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      • id1529
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      • abstract_of_study<p>\n <strong><u>Trial Design:</u></strong></p>\n<p>\n This is a Phase III multicenter, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of crizanlizumab 5 mg/kg versus placebo, with or without concurrent HU/HC therapy in patients with SCD who experience frequent VOCs (4-12 events in the 12 months prior to the screening visit).</p>\n<p>\n <strong><u>Purpose of the study:</u></strong></p>\n<p>\n The main purpose of this study is to determine whether crizanlizumab may reduce the number of VOCs when compared to placebo, with or without standard of care medications in adolescent and adult SCD patients with frequent VOCs leading to healthcare visits. The study duration will be approximately 2 years.</p>\n<p>\n <strong><u>Study Rationale:</u></strong></p>\n<p>\n Crizanlizumab was first approved in the USA (BLA 761128) under the trade name Adakveo® on 15-Nov-2019. This BLA approval was based on the results from the Phase II Study CSEG101A2201 (SUSTAIN), a 52-week, randomized, placebo-controlled study (N=198) of crizanlizumab 2.5 and 5 mg/kg. In Study A2201, a vasoocclusive crises (VOC) was defined as an acute episode of pain with no other cause than a vasoocclusion, which required a visit to a medical facility and treatment with oral or parenteral opioids or parenteral non-steroidal anti-inflammatory drugs (NSAIDs). This included both uncomplicated VOCs as well as complicated VOCs such as acute chest syndrome, hepatic sequestration, splenic sequestration, and priapism. These visits required a visit to a medical facility. An uncomplicated crisis was defined as a VOC that was not classified as acute chest syndrome, hepatic sequestration, splenic sequestration, priapism, and which did not lead to death.</p>\n<p>\n Treatment with crizanlizumab 5 mg/kg in Study A2201 resulted in a median annual rate of VOCs leading to a healthcare visit that was 45.3% lower than the median annual rate with placebo, which was statistically significant (p=0.010). The median annual rate of uncomplicated crises and median number of days hospitalized were 62.9% and 41.8% lower than in the placebo group, respectively. These constitute meaningful reductions in the frequency of VOCs and hospitalizations that can be expected to have a significant impact on quality of life (QoL), morbidity and mortality in patients with SCD.</p>\n<p>\n Study CSEG101A2301 is an ongoing Phase III, multicenter, randomized, double-blind study to assess efficacy and safety of two doses of crizanlizumab (5 mg/kg and 7.5 mg/kg) versus placebo, with or without hydroxyurea/ hydroxycarbamide therapy (HU/HC), in adolescent and adult patients with SCD. VOC was defined the same way as previously noted in the SUSTAIN trial.</p>\n<p>\n In Dec-2022, the results of the primary analysis of Study CSEG101A2301 did not show evidence of superiority of either dose of crizanlizumab (5 mg/kg or 7.5 mg/kg) over placebo on the primary or key secondary endpoints and therefore are not consistent with the results from Study CSEG101A2201.</p>\n<p>\n While the endpoint of VOC leading to a healthcare visit reflects a key aim of treatment in SCD, i.e., prevention/reduction of VOCs, it is important to note that it is dependent on patients making the decision to go or not go to the hospital. The different results in Study CSEG101A2301 compared with Study CSEG101A2201 could be due to various factors/differences between the studies, including but not limited to:</p>\n<ol style=\"list-style-type:lower-roman;\">\n <li value=\"5\">\n The impact of the COVID-19 global pandemic, which may have caused a masking effect/reduction in reporting of VOCs as well as a potential reduction in triggers for VOCs in Study CSEG101A2301.\n <ol style=\"list-style-type:lower-roman;\">\n <li value=\"5\">\n Differences in the geographic location of participating patients, thereby factoring in the differences in healthcare utilization: patients were located primarily in the USA in Study CSEG101A2201 vs. globally dispersed in Study CSEG101A2301.</li>\n </ol>\n </li>\n</ol>\n<p>\n Thus, while the initial randomized, placebo-controlled trial (Study CSEG101A2201), the open label studies (Study SEG101A2202, Study SEG101B2201 and Study SEG101AUS05) and real-world data (MAP data and registries) have all demonstrated clinical benefit with crizanlizumab, the second, randomized, placebo-controlled Study CSEG101A2301 did not.</p>\n<p>\n The current study (Study CSEG101A2303; hereafter referred to as Study A2303), a randomized, placebo-controlled Phase III study, was developed to overcome the uncertainties raised by the conflicting results of Studies CSEG101A2301 and CSEG101A2201. The purpose of this study is to compare the efficacy of crizanlizumab (5 mg/kg) versus placebo, with or without HU/HC in adolescent and adult SCD patients with frequent VOCs (4 to 12 per year) that are Health care practitioner-managed (including VOCs leading to management at a health care facility or those managed via remote consultation).</p>\n<p>\n Data from this study will be used to evaluate the effect of crizanlizumab versus placebo, with or without concurrent HU/HC therapy, on VOC rate in SCD patients aged 12 years and older who experience frequent VOCs.</p>\n<p>\n <strong><u>Study Population:</u></strong></p>\n<p>\n The study will include participants aged 12 years and older with confirmed diagnosis of SCD (all genotypes are eligible) who have experienced at least 4-12 VOCs that are HCP-managed (including VOCs leading to management at a health care facility or those managed via remote consultation) within the 12 months prior to the screening visit. Participants may receive HU/HC as a standard of care.</p>\n<p>\n This study plans to enroll 315 participants. Participants will be randomized in a 2:1 ratio to the crizanlizumab 5 mg/kg or placebo treatment arm (see Section 9.9 of the Protocol v00 for more details on sample size determination).</p>\n
      • study_title<p>\n A phase III, Multicenter, Randomized, Placebo Controlled, Double blind Study to Assess Efficacy and Safety of Crizanlizumab (5 mg/kg) versus placebo, with or without Hydroxyurea/Hydroxycarbamide Therapy, in Adolescent and Adult Sickle Cell Disease Patients with Frequent Vaso-Occlusive Crises</p>\n
      • laymans_summary<div>\n  Sickle cell disease is one of the most common blood disease in the world that is passed down from generation to another and is characterized by frequent pain episodes, reduced blood levels as well as multiple organ damage. Painful episodes are the most common presentation of sickle cell disease. These are caused by activation of different components of blood triggered by the sickled red blood cells. The activation of these blood components leads to their expression of the p-selectin molecule found in blood which promotes sticking together of cells to each other resulting in blockage of blood vessels. Painful episodes are a clinical hallmark of SCD and cause considerable acute and chronic reduction in quality of life as well as death. L-glutamine and Hyrdoxyurea have been approved by the food and drug administration to reduce VOCs in patients with SCD. Crizanlizumab is a potent and selective IgG2 (immunoglobulin G2) kappa humanized monoclonal antibody that binds to human P-selectin with high affinity, blocking its interaction with its ligands, including P-selectin glycoprotein ligand 1 (PSGL-1). Extensive pre-clinical data have established P-selectin as a key mediator of VOC in SCD (Matsui et al 2001) and suggest that blockade of P-selectin could eliminate or reduce VOC. </div>\n<div>\n  </div>\n<div>\n This study is a drug clinical trial sponsored by Norvatis Research and Development and is to be implemented at KEMRI CRDR Siaya Clinical Research Annex by Professor Videlis Nduba as the Principal Investigators alongside Dr. Mercy Mwale and Dr. Mike Odoyo as the Sub-investigators. This study will be conducted in many sites globally in a randomized manner where a participant will either get inactive or active form of treatment as assigned by the Investigator or designee through a system generated method provided by sponsor. Both the participants as well as the study staff will not know the treatment administered to the participant. </div>\n<div>\n  </div>\n<div>\n It is a Phase 3 study comparing crizanlizumab 5 mg/kg to inactive form of treatment with or without simultaneous use of Hydroxyurea/Hydroxycarbamide treatment in adolescent and  adult SCD patients who experience frequent painful episodes. The study will include participants aged 12 years and older with confirmed diagnosis of SCD (all variants of sickle cell disease are eligible) who have experienced at least 4-12 painful episodes that are Healthcare professional-managed (including painful episodes leading to management at a health care facility or those managed via remote consultation) within the 12 months prior to the screening visit. Participants may receive Hydroxyurea/Hydroxycarbamide  as standard of care. </div>\n<div>\n  </div>\n<div>\n Globally 315 participants will be enrolled. Kenya has been allocated 30 participants to be competitively enrolled among 6 sites sites which are: Getrude’s Children’s Hospital; International Cancer Institute; KEMRI Kondele Children’s Hospital; CREATES Ahero Clinical Ahero and Victoria Biomedical Research. Therefore, at least 5 participants will be enrolled by the Siaya site. For every 3 participants enrolled into the study, 2 will receive crizanlizumab 5mg/kg whereas 1 will receive the inactive form of treatment. Central assignment of the treatment arm will be grouped according to simultaneous Hydroxyurea/Hydroxycarbamide usage (yes/no) and region (South America, North America, and sub- Saharan Africa) at baseline. There is a potential side effect of infusion related reaction with the administration of crizanlizumab that has been observed so far. </div>\n<div>\n  </div>\n<div>\n Data from this study will be used to evaluate the effect of crizanlizumab versus inactive form of treatment, with or without concurrent Hydroxyurea/Hydroxycarbamide treatment, on painful episodes rate in SCD patients aged 12 years and older who experience frequent painful episodes. The study will be conducted according to the protocol, guidelines established by the ICH for GCP in clinical studies. The study protocol, informed consent forms, electronic case report forms and site specific protocol will be submitted to the regulatory bodies as required, and once approval is received from the Ethics Committee and Pharmacy and Poisons Board of Kenya , the site will be initiated and activated. </div>\n<div>\n  </div>\n<div>\n  </div>\n
      • short_titleSparkle - Site 1405
      • protocol_noECCT/25/03/07
      • version_no00
      • date_of_protocol02-02-2024
      • study_drugCrizanlizumab
      • disease_conditionSickle Cell Disease
      • 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_nameNot Applicable
      • comparator_registeredNot Applicable
      • comparator_countriesNot Applicable
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressraps.clinicaltrials@novartis.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_applicantDenish Kineni
      • declaration_date130-03-2025
      • declaration_principal_investigatorProf Videlis Nduba
      • declaration_date230-03-2025
      • placebo_presentYes
      • study_objectives<p>\n <strong>Primary Objective:</strong></p>\n<p>\n To compare the efficacy of 5 mg/kg of crizanlizumab versus placebo, with or without hydroxyurea/hydroxycarbamide, on the annualized rate of VOCs* that are HCPmanaged (including VOCs leading to management at a health care facility or those managed via remote consultation) over the planned 52-week treatment period in SCD patients aged 12 years and older with a history of frequent VOCs (4-12 events in 12 months prior to the screening visit).</p>\n<p>\n <strong>Secondary Objective:</strong></p>\n<ul>\n <li>\n To compare the efficacy of 5 mg/kg of crizanlizumab versus placebo, with or without hydroxyurea/hydroxycarbamide, on the annualized rate of all VOCs including VOCs that are HCP-managed (including VOCs leading to management at a health care facility or those managed via remote consultation) and VOCs that are self-managed without recommendations from HCP during the event over the planned 52- week treatment period in SCD patients aged 12 years and older with a history of frequent VOCs (4-12 events in the 12 months prior to the screening visit).</li>\n <li>\n To evaluate the annualized rate of VOCs by type of management between treatment arms over the planned 52-week treatment period:</li>\n</ul>\n<ol style=\"list-style-type:lower-roman;\">\n <li value=\"5\">\n VOCs that are HCP-managed at a health care facility\n <ol style=\"list-style-type:lower-roman;\">\n <li value=\"5\">\n VOCs that are HCP-managed via remote consultation</li>\n <li value=\"5\">\n VOCs that are self-managed without recommendations from HCP during the event</li>\n </ol>\n </li>\n <li value=\"5\">\n VOCs that are HCP-managed via remote consultation or self-managed without recommendations from HCP during the event</li>\n</ol>\n<ul>\n <li>\n To evaluate the time to first VOC that is HCPmanaged (including VOCs leading to management at a health care facility or those managed via remote consultation) between treatment arms over the planned 52-week treatment period.</li>\n <li>\n To evaluate the proportion of participants free from VOCs that are HCP-managed (including VOCs leading to management at a health care facility or those managed via remote consultation) between treatment arms over the planned 52-week treatment period.</li>\n <li>\n To evaluate the duration of VOCs that are HCP managed (including VOCs leading to management at a health care facility or those managed via remote consultation) between treatment arms over the planned 52-week treatment period.</li>\n <li>\n To evaluate the safety and immunogenicity of crizanlizumab 5 mg/kg over the 2-year study period.</li>\n</ul>\n<p>\n <strong>Exploratory Objectives:</strong></p>\n<ul>\n <li>\n To explore the efficacy of crizanlizumab 5 mg/kg over the 2-year study period.</li>\n <li>\n To explore the proportion of VOCs that are self-managed without recommendations from HCP during the event, versus VOCs that are HCP managed (including VOCs leading to management at a health care facility or those managed via remote consultation) between treatment arms over the planned treatment period of 52 weeks.</li>\n <li>\n To explore the proportion of VOCs that are HCP managed via remote consultation versus VOCs that are HCP-managed at a healthcare facility between treatment arms over the planned 52- week treatment period.</li>\n <li>\n To explore the incidence rates of all VOCs, VOCs that are HCP-managed at a healthcare facility, VOCs that are HCP-managed via remote consultation, VOCs that are HCP-managed, VOCs that are self-managed without recommendations from HCP during the event, VOCs that are HCP-managed via remote consultation or self-managed without recommendations from HCP during the event, by treatment arm.</li>\n <li>\n To explore quality of life in each treatment arm (ASCQ-Me Short Forms: emotional impact, sleep impact, and joint stiffness).</li>\n</ul>\n<ul>\n <li>\n To explore healthcare facility resource utilization (inpatient hospital admission, emergency room visit, urgent care/clinic visit, infusion center visit) between treatment arms over the planned 52- week treatment period.</li>\n <li>\n To explore the pharmacokinetics (PK) profile of crizanlizumab at 5 mg/kg.</li>\n <li>\n To explore the pharmacodynamics (PD) (P selectin inhibition) of crizanlizumab at 5 mg/kg.</li>\n <li>\n To explore biomarkers [p-selectin (free and total)] and CRP].</li>\n <li>\n To explore exposure-response relationship</li>\n</ul>\n<p>\n  </p>\n
      • principal_inclusion_criteria<p>\n <strong><u>Principal Inclusion Criteria:</u></strong></p>\n<p>\n 1. Signed informed consent must be obtained prior to participation in the study.</p>\n<p>\n 2. Participants must be aged 12 years and older on the day of signing informed consent. Adolescents include participants aged 12 to <18 years old and adults include participants aged 18 years and older.</p>\n<p>\n 3. Confirmed diagnosis of SCD by Hb electrophoresis or high-performance liquid chromatography (HPLC) (performed locally or by central laboratory if not available locally). All SCD genotypes are eligible.</p>\n<p>\n 4. Experienced 4 to 12 VOCs that are HCP-managed (including VOCs leading to management at a health care facility or those managed via remote consultation) within the 12 months prior to the screening visit. Baseline VOCs are determined by medical history and are required to be documented at source.</p>\n<p>\n Prior VOCs that were HCP-managed at a health care facility or managed via remote consultation must have resolved at least 7 days prior to Week 1 Day 1 dosing.</p>\n<p>\n 5. If the participant is on HU/HC, they must be taking it for at least 6 months and at stable dose for at least 3 months prior to the Screening visit and plan to continue taking it at the same dose and schedule until at least the participant has reached 52 weeks of the planned study treatment. Participants who have initiated HU/HC 6-12 months prior to the screening visit must have evidence of insufficient control of acute pain despite initiation. These participants must have a cumulative of 4-12 VOCs in the 12 months prior to the screening period, with at least 2 during the last 6 months while on HU/HC. If receiving erythropoietin stimulating agent, the participant must have been receiving the drug for at least 6 months prior to screening visit and plan to continue taking the drug at the same dose and schedule until the participant has reached 52 weeks of the planned study treatment.</p>\n<p>\n Participants who have not been receiving HU/HC, and/or erythropoietin stimulating agent must not have received it for at least 6 months prior to screening visit.</p>\n<p>\n 6. Participants must meet the following central laboratory values prior to Week1 Day 1. In case re-sampling is needed, local laboratory values are allowed.</p>\n<ol style=\"list-style-type:lower-roman;\">\n <li value=\"5\">\n Absolute Neutrophil Count ≥1.0 x 109/L</li>\n <li value=\"5\">\n Platelet count ≥75 x 109/L</li>\n <li value=\"5\">\n Hemoglobin: for adults (Hb) ≥5.0 g/dL and for adolescents (Hb) ≥5.5 g/dL</li>\n <li value=\"5\">\n Glomerular filtration rate ≥45 mL/min/1.73 m2 based on CKD-EPI formula (patients ≥18), or the Creatinine-based “Bedside Schwartz” equation (patients <18)</li>\n <li>\n Direct (conjugated) bilirubin ≤3.0 x ULN</li>\n <li value=\"5\">\n Alanine transaminase (ALT) <3.0 x ULN</li>\n</ol>\n<p>\n 7. Score of 50% or higher on the Karnofsky Performance Scale at screening.</p>\n<p>\n 8. Received standard age-appropriate care for SCD, including an up-to-date record of immunizations, as per local requirements.</p>\n
