is designed to provide an integrated, patient-centered service across the care cycle from diagnosis through treatment, survivorship and palliative care.</p>\n<p>\n Cancer patients treated at AKUHN have access to psychosocial and support counselling  as part of AKUH, N best practice.  This is not limited to non-study patients and thus will be available to study patients as well. F</p>\n<p>\n The Outpatient Cancer Care also offers streamlined, efficient care by multidisciplinary team of specialists. This coordinated approach allows for all-inclusive care to cancer patients and their families as a one stop service. ​</p>\n<p>\n The AKUH, N approach to care is guided by core principles of Quality, Access, Impact and Relevance and its healthcare practices are of the highest quality, as benchmarked against international standards including accreditation by:</p>\n<ul>\n <li>\n Joint Commission International (JCI)</li>\n <li>\n College of American Pathologists (CAP)</li>\n <li>\n International Quality Assurance 9001:2008</li>\n</ul>\n<p>\n  </p>\n
      • other_details_explanation<p>\n Not Applicable</p>\n
      • other_details_regulatory_notapproved<p>\n 1. Brazil - submission date 08Mar2021</p>\n<p>\n 2. France - submission date 26Apr2021</p>\n<p>\n 3. Italy - submission date 15Mar2021</p>\n<p>\n 4. South Africa - submission date 14May2021</p>\n<p>\n 5. Ukraine - submission date 16Mar2021</p>\n
      • other_details_regulatory_approved<p>\n 1. Belgium - 27May2021 - 2 sites</p>\n<p>\n 2. Czech Republic - 15Jun2021 - 2 sites</p>\n<p>\n 3. Denmark - 02Jun2021 - 2 sites</p>\n<p>\n 4. Germany - 23Jun2021 - 4 sites</p>\n<p>\n 5. Hungary - 17May2021 - 3 sites</p>\n<p>\n 6. South Korea - 04Mar2021 - 5 sites</p>\n<p>\n 7. Poland - 21May2021 -  5 sites</p>\n<p>\n 8. Russia - 25Mar2021 - 5 sites</p>\n<p>\n 9. Singapore - 28May2021 - 2 sites</p>\n<p>\n 10. Spain - 26Feb2021 - 6 sites</p>\n<p>\n 11. Taiwan - 21Apr2021 - 3 sites</p>\n<p>\n 12. Thailand - 02Jun2021 - 3 sites</p>\n<p>\n 13. Turkey - 19Apr2021 - 6 sites</p>\n<p>\n 14. UK - 17May2021 - 6 sites</p>\n<p>\n  </p>\n
      • other_details_regulatory_rejected<p>\n Not Applicable</p>\n
      • other_details_regulatory_halted<p>\n Not Applicable</p>\n
      • estimated_duration3 years (Jun 2021 to August 2024)
      • 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_comparatorNivolumab
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states20
      • number_of_sites2
      • multi_country_listKorea, Taiwan, Singapore, Thailand, Germany, UK France, Spain, Italy, Czech Republic, Poland, Hungary, Turkey, Russia, Ukrane, Denmark, Belgium, Brazil, South Africa & Kenya
      • data_monitoring_committeeYes
      • total_enrolment_per_siteAga Khan University, Nairobi - 5-10\nInternational Cancer Institute - 10-20
      • total_participants_worldwide255
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_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_nameMansoor
      • investigator1_middle_name
      • investigator1_family_nameSaleh
      • investigator1_qualificationProfessor of Hematology and Oncology
      • investigator1_professional_addressAga Khan University, Nairobi, 3rd Parklands Avenue, Nairobi-Kenya
      • investigator1_telephone+254 709 93 1500
      • investigator1_emailmansoor.saleh@aku.edu
      • organisations_transferred_Yes
      • number_participants15-30
      • notification<p>\n Dear ECCT Reviewers, </p>\n<p>\n This is a novel interventional trial for esophageal cancer, which has limited treatment options in Kenya. </p>\n<p>\n To be able to recruit a sizeable number of Kenyan patients in this competitive recruitment study, we would like to submit the relevant protocol and related documents for your review and approval. The lead institution is AgaKhan University Hospital Nairobi, under PI Prof. Mansoor Saleh. The second site is Internatlonal Cancer Institute Eldoret (ICI) under PI Prof Fred Asirwa Chite. Ethics Committee approval through KEMRI SERU for ICI is unforunately still pending at this time point, but expected soon. We are kindly requesting that you begin reviewing the study documentation, pending PPB approval only once the ICI EC approval is supplied. AKUH Nairobi EC approval has been supplied for your review. </p>\n<p>\n We appreciate the consideration.</p>\n<p>\n Sincerely,</p>\n<p>\n Dr. Huwaida Bulhan (Roche Kenya Ltd)</p>\n
      • approval_date01-11-2021
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted16-09-2021
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonThe application has been approved by the experts
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-02-04 15:29:06
      • created2021-06-21 14:40:09
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id685
        • application_id1029
        • given_nameFredrick
        • middle_nameChite
        • family_nameAsirwa
        • qualificationProfessor of Hematology and Oncology
        • professional_addressInternational Cancer Institute, Nandi Road 8/10, Eldoret, Kenya, 8088-30100
        • telephone+254 700 522 149
        • emaildirector@intercancer.com
        • created2021-06-21 15:04:04
        • modified2021-09-16 12:06:55
    • SiteDetail(array)
      • 0(array)
        • id947
        • application_id1029
        • county_id47
        • site_nameAga Khan University, Nairobi
        • physical_address3rd Parklands Avenue, Off Limuru Road
        • contact_detailsP.O. Box 30270, Nairobi 00100
        • contact_personProf Mansoor Saleh
        • site_capacity(null)
        • misc(null)
        • created2021-06-21 15:04:04
        • modified2021-09-16 12:06:55
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 1(array)
        • id970
        • application_id1029
        • county_id27
        • site_nameInternational Cancer Institute
        • physical_addressNandi Road 8/10, Eldoret, Kenya, 8088-30100
        • contact_detailsP.O. Box 8088-30100, Eldoret Kenya
        • contact_personProf Fredrick Chite Asirwa
        • site_capacity(null)
        • misc(null)
        • created2021-06-23 11:00:39
        • modified2021-09-16 12:06:55
        • County(array)
          • id27
          • county_nameUasin Gishu
          • created2012-06-15 10:25:15
          • modified2012-06-15 10:25:15
    • Sponsor(array)
      • 0(array)
        • id517
        • application_id1029
        • sponsorHoffmann La Roche
        • sponsor_typeIndustry
        • contact_personHuwaida Bulhan
        • addressThe Atrium, 6th Floor Chaka Road, off Lenana Road P.O. Box 44212-00100 Nairobi, Kenya
        • telephone_number+254 780 888 997
        • fax_number
        • cell_number+254 780 888 997
        • email_addresshuwaida.bulhan@roche.com
        • created2021-06-21 15:04:04
        • modified2021-09-16 12:06:55
  • 1(array)
    • Application(array)
      • id1034
      • user_id693
      • trial_status_id4
      • abstract_of_study<div>\n Sickle cell disease (SCD) is an inherited blood disorder caused by a point mutation in the β globin gene resulting in the formation of “sickle hemoglobin” (HbS), which</div>\n<div>\n polymerizes in the deoxygenated state and leads to red blood cell (RBC) sickling.</div>\n<div>\n Leg ulcers are a common complication of SCD, particularly among individuals with the more severe genotypes. Global prevalence of leg ulcers in the SCD population varies</div>\n<div>\n geographically, with estimates of 14% to 18% in the United States (US) and Europe, 10% to 30% in sub-Saharan Africa, and 30% to 40% in Jamaica and Brazil. There is a large</div>\n<div>\n unmet need for effective treatment for leg ulcers. In a Cochrane review of 5 randomized trials of interventions for treating leg ulcers in patients with SCD, none of the</div>\n<div>\n therapies resulted in complete ulcer healing (Marti-Carvajal, 2014). Current management of SCD leg ulcers relies primarily on the practice approach used for other cutaneous</div>\n<div>\n ulcers, involving debridement, wet to dry dressings, and topical agents.</div>\n<div>\n Voxelotor (previously GBT440) is an HbS polymerization inhibitor that binds to HbS with a 1:1 stoichiometry and exhibits preferential partitioning to RBCs. The binding</div>\n<div>\n increases HbS-oxygen (O2) affinity, stabilizing the oxyhemoglobin (oxyHb) state and inhibiting polymerization. Findings from the HOPE trial (study GBT440-031) suggest that</div>\n<div>\n voxelotor may be an effective treatment for leg ulcers.</div>\n<div>\n The effect of voxelotor on leg ulcer healing and safety will be assessed in participants 12 years of age and older with SCD and active leg ulcer(s) in this study. The study will</div>\n<div>\n be conducted in approximately 80 eligible participants at approximately 10 global clinical trial sites. In our site we plan to recruit at least 20 patients. The primary objective of</div>\n<div>\n this study is to assess the effect of voxelotor and SOC compared to placebo and SOC on leg ulcer healing in participants ≥ 12 years of age with SCD. The secondary objectives</div>\n<div>\n of this study are to evaluate the effect of voxelotor and SOC compared to placebo and SOC on • Time to resolution of target ulcer(s) • Change in total surface area(s) of</div>\n<div>\n target ulcer(s) • Incidence of new ulcers. The proportion of participants achieving resolution of the target ulcer will measure the primary endpoint. The analysis will use a</div>\n<div>\n Cochran-Mantel-Haenszel (CMH) test to compare voxelotor + SOC with placebo + SOC groups, stratified by target ulcer size and target ulcer duration. For the time to</div>\n<div>\n resolution, a stratified log-rank test will be used to compare the treatment groups. A Cox regression model will be used to estimate the hazard ratio between voxelotor +SOC</div>\n<div>\n and placebo + SOC groups, as appropriate. Exploratory endpoints will be summarized by descriptive statistics. Safety Analysis will be performed on all participants receiving</div>\n<div>\n at least 1 dose of study drug.</div>\n
      • study_title<p>\n A Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy of Voxelotor for the Treatment of Leg Ulcers in Patients with Sickle Cell DiseaseA Phase 4, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy of Voxelotor for the Treatment of Leg Ulcers in Patients with Sickle Cell Disease</p>\n
      • laymans_summary<div>\n Sickle cell disease is an inherited blood abnormality caused by a change in the makeup of the Red blood cell forming genes that result in the clumping of the red cells. These</div>\n<div>\n abnormal red cells tend to change shape and stick to each other and walls of blood vessels whenever they are exposed to low oxygen levels.</div>\n<div>\n Persons with this gene abnormality experience several complications among them being leg ulcers because of damage of blood vessels. The prevalence of the leg ulcers</div>\n<div>\n varies with geographical location and is estimated to be about 30% in Sub Sahara Africa among people with Sickle cell disease (SCD). No data on the prevalence of leg ulcers</div>\n<div>\n in Kenya is available. There are no known effective treatments for leg ulcers in people with SCD. Current management is based on practice guidelines for treating other skin</div>\n<div>\n ulcers which include use of dressings and application of medications on the ulcers and or surgical trimming and cleaning of the wounds.</div>\n<div>\n Voxelotor is medicine that prevents the change on the shape of the red cells that causes clumping of the red cells. In the HOPE trial, though this was not among the main</div>\n<div>\n study objectives, it was found that participants who had initially joined the study with leg ulcers experienced complete resolution of the ulcers and implies that voxelotor may</div>\n<div>\n be useful in management of leg ulcers.</div>\n<div>\n In this study, the effect of voxelotor on leg ulcer healing and safety will be studied in participants 12 years of age and older with SCD and active leg ulcer(s). Eighty (80)</div>\n<div>\n participants will be recruited globally from the approximately 10 global sites. The primary objective of this study is to assess the effect of voxelotor and SOC compared to</div>\n<div>\n placebo and SOC on leg ulcer healing in participants ≥ 12 years of age with SCD. The secondary objectives of this study are to evaluate the effect of voxelotor and SOC</div>\n<div>\n compared to placebo and SOC on: • Time to healing of target ulcer(s) • Change in total surface area(s) of target ulcer(s), incidence of new ulcers. The primary outcome will be</div>\n<div>\n measured by the proportion of participants achieving healing of the target ulcer(s). Exploratory outcomes will be summarized by descriptive statistics. Safety Analysis will be performed on all participants receiving at least 1 dose of study drug.</div>\n<div>\n  </div>\n<div>\n <p>\n  </p>\n <p>\n Sickle cell disease (SCD) is a condition where red blood cells are shaped like a “sickle” (crescent moon) instead of being round. These sickle cells break down more quickly asnd can block blood flow. This makes it harder for the blood to carry oxygen around the body, leading to problems such as anemia (low levels of red blood cells). A complication of SCD includes open sores (“ulcers”) on the legs, likely due to poor blood flow and the breakdown of red blood cells. Leg ulcers are very painful, heal slowly, and even after they heal, often come back again. No therapies are available for treating or managing leg ulcers caused by SCD.</p>\n <p>\n The main purpose of this study was to find out whether voxelotor could help treat leg ulcers in participants with SCD compared to placebo. A placebo does not have any medicine in it, but it looks just like voxelotor</p>\n <p>\n Researchers wanted to know:</p>\n <p>\n · Can voxelotor help treat leg ulcers compared to placebo after 12 weeks of treatment?</p>\n <p>\n  · What medical problems did participants have during the study?</p>\n <p>\n  </p>\n <p>\n This study stopped early and was not completed as planned.</p>\n <p>\n  </p>\n <p>\n  </p>\n <p>\n How was the study done?</p>\n <p>\n During the Screening and Run-in Periods, researchers checked the participants’ health to make sure they could join the study.</p>\n <p>\n After the Screening Period, participants entered the 2-week Run-in Period, wherein researchers checked the participants’ leg ulcers. During this period, participants started wound care for their leg ulcers according to the study plan.</p>\n <p>\n Double-blind Period Researchers used a computer program to randomly divide the participants into 2 groups.</p>\n <p>\n  · Voxelotor Group: Participants took voxelotor tablets once per day.</p>\n <p>\n  · Placebo Group: Participants took placebo tablets once per day.</p>\n <p>\n Participants took voxelotor or placebo for 12 weeks while continuing wound care for their leg ulcers according to the study plan. During this period, the participants and researchers did not know to which treatment group the participants were assigned. This is known as the “Double-blind” Period. During this period, researchers looked at the participants’ leg ulcers to answer the main question of the study. </p>\n <p>\n  </p>\n <p>\n  Open-label Period</p>\n <p>\n  </p>\n <p>\n After the 12-week Double-blind Period, participants entered the “Open-label” Period. During this period, the participants and researchers knew that all participants were taking voxelotor. · Voxelotor Group: Participants who took voxelotor in the Double-blind Period continued to take voxelotor. · Delayed Voxelotor Group: Participants who took placebo during the Double-blind Period were switched to start voxelotor. Participants took voxelotor for at least 12 weeks while continuing wound care for their leg ulcers according to the study plan. Participants who completed the 12- week treatment in the Open-label Period could keep taking voxelotor as long as they were receiving clinical benefit as observed by the researchers. Throughout the study, researchers checked on the participants’ health and asked them how they were feeling.</p>\n <p>\n  </p>\n <p>\n The Sponsor ran this study at 19 locations in 3 countries: Brazil, Kenya, and Nigeria.</p>\n <p>\n It began on 30 May 2022 and ended on 22 October 2024.</p>\n <p>\n The study included participants who were at least 12 years old with SCD and had at least 1 leg ulcer.</p>\n <p>\n  · A total of 50 boys/men and 38 girls/women participated.</p>\n <p>\n · All participants were between the ages of 12 and 54 years.</p>\n <p>\n  </p>\n <p>\n Study participants were in the study for about 34 weeks (8 months). The study ran for about 2 years and 4 months before the Sponsor stopped the study. This study stopped early and was not completed as planned.</p>\n</div>\n<div>\n  </div>\n
