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  • 1Recruiting
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• applications(array)
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    • Application(array)
      • id1392
      • user_id81
      • trial_status_id6
      • abstract_of_study<p>\n Sickle cell anaemia is common in Kenya where more than 4000 children are born with the condition each year. Based on positive data from clinical trials, an increasing number of patients in resource rich countries are now being treated with hydroxyurea. In the first phase of this trial, we conducted a multi-center phase I/II clinical trial to investigate the safety of hydroxyurea as a supportive treatment in children with sickle cell anaemia in Kenya, Angola, Uganda and the DRC. In total, 600 children aged 12 months - 10 years (150 in each site) were enrolled into the study. All were placed on hydroxyurea and monitored closely to investigate both safety and efficacy of the drug. We now propose a larger trial that will investigate long term exposure to hydroxyurea in both these same and a second set of cohorts with the aim of shaping national management policies for all children born with sickle cell anaemia in Africa.</p>\n<p>\n  </p>\n
      • study_title<address>\n <strong>Realizing Effectiveness Across Continents with Hydroxyurea (REACH):  A Phase I/II Prospective Trial of Hydroxyurea for Children and Young Adults with Sickle Cell Anaemia</strong></address>\n<p>\n  </p>\n
      • laymans_summary<p>\n <strong>Lay Title: </strong>Checking doses, long-term risks, and benefits of Hydroxyurea in treating children and young adults with Sickle Cell Anaemia in four countries in Africa.</p>\n<p>\n  </p>\n<p>\n <strong>What is the problem/background?</strong></p>\n<p>\n Sickle cell anaemia is common in Kenya, where more than 4000 children are born with the condition each year. Based on positive data from clinical trials, an increasing number of patients in resource rich countries are now being treated with hydroxyurea. In the first phase of REACH, we conducted a clinical trial to investigate the safety of hydroxyurea as a supportive treatment in children with sickle cell anaemia in Kenya, Angola, Uganda and the DRC. In total, 600 children (150 in each site) aged 12 months - 10 years were enrolled into the study. The Protocol number for the Kilifi trial was SSC Protocol # 2752.  All participants were placed on hydroxyurea and monitored closely to investigate both safety and efficacy of the drug. Though our initial results are encouraging, the first phase of the REACH trial did not include a group who were not taking hydroxyurea for comparison with those who take it with regard to a range of specific parameters. For this reason, we now propose to end the current REACH clinical trial and start a larger trial that will investigate long term exposure to hydroxyurea in both these same patients and in a new group of 75 children with confirmed SCA between 3.0 and 10.0 years at each site. Young adults who completed the first phase of this trial will also be asked to rejoin this second phase of the trial.</p>\n<p>\n  </p>\n<p>\n <strong>What questions are we trying to answer?</strong></p>\n<p>\n In the first phase of this trial, we conducted a multi-center phase I/II clinical trial to investigate the safety of hydroxyurea as a supportive treatment in children with sickle cell anaemia in Kenya, Angola, Uganda, and the DRC. We now propose a larger trial that will investigate long term risks and benefits to hydroxyurea in both these same and a second set of cohorts.</p>\n<p>\n  </p>\n<p>\n <strong>Where is the study taking place, how many people does it involve and how are they selected?</strong></p>\n<p>\n The study will take place at four sites throughout Africa. At the Kilifi site, participants will be recruited following written informed consent, from among children diagnosed with SCD at Kilifi County Referral Hospital. There will be a total of 225 participants in the Kilifi study - 150 from the original cohort and 75 new participants. The participants currently range in age from 10 to 18 years, with the exception of a few young adults who exited the study upon turning 18 years old in accordance with the previous protocol schedule. The latter will be invited to rejoin the current phase of the trial. All participants will be followed for four years.</p>\n<p>\n  </p>\n<p>\n <strong>What does the study involve for those who are in it?