      • principal_exclusion_criteria<p>\n <strong><u>Principal Exclusion Criteria:</u></strong></p>\n<p>\n Participants meeting any of the following criteria are not eligible for inclusion in this study.</p>\n<p>\n 1. Fewer than 4 or more than 12 VOCs that are HCP-managed (including VOCs leading to management at a health care facility or those managed via remote consultation) within the 12 months prior to screening visit as determined by medical history and documented at source.</p>\n<p>\n 2. History of stem cell transplant and/or gene therapy.</p>\n<p>\n 3. Received blood products within 30 days prior to Week 1 Day 1 dosing.</p>\n<p>\n 4. Any documented history of a clinical stroke or intracranial hemorrhage, or an uninvestigated neurologic finding within the past 12 months before screening visit. Silent infarct only present on imaging is not excluded.</p>\n<p>\n 5. Clinically significant bleeding disorder.</p>\n<p>\n 6. Use of therapeutic anticoagulation or antiplatelet therapy (other than aspirin or NSAIDs) within the 10 days prior to Week 1 Day 1 dosing. Note: Prophylactic anticoagulant dose is permitted, as per local guidelines.</p>\n<p>\n 7. Participating in a chronic transfusion program (pre-planned series of transfusions for prophylactic purposes) and/or planning to undergo an exchange transfusion during the duration of the study; episodic transfusion in response to worsened anemia or VOC is permitted.</p>\n<p>\n 8. Contraindication or hypersensitivity to any drug or metabolites from similar class as study drug or to any excipients of the study drug formulation. History of severe hypersensitivity reaction to other monoclonal antibodies, which in the opinion of the investigator may pose an increased risk of serious infusion reaction.</p>\n<p>\n 9. Received active treatment on another investigational trial within 30 days (or 5 half-lives of that agent, whichever is greater) prior to Screening visit or plans to participate in another investigational drug trial.</p>\n<p>\n 10. Participants of child-bearing potential who are or might become sexually active, must be informed of the potential teratogenic risk with crizanlizumab and the need for highly effective contraception methods to prevent pregnancy while on crizanlizumab therapy. Any participant with the biologic potential to become pregnant must agree to the use of oral, injected or implanted hormonal methods of</p>\n<p>\n contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS) or other forms of hormonal contraception that have comparable efficacy (failure rate <1%), for example hormone vaginal ring or transdermal hormone contraception is required if sexually active. Patients should also follow other guidelines for contraception in the setting of other standard of care therapies. Contraception must be used during the study and for 15 weeks after stopping treatment. The decision on the contraceptive method should be reviewed at least every 3 months to evaluate the individual need and compatibility of the method chosen.</p>\n<p>\n 11. Pregnant females or females who have given birth within the past 90 days or who are breastfeeding.</p>\n<p>\n 12. Planning to undergo a major surgical procedure during the duration of the study.</p>\n<p>\n 13. Hospitalized within 7 days prior to Week 1 Day 1 dosing.</p>\n<p>\n 14. Acute VOCs ending within 7 days prior to Week 1 Day 1 dosing.</p>\n<p>\n 15. Participants with active HIV infection (detectable viral load) at screening.</p>\n<p>\n 16. Participants with active Hepatitis B infection (HBsAg positive) at screening. Note: Participants with antecedent but no active Hepatitis B (i.e., anti-HBs positive, HBsAg and HBV-DNA negative) are eligible.</p>\n<p>\n 17. Positive test for hepatitis C ribonucleic acid (HCV RNA) at screening. Note: Participants in whom HCV infection resolved spontaneously (positive HCV antibodies without detectable HCV-RNA) or those that achieved a sustained virological response after antiviral treatment and show absence of detectable HCV RNA ≥6 months (with the use of IFN-free regimes) or ≥12 months (with the use of IFN-based regimes) after cessation of antiviral treatment are eligible.</p>\n<p>\n 18. Malignant disease. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 3 years prior to study treatment; completely resected basal cell and squamous cell skin cancers and any completely resected carcinoma in situ.</p>\n<p>\n 19. Concurrent severe and/or uncontrolled medical conditions which, in the opinion of the investigator, could cause unacceptable safety risks or compromise participation in the study.</p>\n<p>\n 20. Any condition which, in the opinion of the investigator, is likely to interfere with the successful collection of the measurements required for the study. This can include inability to understand and comply with study instructions and requirements.</p>\n<p>\n 21. Received prior treatment with crizanlizumab or other selectin targeting agent or plans to receive these therapies outside of the study during the duration of the study.</p>\n<p>\n 22. Use of HA approved form(s) of L-glutamine within 6 months of screening or plans to receive it during the study.</p>\n<p>\n 23. Currently on voxelotor or received voxelotor within 6 months of screening or plans to receive it during the study.</p>\n<p>\n 24. Participants taking prohibited therapies </p>\n
      • primary_end_points<p>\n <strong><u>Primary Endpoint:</u></strong></p>\n<p>\n Annualized rate of VOCs that are HCPmanaged (including VOCs leading to management at a health care facility or those managed via remote consultation) in each treatment arm over the planned 52-week treatment period.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic1
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others1
      • scope_others_specifyBiomarkers
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n <strong><u>Site 1405</u></strong>:</p>\n<p>\n KEMRI/CRDR Siaya Clinical Research Center:</p>\n<p>\n Kenya Medical Research Institute-Centre for Respiratory Disease Research (KEMRI/CRDR) Siaya Site is located within Siaya County Referral hospital in Siaya County, Western Kenya, about 67-74 (Route dependent) KM from Kisumu City. KEMRI CRDR has been in operation since its inception in 2007. It is part of the larger KEMRI which is a state corporation established through since and technology (Amendment) ACT of 1979. KEMRI has gradually grown over 40 years to become the national leading institute in clinical human health research. Our mission is to improve human health and quality of life through research, capacity building, innovation and service delivery.</p>\n<p>\n <strong>Staffing Structure:</strong></p>\n<p>\n The research activities at the KEMRI/CRDR are under the overall leadership of Prof Videlis Nduba, assisted by the delegated Sub-Investigators who are medical doctors. The site leadership is organized as per the organogram below, figure 1 whereby each department has a section leader who reports to the delegated sub-investigators doubling up as study coordinators at the site and sub-investigator reports to the PI.</p>\n<p>\n The site duties and responsibilities for the protocol implemented at the site are assigned to key study staff as appropriate, based on background, training, and experience. All study staff work on the various protocols being implemented at the site and report to section leads; however, each protocol has a study champion to ensure full compliance with all protocols as well as regulatory requirements, such coordination ensures sustainability and cost-effective use of available resources while avoiding waste or redundant parallel facilities.</p>\n<p>\n The research team meets every week and ad hoc to discuss research activities of the previous week, including protocol visits and safety issues, challenges or concerns, quality control findings, laboratory activities and community updates. These meetings also act as a platform for training, discussing regulatory updates, planning research activities and continuous medical education in disease of interest.</p>\n<p>\n The site has a total of approximately 43 staff, including the principal Investigator, 2 Sub Investigators, 4 Clinical Officers, 2 Pharmacists, 1 pharmaceutical Technologist, 5 Laboratory technologists, 6 Nurses, 4 Data Officers, 3 Drivers, 8 Community Engagement Officers, 6 QA/QC Officers including the regulatory office, 1 administrative officer and 1 receptionist.</p>\n<p>\n <strong>Experience:</strong></p>\n<p>\n The site has experienced research staff cutting across different studies in different networks, with the distribution of staff full time -equivalents across the different studies. Some of the study personnel have a wealth of experience of more than 10 years in clinical research. This allows for continuity and shared experiences by having staff engaged throughout the research portfolio across different studies and cohorts.</p>\n<p>\n The study team is trained on standard operating procedures, study protocol, and study manuals before conducting study procedures, ensuring the site complies with the protocol, Regulatory, IRB and GCP Guidelines.</p>\n<p>\n All study staff are human subjects’ protection and good clinical practice certified. All laboratory staff are good clinical laboratory Practice and IATA certified, and the community engagement team are Good Participatory Practice trained.</p>\n<p>\n Since 2007, the site has gained experience conducting research activities across diverse age cohorts and various vaccine and therapeutic areas in disease such as malaria, sickle cell disease, TB, Marburg, Ebola , Covid 19 etc.</p>\n<p>\n <strong><u>Facilities and Equipment:</u></strong></p>\n<p>\n The site is a modern research facility that is well equipped with the capacity to conduct Phase I-IV studies of all age groups. The site has a dedicated research space with patient assessment and examination rooms, an on-site drug storage are the site pharmacy (which is access and temperature controlled) an on-site laboratory area, a crash cart that is fully equipped with emergency medication,a secure fireproof and access-controlled area for archiving of documents, monitoring office rooms to accommodate monitors , auditors or inspectors and a stable internet and IT support.</p>\n<p>\n The research clinic is also laced within the referral hospital, a level 5 health facility. This strategic location and collaboration allow feasible referral of participants who require special services, and it is primary source of participants for hospital-based clinical trials.</p>\n<p>\n <strong><u>Patent Recruitment & Retention:</u></strong></p>\n<p>\n For SCD clinical trials, the site maintains a database of people living with SCD, the database was generated from welfare and support groups of SCD patients, snowballing, referrals from health facilities and participants who participated in previous studies.</p>\n<p>\n The site has maintained outstanding performance ratings on enrolment and retention based on sponsor monitoring reports.</p>\n<p>\n <strong><u>Quality assurance policies and protocols:</u></strong></p>\n<p>\n The principal Investigator maintains overall responsibility for protocol compliance. He provides overall study oversight and delegates some duties to key study personnel, sub-investigators and section leads to assist in implementing the study protocols at the site.</p>\n<p>\n Quality Assurance ensures protocols are implemented at the site in compliance with good clinical practice, regulatory requirements, sponsor guidelines, and internal standard operating procedures. The primary objective is to maintain high-quality data integrity subject safety, and protocol adherence.</p>\n<p>\n The quality team ensures all sites personnel undergo mandatory GCP and study-specific training before trial initiation. Training records are maintained in the site training logs. Continuous training updates are provided when protocol amendments or regulatory changes occur.</p>\n<p>\n Non-compliance and deviations are assessed and reported to the sponsor and IRB/IEC per regulatory requirements and corrective action plans are implemented to prevent recurrence.</p>\n<p>\n The site does pre-audit or pre-inspection self-assessment to ensure compliance and always strives to be audit or inspection ready. Essential documents are maintained per ICH-GCP guidelines. Archival and Retention policies such as the archival SOP are in place to ensure proper storage of clinical trial records for the required period.</p>\n<p>\n In QC procedure for study visits, a 100% two-tiered quality control process is performed on all study records and 25% on the 3^rd level on randomly selected binders. Focus is put on ensuring that all requisite data is collected and procedures stipulated for each study visit are completed as appropriate. The staff performing study procedures does 100% first-level QC, ensuring that all procedures are done and documented appropriately; this process is captured in the source document worksheet used to collect data (this process is done before the participant moves to the next stage as applicable). The delegated QA/QC officer does real-time 100% second-level quality checks in between procedures, ensuring that all procedures are done and documented well.</p>\n<p>\n  </p>\n
      • other_details_explanation<p>\n <span style=\"font-size: 10pt; line-height: 107%; font-family: Calibri, sans-serif; color: black; background-image: initial; background-position: initial; background-size: initial; background-repeat: initial; background-attachment: initial; background-origin: initial; background-clip: initial;\">Switzerland is the host country of the Sponsor however the study will not be conducted in the host country because the birth incidence of disease is far lower in Switzerland than in Kenya.</span></p>\n
      • other_details_regulatory_notapproved<p>\n  </p>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td style=\"width:160px;\">\n <p align=\"center\">\n  </p>\n <p align=\"center\">\n <strong>Country</strong></p>\n </td>\n <td style=\"width:160px;\">\n <p align=\"center\">\n <strong>Agency</strong></p>\n </td>\n <td style=\"width:160px;\">\n <p align=\"center\">\n <strong>HA submission Date</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:160px;\">\n <p align=\"center\">\n Brazil</p>\n </td>\n <td style=\"width:160px;\">\n <p align=\"center\">\n Agência Nacional de Vigilância Sanitária  - ANVISA</p>\n </td>\n <td style=\"width:160px;\">\n <p align=\"center\">\n 10-May-2024</p>\n <p align=\"center\">\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:160px;\">\n <p align=\"center\">\n Colombia</p>\n </td>\n <td style=\"width:160px;\">\n <p align=\"center\">\n Instituto de Vigilancia de Medicamentos y Alimentos INVIMA</p>\n </td>\n <td style=\"width:160px;\">\n <p align=\"center\">\n 09-Jul-2024</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:160px;\">\n <p align=\"center\">\n Ghana</p>\n </td>\n <td style=\"width:160px;\">\n <p align=\"center\">\n Food and Drug Authority (FDA) Ghana</p>\n </td>\n <td style=\"width:160px;\">\n <p align=\"center\">\n 28-Feb-2025</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:160px;\">\n <p align=\"center\">\n Kenya</p>\n </td>\n <td style=\"width:160px;\">\n <p align=\"center\">\n Pharmacy and Poisons Board (PPB)</p>\n </td>\n <td style=\"width:160px;\">\n <p align=\"center\">\n Initial iCTA: 13Nov2024 (Only site 1401 was submitted with the initial clinical trial application)</p>\n <p align=\"center\">\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:160px;\">\n <p align=\"center\">\n Nigeria</p>\n </td>\n <td style=\"width:160px;\">\n <p align=\"center\">\n National Agency for Food and Drug Administration and Control</p>\n </td>\n <td style=\"width:160px;\">\n <p align=\"center\">\n 28-Feb-2025</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:160px;\">\n <p align=\"center\">\n Tanzania</p>\n </td>\n <td style=\"width:160px;\">\n <p align=\"center\">\n TANZANIA MEDICINES AND MEDICAL DEVICES AUTHORITY (TMDA)</p>\n </td>\n <td style=\"width:160px;\">\n <p align=\"center\">\n 21-Feb-2025</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:160px;\">\n <p align=\"center\">\n Uganda</p>\n </td>\n <td style=\"width:160px;\">\n <p align=\"center\">\n National Drug Authority (NDA)</p>\n </td>\n <td style=\"width:160px;\">\n <p align=\"center\">\n 20-Feb-2025</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:160px;\">\n <p align=\"center\">\n Zambia</p>\n </td>\n <td style=\"width:160px;\">\n <p align=\"center\">\n Zambia Medicines Regulatory Authority ZAMRA</p>\n <p align=\"center\">\n  </p>\n </td>\n <td style=\"width:160px;\">\n <p align=\"center\">\n Planned</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:160px;\">\n <p align=\"center\">\n United States</p>\n </td>\n <td style=\"width:160px;\">\n <p align=\"center\">\n U.S. Food and Drug Administration</p>\n </td>\n <td style=\"width:160px;\">\n <p align=\"center\">\n 06-Mar-2024</p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_regulatory_approved<p>\n United States – Silent Approval_20 Sites in the US</p>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\">\n <tbody>\n <tr>\n <td style=\"width:68px;height:20px;\">\n <p align=\"center\">\n <strong>Country</strong></p>\n </td>\n <td style=\"width:128px;height:20px;\">\n <p align=\"center\">\n <strong>Agency</strong></p>\n </td>\n <td style=\"width:112px;height:20px;\">\n <p align=\"center\">\n <strong>HA submission Date</strong></p>\n </td>\n <td style=\"width:123px;height:20px;\">\n <p align=\"center\">\n <strong>Approval date</strong></p>\n </td>\n <td style=\"width:181px;height:20px;\">\n <p align=\"center\">\n <strong>Number of sites </strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:68px;height:20px;\">\n <p align=\"center\">\n Colombia </p>\n </td>\n <td style=\"width:128px;height:20px;\">\n <p align=\"center\">\n Instituto de Vigilancia de Medicamentos y Alimentos INVIMA </p>\n </td>\n <td style=\"width:112px;height:20px;\">\n <p align=\"center\">\n 09-Jul-2024 </p>\n </td>\n <td style=\"width:123px;height:20px;\">\n <p align=\"center\">\n 11-December-2024 </p>\n </td>\n <td style=\"width:181px;height:20px;\">\n <p align=\"center\">\n 4 Sites </p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n
      • other_details_regulatory_rejected<p>\n No Rejections received to date</p>\n
      • other_details_regulatory_halted<p>\n Not Applicable</p>\n
      • estimated_durationapproximately 2 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_comparatorNot Applicable
      • 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_states9
      • number_of_sites6 sites anticipated in Kenya. Kindly note that this application is for site 1405. Site 1401 was submitted to KPPB as part of the iCTA on the 13th of November 2024
      • multi_country_listBrazil\nColombia\nGhana\nKenya\nNigeria\nUganda\nTanzania\nZambia\nUnited States
      • data_monitoring_committeeNo
      • total_enrolment_per_siteMin 5 maximum 15 across 6 sites
      • total_participants_worldwide315 participants
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameVidelis
      • investigator1_middle_name
      • investigator1_family_nameNduba
      • investigator1_qualificationMBchB, MPH, PHD
      • investigator1_professional_addressKEMRI/CRDR Siaya Clinical Research Annex, KEMRI Clinical Research Annex -Siaya County Referral Hospital Grounds. Siaya Kenya
      • investigator1_telephone+254724522474
      • investigator1_emailvnduba@gmail.com
      • organisations_transferred_Yes
      • number_participants60
      • notification
      • approval_date16-09-2025
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted30-03-2025
      • is_child0
      • unsubmitted1
      • initial_date_submitted30-03-2025
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have 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)
      • modified2025-09-16 13:30:10
      • created2025-03-28 09:23:28
      • total_sites1
      • ecitizen_invoice363974
    • InvestigatorContact(array)
      • 0(array)
        • id1245
        • application_id1529
        • given_nameProf Videlis
        • middle_name
        • family_nameNduba
        • qualificationMBchB, MPH, PHD
        • professional_addressKEMRI/CRDR Siaya Clinical Research Annex, Siaya County Referral Hospital Grounds, PO Box 144-4600 Siaya Kenya
        • telephone+254724522474
        • emailvnduba@gmail.com
        • created2025-03-28 09:23:28
        • modified2025-05-19 12:18:56
    • SiteDetail(array)
      • 0(array)
        • id1863
        • application_id1529
        • county_id41
        • site_nameKEMRI/CRDR KEMRI Clinical Research Annex
        • physical_addressKEMRI Clinical Research Annex -Siaya County Referral Hospital Grounds. Siaya Kenya
        • contact_details+254724522474 PO Box 144-4600
        • contact_personProf Videlis Nduba
        • site_capacity(null)
        • misc(null)
        • created2025-03-28 10:00:41
        • modified2025-05-19 12:18:56
        • County(array)
          • id41
          • county_nameSiaya
          • created2012-06-15 10:26:56
          • modified2012-06-15 10:26:56
      • 1(array)
        • id1869
        • application_id1529
        • county_id42
        • site_nameAhero Clinical trials Unit
        • physical_addressAhero County Hospital.