      • short_titleRESOLVE
      • protocol_noECCT/21/07/01
      • version_noOriginal Version
      • date_of_protocol22-09-2020
      • study_drugVoxelotor (GBT440)
      • disease_conditionTreatment of Leg Ulcers in Patients with Sickle 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_nameVoxelotor
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressNolufefe.Deliwe@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_applicantBridget Tshatsinde
      • declaration_date129-06-2021
      • declaration_principal_investigatorDr Bernhards Ogutu
      • declaration_date229-06-2021
      • placebo_presentYes
      • study_objectives<p>\n Primary Objective</p>\n<p>\n The primary objective of this study is to assess the effect of voxelotor and SOC compared to placebo and SOC on leg ulcer healing in participants ≥ 12 years of age with SCD, as measured by the proportion of participants achieving resolution of target ulcer(s) in each treatment group by Week 12.</p>\n<p>\n  </p>\n<p>\n Secondary Objectives</p>\n<p>\n The secondary objectives of this study are to evaluate the effect of voxelotor and SOC compared to placebo and SOC on:</p>\n<ul>\n <li>\n Time to resolution of target ulcer(s)</li>\n <li>\n Change in total surface area(s) of target ulcer(s)</li>\n <li>\n Incidence of new ulcers</li>\n</ul>\n<p>\n Exploratory Objectives</p>\n<p>\n The exploratory objectives will assess the effect of voxelotor and SOC compared to placebo and SOC (or open-label voxelotor and SOC, where applicable) on:</p>\n<ul>\n <li>\n Correlation between change in Hb and target ulcer(s) healing</li>\n <li>\n Correlation between change in hemolytic parameters (% reticulocytes, indirect bilirubin, LDH) and target ulcer(s) healing</li>\n <li>\n Health-related quality of life (HRQOL) using patient-reported outcome (PRO) measures, when available (pending translation and cultural validation requirements)\n <ul>\n <li>\n Patient-Reported Outcome Measurements Information System (PROMIS) Pediatric Profile-37 v2.0/PROMIS-43 v2.1), which measures Physical Functioning, Pain Interference, Pain Behavior, Fatigue, Anxiety, Depression, Ability to Participate in Social Roles and Activities)</li>\n <li>\n Visual analog scale (VAS) assessment of pain level linked to target ulcer(s)</li>\n <li>\n Patient Global Impression of Change (PGIC)</li>\n </ul>\n </li>\n <li>\n Clinician Global Impression of Change (CGIC)</li>\n</ul>\n<p>\n  </p>\n<p>\n Safety Objective</p>\n<p class=\"C-BodyText\">\n <span lang=\"EN-US\">The safety objective is to assess the safety and tolerability of voxelotor compared to placebo based on AEs, clinical laboratory tests, physical examinations, vital signs, and other clinical measures (eg, discontinuations due to AEs, dose reductions).<o:p></o:p></span></p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n
      • principal_inclusion_criteria<p>\n                Inclusion Criteria</p>\n<p>\n Participants who meet all of the following criteria will be eligible for study enrollment:</p>\n<p>\n 1.     Male or female participants with documented diagnosis of SCD (HbSS, HbS/β⁰thalassemia)</p>\n<p>\n 2.     Age 12 years and older</p>\n<p>\n 3.     At least 1 cutaneous ulcer(s) on the lower extremity (leg, ankle, or dorsum of foot) that meets the following criteria:</p>\n<p>\n ·       Duration: ≥ 2 weeks and < 6 months at Screening, and</p>\n<p>\n ·       Size: > 2 cm² prior to randomization</p>\n<p style=\"margin-left:36.0pt;\">\n Note: Participants with multiple ulcers are eligible for the study. For each participant, target ulcer(s) for evaluation in this study will be identified and tracked. To qualify as a target ulcer, the ulcer must meet the criteria above.</p>\n<p>\n 4.     Participants, who if female and of child-bearing potential, agree to use highly effective methods of contraception from study start to 30 days after the last dose of study drug and who if male, agree to use barrier methods of contraception from study start to 30 days after the last dose of study drug</p>\n<p>\n 5.     Females of child-bearing potential are required to have a negative pregnancy test before the administration of study drug.</p>\n<p>\n Written informed consent (≥ 18 years) or parental/guardian consent and participant assent (≥ 12–17 years) per IEC policy and requirements, consistent with International Council for Harmonisation (ICH) guidelines</p>\n
      • principal_exclusion_criteria<p>\n Exclusion Criteria</p>\n<p>\n Participants meeting any of the following exclusion criteria will not be eligible for study enrollment:</p>\n<ol>\n <li>\n Target ulcer(s) healed by ≥ 25% during the SOC Run-in prior to randomization</li>\n</ol>\n<p style=\"margin-left:36.0pt;\">\n Note: For participants with multiple ulcers, the participant is not eligible for the study if all target ulcers have healed by ≥ 25% during the SOC Run-in.</p>\n<ol>\n <li value=\"2\">\n Active infection/purulence at ulcer site, or exposed tendon or bone at the ulcer site, based on Investigator’s clinical judgment</li>\n <li value=\"3\">\n Current osteomyelitis at or near the ulcer site</li>\n <li value=\"4\">\n Known vascular abnormalities that would preclude healing in the opinion of the Investigator (eg, pre-existing severe arterial insufficiency in the affected limb)</li>\n <li value=\"5\">\n Serum albumin < 2.0 g/dL</li>\n <li value=\"6\">\n RBC transfusion within 60 days of initiation of study drug</li>\n <li value=\"7\">\n Receiving regularly scheduled RBC transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) during the study</li>\n <li value=\"8\">\n Planned elective surgery within the next 6 months</li>\n <li value=\"9\">\n Anemia due to bone marrow failure (eg, myelodysplasia)</li>\n <li value=\"10\">\n Absolute reticulocyte count < 100 × 10⁹/L</li>\n <li value=\"11\">\n Screening ALT > 4 × upper limit of normal (ULN)</li>\n <li value=\"12\">\n Severe renal dysfunction (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m² by Schwartz formula) or is on chronic dialysis</li>\n <li value=\"13\">\n Clinically significant bacterial, fungal, parasitic, or viral infection that requires therapy:</li>\n</ol>\n<ul>\n <li>\n Participants with acute bacterial infection requiring systemic antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed.</li>\n <li>\n Participants with known active hepatitis A, B, or C or who are known to be human immunodeficiency virus (HIV) positive</li>\n <li>\n Participants with active SARS-CoV-2 infection (COVID-19)</li>\n</ul>\n<ol>\n <li value=\"14\">\n Females who are breast-feeding or pregnant</li>\n <li value=\"15\">\n History of hematopoietic stem cell transplant or gene therapy</li>\n <li value=\"16\">\n Participated in another clinical trial of an investigational product (or medical device) within 30 days or 5 half-lives of date of informed consent, whichever is longer, or is currently participating in another trial of an investigational product (or medical device)</li>\n <li value=\"17\">\n Medical, psychological, or behavioral condition that, in the opinion of the Investigator, would confound or interfere with evaluation of safety and/or efficacy of the study drug, prevent compliance with the study protocol; preclude informed consent; or render the participant unable/unlikely to comply with the study procedures</li>\n <li value=\"18\">\n Use of herbal medications (eg, St. John’s Wort), sensitive cytochrome P450 (CYP) 3A4 substrates with a narrow therapeutic index, strong CYP3A4 inhibitors, fluconazole, or moderate or strong CYP3A4 inducers</li>\n</ol>\n<p>\n  </p>\n
      • primary_end_points<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><u>Primary Endpoint</u></span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">The primary endpoint will be measured by the proportion of participants achieving resolution of the target ulcer(s), defined as skin re-epithelialization confirmed at 2 consecutive study visits 2 weeks apart during the 12-week Randomized Treatment Period. To qualify as an event, ulcer re‑epithelialization that is first assessed at Week 12 must be confirmed at Week 14.</span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">For participants with more than one target ulcer, all target ulcers must be confirmed resolved in order for the participant to be considered a responder.</span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><u>Secondary Endpoints</u></span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Key secondary endpoints in this study include a comparison of voxelotor and SOC versus placebo and SOC in:</span></span></p>\n<ul>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Time (in days) to resolution of target ulcer(s) up to Week 12</span></span></li>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Change from baseline in total surface area of target ulcer(s) at Week 12</span></span></li>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Incidence of new ulcers by Week 12</span></span></li>\n</ul>\n<p>\n  </p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Exploratory Endpoints</span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Exploratory endpoints include:</span></span></p>\n<ul>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Proportion of participants achieving resolution of target ulcer(s) by Week 24</span></span></li>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Time (in days) to resolution of target ulcer(s) up to Week 24</span></span></li>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Change from baseline in total surface area of target ulcer(s) over time up to Week 24</span></span></li>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Correlation between change in Hb and target ulcer(s) healing at Week 12 and Week 24</span></span></li>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Correlation between change in markers of hemolysis (% reticulocytes, indirect bilirubin, LDH) and target ulcer(s) healing at Week 12 and Week 24</span></span></li>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Change from baseline in PRO HRQOL measures: PROMIS-43 v2.1 (Physical Functioning, Pain Interference, Pain Behavior, Fatigue, Anxiety, Depression, Ability to Participate in Social Roles and Activities) at Week 12 and Week 24</span></span></li>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Change from baseline in pain level linked to target ulcer(s) assessed by VAS at Week 12 and Week 24</span></span></li>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">PGIC score at Week 12 and Week 24</span></span></li>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">CGIC score at Week 12 and Week 24</span></span></li>\n</ul>\n<p>\n  </p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Safety Endpoints</span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">The safety endpoints include assessments of AEs, clinical laboratory parameters, physical examinations, and vital signs.</span></span></p>\n<p>\n  </p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • 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_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use1