</strong></p>\n<p>\n All existing participants (original cohort) will undergo a reconsent process to confirm their willingness to continue to participate in the current phase of the trial. Participants from this cohort who choose not to participate in the current phase of the REACH trial will exit the study and will receive the standard of care available at the Kilifi County referral hospital instead. The standard care of sickle cell disease at Kilifi County Hospital includes the prevention of bacterial infections using penicillin among children <5 years, malaria prevention using proguanil, and folic acid supplementation to maintain good health. Hydroxyurea is also available through KCH and will be made available to former members of the REACH Trial.  </p>\n<p>\n For the new cohort, after obtaining consent, each participant will undergo monthly Eligibility Screening (ES) visits for three months, followed by Baseline Evaluation (BE) and hydroxyurea initiation that occur together at Month 0. </p>\n<p>\n During screening, a medical history, physical examination, and laboratory blood counts at the specified monthly study visits will be performed. Initially, they will attend follow-up visits once a month for 6 months before moving to three monthly visits.</p>\n<p>\n During each screening visit, three after starting hydroxyurea and annually approximately 5 to 10 mls of blood will be drawn at each visit.  Thereafter, at each monthly and quarterly visit less than 5 mls of blood will be drawn for safety laboratory tests. Every 6 months an additional 5 mls will be collected.  The maximum volume of blood collected at any visit will be 10mls.  Each child enrolled in the second cohort will undergo a special drug absorption blood test called PK to determine the starting dose of hydroxyurea at the 2^nd month of the screening visits.  For this PK study, each study participant will first receive a single 500mg capsule of hydroxyurea to swallow and then have 4 blood samples collected at approximately 15, 30, 60, and 180 minutes after the dose. These timed blood collections will be used to measure the hydroxyurea in blood to generate the optimal dose. These blood samples will be collected through separate finger-pricks (like when taking samples for malaria) using tinny tubes, with a total blood volume of <1mL (few drops) for the PK studies.</p>\n<p>\n  </p>\n<p>\n After the 3-month screening procedures, all participants in the second cohort will then commence hydroxyurea at this PK-determined dose and will remain in the study for up to four years of hydroxyurea treatment. </p>\n<p>\n For the existing cohort, hydroxyurea will be maintained at a maximum tolerated dose until the end of study participation. We will monitor this through blood counts taken every three months, with each visit requiring less than 1 ml of blood.</p>\n<p>\n <strong>For all participants,</strong> the following additional non-invasive study procedures will be done at screening and annually thereafter: </p>\n<ul>\n <li>\n A brain examination using an ultrasound machine <em>(TCD)</em> to determine the risk of having a stroke.</li>\n <li>\n An abdominal ultrasound scan to measure both the spleen and kidney sizes.</li>\n <li>\n An exam that uses light to measure how oxygen is supplied to the brain. This exam is called Near Infra-Red Spectroscopy (NIRS).</li>\n <li>\n X-rays of the wrist will be performed at the beginning and at end of the study to measure the growth and bone age.</li>\n <li>\n A urine sample for special tests to measure kidney function.</li>\n <li>\n A blood sample for DNA tests.</li>\n <li>\n Malaria blood tests.</li>\n</ul>\n<p>\n Sperm counts/motility will be an optional collection in adult males. Self-examination of growth and development parameters (tanner staging) such as the size of breasts, presence of pubic hair and size of testicles will be done. After 6 months, the first cohort will undergo regular monitoring, which includes medical history reviews, physical examinations, and blood count assessments (less than 1 ml of blood) during every scheduled visit, every three months. A urine sample will be collected for kidney function tests and checking for body chemicals in the urine once a year. For all female participants who have reached menarche, a urine pregnancy test will be done at every visit.</p>\n<p>\n Young adults who attain/attained 18 years, will also be reconsented to resume study participation.</p>\n<p>\n <strong>What are the benefits and risks/costs of the study for those involved?