        • contact_detailsP.O Box 54- 40100 Kisumu Kenya,Along Nairobi Kisumu Highway
        • contact_personProf Bernhards Ogutu
        • site_capacity(null)
        • misc(null)
        • created2025-03-30 10:40:23
        • modified2025-05-19 12:18:56
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 2(array)
        • id1870
        • application_id1529
        • county_id27
        • site_nameInternational Cancer institute
        • physical_addressInternational Cancer Institute
        • contact_detailsP.O Box 8088-30100 Eldoret Kenya
        • contact_personProf Fredrick Chite
        • site_capacity(null)
        • misc(null)
        • created2025-03-30 10:40:23
        • modified2025-05-19 12:18:56
        • County(array)
          • id27
          • county_nameUasin Gishu
          • created2012-06-15 10:25:15
          • modified2012-06-15 10:25:15
      • 3(array)
        • id1871
        • application_id1529
        • county_id42
        • site_nameKondele Childrens Hospital
        • physical_addressKEMRI Kondele Childrens Hospital within Jaramogi Oginga Odinga Teaching and Referral Hospital Along Kisumu Kakamega Road.
        • contact_detailsPo Box 54-40100 Kisumu kenya
        • contact_personDr Allan Godfrey Otieno
        • site_capacity(null)
        • misc(null)
        • created2025-03-30 10:40:23
        • modified2025-05-19 12:18:56
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 4(array)
        • id1872
        • application_id1529
        • county_id47
        • site_nameGertrudes Children’s Hospital
        • physical_addressGertrude’s Children’s Hospital, Muthaiga,
        • contact_detailsPO Box 42325-00100 Nairobi kenya
        • contact_personDr Doreen Karimi Mutua
        • site_capacity(null)
        • misc(null)
        • created2025-03-30 10:40:23
        • modified2025-05-19 12:18:56
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 5(array)
        • id1873
        • application_id1529
        • county_id42
        • site_nameVictoria Biomedical Research Institute
        • physical_addressVictoria Biomedical Research Institute, Kisumu County Referral Hospital,
        • contact_detailsP.O. Box 7180-40100, Kisumu, Kenya
        • contact_personDr Lucas Tina
        • site_capacity(null)
        • misc(null)
        • created2025-03-30 10:40:23
        • modified2025-05-19 12:18:56
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id821
        • application_id1529
        • sponsorNovartis Pharma AG
        • sponsor_typeIndustry
        • contact_personCelia Huang
        • addressNovartis Campus Lichtstrasse 35 4056 Basel Switzerland
        • telephone_number+41 (79) 9117238
        • fax_numberNot applicable
        • cell_number+41 (79) 9117238
        • email_addresscelia.huang@novartis.com
        • created2025-03-28 10:00:41
        • modified2025-05-19 12:18:56
  • 1(array)
    • Application(array)
      • id1524
      • user_id567
      • trial_status_id1
      • abstract_of_study<p>\n <strong>Background</strong></p>\n<p>\n The majority of people living with HIV (PLWH) on first line antiretroviral therapy (ART) in low- and middle-income countries are on dolutegravir (DTG)-containing regimens.  Different countries have adopted different approaches in the management of people on DTG-based first line ART with repeat HIV viral load (VL) of > 1,000 copies/mL after 3 months of enhanced adherence counseling. For example, Kenya recommends a drug resistance test (DRT) to guide on switch and the optimal second-line regimen; Mozambique and Tanzania recommend switch to 2 nucleoside reverse transcriptase inhibitors (NRTIs) and protease inhibitors (PIs) without drug resistance testing; South Africa does not recommend switch from DTG or DRT for those who are on first-line DTG-containing regimens within the first 2 years of treatment, after which management is guided by possible DRT and expert opinion. The World Health Organization has recognised the role of drug resistance testing (DRT) in a treatment failure algorithm for people living with HIV receiving DTG-based treatment to minimise unnecessary switches from this regimen. The switch to PI has disadvantages including higher cost, higher pill burden, less convenient administration (often should be taken with food), more potential drug-drug interactions, poorer tolerability and more long-term toxicities.</p>\n<p>\n  </p>\n<p>\n <strong>Goal</strong></p>\n<p>\n To assess the efficacy and safety of remaining on DTG compared to switching to DRV/r among people failing DTG-based ART with at least one major DTG drug resistance mutation (DRM).</p>\n<p>\n  </p>\n<p>\n <strong>Methods</strong></p>\n<p>\n This is a phase 3b, multi-country, open label, two arm, active controlled randomized clinical trial (RCT) over 12 months describing the efficacy and safety of switching from DTG to DRV/r among PLWH age ≥ 3 years who are failing DTG-based ART with HIV-1 RNA ≥ 200 copies/mL and ≥ 1 major DTG-associated DRM (and most recent prior HIV-1 RNA ≥ 1,000 copies/mL after at least 6 months on DTG-based ART). The primary efficacy endpoint is the proportion of participants with HIV-1 RNA < 200 copies/mL at month 6. The study will be conducted in 9 sites in Kenya, Mozambique, Tanzania and Lesotho targeting 392 participants including 30 children aged between 3 and 14 years old. The primary efficacy analysis will assess the difference in proportion of participants with viral suppression at month 6 using Cochran-Mantel-Haenszel method. This RCT is nested within an observational cohort study describing HIV-1 viral suppression of people with HIV-1 RNA value of ≥ 1,000 copies/mL after at least six months on DTG-based ART (Ndovu Cohort Study, submitted as a separate protocol).</p>\n<p>\n  </p>\n<p>\n <strong>Study Utility</strong></p>\n<p>\n This RCT will address the gap in published data on the effect of DTG-associated DRMs on viral suppression among people remaining on DTG-based ART while using current NRTI options, as well as the gap on the optimal management strategy for this population.</p>\n
      • study_title<p class=\"BodyB\" style=\"margin: 0cm; font-size: 12pt; font-family: Calibri, sans-serif; color: rgb(0, 0, 0);\">\n <span lang=\"EN-US\">Investigating the optimal management of dolutegravir resistance: an open-label randomised controlled trial of maintaining dolutegravir or switch to ritonavir-boosted darunavir</span><b><span lang=\"EN-US\"><o:p></o:p></span></b></p>\n
      • laymans_summary<p>\n <strong>Background</strong></p>\n<p>\n Many people living with HIV in low- and middle-income countries take a medication called dolutegravir (DTG) as part of their first treatment plan. However, if the amount of HIV virus in their blood (viral load) remains high even after three months of counseling to improve medication adherence, different countries handle the situation in different ways: Kenya does a special test to check for drug resistance before deciding whether to change the medication; Mozambique and Tanzania automatically switch the patient to a different set of drugs without testing for resistance; and South Africa does not recommend switching from DTG within the first two years, unless drug resistance testing and expert advice suggest otherwise. The World Health Organization (WHO) recognizes the importance of drug resistance testing before switching medications, as switching too soon could cause unnecessary problems. The alternative drugs (protease inhibitors) come with drawbacks like higher costs, needing to be taken with food, more side effects, and potential long-term health risks.</p>\n<p>\n  </p>\n<p>\n <strong>What the Study is Trying to Find Out</strong></p>\n<p>\n The study aims to compare two approaches for people whose HIV is not well controlled on DTG and have developed resistance to it: staying on DTG or switching to a different drug called darunavir (DRV/r). The goal is to see which approach is safer and more effective.</p>\n<p>\n  </p>\n<p>\n <strong>How the Study Works</strong></p>\n<p>\n This study is a 12-month clinical trial in four countries: Kenya, Mozambique, Tanzania, and Lesotho. It will involve 392 participants, including 30 children (ages 3–14). Researchers will measure how many people have low HIV viral load (below 200 copies/mL) after six months.</p>\n<p>\n  </p>\n<p>\n To be part of the study, a personshould have been taking DTG for at least six months, still have high HIV viral load, and have at least one major drug resistance to DTG.</p>\n<p>\n  </p>\n<p>\n <strong>Why This Study Matters</strong></p>\n<p>\n Right now, there is inadequate information on how well people with DTG resistance respond to treatment. This study will help doctors make better decisions about treating HIV in the future.</p>\n
      • short_titleNdovu RCT
      • protocol_noECCT/25/03/04
      • version_no1.2
      • date_of_protocol24-02-2025
      • study_drugRitonavir boosted darunavir (DRV/r)
      • disease_conditionHIV
      • 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_nameDarunavir and Ritonavir Tablets
      • product_type_medical_device_name
      • comparatorYes
      • comparator_nameDolutegravir
      • comparator_registeredYes
      • comparator_countriesDTG is registered in 109 countries including Kenya, Tanzania, Mozambique, Lesotho, Malawi, Uganda Rwanda, Zambia, Zimbabwe, South Africa among others
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressloisea@uonbi.ac.ke
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_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_applicantLoice Achieng Ombajo
      • declaration_date121-03-2025
      • declaration_principal_investigatorLoice Achieng Ombajo
      • declaration_date221-03-2025
      • placebo_presentNo
      • study_objectives<p>\n <strong>Specific Objectives</strong></p>\n<p>\n <strong>Primary objective</strong></p>\n<ul>\n <li>\n To assess the comparative efficacy of switching to DRV/r-based regimen after confirmed virologic failure and of remaining on DTG-based ART in achieving viral suppression of <200 copies/mL at 6 months from randomization among participants with ≥1 major DTG-associated DRM</li>\n</ul>\n<p>\n <strong>Secondary objectives</strong></p>\n<ul>\n <li>\n To evaluate difference in viral suppression to HIV-RNA < 200 copies/mL at 12 months from randomization</li>\n <li>\n To evaluate if switching to DRV/r-based ART after virologic failure is superior to remaining on DTG-based ART in achieving viral suppression to <200 copies/mL at 6 months from randomisation</li>\n <li>\n To evaluate difference in viral suppression using HIV-RNA cut-off of < 50 copies/mL at 6 and 12 months from randomization</li>\n <li>\n To evaluate difference in viral suppression using HIV-RNA cut-off of < 1,000 copies/mL at 6 and 12 months from randomization</li>\n <li>\n To assess viral suppression among different age strata (3-9 years, 10-19 years, ≥20 years, 20-24 years, 25-34 years, 35-44 years, ≥45 years)</li>\n <li>\n To assess viral suppression based on prior PI or INSTI exposure</li>\n <li>\n To assess viral suppression based on prior PI or INSTI failure</li>\n <li>\n To assess viral suppression based on participant sex</li>\n <li>\n To evaluate the incidence of adverse events by study arm</li>\n <li>\n To determine adherence levels, based on DBS TFV-DP levels, associated with: suppression; selection of treatment-emergent DRMs</li>\n <li>\n To determine incidence of treatment-emergent DRMs</li>\n <li>\n To describe patterns of accumulated DRMs</li>\n <li>\n To evaluate DRM patterns associated with sustained non-suppression</li>\n <li>\n To investigate predictors of development of DTG-associated DRMs (age, other non-INSTI DRMs, VL at switch to DTG, time with viremia, etc.)</li>\n <li>\n To assess viral suppression based on pre-enrollment NRTI</li>\n <li>\n To assess viral suppression based on TDF vs TAF as the study NRTI</li>\n <li>\n To assess the impact of regimen on change in CD4 count</li>\n <li>\n To assess the impact of regimen on participant satisfaction</li>\n <li>\n To explore the experiences and acceptability of remaining on DTG containing ART or switching to DRV-containing ART for management of treatment failure to DTG based ART regimens from perspectives of health care providers, policy makers and PLWH enrolled in Ndovu study</li>\n <li>\n To understand barriers and facilitators of managing treatment failure to DTG based regimens by:\n <ul>\n <li>\n remaining on DTG based regimens</li>\n <li>\n switching to DRV based  regimens among health care providers, policy makers and PLWH enrolled in Ndovu study</li>\n </ul>\n </li>\n</ul>\n
      • principal_inclusion_criteria<ul>\n <li class=\"Default\" style=\"margin: 0cm; font-size: 12pt; font-family: Calibri, sans-serif; color: rgb(0, 0, 0); text-align: justify;\">\n <span lang=\"EN-US\">Enrolled in the Ndovu cohort study<o:p></o:p></span></li>\n <li class=\"Default\" style=\"margin: 0cm; font-size: 12pt; font-family: Calibri, sans-serif; color: rgb(0, 0, 0); text-align: justify;\">\n <span lang=\"EN-US\">Able and willing to understand and comply with the protocol requirements, instructions and restrictions<o:p></o:p></span></li>\n <li class=\"Default\" style=\"margin: 0cm; font-size: 12pt; font-family: Calibri, sans-serif; color: rgb(0, 0, 0); text-align: justify;\">\n <span lang=\"EN-US\">Able and willing to provide informed consent for the nested clinical trial (assent as appropriate and legal guardian consent if < <span style=\"background: rgb(254, 255, 254);\">18</span> years)<o:p></o:p></span></li>\n <li class=\"Default\" style=\"margin: 0cm; font-size: 12pt; font-family: Calibri, sans-serif; color: rgb(0, 0, 0); text-align: justify;\">\n <span lang=\"EN-US\">Age ≥ 3 years<o:p></o:p></span></li>\n <li class=\"Default\" style=\"margin: 0cm; font-size: 12pt; font-family: Calibri, sans-serif; color: rgb(0, 0, 0); text-align: justify;\">\n <span lang=\"EN-US\">Most recent HIV-1 RNA <span style=\"background: rgb(254, 255, 254);\">≥ 200 copies/mL</span><o:p></o:p></span></li>\n <li class=\"Default\" style=\"margin: 0cm; font-size: 12pt; font-family: Calibri, sans-serif; color: rgb(0, 0, 0); text-align: justify;\">\n <span lang=\"EN-US\">At least one major DTG-associated DRM (substitution at codon 66K, 92Q, 118R, 138K/A/T, 140S/A/C, 148H/R/K, 155H or 263K)<o:p></o:p></span></li>\n</ul>\n
      • principal_exclusion_criteria<ul>\n <li class=\"Default\" style=\"margin: 0cm; font-size: 12pt; font-family: Calibri, sans-serif; color: rgb(0, 0, 0); text-align: justify;\">\n <span lang=\"EN-US\">Pregnant or breastfeeding<o:p></o:p></span></li>\n <li class=\"Default\" style=\"margin: 0cm; font-size: 12pt; font-family: Calibri, sans-serif; color: rgb(0, 0, 0); text-align: justify;\">\n <span lang=\"EN-US\">Using any concomitant therapy disallowed as per the reference safety information and product labeling for the study drugs<o:p></o:p></span></li>\n <li class=\"Default\" style=\"margin: 0cm; font-size: 12pt; font-family: Calibri, sans-serif; color: rgb(0, 0, 0); text-align: justify;\">\n <span lang=\"EN-US\">WHO stage 3 or 4 opportunistic infection which would prevent randomisation to either arm (e.g. due to drug interactions or significant liver or renal injury) within 4 weeks prior to RCT screening<o:p></o:p></span></li>\n <li class=\"Default\" style=\"margin: 0cm; font-size: 12pt; font-family: Calibri, sans-serif; color: rgb(0, 0, 0); text-align: justify;\">\n <span lang=\"EN-US\">Investigator opinion that the potential participant should discontinue DTG immediately for clinical reasons<o:p></o:p></span></li>\n <li class=\"Default\" style=\"margin: 0cm; font-size: 12pt; font-family: Calibri, sans-serif; color: rgb(0, 0, 0); text-align: justify;\">\n <span lang=\"EN-US\">Investigator opinion that the potential participant should not switch to DRV/r for clinical reasons<o:p></o:p></span></li>\n</ul>\n