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<table border=\"1\" cellpadding=\"1\" cellspacing=\"1\" style=\"width:500px;\">\n <caption>\n Dr Ogutu's Site Capacity</caption>\n <tbody>\n <tr>\n <td>\n Number of Staff</td>\n <td>\n Name of staff</td>\n <td>\n Qualification</td>\n <td>\n Role in the study</td>\n </tr>\n <tr>\n <td>\n 1</td>\n <td>\n Dr Bernhard Ogutu</td>\n <td>\n MBChB, Master of Medicine (MMed) (Paediatrics), PhD (Clinical\n <div>\n Pharmacology)</div>\n </td>\n <td>\n Principal Investigator</td>\n </tr>\n <tr>\n <td>\n 1</td>\n <td>\n Dr Anastacia Omoding</td>\n <td>\n (MMed) (Paediatrics), MBChB, C.P.A 1 & 2</td>\n <td>\n Sub-Investigator</td>\n </tr>\n <tr>\n <td>\n 1</td>\n <td>\n Dr Godfrey Allan Otieno</td>\n <td>\n (MMed) (Paediatrics), MBChB,</td>\n <td>\n Sub-Investigator</td>\n </tr>\n <tr>\n <td>\n 1</td>\n <td>\n Dr Ruth Wasuna</td>\n <td>\n Bachelor of Pharmacy, MBA, PhD in Business Administration</td>\n <td>\n Pharmacist</td>\n </tr>\n <tr>\n <td>\n 1</td>\n <td>\n Dr Elizabeth Opondo</td>\n <td>\n Bachelor of Pharmacy</td>\n <td>\n Pharmacist</td>\n </tr>\n </tbody>\n</table>\n<table border=\"1\" cellpadding=\"1\" cellspacing=\"1\" style=\"width: 500px;\">\n <caption>\n <br />\n Prof Githanga's Site Capacity</caption>\n <tbody>\n <tr>\n <td>\n Number of Staff</td>\n <td>\n Name of staff</td>\n <td>\n Qualification</td>\n <td>\n Role in the study</td>\n </tr>\n <tr>\n <td>\n 1</td>\n <td>\n Prof Jessie Nyokabi Githanga</td>\n <td>\n MBChB, MMed (Path)(UON), FCPath ECSA</td>\n <td>\n Principal Investigator</td>\n </tr>\n <tr>\n <td>\n 1</td>\n <td>\n Dr Joy Githua</td>\n <td>\n MBChB</td>\n <td>\n Sub-Investigator</td>\n </tr>\n <tr>\n <td>\n 1</td>\n <td>\n Dr Doreen Mutua</td>\n <td>\n MBChB</td>\n <td>\n Sub-Investigator</td>\n </tr>\n <tr>\n <td>\n 1</td>\n <td>\n Samuel Madere</td>\n <td>\n Bachelor of Pharmacy</td>\n <td>\n Pharmacist</td>\n </tr>\n </tbody>\n</table>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Please refer to attached Site Specific Addendum for full site capacity information</span></span></p>\n<p color:=\"\" font-size:=\"\" line-height:=\"\" style=\"margin: 10px 0px; font-family: \" text-rendering:=\"\" trebuchet=\"\">\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><u><span style=\"color: rgb(34, 34, 34);\">Strathmore University Medical Centre (SUMC)</span></u></span></span></p>\n<p color:=\"\" font-size:=\"\" line-height:=\"\" style=\"margin: 10px 0px; font-family: \" text-rendering:=\"\" trebuchet=\"\">\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><span style=\"color:#000000;\">The SUMC is designed for clinical trials and has a full clinical laboratory with bioanalytical capability. The Centre is managed by Strathmore University and the Centre for Research in Therapeutic Sciences (CREATES) consortium. The Centre also has a dental unit. The medical centre is staffed by 2 pediatricians, 2 physicians, 2 medical officer, 1 clinical officer, 4 dental surgeons, 3 psychologists, 1 pharmacist, 1 visiting psychiatrist, 1 physician assistant, 4 nurses and 4 laboratory technologists. The facility supports healthcare to university students and staff and also general public. The centre has previously run a SCD clinic every Tuesday</span></span></span></p>\n<div>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">The sickle cell study will be conducted at SUMC, recruitment will occur at the clinic. SUMC is located at Strathmore University in Madaraka Estate of Nairobi west, Nairobi County.</span></span></div>\n<div>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">SUMC will be staffed by qualified research personnel from KEMRI and SUMC. The site has a pharmacy, treatment area, clinical assessment area, data entry area, internal quality control and registration area and space where monitoring can be done. SUMC has a data base from the SCD clinic it previously ran with more than 200 patients on follow up comprising of both adults and children.</span></span></div>\n<div>\n  </div>\n<div>\n <div>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">SUMC is an outpatient facility with a 2-bed holding unit and a separate emergency resuscitation area. The centre serves as a clinical trials facility for both paediatric and adult studies as proposed in this study. The participants who will require inpatient care will be admitted to Coptic Hospital Ngong Road as SUMC already has an existing working arrangement.</span></span></div>\n <div>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">As for sickle cell disease, there is a database in place that has over 200 patients and we hope to base our recruitment on this list. The SUMC is also linked to other private, government, non-governmental and county health facilities, in Nairobi County that take care of patients with SCD. For the care of sickle cell patients, the SCD clinic will work closely with the study team.</span></span></div>\n</div>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">The site has a multidisciplinary study team that comprises specialists and professionals in many fields of medicine including; medical officers, paediatricians, haematologists, oncologists, pathologists, nurses, pharmacists, medical laboratory technologists.  The Team has members who have been trained on the job as study coordinators.  The team members are experienced in clinical trials and have all been trained in Good Clinical Practice and most have successfully participated in several other clinical trials. </span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><strong><u>KEMRI Kondele Children’s Hospital</u></strong></span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">The Kondele Children’s Hospital is designed for large clinical trials and has a full clinical laboratory including microbiology capability. The hospital is a KEMRI facility managed in collaboration with Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH)</span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><strong>Location.</strong></span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">The study will be carried out at the KCH which is within Jaramogi Oginga Odinga Teaching and Referral Hospital (JOOTRH). Recruitment will take place at KCH.</span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">KCH will be staffed by qualified research personnel from KEMRI.  The site has a pharmacy, vaccination area, clinical assessment area, data entry area, internal quality control and registration area and space where monitoring can be done.</span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><strong>Provision of medical care</strong></span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">The Kondele Children Hospital is a 71 bed unit hospital run by the Ministry of Health. However, KEMRI doctors’ and other clinical staff currently supplement the clinical care services at this children’s hospital. The Kondele Children’s Hospital offers both outpatient and inpatient services. The outpatient is served by clinical officers (physician assistants) who are the primary (first) contacts with the patients. Those who require inpatient care are admitted to the hospital for further clinical evaluation, treatment and care by the medical team (Paediatricians, Medical Officers, Nurses, and Nutritionists). The unit serves as a clinical trials facility for both paediatric and adult studies as proposed in this study.</span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">At KCH, children with sickle cell disease are followed up on a regularly in the weekly sickle cell disease clinic. There is a database of children with SCD that has about over 300 patients, and the study team hope to base the recruitment based on this database. The children’s hospital is part of the Jaramogi Oginga Odinga Teaching and Referral Hospital with medical outpatient clinic and adult inpatient care where some of the older patients with SCD are taken care. The study team will work closely with the hospital clinical team to provide medical care for patients with SCD. The hospital too is surrounded by private, governmental, non-governmental health facilities, in the Kisumu county.   </span></span></p>\n<p>\n  </p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><strong><u>Site personnel roles and responsibilities at Gertrude’s Children’s Hospital,</u></strong></span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><u>Principal Investigator </u></span></span></p>\n<ul>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Prof Jessie Githanga</span></span></li>\n</ul>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">A qualified haematologist/clinical pathologist, registered by the Kenya Medical Practitioners and Dentists Board (KMPD).  She will be responsible for the overall conduct of the trial at the study site, budgetary negotiations, administrative actions and communication between Institutional Review Boards, and the sponsor and oversight of patient care. She will oversee the recruitment of the subjects and supervision of the staff.</span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><u>Co-Investigator/main coordinator</u></span></span></p>\n<ul>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Dr. Doreen Karimi Mutua</span></span></li>\n</ul>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">A qualified paediatrician, with subspecialty training in paediatric haemato-oncology working at Gertrude’s Children’s Hospital (GCH) and registered by the KMPD.  Dr Mutua will be responsible for clinical care provision of the patients, direct supervision of study staff and will also participate in study recruitment.  Dr Mutua supports PI and has roles that may be delegated such as ethical and sponsor communication and may be delegated related roles.</span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><u>Study Coordinator :</u></span></span></p>\n<ul>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Dr Joy Githua</span></span></li>\n</ul>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">A qualified medical officer, registered by the KMPDB working at Gertrude’s Children’s Hospital (GCH). She will be the main coordinator for the study and will be responsible for day to day management of trial aspects including participant recruitment, follows up, safety monitoring, data entry and maintaining the site files and other study records and may be delegated related roles. </span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><u>Study Pharmacists</u>:</span></span></p>\n<ul>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Dr Samuel Madere</span></span></li>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Dr Cresencia N. Makokha</span></span></li>\n</ul>\n<p>\n  </p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Qualified pharmacists, registered by the PPB, will be delegated roles of the IP storage and related duties, IP dispensing, processing of import permit for IP and may be delegated related roles.</span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><u>Study nurses:</u></span></span></p>\n<ul>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Hannah Wanjiku (assistant study coordinator)</span></span></li>\n</ul>\n<ul>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Felicity Kamundi</span></span></li>\n</ul>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">A registered nurse, registered by the Nursing Council of Kenya,  will be responsible for co-ordinating the patient visits and patient training. The assistant study coordinator will in addition play a role in study coordination.</span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><u>Laboratory Manager:</u></span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Peninah Chege:</span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Laboratory manager registered by the Kenya Medical Laboratory Technologists and Technicians Board (KMLTTB) will coordinate laboratory functions, process the import permits for laboratory items, patient and may be delegated related roles.</span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><u>Laboratory technologist/phlebotomist</u></span></span></p>\n<ul>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Charles Muia (technologist)</span></span></li>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Herman Akumu(technologist)</span></span></li>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Joseph Langat (phlebotomist)</span></span></li>\n</ul>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Trained laboratory technologists registered by the KMLTTB, GCP trained. and phlebotomist who will obtain specimens from study participants.  The technologists will perform any local laboratory testing where necessary and package specimens for shipping to Central or other local labs.</span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><u>Quality Assurance Officer</u></span></span></p>\n<ul>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Winnie Abuto</span></span></li>\n</ul>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Quality Assurance Officer Nurse registered by the Nursing Council of Kenya, and GCP trained. She will be tasked with ensuring that study documents are quality controlled so that they are Attributable, Legible, Contemporaneous, Original, and Accurate (ALCOA) in accordance ICH-GCP guidelines.  She will ensure that staff are alerted to changes in SOPs as necessary.</span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><u>Administrative assistant</u></span></span></p>\n<ul>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Truphena Otinyo</span></span></li>\n</ul>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">The Administrative assistant will coordinate and maintain the records of communications with the ERC, assist the main coordinator in patient visit coordination.  She may be delegated related roles.</span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">The site has a multidisciplinary study team that comprises specialists and professionals in many fields of medicine including; medical officers, paediatricians, haematologists, oncologists, pathologists, nurses, pharmacists, medical laboratory technologists.  The Team has members who have been trained on the job as study coordinators.  The team members are experienced in clinical trials and have all been trained in Good Clinical Practice and most have successfully participated in several other clinical trials. </span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><em>Site personnel roles and responsibilities</em></span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><u>Principal Investigator </u></span></span></p>\n<ul>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Prof Jessie Githanga</span></span></li>\n</ul>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">A qualified haematologist/clinical pathologist, registered by the Kenya Medical Practitioners and Dentists Board (KMPD).  She will be responsible for the overall conduct of the trial at the study site, budgetary negotiations, administrative actions and communication between Institutional Review Boards, and the sponsor and oversight of patient care. She will oversee the recruitment of the subjects and supervision of the staff.</span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><u>Co-Investigator/main coordinator</u></span></span></p>\n<ul>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Dr. Doreen Karimi Mutua</span></span></li>\n</ul>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">A qualified paediatrician, with subspecialty training in paediatric haemato-oncology working at Gertrude’s Children’s Hospital (GCH) and registered by the KMPD.  Dr Mutua will be responsible for clinical care provision of the patients, direct supervision of study staff and will also participate in study recruitment.  Dr Mutua supports PI and has roles that may be delegated such as ethical and sponsor communication and may be delegated related roles.</span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><u>Study Coordinator :</u></span></span></p>\n<ul>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Dr Joy Githua</span></span></li>\n</ul>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">A qualified medical officer, registered by the KMPDB working at Gertrude’s Children’s Hospital (GCH). She will be the main coordinator for the study and will be responsible for day to day management of trial aspects including participant recruitment, follows up, safety monitoring, data entry and maintaining the site files and other study records and may be delegated related roles. </span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><u>Study Pharmacists</u>:</span></span></p>\n<ul>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Dr Samuel Madere</span></span></li>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Dr Cresencia N. Makokha</span></span></li>\n</ul>\n<p>\n  </p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Qualified pharmacists, registered by the PPB, will be delegated roles of the IP storage and related duties, IP dispensing, processing of import permit for IP and may be delegated related roles.</span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><u>Study nurses:</u></span></span></p>\n<ul>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Hannah Wanjiku (assistant study coordinator)</span></span></li>\n</ul>\n<ul>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Felicity Kamundi</span></span></li>\n</ul>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">A registered nurse, registered by the Nursing Council of Kenya,  will be responsible for co-ordinating the patient visits and patient training. The assistant study coordinator will in addition play a role in study coordination.</span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><u>Laboratory Manager:</u></span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Peninah Chege:</span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Laboratory manager registered by the Kenya Medical Laboratory Technologists and Technicians Board (KMLTTB) will coordinate laboratory functions, process the import permits for laboratory items, patient and may be delegated related roles.</span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><u>Laboratory technologist/phlebotomist</u></span></span></p>\n<ul>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Charles Muia (technologist)</span></span></li>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Herman Akumu(technologist)</span></span></li>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Joseph Langat (phlebotomist)</span></span></li>\n</ul>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Trained laboratory technologists registered by the KMLTTB, GCP trained. and phlebotomist who will obtain specimens from study participants.  The technologists will perform any local laboratory testing where necessary and package specimens for shipping to Central or other local labs.</span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><u>Quality Assurance Officer</u></span></span></p>\n<ul>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Winnie Abuto</span></span></li>\n</ul>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Quality Assurance Officer Nurse registered by the Nursing Council of Kenya, and GCP trained. She will be tasked with ensuring that study documents are quality controlled so that they are Attributable, Legible, Contemporaneous, Original, and Accurate (ALCOA) in accordance ICH-GCP guidelines.  She will ensure that staff are alerted to changes in SOPs as necessary.</span></span></p>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\"><u>Administrative assistant</u></span></span></p>\n<ul>\n <li>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">Truphena Otinyo</span></span></li>\n</ul>\n<p>\n <span style=\"font-size:12px;\"><span style=\"font-family:arial,helvetica,sans-serif;\">The Administrative assistant will coordinate and maintain the records of communications with the ERC, assist the main coordinator in patient visit coordination.  She may be delegated related roles.</span></span></p>\n
      • other_details_explanation<p>\n This study is being conducted worldwide in different regions.</p>\n
      • other_details_regulatory_notapproved<p>\n National Agency for Food and Drug Administration and Control (Nigeria) - date of application was 03 February 2021.</p>\n
      • other_details_regulatory_approved<p>\n The study is not yet approved by any Regulatory Authorities.</p>\n<p>\n 6 sites submitted in Nigeria.</p>\n
      • other_details_regulatory_rejected<p>\n Not Applicable</p>\n
      • other_details_regulatory_halted<p>\n Not Applicable</p>\n
      • estimated_duration2 Years
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo controlled
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states2 Countries
      • number_of_sites6
      • multi_country_listKenya and Nigeria
      • data_monitoring_committeeNo
      • total_enrolment_per_siteminimum 10 and maximum 20 per site
      • total_participants_worldwide80
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenYes
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationYes
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameBernhards
      • investigator1_middle_name
      • investigator1_family_nameOgutu
      • investigator1_qualificationMBchB, MMed (Peds), PhD
      • investigator1_professional_addressP.O BOX 59857-00200
      • investigator1_telephone+254733812613
      • investigator1_emailogutu6@gmail.com
      • organisations_transferred_Yes
      • number_participants30
      • notification
      • approval_date10-11-2021
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted02-07-2021
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonThe application has been approved by the experts
      • final_report<p>\n Number of Study Center(s) and Investigator(s):</p>\n<p>\n A total of 206 participants were screened at 17 centers in 3 countries, and 88 participants were randomized at 16 centers. A list of study centers and investigators involved in this study is provided in Appendix 16.1.4.1.</p>\n<p>\n Publications: None.</p>\n<p>\n Brief Description of the Trial Design and Methodology:</p>\n<p>\n This study was a Phase 3, multicenter, randomized, placebo-controlled study to evaluate the efficacy of voxelotor and standard of care (SOC) for the treatment of leg ulcers in participants with sickle cell disease (SCD). The study was divided into 5 study periods: Screening, Run-in, blinded Randomized Treatment, Open-Label Treatment, and Follow-up/End of Study After the Screening Period, participants entered a 2-week Run-in Period (Day -14 to Day -1 [+3 days]), during which assessments, including target leg ulcer surface area measurements by digital photography were conducted and SOC was initiated per protocol, following best practices. After completion of Run-in period, eligible participants were stratified, at the time of randomization (Day 1), by target ulcers(s) size (<8 cm2 versus ≥8 cm2) and duration (<9 weeks versus ≥9 weeks) at presentation to evenly balance factors known to affect the likelihood of healing. For participants with 1 target ulcer, stratification was based on the total target ulcer surface area (ie, sum of all target ulcer surface areas) and longest duration of any individual target ulcer(s) present. The Randomized Treatment Period was considered the continuous 12 weeks of voxelotor and SOC, or placebo and SOC treatment from date of randomization (first dose, Day 1). The target leg ulcer(s) was/were assessed by visual inspection and surface area measurement(s) using digital photography at scheduled visits every 2 weeks during the 12-week Randomized. Treatment Period. Target ulcer resolution was defined as skin re-epithelialization confirmed at 2 consecutive study visits 2 weeks apart. To qualify as an event, ulcer re-epithelialization that was first assessed at Week 12 must be confirmed at Week 14. Participants demonstrating initial ulcer re-epithelialization at Week 12 continued treatment in their assigned treatment group for an additional 2 weeks to confirm ulcer resolution. At the end of the 12-week Randomized Treatment Period, all participants (with the exception of those demonstrating initial ulcer re-epithelialization at Week 12) received open-label voxelotor 1500 mg once a day (QD) and SOC for a minimum 12 weeks and target ulcer(s) that had failed to heal during the initial 12 weeks was/were followed for delayed healing.Participants who had completed 12 weeks in the Open-Label Treatment Period might continue to receive voxelotor as long as they continued to receive clinical benefit that outweighed risk as determined by the investigator or until the participant had access to voxelotor from an alternative source not associated with this protocol (eg, through a clinical Open-Label Extension [OLE] study sponsored by Pfizer, commercialization of the product, or a managed access program). Participants who planned not to continue to receive voxelotor from an alternative source continued to the follow-up period after completing 12 weeks in the Open-Label Treatment Period. This report provides full data of efficacy and safety for all the treated participants at the end of study, ie, last participant last visit (LPLV). Number of Participants (planned and analyzed): Approximately 80 participants were planned and a total of 88 participants were randomized and treated. Two analysis sets were predefined for the study: intent-to-treat (ITT) population, which included all randomized participants; and safety-evaluable population, which included all randomized participants who received at least one dose of study intervention. All of the 88 randomized participants were treated and thus included in both the ITT and safety-evaluable populations. Study Intervention: During the Randomized Treatment Period, participants were randomized in a 1:1 ratio to receive voxelotor 1500 mg QD (500 mg ×3 tablets) or matching placebo orally administered for 12 weeks. During the Open-Label Treatment Period, all participants received voxelotor 1500 mg QD (500 mg ×3 tablets) for a minimum of 12 weeks. In this study, all participants received the SOC per protocol for SCD leg ulcers during the Run-in, Randomized Treatment,and Open-Label Treatment periods. Global Interruptions and Re-starts On 10 May 2024, the administration of the study intervention, voxelotor, was voluntarily paused by Pfizer (the sponsor) due to the overall number of fatal events observed in the studywhich required further assessment of accrued data. On 25 September 2024, voxelotor was voluntarily withdrawn by Pfizer from all markets inwhich it was approved, and all ongoing voxelotor clinical studies and early access and compassionate use programs have been discontinued.</p>\n<p>\n SUMMARY OF RESULTS:</p>\n<p>\n Participant Disposition Of the 206 participants screened, 88 were randomized and treated, including 43 in the placebo group and 45 in the voxelotor group. Of these participants, 79 (89.8%) were in Africa (62 [70.5%] in Kenya and 17 [19.3%] in Nigeria), and 9 (10.2%) were in Latin America (all in Brazil). Out of 88 participants, 2 discontinued the study intervention during the Randomized Treatment Period, both in the voxelotor group, 1 due to AE, and the other due to withdrawal by participant. After the Randomized Treatment Period, 86 out of 88 participants entered the Open-Label Treatment Period. Of the 86 participants, 43 originally randomized to the placebo group received voxelotor (referred to “delayed voxelotor” hereafter), and 43 originally randomized to the voxelotor group continued voxelotor treatment. During the Open-Label Treatment Extension Period (including the Open-Label Treatment Period and the Follow-up Period), 75 (87.2%) participants discontinued study intervention (37 in the delayed voxelotor group and 38 in the voxelotor group), among whom the majority [59 (68.6%) participants] were discontinued due to study termination, and a total of 10 (11.6%) participants discontinued due to AEs (4 in the delayed voxelotor group and 6 in the voxelotor group).</p>\n
      • implication_results<p>\n “There are no changes proposed to the current practice for the treatment of leg ulcers in patients with sickle cell disease at this time.”</p>\n
      • quantity_imported1032
      • quantity_dispensed419
      • quantity_destroyed613
      • quantity_exported0
      • balance_siteo
      • final_date2025-10-24 12:39:30
      • modified2025-10-24 12:39:30
      • created2021-06-29 14:21:43
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id688
        • application_id1034
        • given_nameBernhards
        • middle_nameRagama
        • family_nameOgutu
        • qualificationMBchB, MMed (Peds), PhD
        • professional_addressP.O BOX 59857-00200
        • telephone+254733812613
        • emailogutu6@gmail.com
        • created2021-06-29 14:33:47
        • modified2021-07-02 20:34:34
      • 1(array)
        • id689
        • application_id1034
        • given_nameJessie
        • middle_nameNyokabi
        • family_nameGithanga
        • qualificationMBChB, MMed (Path)(UON), FCPath ECSA Associate Professor
        • professional_addressP. O. Box 19676-00200, Nairobi, Kenya
        • telephone+254 721245721
        • emailJessie.githanga@uonbi.ac.ke
        • created2021-06-29 14:41:47
        • modified2021-07-02 20:34:34
    • SiteDetail(array)
      • 0(array)
        • id1065
        • application_id1034
        • county_id47
        • site_nameStrathmore University Medical Center
        • physical_addressOle Sangale Road P.O Box 59857-00200
        • contact_detailsOle Sangale Road P.O Box 59857-00200, Tel: 254 (0) 703 034375
        • contact_personVictoria Sidi
        • site_capacity(null)
        • misc(null)
        • created2021-06-29 14:33:47
        • modified2021-07-02 20:34:34
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 1(array)
        • id1066
        • application_id1034
        • county_id42
        • site_nameKEMRI Kondele children\'S Hospital
        • physical_addressP.O BOX 6049 40103 Kondele children\'s Hospital
        • contact_detailsP.O BOX 6049 40103 Kondele children\'s Hospital Tel:0724106654
        • contact_personIshmael sports
        • site_capacity(null)
        • misc(null)
        • created2021-06-29 14:58:49
        • modified2021-07-02 20:34:34
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 2(array)
        • id1067
        • application_id1034
        • county_id47
        • site_nameGertrude\'s Children\'s Hospital
        • physical_address34 Muthaiga road, P.O BOX 42325-00100, Nairobi, Kenya
        • contact_details P.O BOX 42325-00100, Nairobi, Kenya Tel +254 721245721
        • contact_personProfessor Jessie Githanga
        • site_capacity(null)
        • misc(null)
        • created2021-06-29 15:01:34
        • modified2021-07-02 20:34:34
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
    • Sponsor(array)
      • 0(array)
        • id520
        • application_id1034
        • sponsorGlobal Blood Therapeutics, Inc.