      • primary_end_points<p class=\"Default\" style=\"margin: 0cm; font-size: 12pt; font-family: Calibri, sans-serif; color: rgb(0, 0, 0); text-align: justify;\">\n <span lang=\"EN-US\">Proportion of participants with HIV-1 RNA < 200 copies/mL at month 6 from randomization using a modified US Food and Drug Administration (FDA) snapshot algorithm<o:p></o:p></span></p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<h1>\n <strong style=\"font-size: 12px;\">Kenyatta National Hospital</strong></h1>\n<p>\n Kenyatta National Hospital is a National Referral Hospital, and its HIV clinic has one of the oldest cohorts of people living with HIV, as it was one of the first clinics to offer HIV care and treatment. There are approximately 10,000 people living with HIV who are followed up in this clinic. On a daily basis, 30-40 clients are seen in the HIV clinic on a daily basis. It has viremia clinics twice a week for those who have high viral loads on Tuesdays and Thursdays. It has a multi-disciplinary team of doctors, one pharmacist, clinical officers, nurses, psychologists, and adherence counsellors who are trained in providing advanced and complex HIV care. The health facilities that will act as spokes to Kenyatta National Hospital are those from the south and west of Nairobi including Dreams Center, Kibera Community Health Centre (AHF), Mbagathi District Hospital, Mater Hospital, Coptic Hospital, Riruta Health Center and Karen Health Center.</p>\n<p>\n Kenyatta National Hospital also serves as one of the regional reference labs, which is ISO 1589 certified for carrying out viral load testing and has the capacity to store frozen samples.</p>\n<p>\n <br />\n <strong>Jaramogi Oginga Odinga Teaching and Referral Hospital</strong></p>\n<p>\n JOOTRH is a 530-bed capacity referral hospital built initially in 19639. It is currently as Level 6 referral facility serving the 10 counties of the Nyanza and Western Kenya regions. It is located within an urban and peri-urban catchment area and provides in-patient and out-patient services, including ART services. It has 640 hospital staff consisting of 486 regular staff and 154 who are supported by the implementing partner.</p>\n<p>\n 4% of those PLHIV on ART within Siaya County are enrolled at JOOTRH at the Comprehensive Care Centre which began services in 2002. The cumulative number of PLHIV ever enrolled into care at the facility is 28,000 and the active PLHIV on ART currently stands at 6,842. In terms of staffing, there is a total of 45 members of staff providing a wide range of HIV prevention, testing and treatment services with most (39) mainly implementing partner supported.</p>\n<p>\n <strong>Bomu Hospital</strong></p>\n<p>\n Bomu Hospital is a social enterprise whose mandate is to provide safe, affordable and high-quality health and wellness services, and is so doing increase access to quality healthcare to all people regardless of their economic status. It operates as a hospital with 7 branches in which out-patient services are offered including specialized medical and surgical clinics, reproductive health services, diagnostic and therapeutic services. The main hospital in Changamwe offers in-patient services. Bomu provides HIV Care and Treatment services to approximately 26,000 people living with HIV in four Bomu Clinics: Bomu Changamwe (12,000), Bomu Likoni (5660), Bomu Wema (3200), Bomu City Centre (300) and in 3 catholic supports HIV Care and Treatment services in 3 catholic hospital clinics in the county.</p>\n<p>\n Bomu Hospital Changamwe will be the hub for the other Bomu Clinics to refer patients with high viral load from Bomu Likoni, Bomu Wema and Bomu City Center for inclusion in the study. Bomu Changamwe HIV clinic is run by a multi-disciplinary team consisting of clinical officers, nurses, adherence counsellors, peer mentors, health records information officers and data officers all who are trained and sensitized in preventing and managing HIV as per the 2022 Kenya HIV Prevention and Treatment Guidelines. It sends samples for viral load processing at the Coast General Teaching and Referral’s HIV Reference Lab. Its inter-operability layer with the lab enables them to receive viral load results in real-time as they are processed. HIV Care and Treatment services are overseen by medical doctors. There are about 100 people living with HIV seen daily in the clinic. It holds weekly viremia clinics and monthly psychosocial support groups for people living with HIV with high viral loads.<br />\n  </p>\n
      • other_details_explanation<p>\n Not applicable</p>\n
      • other_details_regulatory_notapproved<p>\n The study protocol will be submitted (not yet submitted) to the:</p>\n<ul>\n <li>\n Tanzania Medicines and Medical Devices Authority (TMDA) in Tanzania</li>\n <li>\n Comite Nacional de Bioetica para Saude (CNBS) in Mozambique</li>\n <li>\n National Health Research Ethics Committee in Lesotho</li>\n</ul>\n
      • other_details_regulatory_approved<p>\n Not yet submitted to other regulatory authorities. First submission is to the Pharmamcy and Poisons Board in Kenya since the trial sponsor (University of Nairobi) is in Kenya.</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n Not applicable</p>\n
      • estimated_duration2 years
      • 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_comparatorMaintaining dolutegravir
      • 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_states4
      • number_of_sites3
      • multi_country_listKenya, Mozambique, Tanzania and Lesotho
      • data_monitoring_committeeYes
      • total_enrolment_per_siteKNH - 60-70\nJOOTRH - 30-40\nBomu Hospital - 30-40
      • total_participants_worldwide392
      • 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_situationNo
      • subjects_incapable_consentYes
      • subjects_specifyChildren and adolescents aged less than 18 years old
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameLoice
      • investigator1_middle_nameAchieng
      • investigator1_family_nameOmbajo
      • investigator1_qualificationMBChB, M.Med, DLSHTM, MSc (ID), FRCP
      • investigator1_professional_addressUniversity of Nairobi, P.O. Box 19676 - 00202 Nairobi
      • investigator1_telephone+254722576984
      • investigator1_emailloisea@uonbi.ac.ke
      • organisations_transferred_No
      • number_participants144
      • notification
      • approval_date14-07-2025
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted21-03-2025
      • is_child0
      • unsubmitted1
      • initial_date_submitted21-03-2025
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-09-12 10:28:42
      • created2025-03-11 08:59:29
      • total_sites3
      • ecitizen_invoice361002
    • InvestigatorContact(array)
      • 0(array)
        • id1240
        • application_id1524
        • given_nameLoice
        • middle_nameAchieng
        • family_nameOmbajo
        • qualificationMBChB, M.Med, DLSHTM, MSc (ID), FRCP
        • professional_addressUniversity of Nairobi, P.O. Box 19676 - 00202 Nairobi
        • telephone+254722576984
        • emailloisea@uonbi.ac.ke
        • created2025-03-11 08:59:29
        • modified2025-05-28 09:21:23
    • SiteDetail(array)
      • 0(array)
        • id1852
        • application_id1524
        • county_id47
        • site_nameKenyatta National Hospital (KNH)
        • physical_addressComprehensive Care Centre, Hospital Road, Nairobi
        • contact_detailsP.O. Box 20723 - 00202, Nairobi
        • contact_personDr Loice Achieng Omabjo
        • site_capacity(null)
        • misc(null)
        • created2025-03-11 09:21:07
        • modified2025-05-28 09:21:23
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 1(array)
        • id1853
        • application_id1524
        • county_id42
        • site_nameJaramogi Oginga Odinga Teaching and Referral Hospital
        • physical_addressPatient Support Centre, Jomo Kenyatta Highway, Kaloleni, Kisumu
        • contact_detailsP.O. Box 849 - 40100, Kisumu
        • contact_personDr Florentius Ndinya
        • site_capacity(null)
        • misc(null)
        • created2025-03-11 09:34:58
        • modified2025-05-28 09:21:23
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 2(array)
        • id1854
        • application_id1524
        • county_id1
        • site_nameBomu Hospital
        • physical_addressOff Refinery Road, Near Redeemed Church, Changamwe
        • contact_detailsP.O. Box 95683 - 80106, Mombasa
        • contact_personDr Nashina Admani
        • site_capacity(null)
        • misc(null)
        • created2025-03-11 09:34:58
        • modified2025-05-28 09:21:23
        • County(array)
          • id1
          • county_nameMombasa
          • created2012-05-31 16:15:11
          • modified2012-07-09 13:06:23
    • Sponsor(array)
      • 0(array)
        • id817
        • application_id1524
        • sponsorUniversity of Nairobi
        • sponsor_typeResearch Institution
        • contact_personProf Erastus Amayo
        • addressP.O. Box 19676 - 00202 Nairobi, Kenya
        • telephone_number+254204915041
        • fax_number
        • cell_number+254733611557
        • email_addresserastus.amayo@uonbi.ac.ke
        • created2025-03-11 09:21:07
        • modified2025-05-28 09:21:23
  • 2(array)
    • Application(array)
      • id1484
      • user_id612
      • trial_status_id2
      • abstract_of_study<p>\n Protocol Title: A Phase 3, Randomized, Open-label Study of MK-5684 Versus Alternative Abiraterone Acetate or Enzalutamide in Participants with Metastatic Castration-resistant Prostate Cancer (mCRPC) That Progressed On or After Prior Treatment with One Nextgeneration Hormonal Agent (NHA)</p>\n<p>\n Short Title: Phase 3 study of MK-5684 versus alternative NHA in mCRPC post one NHA</p>\n<p>\n Primary Objectives</p>\n<p>\n To compare MK-5684 to alternative abiraterone acetate or enzalutamide with respect to rPFS per PCWG Modified RECIST 1.1, as assessed by BICR in participants with mCRPC</p>\n<p>\n To compare MK-5684 to alternative abiraterone acetate or enzalutamide with respect to overall survival in participants with mCRPC. </p>\n<p>\n Secondary Objectives </p>\n<p>\n To evaluate the TFST of participants treated with MK-5684 compared with participants treated with alternative abiraterone acetate or enzalutamide</p>\n<p>\n To evaluate the OR and DOR per PCWG Modified RECIST 1.1 as assessed by BICR of participants treated with MK-5684 compared with participants treated with alternative abiraterone acetate or enzalutamide.</p>\n<p>\n To evaluate the TTPP of participants treated with MK-5684 compared with participants treated with alternative abiraterone acetate or enzalutamide</p>\n<p>\n To evaluate MK-5684 and abiraterone acetate or enzalutamide with respect to HRQoL using the FACT-P questionnaire. </p>\n<p>\n To evaluate the time to PSA progression of participants treated with MK-5684 compared with participants treated with alternative abiraterone acetate or enzalutamide.</p>\n<p>\n To evaluate the PSA response rate of participants treated with MK-5684 compared with participants treated with alternative abiraterone acetate or enzalutamide.</p>\n<p>\n To evaluate the time to first SSRE of participants treated with MK-5684 compared with participants treated with alternative abiraterone acetate or enzalutamide</p>\n<p>\n To evaluate the safety and tolerability of MK-5684</p>\n<p>\n Study Phase Phase 3 </p>\n<p>\n Indication Prostate cancer metastatic</p>\n<p>\n Population Participants ≥18 years of age with metastatic castration-resistant-prostate cancer</p>\n<p>\n Study Type Interventional</p>\n<p>\n Intervention Model Parallel This is a multi site study.</p>\n<p>\n Type of Control Active Control Without Placebo</p>\n<p>\n Study Blinding Unblinded open-label Blinding Roles No blinding Estimated</p>\n<p>\n Duration of Study The Sponsor estimates that the study will require approximately 7 years from the time the first participant (or their legally acceptable representative) provides documented informed consent until the last participant’s last study-related contact. </p>\n
      • study_title<p>\n  A Phase 3, Randomized, Open-label Study of MK-5684 Versus Alternative Abiraterone Acetate or Enzalutamide in Participants with Metastatic Castration-resistant Prostate Cancer (mCRPC) That Progressed On or After Prior Treatment with One Next-generation Hormonal Agent (NHA) </p>\n
      • laymans_summary<p>\n This study is testing MK-5684 in men who have prostate cancer that has gotten worse and spread beyond the prostate after drug therapy or surgery to block the testes from producing hormones. This is called metastatic castration-resistant prostate cancer (mCRPC). MK-5684 is experimental. It has not been approved for any disease or condition by the Pharmacy and Poisons Board (PPB) or other Regulatory Authorities. This study will compare MK-5684 to abiraterone acetate and enzalutamide. Abiraterone acetate and enzalutamide are standard treatments for mCRPC.</p>\n<p>\n This study is being done to: </p>\n<p>\n Test the safety of MK-5684</p>\n<p>\n See how well MK-5684 works, compared to abiraterone acetate or enzalutamide </p>\n<p>\n See if participants who get MK-5684 live longer compared to those who get abiraterone acetate or enzalutamide</p>\n<p>\n See if participants who get MK-5684 live longer before their disease worsens, compared to those who get abiraterone acetate or enzalutamide</p>\n<p>\n Who can be in this study? Patient  at least 18 years old</p>\n<p>\n Patient who have advanced mCRPC (Stage 4 metastatic prostate cancer)</p>\n<p>\n ï‚· Patient who mCRPC that has become worse within 6 months before starting the study and: </p>\n<p>\n After being treated with drugs or surgery to block the testes from making hormones</p>\n<p>\n AND </p>\n<p>\n After treatment with other drugs for prostate cancer</p>\n
      • short_title MK-5684_MSD (mCRPC)
      • protocol_noECCT/25/03/01
      • version_no04
      • date_of_protocol11-04-2024
      • study_drugMK-5684
      • disease_conditionmetastatic castration-resistant-prostate cancer
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones1
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorYes
      • comparator_nameAbiraterone Acetate or Enzalutamide
      • comparator_registeredYES
      • comparator_countriesKenya
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressstacey.gondi@aku.edu
      • 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_applicantPROF MANSOOR NOORALI SALEH
      • declaration_date104-03-2025
      • declaration_principal_investigatorPROF MANSOOR NOORALI SALEH
      • declaration_date204-03-2025
      • placebo_presentNo
      • study_objectives<p>\n Primary Objectives</p>\n<p>\n To compare MK-5684 to alternative abiraterone acetate or enzalutamide with respect to rPFS per PCWG Modified RECIST 1.1, as assessed by BICR in participants with mCRPC</p>\n<p>\n To compare MK-5684 to alternative abiraterone acetate or enzalutamide with respect to overall survival in participants with mCRPC</p>\n<p>\n Secondary Objectives</p>\n<p>\n To evaluate the TFST of participants treated with MK-5684 compared with participants treated with alternative abiraterone acetate or enzalutamide.</p>\n<p>\n To evaluate the OR and DOR per PCWG Modified RECIST 1.1 as assessed by BICR of participants treated with MK-5684 compared with participants treated with alternative abiraterone acetate or enzalutamide. </p>\n<p>\n To evaluate the TTPP of participants treated with MK-5684 compared with participants treated with alternative abiraterone acetate or enzalutamide</p>\n<p>\n To evaluate MK-5684 and abiraterone acetate or enzalutamide with respect to HRQoL using the FACT-P questionnaire</p>\n<p>\n To evaluate the time to PSA progression of participants treated with MK-5684 compared with participants treated with alternative abiraterone acetate or enzalutamide.</p>\n<p>\n To evaluate the PSA response rate of participants treated with MK-5684 compared with participants treated with alternative abiraterone acetate or enzalutamide.</p>\n<p>\n To evaluate the time to first SSRE of participants treated with MK-5684 compared with participants treated with alternative abiraterone acetate or enzalutamide.</p>\n<p>\n To evaluate the safety and tolerability of MK-5684.</p>\n