        • sponsor_typeResearch Institution
        • contact_personCarolyn Hoppe, MD, Senior Medical Director
        • addressGlobal Blood Therapeutics, Inc. 181 Oyster Point Blvd South San Francisco, CA 94080 United States of America
        • telephone_number(650) 741-7741
        • fax_number
        • cell_number(650) 741-7741
        • email_addresschoppe@gbt.com
        • created2021-06-29 14:33:47
        • modified2021-07-02 20:34:34
  • 2(array)
    • Application(array)
      • id1024
      • user_id695
      • trial_status_id7
      • abstract_of_study<p>\n In line with WHO recommendations, Kenya conducts Therapeutic Efficacy Studies (TES) for 1^st and 2^nd line antimalarial medicines to monitor the threat of emergence and spread of artemisinin resistance. The objective of this four-arm prospective study is to assess the efficacy of Artemether Lumefantrine (AL) and Dihydroartemisinin-Piperaquine (DHP) used for the treatment of uncomplicated <em>P. falciparum </em>malaria among febrile patients aged between 6 and 59 months, with confirmed uncomplicated <em>P.Falciparum</em> monoinfection at one selected site in both Siaya and Bungoma Counties with a high out-patient attendance of malaria patients. At each site, at least 100 patients will be enrolled per drug (200 patients per site, 400 patients total) between July and December 2020. Clinical and parasitological parameters will be monitored over a 28-day follow-up period to evaluate AL efficacy, and over a 42-day follow-up period to evaluate DHP efficacy. The study will determine proportion of patients with an adequate clinical and parasitological response (as indicators of efficacy). Recrudescence will be distinguished from re-infection by polymerase chain reaction (PCR) analysis. The study will further determine the polymorphism of molecular markers of drug resistance and evasion of diagnostic testing. The results will enable Ministry of Health (MOH) make timely update of its malaria treatment and diagnostic policies and ensure global exchange of resistance data.</p>\n<p>\n  </p>\n
      • study_title<p>\n Efficacy of Artemether Lumefantrine (AL) and Dihydroartemisinin-Piperaquine (DHP) for the treatment of uncomplicated <em>Plasmodium</em> <em>falciparum</em> malaria in Siaya and Bungoma counties, Kenya.</p>\n
      • laymans_summary<p>\n Jhpiego through the Impact Malaria project funded by the US President’s Malaria Initiative (PMI) and in Collaboration with National Malaria Control Program-Ministry of Health, US Centers of Disease Control and Prevention (CDC), and the County Governments of Siaya and Bungoma plan to carry out a study to test how effective<em> Artemether Lumefantrine (AL) and Dihydroartemisinin-Piperaquine (DHP) are still in the treatment of uncomplicated Plasmodium falciparum malaria in Siaya and Bungoma counties, Kenya</em>. The purpose of the study is to assess whether these two medicines are currently still effective in the treatment of malaria. The selected project sites will include  one health facility in Siaya and one in Bungoma County. The primary sample will consist of children aged between 6 months and 59 months who are eligible and whom have been confirmed to have uncomplicated malaria and their parents have consented for them to be in the study. Participants who meet the study inclusion criteria will be enrolled, treated on site and monitored.</p>\n<p>\n The results from the study will inform the Ministry of Health on effective current medicines used to treat malaria and if there is any growing resistance in Kenya.</p>\n
      • short_titleTherapeutic Efficacy Study
      • protocol_noECCT/21/06/15
      • version_no1
      • date_of_protocol01-03-2020
      • study_drugArtemether-Lumefantrine and Dihydroartemisinin-Piperaquine
      • disease_conditionUncomplicated malaria
      • 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_nameArtemether-Lumefantrine and Dihydroartemisinin-Piperaquine
      • product_type_medical_device_name
      • comparatorYes
      • comparator_nameDihydroartemisinin-Piperaquine
      • comparator_registeredYes
      • comparator_countriesKenya
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressfredouma12@gmail.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantDr. Fredrick Ouma
      • declaration_date115-06-2021
      • declaration_principal_investigatorDr. Willis Akhwale
      • declaration_date215-06-2021
      • placebo_presentNo
      • study_objectives<ol style=\"list-style-type:upper-alpha;\">\n <li>\n General objective: To assess the therapeutic efficacy of Artemether Lumefantrine (AL) and Dihydroartemisinin-Piperaquine (DHP) for the treatment of uncomplicated <em>P. falciparum</em> malaria in Siaya and Bungoma counties, Kenya.</li>\n</ol>\n<p>\n (B) Specific objectives:</p>\n<ol>\n <li>\n To measure the clinical and parasitological efficacy of AL and DHP in patients aged between 6 months and 59 months, suffering from uncomplicated <em>P. falciparum </em>malaria by determining the proportion with early treatment failure, late clinical failure, late parasitological failure or an adequate clinical and parasitological response as indicators of efficacy;</li>\n <li>\n To differentiate recrudescence from new infection by polymerase chain reaction (PCR) analysis.</li>\n <li>\n To determine the polymorphism of molecular markers of drug resistance and evasion of diagnostic testing.</li>\n <li>\n To determine the blood concentration of AL</li>\n</ol>\n<p>\n  </p>\n
      • principal_inclusion_criteria<ul>\n <li>\n Age between 6 months to 59 months</li>\n <li>\n Mono-infection with <em>p. Falciparum</em> confirmed by positive blood smear (i.e. No mixed infection)</li>\n <li>\n Parasitaemia of 1,000 – 100,000/µl asexual forms</li>\n <li>\n Presence of axillary temperature ≥ 37.5 °c or history of fever during the past 24 h</li>\n <li>\n Ability to swallow oral medication</li>\n <li>\n Haemoglobin >8.0 g/dl at admission</li>\n <li>\n Informed consent from a parent or guardian</li>\n <li>\n Parent/guardian agrees to bring the patient for the completion of AL and DHP doses and planned follow-up visits at day 7, 14, 21, and 28 plus days 35 and 42 for DHP follow up.</li>\n</ul>\n<p>\n  </p>\n
      • principal_exclusion_criteria<ul>\n <li>\n General danger signs or signs of severe falciparum malaria according to the definitions of WHO (Appendix 2)</li>\n <li>\n Severe malnutrition according to WHO child growth standards (WHO, 2006), children with marasmus or oedematous malnutrition</li>\n <li>\n Mixed or mono-infection with another <em>Plasmodium</em> species detected by microscopy</li>\n <li>\n Presence of febrile conditions due to diseases other than malaria (e.g. measles, acute lower respiratory tract infection, severe diarrhea with dehydration) or other known underlying chronic or severe diseases (e.g. cardiac, renal and hepatic diseases, HIV/AIDS)</li>\n <li>\n Regular medication, which may interfere with antimalarial pharmacokinetics</li>\n <li>\n History of hypersensitivity reactions or contraindications to any of the medicine(s) being tested or used as alternative treatment(s)</li>\n <li>\n History of receiving any antimalarial treatment in the preceding 72 hours</li>\n</ul>\n<p>\n  </p>\n
      • primary_end_points<p>\n Treatment outcomes will be classified on the basis of an assessment of the parasitological and clinical outcomes of antimalarial treatment according to the latest WHO guidelines. Thus, all patients will be classified as having early treatment failure, late clinical failure, late parasitological failure or an adequate clinical and parasitological response, as defined in Appendix 5.</p>\n<p>\n As parasitological cure is the goal of antimalarial therapy, all study patients who show treatment failure will be given rescue treatment. Follow-up will continue until recovery. The outcome of the rescue treatment in these patients does not need to be recorded systematically for the purpose of the surveillance study.</p>\n<p>\n  </p>\n
      • scope_diagnosis1
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety0
      • 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 Kaluo Health Center: They have an inpatient maternity that has 200 deliveries in a month. Kaluo is headed by an experienced Nursing officer in-charge. There are 2 Clinical officer, 1 Lab officer, 1 pharmaceutical officer, 6 Nursing officer, 2 Peer educators, 1 Health and records officer, 1 Data clerk, 2 Adherence counselors and 2 HIV Testing counsellors among other CHVS and support staff.  Three community Units are attached to Kaluo Health centers. Kaluo receives adequate support from Alego Usonga Health Management Team especially the expert Microscopists. Their Infrastructure is adequate with their Lab having listed as a QI lab. The la conducts Tuberculosis, AFBs, Malaria, HB, O/C, Rapid Tests successfully among other biochemistry Tests. The staff undergo frequent trainings for Malaria.</p>\n<p>\n  </p>\n<p>\n Makhonge Health Center: The total case load between Oct 2018 – Sept 2019 was 7021 at the child Welfare clinic. Out of the 2480 suspected Malaria cases from the case load, 957 were positive (prevalence 38.5%). Makhonge is adequately stffed with an inpatient Maternity, Outpatient department, Lab and pharmacy. They have a facility Incharge, 2 Lab staff, 2 Clinical officer, 6 Nursing officers. A pharmacist is set to be posted as the medical supritendent in April 2021. The Lab has the capacity to conduct both Malaria Microscopy and Rapid tests.</p>\n<p>\n  </p>\n<p>\n Impact Malaria funded by PMI will be supporting the facilities with Key Equipment needed for the study as well as consumable items. These included Haemoque machines, Weighing scales, Thermometers, Microscopes, Cuvettes. </p>\n
      • other_details_explanation<p>\n Kenya has high malaria prevalence and endemicity</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n KEMRI SERU</p>\n
      • other_details_regulatory_rejected
      • other_details_regulatory_halted
      • estimated_durationDecember 2021
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindYes
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPatients on DHAP
      • design_controlled_other_medicinalYes
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherYes
      • design_controlled_medicinal_specifyDihydroartemisinin-Piperaquine
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites2
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_site200
      • total_participants_worldwide400
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerYes
      • population_childrenYes
      • population_adolescentNo
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyChildren aged under 5 years (6 to 59 months)
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameMaureen
      • investigator1_middle_nameMoraa
      • investigator1_family_nameMabiria
      • investigator1_qualificationMBChB
      • investigator1_professional_addressImpact Malaria Office - 14 Riverside, Arlington Block
      • investigator1_telephone+254722924636
      • investigator1_emailMaureen.Mabiria@jhpiego.org
      • organisations_transferred_Yes
      • number_participants400
      • notification
      • approval_date11-08-2021
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted25-06-2021
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonThe application has been approved
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2023-10-30 16:03:55
      • created2021-06-15 11:52:20
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id672
        • application_id1024
        • given_nameDr. Sarah-Blythe
        • middle_name
        • family_nameBallard
        • qualificationMD, MPH, PhD
        • professional_addressCDC
        • telephone+254722509168
        • emailzlo3@cdc.gov
        • created2021-06-15 11:55:00
        • modified2021-06-25 11:52:56
      • 1(array)
        • id673
        • application_id1024
        • given_nameDr. Willis
        • middle_name
        • family_nameAkhwale
        • qualificationMBChB, PhD
        • professional_addressALMA - Ministry of Health, Afya House
        • telephone+254721788913
        • emailwakhwale@alma2030.org
        • created2021-06-15 12:11:37
        • modified2021-06-25 11:52:56
      • 2(array)
        • id678
        • application_id1024
        • given_nameDr. Grace
        • middle_name
        • family_nameIkahu
        • qualificationMBChB, MPH
        • professional_addressAfya House, Nairobi
        • telephone+254721238791
        • emailmuchangigrace@gmail.com
        • created2021-06-17 20:51:59
        • modified2021-06-25 11:52:56
      • 3(array)
        • id679
        • application_id1024
        • given_nameDr. George
        • middle_name
        • family_nameGithuka
        • qualificationMBChB, MSc Field Epidemiology
        • professional_addressKNH Grounds, Nairobi
        • telephone+254722303481
        • emailgngithuka@yahoo.com
        • created2021-06-17 20:51:59
        • modified2021-06-25 11:52:56
      • 4(array)
        • id680
        • application_id1024
        • given_nameDr. Dickson
        • middle_nameMtungu
        • family_nameMwakangalu
        • qualificationMBChB, MPH
        • professional_addressImpact Malaria Office - 14 Riverside, Arlington Block
        • telephone+254722726184
        • emaildmtungu@gmail.com
        • created2021-06-17 20:51:59
        • modified2021-06-25 11:52:56
      • 5(array)
        • id681
        • application_id1024
        • given_nameDr. Elvis
        • middle_nameOmondi
        • family_nameOyugi
        • qualificationMBChB, MSc Field Epidemiology
        • professional_addressDNMP, KNH Grounds, Nairobi
        • telephone+254720483652
        • emaileloyugi@gmail.com
        • created2021-06-17 21:09:23
        • modified2021-06-25 11:52:56
      • 6(array)
        • id682
        • application_id1024
        • given_nameHellen
        • middle_name
        • family_nameGatakaa
        • qualificationBSc, MSc
        • professional_addressImpact Malaria Office - 14 Riverside, Arlington Block
        • telephone+254722865158
        • emailHellen.Gatakaa@jhpiego.org
        • created2021-06-17 21:09:23
        • modified2021-06-25 11:52:56
      • 7(array)
        • id683
        • application_id1024
        • given_nameRegina
        • middle_nameJepkosgei
        • family_nameKandie
        • qualificationBSc, MSc
        • professional_addressDNMP, KNH Grounds, Nairobi
        • telephone+254722841252
        • emailregkandie@gmail.com
        • created2021-06-17 21:09:23
        • modified2021-06-25 11:52:56
      • 8(array)
        • id684
        • application_id1024
        • given_nameDr. Fredrick
        • middle_nameOuma
        • family_nameOdhiambo
        • qualificationBPharm
        • professional_addressDNMP, KNH Grounds, Nairobi
        • telephone+254724976545
        • emailfredouma12@gmail.com
        • created2021-06-18 09:42:53
        • modified2021-06-25 11:52:56
    • SiteDetail(array)
      • 0(array)
        • id939
        • application_id1024
        • county_id39
        • site_nameMahonge Health Center
        • physical_addressMahonge Market, Kimilili Sub-county, Bungoma County
        • contact_details+254724514760