      • principal_inclusion_criteria<ol>\n <li>\n Have histologically or cytologically confirmed (if acceptable according to local health authority regulations) adenocarcinoma of the prostate without small cell histology. The diagnosis must be stated in a pathology report and confirmed by the investigator.</li>\n <li>\n Have prostate cancer progression while receiving ADT (or post bilateral orchiectomy) within 6 months before screening. Prostate cancer progression will be determined by the investigator through 1 of the following:\n <ul>\n <li>\n PSA progression shown by local laboratory values, as defined by a minimum of 2 consecutive rising PSA levels with an interval of ≥1 week between each assessment, where PSA at screening should be ≥1 ng/mL. Refer to Section 8.2.2 for further details.</li>\n </ul>\n </li>\n</ol>\n<p style=\"margin-left:36.5pt;\">\n Note: A PSA level obtained during the screening period can count as the confirmatory second rising PSA.</p>\n<ul>\n <li>\n Radiographic disease progression in soft tissue based on RECIST 1.1, with or without PSA progression.</li>\n <li>\n Radiographic disease progression in bone per PCWG, defined as the appearance of 2 or more new bone lesions on bone scan with or without PSA progression.</li>\n</ul>\n<ol>\n <li value=\"3\">\n Have disease progression under the following conditions if the participant received first generation antiandrogen therapy before screening:\n <ul>\n <li>\n Evidence of progression >4 weeks since the last flutamide treatment. • Evidence of progression >6 weeks since the last bicalutamide or nilutamide treatment.</li>\n </ul>\n </li>\n <li value=\"4\">\n Have current evidence of metastatic disease documented by either bone lesions on bone scan and/or soft tissue disease shown by CT/MRI.</li>\n <li value=\"5\">\n Participants who are ineligible for docetaxel treatment as determined by the investigator or have refused docetaxel treatment.</li>\n</ol>\n<p style=\"margin-left:18.5pt;\">\n EU participants only: Participants who are ineligible for docetaxel treatment as determined by the investigator. </p>\n<ol>\n <li value=\"6\">\n Have disease that progressed during or after treatment with one NHA (eg, abiraterone acetate, enzalutamide, apalutamide, darolutamide) for HSPC (mHSPC or nmHSPC), or nmCRPC, for at least 8 weeks (at least 14 weeks for participants with bone progression). Note: Participants may have received abiraterone acetate and docetaxel or darolutamide and docetaxel for HSPC. However, participants must have received no more than 6 cycles of docetaxel and had no radiographic disease progression while receiving docetaxel.</li>\n <li value=\"7\">\n Have had prior treatment with PARPi or were deemed ineligible to receive treatment by the investigator or have refused PARPi treatment.</li>\n</ol>\n<p style=\"margin-left:18.5pt;\">\n EU participants only: Have had prior treatment with PARPi or were deemed ineligible to receive treatment by the investigator.</p>\n<ol>\n <li value=\"8\">\n Participants who have had prior treatment with 177Lu-PSMA-617, are deemed ineligible to receive 177Lu-PSMA-617 treatment as determined by the investigator, have refused 177Lu-PSMA-617 treatment, or do not have access to 177Lu-PSMA-617 treatment. EU participants only: Participants who have had prior treatment with 177Lu-PSMA-617, are deemed ineligible to receive 177Lu-PSMA-617 treatment as determined by the investigator, or do not have access to 177Lu-PSMA-617 treatment.</li>\n <li value=\"9\">\n Have ongoing ADT with serum testosterone <50 ng/dL (<1.7 nM). If the participant is currently being treated with luteinizing hormone-releasing hormone agonists or antagonists (in participants who have not undergone orchiectomy), this therapy must have been initiated at least 4 weeks before the date of randomization, and treatment must be continued throughout the study.</li>\n <li value=\"10\">\n Participants receiving bone resorptive therapy (including, but not limited to, bisphosphonate or denosumab) must have been on stable doses for ≥4 weeks before randomization.</li>\n <li value=\"11\">\n Have an ECOG performance status of 0 or 1 assessed within 7 days before randomization.</li>\n <li value=\"12\">\n Adequate organ function as defined in the following table (Table 3). Specimens must be collected within 10 days before the start of study intervention.</li>\n</ol>\n<p>\n                                     Table 3            Adequate Organ Function Laboratory Values</p>\n<table border=\"0\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:599px;\" width=\"599\">\n <tbody>\n <tr>\n <td style=\"width:282px;height:16px;\">\n <p>\n <strong>System</strong></p>\n </td>\n <td style=\"width:317px;height:16px;\">\n <p>\n <strong>Laboratory Value</strong></p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:599px;height:17px;\">\n <p>\n Hematological</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:282px;height:17px;\">\n <p style=\"margin-left:18.35pt;\">\n Absolute neutrophil count (ANC)</p>\n </td>\n <td style=\"width:317px;height:17px;\">\n <p>\n ≥1500/µL</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:282px;height:17px;\">\n <p style=\"margin-left:18.35pt;\">\n Platelets</p>\n </td>\n <td style=\"width:317px;height:17px;\">\n <p>\n ≥100,000/µL</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:282px;height:17px;\">\n <p style=\"margin-left:18.35pt;\">\n Hemoglobin</p>\n </td>\n <td style=\"width:317px;height:17px;\">\n <p>\n ≥9.0 g/dL or ≥5.6 mmol/L^a</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:599px;height:17px;\">\n <p>\n Renal</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:282px;height:17px;\">\n <p style=\"margin-left:18.35pt;\">\n Measured or calculated creatinine clearance^b</p>\n </td>\n <td style=\"width:317px;height:17px;\">\n <p>\n ≥30 mL/min</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:599px;height:17px;\">\n <p>\n Hepatic</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:282px;height:33px;\">\n <p style=\"margin-left:18.35pt;\">\n Total bilirubin</p>\n </td>\n <td style=\"width:317px;height:33px;\">\n <p>\n ≤1.5 × ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels >1.5 × ULN</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:282px;height:33px;\">\n <p style=\"margin-left:18.35pt;\">\n AST (SGOT) and ALT (SGPT)</p>\n </td>\n <td style=\"width:317px;height:33px;\">\n <p>\n ≤2.5 × ULN (≤5 × ULN for participants with liver metastases)</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:599px;height:17px;\">\n <p>\n Coagulation</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:282px;height:49px;\">\n <p style=\"margin-left:18.35pt;\">\n International normalized ratio (INR) OR prothrombin time (PT)</p>\n <p style=\"margin-left:18.35pt;\">\n Activated partial thromboplastin time (aPTT)</p>\n </td>\n <td style=\"width:317px;height:49px;\">\n <p>\n ≤1.5 × ULN unless participant is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants</p>\n </td>\n </tr>\n <tr>\n <td colspan=\"2\" style=\"width:599px;height:78px;\">\n <p style=\"margin-left:.25in;\">\n ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); ULN=upper limit of normal.</p>\n <ol style=\"list-style-type:lower-alpha;\">\n <li>\n Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.</li>\n <li>\n Cockcroft-Gault CrCl formula =[[140 – age (yr)] × weight (kg)] / [72 × serum Cr (mg/dL)]</li>\n </ol>\n </td>\n </tr>\n </tbody>\n</table>\n<p style=\"margin-left:-.25pt;\">\n <strong>Demographics</strong></p>\n<ol>\n <li value=\"13\">\n Is at least 18 years of age at the time of providing informed consent.</li>\n</ol>\n<p style=\"margin-left:-.25pt;\">\n <strong>Participants</strong></p>\n<ol>\n <li value=\"14\">\n If capable of producing sperm, the participant agrees to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention. The length of time required to continue contraception for each study intervention is:\n <ul>\n <li>\n MK-5684: 7 days</li>\n <li>\n Abiraterone acetate: 30 days</li>\n <li>\n Enzalutamide: 3 months</li>\n </ul>\n </li>\n</ol>\n<ul>\n <li>\n Abstains from penile-vaginal intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) and agrees to remain abstinent</li>\n</ul>\n<p style=\"margin-left:18.5pt;\">\n OR</p>\n<ul>\n <li>\n Uses a penile/external condom when having penile-vaginal intercourse with a nonparticipant of childbearing potential who is not currently pregnant (see Section 10.5.2).</li>\n <li>\n Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions are more stringent than the requirements above, the local label requirements are to be followed.</li>\n</ul>\n<p style=\"margin-left:18.5pt;\">\n Note: If the participant is azoospermic (vasectomized or secondary to medical cause, documented from the site personnel’s review of the participant’s medical records, medical examination, or medical history interview), no contraception is required.</p>\n<p style=\"margin-left:-.25pt;\">\n <strong>Informed Consent</strong></p>\n<ol>\n <li value=\"15\">\n The participant (or legally acceptable representative) has provided documented informed consent for the study.</li>\n</ol>\n<p style=\"margin-left:18.5pt;\">\n EU participants only: For a participant to be eligible to participate in the EU, they must be capable of providing documented full informed consent; therefore, all references to a participant’s legally acceptable representative in the protocol are not applicable for participants in the EU.</p>\n<p style=\"margin-left:18.5pt;\">\n Where the subject is unable to read or write, consent may be given and recorded through appropriate alternative means in the presence of at least 1 impartial witness. In that case, the witness shall sign and date the informed consent document.</p>\n<p style=\"margin-left:-.25pt;\">\n <strong>Additional Categories</strong></p>\n<ol>\n <li value=\"16\">\n Have provided tumor tissue from a fresh core or excisional biopsy from soft tissue not previously irradiated. Samples from tumors progressing at a prior site of radiation are allowed. Participants with bone-only or bone-predominant disease may provide a bone biopsy sample. Tumor sample is preferably obtained within 12 months of screening; however, if a recent sample is not available, participants may provide a tumor tissue sample greater than 12 months from screening. Formalin-fixed, paraffin embedded tissue blocks are preferred to slides. Other exceptions may be considered after Sponsor consultation.</li>\n</ol>\n<p style=\"margin-left:18.5pt;\">\n Note: Details pertaining to tumor tissue submission are in the Laboratory Manual.</p>\n<ol>\n <li value=\"17\">\n Participants who are HBsAg positive are eligible if they have received HBV antiviral therapy for at least 4 weeks, and have undetectable HBV viral load before randomization.</li>\n</ol>\n<p style=\"margin-left:18.5pt;\">\n Note: Participants should remain on antiviral therapy throughout study intervention and follow local guidelines for HBV antiviral therapy post completion of study intervention. • Hepatitis B screening tests are not required unless:</p>\n<p>\n                 â—¦     Known history of HBV infection</p>\n<p>\n                 â—¦     As mandated by local health authority</p>\n<ol>\n <li value=\"18\">\n Participants with history of HCV infection are eligible if HCV viral load is undetectable at screening.</li>\n</ol>\n<p style=\"margin-left:18.5pt;\">\n Note: Participants must have completed curative antiviral therapy at least 4 weeks before randomization. • Hepatitis C screening tests are not required unless:</p>\n<p>\n                 â—¦     Known history of HCV infection</p>\n<p>\n                 â—¦     As mandated by local health authority</p>\n<ol>\n <li value=\"19\">\n Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline. Participants with endocrine-related AEs who are adequately treated with HRT or participants who have ≤Grade 2 neuropathy are eligible.</li>\n <li value=\"20\">\n HIV-infected participants must have well controlled HIV on ART, defined as:\n <ol style=\"list-style-type:lower-alpha;\">\n <li>\n Participants on ART must have a CD4+ T-cell count ≥350 cells/mm³at the time of screening</li>\n <li>\n Participants on ART must have achieved and maintained virologic suppression defined as confirmed HIV RNA level below 50 or the LLOQ (below the limit of detection) using the locally available assay at the time of screening and for at least</li>\n </ol>\n </li>\n</ol>\n<p style=\"margin-left:36.5pt;\">\n 12 weeks before screening</p>\n<ol style=\"list-style-type:lower-alpha;\">\n <li value=\"3\">\n It is advised that participants must not have had any AIDS-defining opportunistic infections within the past 12 months</li>\n <li value=\"4\">\n Participants on ART must have been on a stable regimen, without changes in drugs or dose modification, for at least 4 weeks before study entry (Day 1) and agree to continue ART throughout the study</li>\n <li value=\"5\">\n The combination ART regimen must not contain any antiretroviral medications that interact with CYP3A4 inhibitors/inducers/substrates</li>\n</ol>\n<p style=\"margin-left:36.5pt;\">\n (https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-druginteractions-table-substrates-inhibitors-and-inducers)</p>\n
      • principal_exclusion_criteria<p style=\"margin-left:.85pt;\">\n An individual must be excluded from the study if the individual meets any of the following criteria:</p>\n<p style=\"margin-left:-.25pt;\">\n <strong>Medical Conditions</strong></p>\n<ol>\n <li>\n Has presence of gastrointestinal condition, eg, malabsorption, that might affect the absorption of study medication.</li>\n <li>\n Is unable to swallow capsules/tablets.</li>\n <li>\n History of pituitary dysfunction.</li>\n</ol>\n<p style=\"margin-left:18.5pt;\">\n Note: Exceptions may be considered after Sponsor consultation.</p>\n<ol>\n <li value=\"4\">\n Poorly controlled diabetes mellitus.</li>\n <li value=\"5\">\n Clinically significant abnormal serum potassium or sodium level.</li>\n <li value=\"6\">\n Has any of the following at Screening Visit:\n <ul>\n <li>\n Hypotension: systolic BP <110 mm Hg, or</li>\n <li>\n Uncontrolled hypertension: systolic BP ≥160 mm Hg or diastolic BP ≥90 mm Hg, in 2 of 3 recordings with optimized antihypertensive therapy.</li>\n </ul>\n </li>\n <li value=\"7\">\n Has a history of active or unstable cardio/cerebro-vascular disease, including thromboembolic events and the following:</li>\n</ol>\n<p style=\"margin-left:18.5pt;\">\n History of stroke or transient ischemic attack within 6 months prior to first dose of study drug, history of myocardial infarction within 6 months prior to first dose of study drug, NYHA Class III or IV cardiac disease or congestive heart failure, coronary heart disease that is symptomatic, or unstable angina.</p>\n<ol>\n <li value=\"8\">\n History or family history of long QTc syndrome.</li>\n <li value=\"9\">\n Has a resting ECG indicating uncontrolled, potentially reversible cardiac conditions as judged by the investigator (eg, unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation >470 msec, electrolyte disturbances, etc.), or has congenital long QT syndrome.</li>\n <li value=\"10\">\n Has a history of seizure(s) within 6 months before providing documented informed consent or has any condition that may predispose to seizure within 12 months before the date of enrollment, including, but not limited to loss of consciousness or prior cerebrovascular accident, transient ischemic attack, or brain arteriovenous malformation; or intracranial masses such as a schwannoma or meningioma that is causing edema or mass effect.</li>\n <li value=\"11\">\n Has a history of clinically significant ventricular arrhythmias (eg, ventricular tachycardia, ventricular fibrillation, torsades de pointes) or Mobitz II second degree or third-degree heart block without a permanent pacemaker in place.</li>\n</ol>\n<p style=\"margin-left:-.25pt;\">\n <strong>Prior/Concomitant Therapy</strong></p>\n<ol>\n <li value=\"12\">\n Has received a taxane-based chemotherapy and or NHA for mCRPC.</li>\n <li value=\"13\">\n Participants who received a total of more than one NHA before enrollment are not eligible (this includes nmHSPC, mHSPC, and nmCRPC).</li>\n <li value=\"14\">\n Has received an anticancer mAb within 4 weeks before the date of randomization, or has not recovered to Grade ≤1 or baseline, from AEs due to mAbs administered more than 4 weeks before the date of randomization.</li>\n</ol>\n<p style=\"margin-left:18.5pt;\">\n Note: Treatment with denosumab as SOC for bone metastases is permitted.</p>\n<ol>\n <li value=\"15\">\n Has undergone major surgery, including local prostate intervention (except prostate biopsy), within 28 days before the date of randomization, and has not recovered from the toxicities and/or complications.</li>\n <li value=\"16\">\n Participants who have not adequately recovered from major surgery or have ongoing surgical complications.</li>\n <li value=\"17\">\n Has used herbal or medicinal products that may have hormonal antiprostate cancer activity and/or are known to decrease PSA (eg, saw palmetto, megesterol acetate) within 4 weeks before the date of randomization.</li>\n <li value=\"18\">\n Has received prior treatment with radium-223 for prostate cancer.</li>\n <li value=\"19\">\n Is currently being treated with CYP450-inducing antiepileptic drugs for seizures. Note: Use of antiepileptic drugs for pain control is allowed in participants without seizures, unless these drugs are excluded due to CYP450 induction (eg, phenytoin, carbamazepine, and phenobarbital)</li>\n <li value=\"20\">\n Has received treatment with 5-α reductase inhibitors (eg, finasteride, dutasteride), estrogens, and/or cyproterone within 4 weeks before randomization.</li>\n <li value=\"21\">\n Use of aldosterone antagonist (eg, spironolactone, eplerenone) and phenytoin within 4 weeks before the start of the study intervention.</li>\n <li value=\"22\">\n Participants on an unstable dose of thyroid hormone therapy within 6 months before the start of the study intervention.</li>\n <li value=\"23\">\n Has received colony-stimulating factors (eg, granulocyte colony-stimulating factor, GMCSF, or recombinant erythropoietin) within 28 days before the date of randomization.</li>\n <li value=\"24\">\n Has received a whole blood transfusion in the last 120 days before the date of randomization. Packed red blood cells and platelet transfusions are acceptable if not given within 28 days before the date of randomization.</li>\n <li value=\"25\">\n Received prior radiotherapy within 2 weeks before the first dose of study intervention, or radiation-related toxicities, requiring corticosteroids.</li>\n</ol>\n<p style=\"margin-left:18.5pt;\">\n Note: 2 weeks or fewer of palliative radiotherapy for non-CNS disease is permitted. The last radiotherapy treatment must have been performed at least 7 days before the first dose of study intervention.</p>\n<ol>\n <li value=\"26\">\n Received prior systemic anticancer therapy including investigational agents within 4 weeks before the first dose of study intervention.</li>\n <li value=\"27\">\n Systemic use of the following medications within 2 weeks before the first dose of study intervention:\n <ul>\n <li>\n Strong CYP3A4 inducers: eg, avasimibe, carbamazepine, lumacaftor, phenobarbital, rifampicin, rifapentine, St John’s Wort</li>\n <li>\n P-gp inhibitors: erythromycin, clarithromycin, rifampicin, ketoconazole, itraconazole, posaconazole, artesunate-pyronaridine, ritonavir, indinavir, nelfinavir, atazanavir, glecaprevir-pibrentasvir, simeprevir, ledipasvir-sofosbuvir, verapamil, diltiazem, dronedarone, propafenone, quinidine, cyclosporine, valspodar, milk thistle (Silybum marianum)</li>\n </ul>\n </li>\n <li value=\"28\">\n Has received prior targeted small molecule therapy or NHA treatment within 4 weeks before the first dose of study intervention as follows:\n <ul>\n <li>\n Abiraterone acetate + prednisone or darolutamide within 2 weeks</li>\n <li>\n Enzalutamide or apalutamide within 3 weeks</li>\n </ul>\n </li>\n <li value=\"29\">\n Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed.</li>\n</ol>\n<p style=\"margin-left:18.5pt;\">\n Refer to Section 6.5 for information on COVID-19 vaccines.</p>\n<p style=\"margin-left:-.25pt;\">\n <strong>Prior/Concurrent Clinical Study Experience</strong></p>\n<ol>\n <li value=\"30\">\n Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.</li>\n <li value=\"31\">\n Has known hypersensitivity to the components or excipients in abiraterone acetate, prednisone or prednisolone, enzalutamide, fludrocortisone, dexamethasone, or MK-5684.</li>\n</ol>\n<p style=\"margin-left:-.25pt;\">\n <strong>Diagnostic Assessments</strong></p>\n<ol>\n <li value=\"32\">\n Has a “superscan” bone scan. This is defined as an intense symmetric activity in the bones and diminished renal parenchymal activity on baseline bone scan such that the presence of additional metastases in the future could not be evaluated.</li>\n <li value=\"33\">\n Known additional malignancy that is progressing or has required active treatment within the past 3 years.</li>\n</ol>\n<p style=\"margin-left:18.5pt;\">\n Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded.</p>\n<ol>\n <li value=\"34\">\n Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication.</li>\n <li value=\"35\">\n Known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, (ie, without evidence of progression) for at least 4 weeks as confirmed by repeat imaging performed during study screening, are clinically stable and have not required steroid treatment for at least 14 days prior to the first dose of study intervention.</li>\n <li value=\"36\">\n Active autoimmune disease that has required systemic treatment in the past 2 years.</li>\n</ol>\n<p align=\"center\" style=\"margin-left:.6pt;\">\n Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) is allowed.</p>\n<ol>\n <li value=\"37\">\n Active infection requiring systemic therapy, as judged by the investigator.</li>\n <li value=\"38\">\n Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and HCV (defined as anti-HCV Ab positive and detectable HCV RNA) infection. Note: Hepatitis B and C screening tests are not required unless:</li>\n</ol>\n<p style=\"margin-left:18.5pt;\">\n Known history of HBV and HCV infection</p>\n<p style=\"margin-left:18.5pt;\">\n As mandated by local health authority</p>\n<ol>\n <li value=\"39\">\n History or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant’s participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator.</li>\n <li value=\"40\">\n Known psychiatric or substance abuse disorder that would interfere with the participant’s ability to cooperate with the requirements of the study, as judged by the investigator.</li>\n</ol>\n<p style=\"margin-left:-.75pt;\">\n <strong>5.3        Lifestyle Considerations</strong></p>\n<p style=\"margin-left:-.75pt;\">\n <strong>5.3.1         Meals and Dietary Restrictions</strong></p>\n<p style=\"margin-left:.85pt;\">\n Participants should maintain a normal diet unless modifications are required to manage an AE such as diarrhea, nausea, or vomiting.</p>\n<p style=\"margin-left:.85pt;\">\n MK-5684 should be taken with food.</p>\n<p style=\"margin-left:.85pt;\">\n Foods that are CYP3A4 inhibitors should not be consumed during the study. Grapefruit and star fruit are known to be CYP3A4 inhibitors and should not be consumed for 2 weeks before the first dose of MK-5684 and for the entire duration of the study. Consumption of CYP3A4 inhibitors, such as grapefruit juice, may significantly increase the levels of MK-5684 and cause increased toxicity. St. John's wort is a CYP3A4 inducer, and the consumption of St. John's wort or products containing St. John's wort may reduce the levels of MK-5684. A partial list of examples of CYP3A4 inhibitors is provided in Section 6.5.</p>\n<p style=\"margin-left:-.75pt;\">\n <strong>5.3.2         Caffeine, Alcohol, and Tobacco Restrictions</strong></p>\n<p style=\"margin-left:.85pt;\">\n No restrictions are required.</p>\n<p style=\"margin-left:-.75pt;\">\n <strong>5.3.3         Activity Restrictions</strong></p>\n<p style=\"margin-left:.85pt;\">\n No restrictions are required.</p>\n
      • primary_end_points<p>\n <span style=\"font-size:14px;\"><span style=\"font-family:times new roman,times,serif;\"><span new=\"\" style=\"line-height: 104%;\" times=\"\">Radiographic progression-free survival (rPFS) The time from randomization to the first documented disease progression or death due to any cause, whichever occurs first</span></span></span></p>\n<p>\n <span style=\"font-size:14px;\"><span style=\"font-family:times new roman,times,serif;\"><span new=\"\" style=\"line-height: 104%;\" times=\"\">Overall survival: The time from randomization to death due to any cause</span></span></span></p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p align=\"left\" style=\"margin-left:-.2pt;\">\n The study will be conducted at the Aga Khan University, Clinical Research Unit (CRU) which 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 align=\"left\" style=\"margin-left:-.2pt;\">\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 style=\"margin-left:-.2pt;\">\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<p align=\"left\" style=\"margin-left:.05pt;\">\n  </p>\n<ul>\n <li>\n Clinical Research Nurses: Obtain Informed consents, Make CRF entries/resolve queries; Collect medical information; Vital signs; Collect adverse events; Administer IP; Collect lab samples; Participant recruitment and retention.</li>\n <li>\n Pharmacist and Pharmacy Technologist: Investigational Drug Services:</li>\n</ul>\n<p align=\"center\" style=\"margin-left:7.3pt;\">\n Manage IP receipt/return; Prepare and dispense IP; Unbinding procedures.</p>\n<ul>\n <li>\n Regulatory Affairs: Manage submissions to ethics and regulatory authorities. Maintain essential documents and ensure compliance</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 align=\"left\" style=\"margin-left:.05pt;\">\n  </p>\n<p align=\"left\" style=\"margin-left:-.2pt;\">\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 align=\"left\" style=\"margin-left:-.2pt;\">\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 style=\"margin-left:-.2pt;\">\n All cancer patients treated at AKUHN have access to psychosocial and support counselling as well as palliative care support as part of AKUH, N best practice. This is not limited to non-study patients and thus is available to study patients as well. </p>\n<p align=\"left\" style=\"margin-left:.05pt;\">\n  </p>\n<p style=\"margin-left:-.2pt;\">\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<p align=\"left\" style=\"margin-left:.05pt;\">\n  </p>\n<p align=\"left\" style=\"margin-left:.05pt;\">\n  </p>\n<ul>\n <li>\n Joint Commission International (JCI)</li>\n</ul>\n<p align=\"left\" style=\"margin-left:.05pt;\">\n  </p>\n<ul>\n <li>\n College of American Pathologists (CAP)</li>\n</ul>\n<p align=\"left\" style=\"margin-left:.05pt;\">\n  </p>\n<ul>\n <li>\n South African National Accreditation Service (SANAS)</li>\n</ul>\n<p>\n  </p>\n
      • other_details_explanation<p>\n N/A</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n South African Health Products Regulatory Authority (SAHPRA). Date of approval  27Aug2024 and 6 sites in South Africa</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_durationThe Sponsor estimates that the study will require approximately 7 years from the time the first participant (or their legally acceptable representative) provides documented informed consent until the last participant’s last study-related contact
      • design_controlled_randomisedNo
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorAbiraterone Acetate
      • design_controlled_other_medicinalYes
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherYes
      • design_controlled_medicinal_specify2nd comparator is Enzalutamide
      • single_site_member_stateYes
      • location_of_areaAGA KHAN UNIVERSITY HOSPITAL NAIROBI
      • single_site_physical_address3RD PARKLANDS AVENUE
      • single_site_contact_personPROF MANSOOR SALEH
      • single_site_telephone0780428334
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_statesAustralia Brazil Canada Chile China Colombia Costa Rica Czech Republic Estonia France Germany Greece Guatemala Hong Kong Hungary Ireland Israel Italy Japan Latvia Lithuania Malaysia Mexico Netherlands New Zealand Peru Portugal Puerto Rico Romania Singapor
      • number_of_sites
      • multi_country_listAustralia\nBrazil\nCanada\nChile\nChina\nColombia\nCosta Rica\nCzech Republic\nEstonia\nFrance\nGermany\nGreece\nGuatemala\nHong Kong\nHungary\nIreland\nIsrael\nItaly\nJapan\nLatvia\nLithuania\nMalaysia\nMexico\nNetherlands\nNew Zealand\nPeru\nPortugal\nPuerto Rico\nRomania\nSingapore\nSlovakia\nSouth Korea\nSpain\nSweden\nTaiwan\nThailand\nTürkiye\nUnited Kingdom\nUnited State of America\n
      • data_monitoring_committeeYes
      • total_enrolment_per_siteAgakhan is the only site in Kenya
      • total_participants_worldwide1500
      • 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_female0
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_namePROF MANSOOR
      • investigator1_middle_nameNOORALI
      • investigator1_family_nameSALEH
      • investigator1_qualificationMD
      • investigator1_professional_address3rd Parklands Avenue, off Limuru Road, R 0. Box 30270, GPO 00100, Nairobi,
      • investigator1_telephone0780428334
      • investigator1_emailmansoor.saleh@aku.edu
      • organisations_transferred_No
      • number_participants8
      • notification<p>\n None</p>\n
      • approval_date20-05-2025
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted17-04-2025
      • is_child0
      • unsubmitted1
      • initial_date_submitted08-04-2025
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-06-27 16:21:51
      • created2024-11-13 12:20:31
      • total_sites1
      • ecitizen_invoice329152
    • InvestigatorContact(array)
      • 0(array)
        • id1236
        • application_id1484
        • given_namePROF MANSOOR
        • middle_nameNOORALI
        • family_nameSALEH
        • qualificationMD
        • professional_address3rd Parklands Avenue, off Limuru Road, R 0. Box 30270, GPO 00100, Nairobi,
        • telephone0780428334
        • emailmansoor.saleh@aku.edu
        • created2025-02-23 08:44:18
        • modified2025-04-17 17:56:58
    • SiteDetail(array)
      • 0(array)
        • id1849
        • application_id1484
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2025-02-23 08:44:18
        • modified2025-04-17 17:56:58
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id813
        • application_id1484
        • sponsorMerck Sharp & Dohme LLC
        • sponsor_typeIndustry
        • contact_person
        • address126 East Lincoln Avenue P.O. Box 2000 Rahway, NJ 07065 USA
        • telephone_number+1-908-740-4000
        • fax_number
        • cell_number+1-908-740-4000
        • email_addresssanjana.reddy1@merck.com
        • created2025-02-23 08:44:18
        • modified2025-04-17 17:56:58
  • 3(array)
    • Application(array)
      • id1480
      • user_id939
      • trial_status_id(null)
      • abstract_of_study<p>\n <strong>Background:</strong> Cholera, caused by the bacterium <em>Vibrio cholerae</em>, remains a significant public health challenge in low-resource settings, particularly in sub-Saharan Africa. Despite efforts to control the disease, cholera outbreaks continue to occur, with Kenya experiencing several significant epidemics in recent years. Oral cholera vaccines (OCVs) are a critical tool in cholera prevention strategies. This study evaluates the immunogenicity of extended dosing intervals for Euvichol-S, a WHO-prequalified OCV, in a Phase IV non-inferiority trial.</p>\n<p>\n <strong>Overview Design:</strong> This trial is a parallel-group, open-label, randomized, non-inferiority study. It aims to compare the immune response of three dosing schedules of the Euvichol-S OCV: a standard two-week interval, a three-month interval, and a twelve-month interval. The study will enroll 1071 participants, stratified by age into three groups: children aged 1-4 years, children aged 5-14 years, and adults aged 15 years and older. The primary endpoint is the plasma vibriocidal geometric mean titer (GMT) measured two weeks after the second dose. The trial also includes a peripheral blood mononuclear cell (PBMC) sub-cohort, focusing on younger (1-4 years) and older children (5-15 years), to assess the induction of <em>V. cholerae</em> OSP-specific memory B cells and specific immune responses involving gut-homing plasmablasts.</p>\n<p>\n <strong>Primary Objective:</strong> To assess and compare the immune response to Euvichol-S measured by vibriocidal GMT two weeks after the second vaccine dose across different dosing intervals.</p>\n<p>\n <strong>Study Sites:</strong> The study will be conducted in the Mukuru informal settlement in Nairobi, Kenya, a high-priority cholera hotspot area. The Kenya Medical Research Institute (KEMRI) will manage the study, leveraging its established relationship with the community.</p>\n<p>\n <strong>Study Population:</strong> Key inclusion criteria include residents of Mukuru aged 1 year and above, who are healthy as determined by medical history and physical examination. Exclusion criteria include pregnant  women, individuals with severe malnutrition, and those with non-HIV immunosuppressive conditions or severe chronic diseases.</p>\n<p>\n <strong>Study Interventions:</strong> Participants will be randomized to one of three dosing arms: a standard two-week interval, a three-month interval, or an annual booster interval. The arms and randomization will be stratified by age. Participants will receive the Euvichol-S OCV according to the assigned schedule. The follow-up period for participants will be 18 months, during which they will undergo regular scheduled visits and additional unscheduled visits as needed. Participants in the standard dosing arm will have six scheduled visits, those in the three-month interval arm will have seven, and those in the annual booster arm will have six visits. Blood samples will be collected at each vaccination visit and 14 days later and at 6 months, 1 year and 18 months after enrollment to measure plasma vibriocidal GMT and other immunological markers. Children in the PBMC cohort will have  two additional samples collected five days after each vaccine dose and a larger blood volume collected at 14 days after the second dose.</p>\n<p>\n <strong>Outcome Measures:</strong> Primary outcome measures include the plasma vibriocidal GMT two weeks post-second dose. Secondary outcomes include antibody seroconversion rates, longitudinal GMT changes, incidence of cholera disease, and the safety profile of the vaccine. The PBMC sub-cohort will provide detailed insights into memory B cell and plasmablast responses.</p>\n<p>\n <strong>Sample Size:</strong> A total of 1071 participants will be enrolled in the study, with equal distribution across the three dosing arms and age strata. The PBMC sub-cohort will include 360 participants (40 per arm among children 5-14y, 80 per arm among children 1-4y), who will have detailed immunological assessments.</p>\n<p>\n <strong>Data Analysis:</strong> The immunogenicity of the vaccine across different dosing schedules will be compared to determine non-inferiority. Data will be analyzed descriptively to summarize the by-grade incidence of treatment-emergent adverse events (AEs), serious adverse events (SAEs), and other safety indicators. <strong>Impact:</strong> This trial aims to generate evidence on the optimal dosing schedule for Euvichol-S OCV, potentially informing future vaccination strategies in cholera-endemic regions. The findings could enhance public health interventions and improve cholera prevention efforts in resource-limited settings.</p>\n<p>\n <strong>Funding:</strong> The study is funded by the Wellcome Trust, with the Sabin Vaccine Institute as the sponsor.</p>\n
      • study_title<p>\n <span style=\"color: black; font-size: 11pt; line-height: 16.8667px; font-family: Calibri, sans-serif;\">A Phase IV Parallel-Group, Open-Label, Randomized Non-Inferiority Trial Evaluating Immunogenicity of Extended Dosing Intervals for Euvichol-S Oral Cholera Vaccine, Nairobi, Kenya</span></p>\n