        • contact_personFacility In-charge
        • site_capacity(null)
        • misc(null)
        • created2021-06-15 11:55:00
        • modified2021-06-25 11:52:56
        • County(array)
          • id39
          • county_nameBung\'oma
          • created2012-06-15 10:26:45
          • modified2012-06-15 10:26:45
      • 1(array)
        • id946
        • application_id1024
        • county_id41
        • site_nameKaluo Health Center
        • physical_addressAlego-Usonga Sub-county, Siaya County
        • contact_details+254721579199
        • contact_personFacility in-charge
        • site_capacity(null)
        • misc(null)
        • created2021-06-17 20:19:33
        • modified2021-06-25 11:52:56
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
    • Sponsor(array)
      • 0(array)
        • id514
        • application_id1024
        • sponsorPresident Malaria Initiative (PMI)
        • sponsor_typeOthers
        • contact_personDr Sarah-Blythe Ballard
        • addressUS Embassy, United Nations Avenue, Nairobi - Kenya
        • telephone_number+254722509168
        • fax_number
        • cell_number+254722509168
        • email_addresszlo3@cdc.gov
        • created2021-06-15 11:55:00
        • modified2021-06-25 11:52:56
  • 3(array)
    • Application(array)
      • id1031
      • user_id21
      • trial_status_id7
      • abstract_of_study<div>\n <strong>Title</strong></div>\n<div>\n Multi-Center, Randomized, Efficacy Study of COVID-19 mRNA Vaccine in Regions with SARS-CoV-2 Variants of Concern</div>\n<div>\n  </div>\n<div>\n <strong>Primary objectives</strong></div>\n<div>\n Primary objective 1:</div>\n<div>\n To assess vaccine efficacy (VE) of COVID-19 mRNA vaccine to prevent virologically-confirmed symptomatic COVID-19 starting 14 days after dose 2 in adults who are at risk of severe COVID-19</div>\n<div>\n Primary objective 2:</div>\n<div>\n To assess vaccine efficacy (VE) of COVID-19 mRNA vaccine to prevent severe COVID-19 starting 14 days after dose 2 in adults who are at risk of severe COVID-19</div>\n<div>\n Primary objective 3:</div>\n<div>\n To assess safety and tolerability of COVID-19 mRNA vaccine in adults who are at risk of severe COVID-19</div>\n<div>\n  </div>\n<div>\n <strong>Study product and route of administration</strong></div>\n<div>\n Vaccine: COVID-19 mRNA vaccine developed by Moderna, Inc. (mRNA-1273): a lipid nanoparticle (LNP) dispersion of a messenger ribonucleic acid (mRNA) encoding the prefusion stabilized S protein of SARS-CoV-2 formulated in LNPs composed of 4 lipids (1 proprietary and 3 commercially available). COVID-19 mRNA vaccine is a suspension for intramuscular injection (IM) administered as a series of two doses (100 mcg in 0.5 mL each) 1 month apart.</div>\n<div>\n This vaccine has been issued an Emergency Use Authorization (EUA) by the US Food and Drug Administration (FDA) and was granted a conditional marketing authorization (CMA) by the European Commission for active immunization to prevent COVID-19 caused by SARS-CoV-2 virus in individuals 18 years and older.</div>\n<div>\n The vaccine has been granted Emergency Use Listing (EUL) by the World Health Organization and will be administered after authorization by in-country National Regulatory Authorities for active immunization to prevent COVID-19.</div>\n<div>\n  </div>\n<div>\n <strong>Placebo</strong>: Sodium Chloride 0.9 % for injection, administered IM, 0.5 mL.</div>\n<div>\n  </div>\n<div>\n <div>\n <strong>Participants</strong></div>\n <div>\n Approximately 14,000 participants from one or more of these categories: 1) age ≥ 40 and at least one comorbidity known to be associated with severe COVID-19, 2) age ≥ 18 and pregnant, 3) age ≥ 18 and HIV-infected.</div>\n <div>\n  </div>\n <div>\n <strong>Design</strong></div>\n <div>\n Multicenter, sequentially monitored for efficacy, randomized, double blind, immediate vs. deferred vaccination with blinded crossover at approximately month 3.5 post enrollment.</div>\n <div>\n  </div>\n <div>\n <strong>Duration per participant</strong></div>\n <div>\n Up to 12 months per participant.</div>\n <div>\n  </div>\n <div>\n <strong>Estimated total study duration</strong></div>\n <div>\n 14 months (includes enrollment and follow-up).</div>\n</div>\n<p>\n  </p>\n
      • study_title<p>\n Multi-Center, Randomized, Efficacy Study of COVID-19 mRNA Vaccine in Regions with SARS-CoV-2 Variants of Concern</p>\n
      • laymans_summary<p>\n This is a study of a vaccine against SARS-COV-2 . The vaccine is called mRNA-1273.</p>\n<p>\n It has been given Emergency Use Authorization by FDA.</p>\n<p>\n The study is also known as CoVPN 3008</p>\n<p>\n The vaccine is produced by Mordena TX</p>\n<p>\n The study aims to find out if: </p>\n<ol>\n <li>\n The study vaccines can prevent symptomatic COVID-19 illness</li>\n <li>\n The vaccines are safe</li>\n <li>\n The vaccines can prevent infection against SARS-COV-2</li>\n</ol>\n
      • short_titleCoVPN 3008
      • protocol_noECCT/21/06/14
      • version_no1.0
      • date_of_protocol16-05-2021
      • study_drugmRNA-1273
      • disease_conditionCOVID-19
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorYes
      • comparator_nameSodium Chloride 0.9 %
      • comparator_registeredYes
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressviola.kirui@gmail.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantViola Kirui
      • declaration_date124-06-2021
      • declaration_principal_investigatorTaraz Samandari
      • declaration_date224-06-2021
      • placebo_presentYes
      • study_objectives<div>\n Primary objective 1:</div>\n<div>\n To assess vaccine efficacy (VE) of COVID-19 mRNA vaccine to prevent virologically-confirmed symptomatic COVID-19 starting 14 days after dose 2 in adults who are at risk of severe COVID-19</div>\n<div>\n Primary objective 2:</div>\n<div>\n To assess vaccine efficacy (VE) of COVID-19 mRNA vaccine to prevent severe COVID-19 starting 14 days after dose 2 in adults who are at risk of severe COVID-19</div>\n<div>\n Primary objective 3:</div>\n<div>\n To assess safety and tolerability of COVID-19 mRNA vaccine in adults who are at risk of severe COVID-19</div>\n
      • principal_inclusion_criteria<div>\n 1. Age ≥ 18 years if volunteer self-reports pregnant OR HIV-positive, OR age ≥ 40 years with ≥ 1 co-morbidity known to be associated with severe COVID-19, for example:</div>\n<div>\n • Hypertension</div>\n<div>\n • Type 2 diabetes mellitus</div>\n<div>\n • Obesity (body mass index [BMI] of 30 kg/m2 or higher but < 40 kg/m2)</div>\n<div>\n • Severe Obesity (BMI ≥ 40 kg/m2)</div>\n<div>\n • Heart conditions, such as heart failure, coronary artery disease, or cardiomyopathies</div>\n<div>\n • Chronic kidney disease</div>\n<div>\n • COPD (chronic obstructive pulmonary disease)</div>\n<div>\n • Cancer</div>\n<div>\n <div>\n • Non-HIV immunocompromised state (weakened immune system) or solid organ transplant</div>\n <div>\n • Pregnancy</div>\n <div>\n • Sickle cell disease</div>\n <div>\n • Smoking</div>\n <div>\n 2. Willingness to be followed and remain in the catchment area for the planned duration of the study.</div>\n <div>\n 3. Ability and willingness to provide informed consent.</div>\n <div>\n 4. Willingness to discuss HIV infection risks and willing to receive HIV testing, risk reduction counseling, and appropriate referrals to minimize HIV acquisition, if volunteer is pregnant</div>\n <div>\n 5. Assessment of understanding: volunteer demonstrates understanding of this study; completes a questionnaire prior to first vaccination with demonstration of understanding of all questionnaire items answered incorrectly.</div>\n <div>\n 6. Willing to defer SARS-CoV-2 vaccination until the crossover visit (anticipated at approximately Month 3.5).</div>\n <div>\n 7. Agrees not to enroll in another study of an investigational research agent until the end of the study. Enrollment in studies of investigational research agents for the treatment of COVID-19 is allowed for participants who develop COVID-19 disease.</div>\n</div>\n<p>\n  </p>\n
      • principal_exclusion_criteria<div>\n 1. Acutely ill 72 hours prior to or at screening. Volunteers meeting this criterion may be rescheduled within the relevant window periods. Participants with minor illnesses can be enrolled at the discretion of the investigator.</div>\n<div>\n 2. History of angioedema or anaphylaxis</div>\n<div>\n 3. Self-reported previous COVID-19 diagnosis</div>\n<div>\n Vaccines and other Injections</div>\n<div>\n 4. Prior administration of a SARS-CoV-2 vaccine.</div>\n<div>\n <div>\n 5. Live attenuated vaccines received within 30 days before first vaccination or scheduled within 14/28 days after injection (eg, measles, mumps, and rubella [MMR]; oral polio vaccine [OPV]; varicella; yellow fever; live attenuated influenza vaccine).</div>\n <div>\n 6. Any vaccines that are not live attenuated vaccines and were received within 14 days prior to first vaccination (eg, tetanus, pneumococcal, Hepatitis A or B).</div>\n <div>\n 7. Blood products, systemic immunoglobulins, or monoclonal antibodies (including against SARS-CoV-2) received within 90 days before first vaccination.</div>\n</div>\n<p>\n  </p>\n
      • primary_end_points<p>\n 1. COVID-19: Positive result of acute SARS-CoV-2 infection as assessed by nucleic acid amplification testing (NAAT) or antigen testing of a nasal swab whose collection was triggered by a prespecified symptom or symptoms (see footnote 1) in volunteers with no previous COVID-19</p>\n<p>\n 2. Severe COVID-19: COVID-19 that meets the criteria listed in footnote 2 AND adjudicated by an independent endpoint adjudication committee, in baseline SARS-CoV-2 negative participants.</p>\n<p>\n 3. Solicited and unsolicited AEs collected for a subset of study participants after the initial set of vaccinations. Serious adverse events (SAEs), adverse events of special interest (AESIs), collected for all participants throughout the study.</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_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use1
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<ol font-size:=\"\" style=\"padding-right: 0px; padding-left: 0px; margin: 0px 0px 10px 25px; color: rgb(51, 51, 51);\" trebuchet=\"\">\n <li style=\"line-height: 20px;\">\n Prof. Abraham M. Siika                                 Site Leader</li>\n <li style=\"line-height: 20px;\">\n Dr. Charles Kwobah                                         Principal Investigator</li>\n <li style=\"line-height: 20px;\">\n Jairus Kipyego                                                   Study Clinician          </li>\n <li style=\"line-height: 20px;\">\n Vincent KIpchirchir                                                Study Clinician                      </li>\n <li style=\"line-height: 20px;\">\n Chris Sande Mboya                                       Study Nurse</li>\n <li style=\"line-height: 20px;\">\n Viola Kirui                                             Quality Assurance/Control officer</li>\n <li style=\"line-height: 20px;\">\n Cecilia Chebet                                                Recruitment officer</li>\n <li style=\"line-height: 20px;\">\n Julie Choge                                                     Recruitment officer</li>\n <li style=\"line-height: 20px;\">\n Amina Msuo Shali                                         Recruitment officer</li>\n <li style=\"line-height: 20px;\">\n Wilson Ekiru                                                  Assistant data manger</li>\n <li style=\"line-height: 20px;\">\n Martha Mokaya                                             Data manger           </li>\n <li style=\"line-height: 20px;\">\n Natalie Sang                                         Pharmacist of record</li>\n <li style=\"line-height: 20px;\">\n Beatrice Jakait                                               Backup pharmacist</li>\n <li style=\"line-height: 20px;\">\n Salina Cherutich                                            Pharmaceutical technologist</li>\n</ol>\n
      • other_details_explanation<p>\n Not Applicable</p>\n
      • other_details_regulatory_notapproved<p>\n SERU</p>\n<p>\n Moi University/Moi Teaching and Referral IREC</p>\n
      • other_details_regulatory_approved<p>\n None</p>\n
      • other_details_regulatory_rejected<p>\n Not applicable</p>\n
      • other_details_regulatory_halted<p>\n Not applicable</p>\n
      • estimated_duration14 months
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overYes
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorSodium Chloride
      • 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_sites2
      • multi_country_listBotswana, Eswatini, Kenya, Malawi, South Africa, Uganda, Zambia, Zimbabwe
      • data_monitoring_committeeYes
      • total_enrolment_per_site250
      • total_participants_worldwide14000
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenYes
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameTaraz
      • investigator1_middle_name
      • investigator1_family_nameSamandari
      • investigator1_qualificationMBChB, MMed, MPH
      • investigator1_professional_addressKisumu CRS/KEMRI-CDC
      • investigator1_telephone+254-703-485-481
      • investigator1_emailtts0@cdc.gov
      • organisations_transferred_No
      • number_participants500
      • notification
      • approval_date13-12-2021
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted09-12-2021
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonApproved
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-09-03 12:53:12
      • created2021-06-24 11:50:41
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id687
        • application_id1031
        • given_nameAbraham
        • middle_name
        • family_nameSiika
        • qualificationMBChB, MMed, MSc
        • professional_addressP.O Box 4606-30100 Eldoret Kenya
        • telephone254721280785
        • emailabrahamsiika@gmail.com
        • created2021-06-24 13:53:50
        • modified2021-12-09 16:08:04
    • SiteDetail(array)
      • 0(array)
        • id971
        • application_id1031
        • county_id27
        • site_nameMoi University Clinical Research Centre
        • physical_addressChandaria Cancer and Chronic Diseases Centre at MTRH
        • contact_detailsP O Box 4606-30100
        • contact_personViola Kirui
        • site_capacity(null)
        • misc(null)
        • created2021-06-24 13:53:50
        • modified2021-12-09 16:08:04
        • County(array)
          • id27
          • county_nameUasin Gishu
          • created2012-06-15 10:25:15
          • modified2012-06-15 10:25:15
      • 1(array)
        • id972
        • application_id1031
        • county_id42
        • site_nameKEMRI Kisumu Clinical Research Site
        • physical_addressPO Box 1578 – 40100 Kisumu
        • contact_detailsPO Box 1578 – 40100 Kisumu
        • contact_personTaraz Samandari
        • site_capacity(null)
        • misc(null)
        • created2021-06-24 15:50:28
        • modified2021-12-09 16:08:04
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id519
        • application_id1031
        • sponsorSouth African Medical Research Council (SAMRC)
        • sponsor_typeOthers
        • contact_person