      • laymans_summary<p>\n <strong>Why should you do this study?</strong> Cholera is a serious disease that causes severe diarrhea and can be fatal if not treated promptly. It spreads through contaminated water and food and remains a significant health issue in many developing countries, including Kenya. This study aims to find the most effective way to use the Euvichol-S oral cholera vaccine to prevent outbreaks and save lives.</p>\n<p>\n <strong>What questions are we trying to answer?</strong> We are investigating whether extending the time between doses of the Euvichol-S cholera vaccine is as effective as the standard dosing schedule. Specifically, we want to know if longer intervals between doses provide the same level of immunological protection against cholera.</p>\n<p>\n <strong>Where is the study taking place?</strong> The study will be conducted in Mukuru, a large informal settlement in Nairobi, Kenya. This area is prone to cholera outbreaks, making it a good location to test the vaccine's immunogenicity.</p>\n<p>\n <strong>How many participants does it involve and how will they be selected?</strong> The study will involve 1071 participants from different age groups, including children and adults. Participants will be selected from the Mukuru community and must be healthy to enroll. We will ensure a diverse age representation to evaluate the vaccine's immunogenicity across all age groups.</p>\n<p>\n <strong>Who will be selected?</strong> Residents of Mukuru who are at least one year old and in good health are eligible to participate. Pregnant  women and individuals with severe health conditions will not be included in the study.</p>\n<p>\n <strong>What does the study involve for those taking part?</strong> Participants will be randomly assigned to one of three groups: one group will receive the second dose of the vaccine two weeks after the first dose, another group will receive it three months later, and the last group will receive a booster dose one year after the first dose. Participants will attend several clinic visits over an 18-month period for health check-ups and blood samples. A smaller subset will provide additional blood volume to study the vaccine's impact on different parts of the immune response.</p>\n<p>\n <strong>What are the risks and benefits of taking part?</strong> <strong>Risks:</strong> The vaccine might cause mild side effects such as stomach discomfort, nausea, or diarrhea. There is also a small risk of an allergic reaction. Blood sample collection may cause minor pain or bruising. <strong>Benefits:</strong> Participants will likely have a reduced risk of contracting cholera. Additionally, the study will contribute valuable information that can enhance cholera prevention efforts globally.</p>\n<p>\n <strong>How will the study benefit society?</strong> This research will help identify the most effective vaccination schedule for the Euvichol-S oral cholera vaccine. The findings could lead to improved public health strategies and better protection against cholera in regions where the disease is prevalent, ultimately saving many lives.</p>\n
      • short_titleExtended Dosing OCV Trial
      • protocol_noECCT/25/02/11
      • version_no1.0
      • date_of_protocol12-09-2024
      • study_drugOral Cholera Vaccine
      • disease_conditionCholera
      • 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_nameEuvichol-S
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addresssamkariuki2@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_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantProf Sam Kariuki
      • declaration_date118-03-2025
      • declaration_principal_investigatorProf Samuel Kariuki
      • declaration_date218-03-2025
      • placebo_presentNo
      • study_objectives<h2>\n Primary Objective</h2>\n<p style=\"margin-left:36pt;\">\n ●      To assess and compare the immune response to Euvichol-S, measured by plasma vibriocidal geometric mean titer (GMT) two weeks after the second vaccine dose, across different dosing intervals in participants aged 1 year and older.</p>\n<h2>\n Secondary Objectives</h2>\n<p style=\"margin-left:36pt;\">\n ●      To compare plasma vibriocidal GMT across different dosing intervals within specific age groups.</p>\n<p style=\"margin-left:36pt;\">\n ●      To evaluate vibriocidal antibody seroconversion in relation to dosing intervals among all participants and within each age group.</p>\n<p style=\"margin-left:36pt;\">\n ●      To monitor and document the changes in vibriocidal GMT over an 18-month follow-up period, comparing between dosing interval groups and within age groups.</p>\n<p style=\"margin-left:36pt;\">\n ●      To assess and compare the incidence of cholera disease over an 18-month follow-up, focusing on the association with age groups and dosing intervals.</p>\n<p style=\"margin-left:36pt;\">\n ●      To evaluate and describe the safety and tolerability profile of extended dosing intervals of Euvichol-S.</p>\n<p style=\"margin-left:36pt;\">\n  </p>\n<h2>\n Exploratory objectives</h2>\n<p style=\"margin-left:36pt;\">\n ●      Assess and compare the following measures a) among all study participants and b) within each age group:</p>\n<p style=\"margin-left:72pt;\">\n o   Anti-O-specific polysaccharide (OSP) IgA and IgG responses in plasma over an 18-month follow-up period</p>\n<p style=\"margin-left:72pt;\">\n o   Circulating gut-homing anti-OSP plasmablasts at baseline and 5 days after each dose of vaccine in a subcohort of children under 15 years</p>\n<p style=\"margin-left:72pt;\">\n o   Circulating anti-OSP memory B cells at baseline and 14 days after booster doses after each dose of vaccine in a subcohort of children under 15 years</p>\n<p style=\"margin-left:36pt;\">\n ●      Assess and compare the persistence of plasma anti-OSP and vibriocidal immune response over an 18-month follow-up period by age group and dosing interval.</p>\n<p style=\"margin-left:36pt;\">\n ●      Assess and compare immune responses based on baseline vibriocidal titers.</p>\n
      • principal_inclusion_criteria<ol>\n <li>\n Residents of Mukuru, Nairobi, Kenya</li>\n <li>\n Individuals aged 1 year and above</li>\n <li>\n Voluntary written informed consent for study participation provided by an individual or his/her legally acceptable representative. Children aged 13 years and above will also provide assent, with parental permission required for all children.</li>\n <li>\n Ability to comply with study requirements and attend follow-up visits during the study period.</li>\n <li>\n Participants must be in good health, as determined by medical history, physical examination, and the clinical judgment of the investigators. Clinical judgment will consider factors such as the absence of acute illness or, uncontrolled or severe chronic conditions that may affect participation in the study</li>\n</ol>\n
      • principal_exclusion_criteria<p>\n The participant may not enter the trial if ANY of the following apply:</p>\n<ol>\n <li>\n Known history of hypersensitivity reactions to other vaccines.</li>\n <li>\n Pregnant women, due to differences in immune response. A pregnancy test will be administered to all female participants between 15-49 years..</li>\n <li>\n Reported diarrhea or abdominal pain lasting 2 weeks or longer within 6 months prior to study initiation; to avoid confounding the vaccine's effects with pre-existing conditions.</li>\n <li>\n Received a cholera vaccine in the last 24 months: Ensures that the study assesses the vaccine in question without interference from prior vaccinations.</li>\n <li>\n History of cholera disease in the last 24 months: Recent history of cholera infection can interfere with the measurement of vaccine response.</li>\n <li>\n Severely malnourished individuals as determined by Mid-Upper Arm circumference (MUAC) and age-specific Body Mass Index (BMI) measurements: malnutrition can affect immune response and vaccine efficacy. In children below 10 years, severe malnutrition will be defined as MUAC < 11.5 cm and the presence of bilateral oedema, while in older children and adults it will be defined as BMI < 16.</li>\n <li>\n Non-HIV/AIDS immunosuppressive condition or on immunosuppressive therapy: Such conditions can significantly alter vaccine response.</li>\n <li>\n Presence of bleeding disorders or medical contraindication for blood draws: To ensure participant safety during blood collection.</li>\n <li>\n Participation in another clinical trial with investigational product dosing within 6 months prior to study initiation.</li>\n <li>\n An individual thought to have difficulty in participating in the study due to severe chronic diseases, based on the judgment of the investigator.</li>\n <li>\n An individual thought to have difficulty participating in the study due to reasons, such as  significant logistical constraints, or communication barriers, or likely to be away for a period of at least 3 consecutive months in the first 6 months of enrollment based on the judgment of the investigator.</li>\n</ol>\n
      • primary_end_points<p>\n <span style=\"color: black; font-size: 11pt; line-height: 16.8667px; font-family: Calibri, sans-serif;\">Vibriocidal GMT measured two weeks after the second dose of Oral Cholera Vaccine (OCV)</span></p>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • 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_confirmatory0
      • trial_therapeutic_use1
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n <strong>Site Name:</strong></p>\n<p>\n MMM MUKURU HEALTH CENTRE</p>\n<p>\n <strong>Number of Staff and Qualifications:</strong></p>\n<p>\n The facility provides clinical care to various patient populations, including maternal and child health services, Comprehensive Care Clinics (CCC) for HIV management, TB clinics, and outpatient services.</p>\n<p>\n The site is staffed with:</p>\n<ul>\n <li>\n <strong>Clinical Officers:</strong> Experienced in providing diagnostic and therapeutic care across general medical conditions.</li>\n <li>\n <strong>Nurses:</strong> Offering direct patient care, immunization services, and participant monitoring.</li>\n <li>\n <strong>Pharmaceutical Technicians:</strong> Responsible for handling medications</li>\n <li>\n <strong>Laboratory Technologists:</strong> Managing sample collection and laboratory analyses</li>\n <li>\n <strong>Community Health Assistants:</strong> Supporting health education and participant engagement in the study communities.</li>\n</ul>\n<p style=\"margin-left:36pt;\">\n  </p>\n<p>\n <strong>Field Study Staff:</strong></p>\n<ul>\n <li>\n <strong>Study Coordinator:</strong> Responsible for overseeing the day-to-day implementation of the trial, ensuring protocol adherence, and liaising with clinical and laboratory teams.</li>\n <li>\n <strong>Data Assistant:</strong> Responsible for data management using electronic case report forms (eCRFs) via REDCap.</li>\n <li>\n <strong>Nurses:</strong> Administering vaccines, monitoring participants for adverse events, and conducting follow-up visits.</li>\n <li>\n <strong>Laboratory Technologists:</strong> Handling sample collection, processing, and storage, ensuring the integrity of biological samples throughout the study.</li>\n <li>\n <strong>Community Focal Persons:</strong> Acting as liaisons between the study team and the local community, ensuring participant recruitment, retention, and addressing any community concerns.</li>\n</ul>\n<p>\n <strong>Site Facilities:</strong></p>\n<ul>\n <li>\n <strong>Clinical Services:</strong> The health facility offer a broad range of services, including maternal and child health, HIV care through CCCs, TB care, and general outpatient services. Patients are also referred to higher-level care if necessary.</li>\n <li>\n <strong>Laboratory Facilities:</strong> The site is equipped with laboratory facilities to support sample collection and field storage.</li>\n <li>\n <strong>Emergency Facilities:</strong> Emergency care for adverse events or severe reactions will be provided on-site, with the ability to refer participants to nearby hospitals if required.</li>\n <li>\n <strong>Other Relevant Infrastructure:</strong><br />\n The facility is equipped with secure storage for biological samples and vaccines, maintaining cold chain protocols. Data management will be supported through electronic data capture systems, ensuring efficient and compliant handling of study data. The site is also equipped with a backup generator to ensure uninterrupted power supply, and there is reliable internet connectivity to facilitate real-time data transmission and communication.</li>\n</ul>\n<p>\n  </p>\n
      • other_details_explanation<p>\n Not Applicable</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n Approval obtained from KEMRI SERU on 02 December 2024 for one site (MMM Health Centre)</p>\n
      • other_details_regulatory_rejected
      • other_details_regulatory_halted
      • estimated_durationThree years
      • 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_comparatorTwo-week dosing interval
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaMMM MUKURU HEALTH CENTRE
      • single_site_physical_addressP.O BOX 26352-00504 NAIROBI, Mukuru Kwa Njenga, Nairobi
      • single_site_contact_personVictoria Nthenge
      • single_site_telephone0722455922
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
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      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_site1071
      • total_participants_worldwide1071
      • population_less_than_18_yearsYes
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      • gender_female1
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      • subjects_healthyYes
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      • subjects_specify
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      • subjects_others_specify
      • investigator1_given_nameEric
      • investigator1_middle_name
      • investigator1_family_nameOsoro
      • investigator1_qualificationMBChB, MSc., PhD
      • investigator1_professional_address4th Floor, One Padmore Place, George Padmore Road, Nairobi
      • investigator1_telephone+254722216391
      • investigator1_emaileric.osoro@wsu.edu
      • organisations_transferred_No
      • number_participants1071
      • notification
      • approval_date16-07-2025
      • submitted1
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      • initial_date_submitted24-02-2025
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      • modified2025-09-15 18:17:24
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        • id1178
        • application_id1480
        • given_nameSamuel
        • middle_name
        • family_nameKariuki
        • qualificationBVM, MSc., PhD
        • professional_addressCenters for Microbiology Research, Kenya Medical research Institute, Nairobi
        • telephone+254722232467
        • emailsamkariuki2@gmail.com
        • created2024-10-14 15:38:18
        • modified2025-03-19 11:24:37
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          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
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        • application_id1480
        • sponsorSabin Vaccine Institute
        • sponsor_typeResearch Institution
        • contact_personDr Denise Garrett
        • address2000 Pennsylvania Ave, NW, Suite 7000. Washington, DC 20006
        • telephone_number+12028425025
        • fax_number
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        • email_addressDenise.Garrett@Sabin.org
        • created2024-10-14 15:38:18
        • modified2025-03-19 11:24:37
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      • abstract_of_study<div>\n Young women in sub-Saharan Africa are a vulnerable population in terms of HIV acquisition with ~7,000 new infections occurring per week. Oral daily pre-exposure prophylaxis (PrEP) is a highly effective means of HIV prevention when taken regularly during periods of risk. Early experience with the global rollout of PrEP in this population indicates enthusiasm for PrEP, but also barriers to adherence and program retention.</div>\n<div>\n PrEP My Way is a novel PrEP delivery system consisting of clinic-based PrEP initiation, followed by peer-delivered kits for HIV self-testing, PrEP refills, vaginal swabs for gonorrhea and chlamydia self-sampling, pregnancy tests, and contraception refills, if desired. Based on Social Cognitive Theory, our overall hypothesis is that PrEP My Way will overcome critical stigma and structural barriers that currently limit PrEP use and thus empower young women to promote their sexual health.</div>\n<div>\n Preliminary testing of PrEP My Way in Kisumu, Kenya found it to be highly feasible and acceptable, but PrEP use as an oral medication was lower than expected. Now that newer PrEP formulations are becoming available, we are adding choice of PrEP formulation (i.e., oral tenofovir/emtricitabine, injectable cabotegravir-long acting [CAB-LA], or dapivirine ring) as well as choice of adherence support from peers (e.g., SMS, routine check-ins and/or WhatsApp groups) to the intervention. We will then test the effectiveness of the augmented PrEP My Way intervention (with and without testing for STIs due to cost concerns) on PrEP persistence in women with ongoing HIV prevention needs (i.e., self-reported desire for PrEP, self-reported HIV risk, condomless sex, and/or multiple sexual partners). We will also track implementation, service, and client metrics per Proctor’s framework and determine cost-effectiveness of the intervention.</div>\n
      • study_title<p>\n PrEP My Way: A hybrid type 1 clinical effectiveness-implementation trial to promote PrEP persistence among young Kenyan women</p>\n
      • laymans_summary<p>\n The PrEP My Way pilot intervention showed that young women preferred receiving their PrEP pills in a “kit” with other sexual health materials such as HIV tests, sanitary pads, pregnancy tests, etc. In this study, we will adapt the original PrEP My Way kit and delivery systems to include CAB-LA and the dapivirine ring. We will first adapt the original intervention through a series of focus group discussions and in-depth interviews. Then, we will conduct a clinical trial, where participants will be assigned to the enhanced Standard of Care (usual care plus choice of CAB-LA, dapivirine ring, or oral FTC/TDF), the full PrEP My Way intervention, and the intervention without STI testing.</p>\n