        • addressFrancie van Zijl Drive, Parow Valley, Cape Town PO Box 19070, Tygerberg, 7505
        • telephone_number021 938 0911
        • fax_number
        • cell_number021 938 0911
        • email_addressinfo@mrc.ac.za
        • created2021-06-24 13:53:50
        • modified2021-12-09 16:08:04
  • 4(array)
    • Application(array)
      • id1030
      • user_id21
      • trial_status_id5
      • abstract_of_study<div>\n Phase 3b, Randomized, Multicenter, Open-Label Study Evaluating the Efficacy, Safety, and Tolerability of Switching to Long-Acting Cabotegravir Plus Long-Acting Rilpivirine From Current Antiretroviral Regimen in HIV-1 Infected, Virologically Suppressed Adults in Sub-Saharan Africa</div>\n<div>\n  </div>\n<div>\n Cabotegravir And Rilpivirine: Efficacy and Safety (CARES) Study</div>\n<div>\n  </div>\n<div>\n Long-acting (LA) injectable therapy for the treatment of Human Immunodeficiency Virus (HIV)-1 infection offers a reduced dosing frequency and an additional option to the currently available two-drug oral combinations. A parenteral LA formulation of rilpivirine (RPV) for intramuscular (IM) injection in combination with ViiV Healthcare’s parenteral LA formulation of the integrase inhibitor cabotegravir (CAB) may offer a better tolerability and resistance profile, as well as improved adherence and treatment satisfaction in virologically suppressed patients. The combination regimen has been developed for maintenance of viral suppression (HIV-1 RNA <50 copies/mL) in HIV-1 infected individuals previously treated with standard-of-care antiretroviral therapy.</div>\n<div>\n  </div>\n<div>\n OBJECTIVES</div>\n<div>\n Primary</div>\n<div>\n <ul>\n <li>\n To demonstrate the non-inferior antiviral activity of switching to IM RPV LA+CAB LA administered every 2 months compared with continuation of cART administered daily over 12 months in HIV-1 infected participants in a resource limited setting.</li>\n </ul>\n <p>\n Secondary</p>\n <ul>\n <li>\n <div>\n To demonstrate the antiviral and immunologic activity of switching to IM RPV LA+CAB LA every 2 months compared to continuation of cART over 12</div>\n <div>\n and 24 months of follow-up</div>\n </li>\n <li>\n <div>\n To evaluate the safety and tolerability of switching to RPV LA+CAB LA every 2 months compared to continuation of cART.</div>\n </li>\n <li>\n <div>\n To assess viral resistance in participants experiencing protocol-defined confirmed virologic failure (plasma HIV-1 RNA ≥200 c/mL).</div>\n </li>\n <li>\n <div>\n To assess the incidence of on-treatment genotypic resistance to CAB, RPV and other on-study cART up to Month 12 and 24.</div>\n </li>\n <li>\n <div>\n To evaluate adherence to treatment.</div>\n </li>\n </ul>\n</div>\n<div>\n Hypothesis</div>\n<div>\n The antiviral effect of switching to RPV LA+CAB LA is non-inferior (margin -10%) to continuation of first-line treatment with daily triple drug oral cART at Month 12 in HIV-1 infected, virologically suppressed participants.</div>\n<div>\n  </div>\n<div>\n <div>\n OVERALL DESIGN</div>\n <div>\n CARES is a randomized, open-label, active-controlled, multicenter, interventional study in virologically</div>\n <div>\n suppressed (<50 c/mL) HIV-1 infected adult participants to demonstrate that the antiviral effect of</div>\n <div>\n switching to IM RPV LA+CAB LA is non-inferior to continuation of first-line cART containing 2</div>\n <div>\n non-nucleoside reverse transcriptase inhibitor (NRTIs; tenofovir [TDF] plus either lamivudine [3TC] or</div>\n <div>\n emtricitabine [FTC]) plus an INI (dolutegravir [DTG]) or a non-nucleoside reverse transcriptase inhibitors</div>\n <div>\n (NNRTI) (efavirenz [EFV] or nevirapine [NVP]) at Month 12. After providing written informed consent,</div>\n <div>\n participants will be evaluated for eligibility during the 28-day screening period. On Day 1, participants will</div>\n <div>\n be randomized to either continue cART or to discontinue cART and begin therapy with RPV LA+CAB LA</div>\n <div>\n administered every 2 months. Baseline assessments will be performed on Day 1. Participants randomized</div>\n <div>\n to the RPV LA+CAB LA group will be given the option of a 4-week Oral Lead-in (OLI) Phase with oral</div>\n <div>\n RPV and oral CAB, or to directly receive the injectable RPV LA+CAB LA. This decision to dose with or</div>\n <div>\n without an OLI Phase will be determined by the study participant following informed consent discussions</div>\n <div>\n with the investigator.</div>\n <div>\n Starting Day 1, the total duration of the study will be 24 months. Any participant who has received at least</div>\n <div>\n a single dose of RPV LA+CAB LA and discontinues the regimen for any reason before Month 24 must</div>\n <div>\n start suppressive cART within 2 months of the last LA injection. Investigators must discuss the choice of</div>\n <div>\n the follow-up cART regimen with the lead scientist/chief investigator prior to initiating the new regimen</div>\n <div>\n with the participant. The participants must remain in the study unless consent is withdrawn, and complete</div>\n <div>\n their scheduled assessments up to the Month 24 visit.</div>\n</div>\n<div>\n  </div>\n<div>\n <div>\n NUMBER OF PARTICIPANTS</div>\n <div>\n A target of 512 participants will be enrolled in this study and randomized 1:1 to continue cART or switch</div>\n <div>\n to the RPV LA+CAB LA for a treatment period of 24 months. Participants will be recruited across 8 sites</div>\n <div>\n from 3 countries (3 sites in Uganda, 3 sites in Kenya and 2 sites in South Africa).</div>\n <div>\n  </div>\n <div>\n INTERVENTION GROUPS AND DURATION</div>\n <div>\n The interventions received are as follows:</div>\n <div>\n <u>cART Group</u>: Participants will take a regimen of 2 NRTIs (TDF 300 mg + [3TC 300 mg/FTC 200 mg]) +</div>\n <div>\n DTG (50 mg)/EFV (600 mg)/NVP (200 mg), as a single tablet or Fixed-Dose Combination regimen as per</div>\n <div>\n local country guidelines up to Month 24. Participants will be permitted to switch cART drugs in case of</div>\n <div>\n toxicity or for treatment optimization and convenience after viral load testing.</div>\n <div>\n <u>RPV LA+CAB LA Group</u>: The participants who opt for the OLI Phase will receive the study intervention</div>\n <div>\n in 2 phases:</div>\n <div>\n <em>Oral Lead-in Phase</em>: Starting on Day 1, participants will receive RPV 25 mg + CAB 30 mg once daily for</div>\n <div>\n 4 weeks to be taken at approximately the same time each day with a meal. The purpose of the optional</div>\n <div>\n OLI Phase is to allow an opportunity, when desired, for participants to assess tolerability of the combination</div>\n <div>\n prior to administration of RPV LA+CAB LA.</div>\n <div>\n <em>Maintenance Phase</em>: After the 4-week OLI Phase, participants will return for the Month 1 visit to take the</div>\n <div>\n last dose of oral CAB+RPV at the study-site, and to receive the first IM RPV LA 900 mg + CAB LA</div>\n <div>\n 600 mg initiations injections. The second initiation injections with RPV LA 900 mg + CAB LA 600 mg</div>\n <div>\n will be administered at Month 2, and then continuation injections will be administered every 2 months</div>\n <div>\n thereafter.</div>\n <div>\n Participants who opt for direct RPV LA+CAB LA (ie, without the OLI Phase) injections will remain on</div>\n <div>\n cART for 4 weeks after randomization on Day 1, and will receive the first initiation injection of</div>\n <div>\n RPV LA+CAB LA at the Month 1 visit. The second initiation injections with RPV LA+CAB LA will be</div>\n <div>\n administered at Month 2, followed by continuation injections of RPV LA+CAB LA every 2 months</div>\n <div>\n thereafter.</div>\n <div>\n The total duration of the study will be 24 months. At the end of their participation in the study, participants</div>\n <div>\n from the RPV LA+CAB LA group who have completed the study and are benefiting from the study</div>\n <div>\n intervention, as determined by their investigator, will be able to receive continued access to both CAB LA</div>\n <div>\n and RPV LA up to 2 years after study completion or until the participant no longer derives clinical benefit,</div>\n <div>\n the participant meets a protocol-defined reason for discontinuation, until RPV LA and CAB LA are</div>\n <div>\n registered and reimbursed in the country, or until either CAB LA or RPV LA development program is</div>\n <div>\n terminated, whichever occurs earlier. The participant will then be transitioned to a SOC regimen based on</div>\n <div>\n the investigator’s clinical judgment and local country guidelines. Participants in the cART group will</div>\n <div>\n continue to receive cART medications as part of the national program.</div>\n</div>\n<div>\n  </div>\n
      • study_title<div>\n A Phase 3b, Randomized, Multicenter, Open-Label Study Evaluating the Efficacy, Safety,</div>\n<div>\n and Tolerability of Switching to Long-Acting Cabotegravir Plus Long-Acting Rilpivirine</div>\n<div>\n From Current Antiretroviral Regimen in HIV-1 Infected, Virologically Suppressed Adults</div>\n<div>\n in Sub-Saharan Africa</div>\n
      • laymans_summary<p style=\"margin-left:18.0pt;\">\n A Phase 3b, Randomized, Multicenter, Open-Label Study Evaluating the Efficacy, Safety, and Tolerability of Switching to Long-Acting Cabotegravir Plus Long-Acting Rilpivirine From Current Antiretroviral Regimen in HIV-1 Infected, Virologically Suppressed Adults in Sub-Saharan Africa.</p>\n<p style=\"margin-left:18.0pt;\">\n Long-acting (LA) injectable therapy for the treatment of Human Immunodeficiency Virus (HIV)-1 infection offers a reduced dosing frequency and an additional option to the currently available oral combinations.</p>\n
      • short_titleCARES
      • protocol_noECCT/21/06/13
      • version_no1.0
      • date_of_protocol22-11-2020
      • study_drugCabotegravir and Rilpivirine
      • disease_conditionHIV
      • 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_addressviola.kirui@gmail.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter0
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data0
      • 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_applicantViola Kirui
      • declaration_date124-06-2021
      • declaration_principal_investigatorAbraham Siika
      • declaration_date224-06-2021
      • placebo_presentNo
      • study_objectives<div>\n Primary</div>\n<div>\n <ul>\n <li>\n To demonstrate the non-inferior antiviral activity of switching to IM RPV LA+CAB LA administered every 2 months compared with continuation of cART administered daily over 12 months in HIV-1 infected participants in a resource limited setting.</li>\n </ul>\n <p>\n Secondary</p>\n <ul>\n <li>\n <div>\n To demonstrate the antiviral and immunologic activity of switching to IM RPV LA+CAB LA every 2 months compared to continuation of cART over 12</div>\n <div>\n and 24 months of follow-up</div>\n </li>\n <li>\n To evaluate the safety and tolerability of switching to RPV LA+CAB LA every 2 months compared to continuation of cART.</li>\n <li>\n To assess viral resistance in participants experiencing protocol-defined confirmed virologic failure (plasma HIV-1 RNA ≥200 c/mL).</li>\n <li>\n To assess the incidence of on-treatment genotypic resistance to CAB, RPV and other on-study cART up to Month 12 and 24.</li>\n <li>\n To evaluate adherence to treatment.</li>\n </ul>\n <p>\n Exploratory</p>\n <ul>\n <li>\n <div>\n To evaluate the effects of RPV LA+CAB LA every 2 months on BMI over time compared to continuation of cART over time.</div>\n </li>\n <li>\n <div>\n To evaluate the effect of RPV LA+CAB LA on trunk fat compared with cART</div>\n </li>\n <li>\n <div>\n To explore the effect of patient characteristics (eg, demographic factors, baseline disease characteristics) on the virologic and immunologic responses to RPV LA+CAB LA compared to continuation of cART.</div>\n </li>\n <li>\n <div>\n Retrospective analysis of archived resistance and virological outcomes using PBMCs at baseline.</div>\n </li>\n <li>\n <div>\n To evaluate the effect of RPV LA+CAB LA on well-being and health status.</div>\n </li>\n <li>\n <div>\n To evaluate the effect of RPV LA+CAB LA on quality of life.</div>\n </li>\n <li>\n <div>\n To assess participant satisfaction with the injectable intervention.</div>\n </li>\n <li>\n <div>\n To assess preference for RPV LA+CAB LA compared to oral cART.</div>\n </li>\n <li>\n <div>\n To evaluate pharmacokinetics in women who become pregnant on RPV LA+CAB LA.</div>\n </li>\n <li>\n <div>\n To evaluate health resource utilization among participants in the study</div>\n </li>\n </ul>\n</div>\n<p>\n  </p>\n
      • principal_inclusion_criteria<div>\n 1. Male or female</div>\n<div>\n 2. Aged ≥18 years.</div>\n<div>\n 3. On a stable ARV regimen (TDF plus either 3TC or FTC, plus an INI [DTG] or a NNRTI</div>\n<div>\n [EFV or NVP] per local country guidelines) for at least 6 months prior to screening.</div>\n<div>\n 4. Virologically suppressed with documented evidence of:</div>\n<div>\n  Viral load <50 c/mL at screening AND</div>\n<div>\n  Viral load <50 c/mL on a test preceding screening (within 4-12 months prior to</div>\n<div>\n screening) AND</div>\n<div>\n  No two consecutive viral load tests ≥50 c/mL in the 12 months prior to screening</div>\n<div>\n 5. No prior history of virologic failure (defined as a confirmed plasma HIV-1 RNA</div>\n<div>\n measurement >200 c/mL) at any time.</div>\n<div>\n 6. Must sign an ICF indicating that he or she understands the purpose of, and procedures</div>\n<div>\n required for, the study and is willing to participate in the study.</div>\n<div>\n 7. A female participant is eligible to participate if she is not pregnant (as confirmed by a</div>\n<div>\n negative human chorionic gonadotrophin [hCG] urine test at screening and a negative</div>\n<div>\n urine hCG test at randomization), not lactating, and at least one of the following</div>\n<div>\n conditions applies:</div>\n<div>\n a. Non-reproductive potential defined as:</div>\n<div>\n  Pre-menopausal females with one of the following:</div>\n<div>\n  Documented tubal ligation</div>\n<div>\n  Documented hysteroscopic tubal occlusion procedure with follow-up</div>\n<div>\n confirmation of bilateral tubal occlusion</div>\n<div>\n  Hysterectomy</div>\n<div>\n  Documented Bilateral Oophorectomy</div>\n<div>\n  Postmenopausal defined as 12 months of spontaneous amenorrhea [in</div>\n<div>\n questionable cases a blood sample with simultaneous follicle stimulating</div>\n<div>\n hormone (FSH) and estradiol levels consistent with menopause (refer to</div>\n<div>\n laboratory reference ranges for confirmatory levels)]. Females on hormone</div>\n<div>\n replacement therapy and whose menopausal status is in doubt will be required</div>\n<div>\n to use one of the highly effective contraception methods if they wish to continue</div>\n<div>\n their hormone replacement therapy (HRT) during the study. Otherwise, they</div>\n<div>\n must discontinue HRT to allow confirmation of postmenopausal status prior to</div>\n<div>\n study enrollment.</div>\n<div>\n b. Reproductive potential and agrees to follow one of the options listed in the Modified</div>\n<div>\n List of Highly Effective Methods for Avoiding Pregnancy in Females of Reproductive</div>\n<div>\n Potential from 30 days prior to the first dose of study medication, and for at least 30 days</div>\n<div>\n after discontinuation of all oral study medications and for at least 52 weeks after</div>\n<div>\n discontinuation of CAB LA and RPV LA.</div>\n<div>\n The investigator is responsible for ensuring that participants understand how to properly</div>\n<div>\n use these methods of contraception.</div>\n<div>\n 8. A male participant must wear a condom when engaging in any activity that allows for</div>\n<div>\n passage of ejaculate to another. Male participants should also be advised of the benefit</div>\n<div>\n for a female partner to use a highly effective method of contraception as condom may</div>\n<div>\n break or leak.</div>\n<div>\n 9. Male participant must agree not to donate sperm for the purpose of reproduction during</div>\n<div>\n the study and for a minimum of 90 days after receiving the last dose of study intervention.</div>\n<div>\n 10. Participants with asymptomatic chronic hepatitis C virus (HCV) infection will be allowed</div>\n<div>\n entry if liver enzymes meet entry criteria, have undergone appropriate work-up, and are</div>\n<div>\n not in an advanced, unstable liver disease stage (as defined by any of the following:</div>\n<div>\n presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or</div>\n<div>\n gastric varices, or persistent jaundice or cirrhosis, known biliary abnormalities [with the</div>\n<div>\n exception of Gilbert's syndrome or asymptomatic gallstones or otherwise stable chronic</div>\n<div>\n liver disease per investigator assessment]).</div>\n<div>\n 11. Is willing and able to adhere to the lifestyle restrictions specified in this protocol.</div>\n
      • principal_exclusion_criteria<div>\n 1. Is currently participating in any other interventional study.</div>\n<div>\n 2. Is pregnant, breastfeeding or intends to become pregnant or breastfeed during the study,</div>\n<div>\n within the next 1 year.</div>\n<div>\n 3. Has evidence of an active Center for Disease Control and Prevention (CDC) Stage 3</div>\n<div>\n disease, except cutaneous Kaposi’s sarcoma not requiring systemic therapy and</div>\n<div>\n historical or current CD4 cell counts less than 200 cells/mm3</div>\n<div>\n 4. Has active TB co-infection and requires anti-TB treatment.</div>\n<div>\n <div>\n 5. Has severe hepatic impairment, history of liver cirrhosis with or without hepatitis viral</div>\n <div>\n co-infection.</div>\n <div>\n 6. Has preexisting physical or mental condition (including substance abuse disorder and</div>\n <div>\n suicide risk) which, in the opinion of the Investigator, may interfere with the</div>\n <div>\n participant’s ability to comply with the dosing schedule and/or protocol evaluations or</div>\n <div>\n which may compromise the safety of the participant.</div>\n <div>\n 7. Has had more than one seizure within one year (defined as within 365 days) prior to</div>\n <div>\n entry, or unstable or poorly controlled seizure disorder, as determined by the</div>\n <div>\n investigator or designee, based on available medical records.</div>\n <div>\n 8. Has a tattoo or other dermatological condition overlying the gluteus region.</div>\n <div>\n 9. Is positive for HBsAg or anti-HBc at screening.</div>\n <div>\n 10. Has ongoing or clinically significant medical conditions that in the opinion of the</div>\n <div>\n investigator may interfere with the absorption, distribution, metabolism or excretion of</div>\n <div>\n the study interventions or could affect participant safety.</div>\n <div>\n 11. Has a history of coagulopathies, or current or anticipated need for chronic</div>\n <div>\n anticoagulation except for low dose acetylsalicylic acid (daily dose ≤325 mg).</div>\n <div>\n 12. Has known major INI or NNRTI resistance-associated mutation as defined in the</div>\n <div>\n International Antiviral Society-USA 2019 list, except for K103N, based on any</div>\n <div>\n historical resistance test result.</div>\n <div>\n 13. Has any verified Grade 4 laboratory abnormality. A single repeat test is allowed during</div>\n <div>\n the Screening Phase to verify a result.</div>\n <div>\n 14. Has estimated creatinine clearance <50mL/min per 1.73m2 via CKD-EPI Method.</div>\n <div>\n 15. Has Alanine aminotransferase (ALT) ≥3 × ULN.</div>\n <div>\n 16. Has been exposed to any experimental drug or experimental vaccine within either 30</div>\n <div>\n days, 5 half-lives of the test agent, or twice the duration of the biological effect of the</div>\n <div>\n test agent, whichever is longer, prior to Day 1 of this study.</div>\n <div>\n 17. Has been treated with any of the following agents within 28 days of Screening:</div>\n <div>\n ï‚· radiation therapy;</div>\n <div>\n ï‚· cytotoxic chemotherapeutic agents;</div>\n <div>\n ï‚· tuberculosis therapy with the exception of isoniazid (isonicotinylhydrazid, INH);</div>\n <div>\n ï‚· anticoagulation agents;</div>\n <div>\n <div>\n ï‚· immunomodulators that alter immune responses (such as chronic systemic</div>\n <div>\n corticosteroids, interleukins, or interferons). Note: Participants using short-term</div>\n <div>\n steroid tapers, topical, inhaled and intranasal corticosteroids, topical imiquimod are</div>\n <div>\n eligible for enrollment.</div>\n <div>\n 18. Treatment with an HIV-1 immunotherapeutic vaccine within 90 days of Screening.</div>\n <div>\n 19. With the exception of the drugs allowed for the cART standard regimens, has been</div>\n <div>\n treated with any agent with documented activity against HIV-1 within 28 days of</div>\n <div>\n randomization, including but not limited to:</div>\n <div>\n ï‚· Current or prior history of etravirine (ETR) use</div>\n <div>\n ï‚· Current use of tipranavir/ritonavir or fosamprenavir/ritonavir</div>\n <div>\n 20. Has received any prohibited medication listed in Section 6.8.2 and who are unwilling</div>\n <div>\n or unable to switch to an alternate medication. Note: Any prohibited medications listed</div>\n <div>\n in Section 6.8.2 that decrease CAB or RPV concentrations should be discontinued for</div>\n <div>\n a minimum of 4 weeks or a minimum of three half-lives (whichever is longer) prior to</div>\n <div>\n the first dose and any other prohibited medications should be discontinued for a</div>\n <div>\n minimum of 2 weeks or a minimum of three half-lives (whichever is longer) prior to</div>\n <div>\n the first dose (see Section 6.8.2 for details of prohibited medications).</div>\n <div>\n 21. During the 6 weeks prior to baseline, have had ANY of (a) confirmed SARS-CoV-2</div>\n <div>\n (COVID-19) infection (test positive), OR (b) suspected SARS-CoV-2 infection</div>\n <div>\n (clinical features without documented test results), OR (c) close contact with a person</div>\n <div>\n with known or suspected SARS-CoV-2 infection</div>\n <div>\n  Exception: if recommended by local guidelines and as part of SOC in the</div>\n <div>\n respective country, patients may be included with a documented negative</div>\n <div>\n result for a validated SARS-CoV-2 test (direct detection methods)</div>\n <div>\n (i) obtained at least 2 weeks after conditions (a), (b), (c) above (timed from</div>\n <div>\n resolution of key clinical features if present, eg, fever, cough, dyspnea)</div>\n <div>\n AND</div>\n <div>\n (ii) with absence of ALL conditions (a), (b), (c) above during the period</div>\n <div>\n between the negative test result and the baseline study visit</div>\n </div>\n</div>\n<p>\n  </p>\n
      • primary_end_points<div>\n Proportion of participants with a virologic response (plasma</div>\n<div>\n HIV-1 RNA <50 c/mL)* at Month 12</div>\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_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<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 Prof. Abraham M. Siika                                 Principal Investigator</li>\n <li style=\"line-height: 20px;\">\n Dr. Charity Wambui                                      Co-Investigator</li>\n <li style=\"line-height: 20px;\">\n Jairus Kipyego                                                   Study Clinician          </li>\n <li style=\"line-height: 20px;\">\n Vincent KIpchirchir                                                Study Clinician                      </li>\n <li style=\"line-height: 20px;\">\n Chris Sande Mboya                                       Study Nurse</li>\n <li style=\"line-height: 20px;\">\n Viola Kirui                                             Quality Assurance/Control officer</li>\n <li style=\"line-height: 20px;\">\n Cecilia Chebet                                                Recruitment officer</li>\n <li style=\"line-height: 20px;\">\n Julie Choge                                                     Recruitment officer</li>\n <li style=\"line-height: 20px;\">\n Amina Msuo Shali                                         Recruitment officer</li>\n <li style=\"line-height: 20px;\">\n Wilson Ekiru                                                  Assistant data manger</li>\n <li style=\"line-height: 20px;\">\n Martha Mokaya                                             Data manger</li>\n <li style=\"line-height: 20px;\">\n Kennedy Kenina                                            Assistant data manger           </li>\n <li style=\"line-height: 20px;\">\n Natalie Sang                                         Pharmacist of record</li>\n <li style=\"line-height: 20px;\">\n Beatrice Jakait                                               Backup pharmacist</li>\n <li style=\"line-height: 20px;\">\n Salina Cherutich                                            Pharmaceutical technologist</li>\n</ol>\n
      • other_details_explanation<p>\n Not applicable</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<ol style=\"font-family: Tahoma; font-size: 10pt;\">\n <li style=\"margin-left: 15px;\">\n Uganda: National Drug authority. Three sites ( JCRC Lubowa, JCRC Fortportal and IDI)</li>\n <li style=\"margin-left: 15px;\">\n Kenya:  PPB : Three Sites , Aga Khan , Ampath and Kemri : Pending application</li>\n <li style=\"margin-left: 15px;\">\n South Africa: SAHPRAH. Two sites Ezintsha and SAMRC. Waiting for full approval</li>\n</ol>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n None</p>\n
      • estimated_duration24 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_comparatorSOC TDF 300 mg
      • design_controlled_other_medicinalYes
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherYes
      • design_controlled_medicinal_specify3TC 300 mg + DTG (50 mg)
      • 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_states3
      • number_of_sites3
      • multi_country_listKenya, Uganda, South Africa
      • data_monitoring_committeeYes
      • total_enrolment_per_siteMinimum 40\nMaximum 60
      • total_participants_worldwide512
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_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_nameAbraham
      • investigator1_middle_name
      • investigator1_family_nameSiika
      • investigator1_qualificationMBChB, MMed, MSc
      • investigator1_professional_addressP.O Box 4606-30100 Eldoret Kenya
      • investigator1_telephone254721280785
      • investigator1_emailabrahamsiika@gmail.com
      • organisations_transferred_No
      • number_participants160
      • notification
      • approval_date18-11-2021
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted24-06-2021
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonStudy approved by the experts
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-09-03 12:53:26
      • created2021-06-22 09:29:32
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id686
        • application_id1030
        • given_nameAbraham
        • middle_name
        • family_nameSiika
        • qualificationMBChB, MMed, MSc
        • professional_addressP.O Box 4606-30100 Eldoret Kenya
        • telephone254721280785
        • emailabrahamsiika@gmail.com
        • created2021-06-22 12:38:45
        • modified2021-06-24 11:47:25
    • SiteDetail(array)
      • 0(array)
        • id949
        • application_id1030
        • county_id27
        • site_nameMoi University Clinical Research Centre
        • physical_addressP.O Box 4606 - 30100 Eldoret
        • contact_details+254711729856
        • contact_personViola Kirui
        • site_capacity(null)
        • misc(null)
        • created2021-06-22 12:38:45
        • modified2021-06-24 11:47:25
        • County(array)
          • id27
          • county_nameUasin Gishu
          • created2012-06-15 10:25:15
          • modified2012-06-15 10:25:15
      • 1(array)
        • id950
        • application_id1030
        • county_id35
        • site_nameKEMRI Walter Reed Project
        • physical_addressKericho County Hospital Grounds
        • contact_details0722941525
        • contact_personMary Lelgo
        • site_capacity(null)
        • misc(null)
        • created2021-06-22 15:55:59
        • modified2021-06-24 11:47:25
        • County(array)
          • id35
          • county_nameKericho
          • created2012-06-15 10:26:16
          • modified2012-06-15 10:26:16
      • 2(array)
        • id951
        • application_id1030
        • county_id47
        • site_nameAga khan University Hospital
        • physical_addressAga khan University Hospital Nairobi
        • contact_details+254735 338 003
        • contact_personReena Shah
        • site_capacity(null)
        • misc(null)
        • created2021-06-22 15:55:59
        • modified2021-06-24 11:47:25
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
    • Sponsor(array)
      • 0(array)
        • id518
        • application_id1030
        • sponsorJoint Clinical Research Centre
        • sponsor_typeOthers
        • contact_personDr. Ivan Mambule
        • addressPlot 101 Lubowa P.O Box 10005 Kampala, Uganda
        • telephone_number+256 772594411
        • fax_number
        • cell_number+256 772594411
        • email_addressimambule@jcrc.org.ug
        • created2021-06-22 12:38:45
        • modified2021-06-24 11:47:25
• page_options(array)
  • 55
  • 1010
• redir
• $request->data(array)
  • Application(empty)
• $this->validationErrors(array)
  • Permission(empty)
  • Aro(empty)
  • Aco(empty)
  • Application(empty)
  • User(empty)
  • TrialStatus(empty)
  • InvestigatorContact(empty)
  • Sponsor(empty)
  • SiteDetail(empty)
  • County(empty)
• Loaded Helpers(array)
  • 0Html
  • 1Form
  • 2Session
  • 3Text
  • 4Number
  • 5SimpleGraph
  • 6Paginator
  • 7DebugTimer
  • 8Toolbar
  • 9HtmlToolbar

App Constants

CakePHP Constants

PHP Environment

Included Files

Include Paths

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

Included Files

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  • Config(array)
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    • 4CORE/Log/CakeLogInterface.php
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  • Network(array)
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    • 6CORE/Routing/Route/PluginShortRoute.php
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    • 0CORE/View/HelperCollection.php
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• plugins(array)
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