      • short_titlePrEP My Way II
      • protocol_noECCT/25/02/10
      • version_no1.0
      • date_of_protocol09-08-2024
      • study_drugTenofovir+Emtricitabine FDC Tablets; Dapivirine vaginal ring; Cabotegravir injection
      • disease_conditionHuman immunodeficiency virus (HIV)
      • 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_nameTenofovir+Emtricitabine; Dapivirine; Cabotegravir
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressrgreshon@kemri-rctp.org
      • applicant_covering_letter1
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      • declaration_applicantGreshon Rota
      • declaration_date119-02-2025
      • declaration_principal_investigatorElizabeth Anne Bukusi
      • declaration_date219-02-2025
      • placebo_presentNo
      • study_objectives<h1>\n <span style=\"font-size:16px;\">GENERAL OBJECTIVES</span></h1>\n<p style=\"margin-left:9.4pt;\">\n <em>Overall design.</em> We will first augment the initially developed PrEP My Way intervention to include choice of PrEP formulation and choice of adherence support (Aim 1). We will then test the effectiveness of the augmented PrEP My Way intervention (with and without testing for STIs due to cost concerns) on PrEP persistence in women with ongoing HIV prevention needs (i.e., selfreported desire for PrEP, self-reported HIV risk, condomless sex, and/or multiple sexual partners). We will also track implementation, service, and client metrics per Proctor’s framework³ (Aim 2). Finally, we will determine cost-effectiveness of the intervention (Aim 3).</p>\n<h3>\n Specific Objectives</h3>\n<p style=\"margin-left:22.45pt;\">\n 1.  <strong>To augment the initially developed PrEP My Way intervention to include choice of PrEP formulation (CAB-LA, dapivirine ring, or oral FTC/ TDF) and adherence support. </strong>With a Kenyan design firm, we will conduct 28 individual interviews and 2 workshops with young women, young men (as sexual partners), caregivers, nurses, and community health workers to adapt the kit, product guides, and delivery systems. We will use a nurse-delivered model for injections per Kenya regulations and a peer-delivered model for rings/oral PrEP. The Kenya National AIDS/STI Control Program (NASCOP) will review the design to optimize potential uptake and sustainability in routine care.</p>\n<p style=\"margin-left:22.45pt;\">\n 2.  <strong>To conduct a type 1 effectiveness-implementation trial of PrEP My Way. </strong>We will enroll 432 women (age 16-24) in Kisumu, Kenya, and randomize them 1:1:1 to the full intervention vs the intervention without STI testing (i.e., to assess marginal impact of the most costly kit component beyond PrEP) vs enhanced standard of care. Women in the intervention will choose bimonthly (CAB-LA) or quarterly (ring/oral) delivery. Our primary outcome will be PrEP persistence by recorded injection (CAB-LA) or drug levels (ring/oral) at 9 months in women with ongoing HIV prevention needs (i.e., self-reported desire for PrEP, self-reported HIV risk, condomless sex, and/or multiple sexual partners). Secondary/additional outcomes will be persistence and adherence at other time points and with alternative definitions of HIV prevention needs, STI testing, and family planning use. We will also track implementation, service, and client metrics per Proctor’s framework³.</p>\n<p style=\"margin-left:22.45pt;\">\n 3.  <strong>To determine cost and cost-effectiveness of PrEP My Way. </strong>We will conduct micro-costing analyses through time and motion studies and use published cost data, internal reports, and supply-chain data to determine the cost of delivering each PrEP formulation and support option and the marginal cost of STI testing. We will also estimate the incremental costeffectiveness ratio in terms of cost per woman with PrEP persistence. </p>\n
      • principal_inclusion_criteria<ul>\n <li>\n Young woman (age 16-24 years); we will enroll emancipated minors (e.g., those who have been pregnant) per Kenyan national guidelines47 or 16-17 year-olds with parental consent</li>\n <li>\n Interest in PrEP (actual PrEP use is not a requirement for Aim 1)</li>\n <li>\n Sexually active within the last 3 months</li>\n <li>\n Residence in Kisumu County</li>\n <li>\n Phone ownership (N.B., all women approached for the PrEP My Way pilot study had a phone)</li>\n <li>\n Ability to understand KiSwahili, DhoLuo, and/or English</li>\n</ul>\n
      • principal_exclusion_criteria<p>\n Exclusion criteria- inability to provide informed consent (e.g., intoxication, mental disability)</p>\n
      • primary_end_points<p>\n Prevention-effective PrEP persistence (i.e., sustained PrEP use) by documented CAB-LA injection, dapivirine release level, or DBS TFV-DP concentration at Month 9.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • scope_therapy0
      • scope_safety0
      • scope_efficacy0
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use1
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<div>\n PERSONNEL</div>\n<div>\n Prof. Elizabeth Bukusi, Principal Investigator</div>\n<div>\n She is the KEMRI PI and will work in association with the Co-investigators in the overall</div>\n<div>\n implementation of the Project. She is responsible for overseeing the progress of the study and</div>\n<div>\n also the chief liaison with the local government and other regulatory bodies.</div>\n<div>\n  </div>\n<div>\n Kevin Oware, Study Coordinator</div>\n<div>\n The Study Coordinator is responsible for the smooth functioning of the project, coordinating</div>\n<div>\n communications with regulatory boards, staff and investigators, assisting investigators with</div>\n<div>\n implementation, planning and problem-solving on behalf of the PI to ensure project goals are</div>\n<div>\n met. Providing protocol guidance to staff, supervising and monitoring staff performance general</div>\n<div>\n day-to-day study administration.</div>\n<div>\n  </div>\n<div>\n TBN , Field Research Assistant</div>\n<div>\n The field research assistant will be responsible for recruiting of the participants to the study by</div>\n<div>\n using known working strategies. He/She will also be responsible for conducting the scheduled</div>\n<div>\n qualitative interviews/Focus Group discussions for the participants.</div>\n<div>\n  </div>\n<div>\n TBN , Peer Educators</div>\n<div>\n The peer educators will be responsible for recruiting of the participants to the study by using</div>\n<div>\n known working strategies. They will also deliver the study kit to participants in the community.</div>\n<div>\n  </div>\n<div>\n Dr. Greshon Rota, Pharmacist of Records</div>\n<div>\n The Pharmacist of records will be responsible for representation of the Pharmacy and Poisons</div>\n<div>\n Board IRB. He will ensure that the study gets approval from PPB and gets renewal every year</div>\n<div>\n as per the regulations.</div>\n<div>\n  </div>\n<div>\n TBN, Data Manager</div>\n<div>\n The Data Lead will assist in Quality Assurance, Quality Control of data and also be involved in</div>\n<div>\n data collection and management. He will also be instrumental in adopting several datasets for</div>\n<div>\n the study site including creating additional site-specific access data sets for internal monitoring</div>\n<div>\n <div>\n and evaluation. Ensures confidentiality of participant’s information (Consent forms, name charts,</div>\n <div>\n CRFs) by keeping link-logs under double lock system</div>\n <div>\n  </div>\n <div>\n TBN, Reception/Front office</div>\n <div>\n The Receptionist has an overall responsibility to receive and speak with participants in person</div>\n <div>\n about the study and also schedule their appointments. He/She will organize schedule for the</div>\n <div>\n initial and follow-up visits for participants including counter checking completeness of locator</div>\n <div>\n information after enrollment and during follow up visits.</div>\n <div>\n  </div>\n <div>\n TBN, Lab Technologist</div>\n <div>\n The Lab Technologist will be responsible for performing all the lab tests required for the</div>\n <div>\n participants,maintaining and charting of the temperature logs in the laboratory, archiving</div>\n <div>\n samples and ensuring proper storage is done, and maintaining the Study documents in files</div>\n <div>\n and folders appropriately. Monitors abnormal results for participants and communicates the</div>\n <div>\n same to the clinician.</div>\n <div>\n  </div>\n <div>\n TBN, Administrator</div>\n <div>\n This administrator will be responsible for assisting in overall planning for the project in liaison</div>\n <div>\n with the Project coordinator, budget preparation, maintaining of proper audit trail for study funds</div>\n <div>\n and expenditures, generate quarterly invoices, and other financial reports as required in the</div>\n <div>\n subcontract. He will also be responsible for the handling and accounting for the field imprest</div>\n <div>\n given to the project.</div>\n <div>\n  </div>\n <div>\n TBN, Clinician</div>\n <div>\n The clinical officer will assist the study physician in performing clinical assessment carry out</div>\n <div>\n medical examinations including gynecological exams and prescribe medication as required to</div>\n <div>\n the participants. Recognize, monitor and report study adverse events and help in their</div>\n <div>\n management.</div>\n <div>\n  </div>\n <div>\n TBN, Nurses (4)</div>\n <div>\n The Nurses are responsible for assessing and caring for participants in the study. They also</div>\n <div>\n provide HIV, pre/post counseling and testing, contraception counseling and reinforce adherence.</div>\n <div>\n  </div>\n <div>\n Chief Admin Officer, Nairobi</div>\n <div>\n The Finance & Admin Manager is based in Nairobi. She is instrumental in terms of procurement</div>\n <div>\n of equipment and fast tracking of project payments to suppliers. She forwards letters to the</div>\n <div>\n headquarters and follow up payments on behalf of the Kisumu site. She also facilitates staff</div>\n <div>\n contracts, subcontracts and petty cash advances</div>\n</div>\n<p>\n  </p>\n
      • other_details_explanation<p>\n This is an investigator initiated trial that has a keen focus on the adolescent girls and young women at high risk of HIV acquisition in Kisumu.</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n None</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n None</p>\n
      • estimated_duration5 years
      • design_controlled_randomised
      • design_controlled_open
      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
      • design_controlled_cross_over
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      • design_controlled_specify
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      • design_controlled_other_medicinal
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      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKEMRI RCTP
      • single_site_physical_addressKEMRI CIS Building, Lumumba Sub-county Hospital, P.O. Box 614 Kisumu
      • single_site_contact_personDr Victor Omollo
      • single_site_telephone0799580808
      • multiple_sites_member_stateNo
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites
      • multi_country_list
      • data_monitoring_committeeNo
      • total_enrolment_per_site432
      • total_participants_worldwide432
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male0
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenYes
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameElizabeth
      • investigator1_middle_nameAnne
      • investigator1_family_nameBukusi
      • investigator1_qualificationMBChB, M.Med (ObGyn), MPH, PhD, PGD (Research Ethics), MBE (Research Ethics)
      • investigator1_professional_addressKEMRI RCTP, Lumumba Sub-county Hospital, P.O. Box 614 Kisumu
      • investigator1_telephone0733617503
      • investigator1_emailebukusi@rctp.or.ke
      • organisations_transferred_Yes
      • number_participants432
      • notification<p>\n None</p>\n
      • approval_date17-06-2025
      • submitted1
      • deleted0
      • deleted_date(null)
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      • date_submitted27-02-2025
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      • initial_date_submitted21-02-2025
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      • modified2025-06-30 15:09:12
      • created2024-12-11 08:22:40
      • total_sites1
      • ecitizen_invoice335512
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        • id1206
        • application_id1501
        • given_nameElizabeth
        • middle_nameAnne
        • family_nameBukusi
        • qualificationMBChB, M.Med (ObGyn), MPH, PhD, PGD (Research Ethics), MBE (Research Ethics)
        • professional_addressKEMRI RCTP, Lumumba Sub-county Hospital, P.O. Box 614 Kisumu
        • telephone0733617503
        • emailebukusi@rctp.or.ke
        • created2024-12-11 08:33:40
        • modified2025-02-27 16:43:45
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        • created2024-12-11 08:33:40
        • modified2025-02-27 16:43:45
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        • id796
        • application_id1501
        • sponsorThe General Hospital Corporation d/b/a Massachusetts General Hospital
        • sponsor_typeResearch Institution
        • contact_personKarla Ventura
        • address55 Fruit Street, Boston, MA, 02114-2696, USA
        • telephone_number(857) 282 1681
        • fax_number
        • cell_number(857) 282 1681
        • email_addressPHSOIIResearch@partners.org
        • created2024-12-11 08:33:40
        • modified2025-02-27 16:43:45
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    • 7CORE/Event/CakeEventManager.php
    • 8CORE/Core/Object.php
  • Routing(array)
    • 0CORE/Routing/Dispatcher.php
    • 1CORE/Routing/Filter/AssetDispatcher.php
    • 2CORE/Routing/DispatcherFilter.php
    • 3CORE/Routing/Filter/CacheDispatcher.php
    • 4CORE/Routing/Router.php
    • 5CORE/Routing/Route/CakeRoute.php
    • 6CORE/Routing/Route/PluginShortRoute.php
  • Utility(array)
    • 0CORE/Utility/Hash.php
    • 1CORE/Utility/Inflector.php
    • 2CORE/Utility/ObjectCollection.php
    • 3CORE/Utility/Debugger.php
    • 4CORE/Utility/String.php
    • 5CORE/Utility/ClassRegistry.php
    • 6CORE/Utility/Set.php
    • 7CORE/Utility/Sanitize.php
  • View(array)
    • 0CORE/View/HelperCollection.php
• app(array)
  • Behavior(array)
    • 0APP/Model/Behavior/SoftDeleteBehavior.php
  • Config(array)
    • 0APP/Config/core.php
    • 1APP/Config/bootstrap.php
    • 2APP/Config/routes.php
    • 3APP/Config/database.php
  • Controller(array)
    • 0APP/Controller/ApplicationsController.php
    • 1APP/Controller/AppController.php
  • Model(array)
    • 0APP/Model/AppModel.php
    • 1APP/Model/Application.php
    • 2APP/Model/User.php
    • 3APP/Model/TrialStatus.php
    • 4APP/Model/InvestigatorContact.php
    • 5APP/Model/Sponsor.php
    • 6APP/Model/SiteDetail.php
    • 7APP/Model/County.php
  • Other(array)
    • 0APP/webroot/index.php
• plugins(array)
  • CakePdf(array)
    • Config(array)
      • 0CakePdf/Config/bootstrap.php
      • 1CakePdf/Config/routes.php
  • CakeResque(array)
    • Config(array)
      • 0CakeResque/Config/bootstrap.php
    • Plugin(array)
      • 0CakeResque/Lib/CakeResque.php
      • 1CakeResque/vendor/kamisama/php-resque-ex/lib/Resque.php
      • 2CakeResque/vendor/kamisama/php-resque-ex/lib/Resque/Event.php
      • 3CakeResque/vendor/kamisama/php-resque-ex/lib/Resque/Exception.php
  • DebugKit(array)
    • Component(array)
      • 0DebugKit/Controller/Component/ToolbarComponent.php
    • Plugin(array)
      • 0DebugKit/Lib/DebugMemory.php
      • 1DebugKit/Lib/Panel/HistoryPanel.php
      • 2DebugKit/Lib/DebugPanel.php
      • 3DebugKit/Lib/Panel/SessionPanel.php
      • 4DebugKit/Lib/Panel/RequestPanel.php
      • 5DebugKit/Lib/Panel/SqlLogPanel.php
      • 6DebugKit/Lib/Panel/TimerPanel.php
      • 7DebugKit/Lib/Panel/LogPanel.php
      • 8DebugKit/Lib/Log/Engine/DebugKitLog.php
      • 9DebugKit/Lib/Panel/VariablesPanel.php
      • 10DebugKit/Lib/Panel/EnvironmentPanel.php
      • 11DebugKit/Lib/Panel/IncludePanel.php
      • 12DebugKit/Lib/DebugTimer.php
  • Media(array)
    • Config(array)
      • 0Media/Config/bootstrap.php
    • Plugin(array)
      • 0Media/Lib/mm/src/Mime/Type.php
      • 1Media/Lib/mm/src/Mime/Type/Magic/Adapter/Fileinfo.php
      • 2Media/Lib/mm/src/Mime/Type/Magic/Adapter.php
      • 3Media/Lib/mm/src/Mime/Type/Glob/Adapter/Memory.php
      • 4Media/Lib/mm/src/Mime/Type/Glob/Adapter.php
      • 5Media/Lib/mm/src/Media/Process.php
      • 6Media/Lib/mm/src/Media/Info.php
  • Search(array)
    • Component(array)
      • 0Search/Controller/Component/PrgComponent.php
    • Behavior(array)
      • 0Search/Model/Behavior/SearchableBehavior.php
  • Shim(array)
    • Config(array)
      • 0Shim/Config/bootstrap.php
  • Tools(array)
    • Config(array)
      • 0Tools/Config/bootstrap.php