</strong></p>\n<p>\n We anticipate that, as has been the case in studies conducted in the USA and Europe, and in the first phase of the REACH trial, hydroxyurea will make a major positive impact on the lives of study participants. The drug and the monitoring for the drug will be made available free of charge throughout the course of the study. Children and their parents will be informed of the experimental nature of this study such that there should be no prior expectation that it would be safe or appropriate for hydroxyurea to be used long term before we can assess its impact through this trial. Although hydroxyurea is a very well tolerated medication with few significant risks the most significant side effect is mild bone marrow suppression. These are reversible by temporary discontinuation of the medication or dose adjustments.  Given the burden of traveling to the clinic, we will provide an out-of-pocket allowance of 500 Kenyan shillings and reimburse travel expenses during follow-up visits, to help cover the costs of travel  and  out of pocket expenses. The amounts will be based on the most current standard ‘KEMRI-Wellcome Trust Research Programme Guidelines for Study Benefits and Out of Pocket Allowances. If the participant falls sick, we will only reimburse the cost of transport incurred.</p>\n<p>\n  </p>\n<p>\n <strong>How will the study benefit society?</strong></p>\n<p>\n We anticipate that this study will provide key information regarding the use of hydroxyurea in children with SCA in Africa and will provide data to feed into the design of further trials that may affect policy.</p>\n<p>\n  </p>\n<p>\n <strong>When does the study start and finish?</strong></p>\n<p>\n The study will start once ethical approval is obtained and is expected to end in about four years.      At that point, all patients will go back to the standard of care and treatment options provided by the Kilifi County and Referral Hospital.</p>\n<p>\n  </p>\n
      • short_titleREACH 2
      • protocol_noECCT/24/04/06
      • version_no1.1
      • date_of_protocol20-03-2024
      • study_drugHydroxyurea
      • disease_conditionSickle cell disease
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameHydrea, hydrine or droxia
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressCGMRCCSC@kemri-wellcome.org
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_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_applicantgeorge Mochamah
      • declaration_date122-04-2024
      • declaration_principal_investigatorThomas Williams
      • declaration_date222-04-2024
      • placebo_presentNo
      • study_objectives<div>\n 6.2. Primary objective</div>\n<div>\n To conduct an early phase clinical trial to assess long-term risks and benefits of hydroxyurea therapy at Maximum Tolerated Dose on morbidity and mortality, organ damage, growth and development, and the emergence of clonal haematopoiesis for the management of children living with SCA in the African context.</div>\n<div>\n  </div>\n<div>\n <div>\n 6.3. Secondary objective(s)</div>\n <div>\n To evaluate the benefits of hydroxyurea therapy, using both laboratory (e.g., fetal haemoglobin, haemoglobin, white blood cell count) and clinical parameters (e.g., pain, hospitalisation, growth parameters).</div>\n <div>\n To explore the pharmacokinetic and genetic basis for any observed inter-patient variability in the clinical or laboratory response to hydroxyurea.</div>\n <div>\n To investigate the effects of hydroxyurea dose-escalation on laboratory and clinical parameters.</div>\n <div>\n To assess long-term risks and benefits of hydroxyurea therapy at Maximum Tolerated Dose on morbidity and mortality, organ damage, growth and development, and emergence of clonal haematopoiesis.</div>\n <div>\n <div>\n To investigate the reduction of clinical malaria events on hydroxyurea.</div>\n <div>\n To test streamlined dosing strategies using personalized PK-guided methodology with sparse blood sampling to generate individualized first-dose PK curves for the second cohort before commencing treatment. </div>\n </div>\n</div>\n<p>\n  </p>\n
      • principal_inclusion_criteria<div>\n All members of the original REACH trial cohort will be reconsented into the current trial in addition to children recruited to a second cohort that meet the following criteria:</div>\n<div>\n 1. Paediatric patients with documented sickle cell anaemia (typically HbSS supported by haemoglobin electrophoresis, complete blood count, and peripheral blood smear).</div>\n<div>\n 2. Age range 3.0-10.0 years for the newly enrolled cohort; or previous enrollment into the first phase of the REACH trial ((KEMRI SSC Protocol # 2752).</div>\n<div>\n 3. Weight at least 10.0kg at the time of enrollment.</div>\n<div>\n 4. Parent or guardian willing and able to provide written informed consent, with child's verbal assent as per local IRB/Ethics Board requirements.</div>\n<div>\n 5. Willingness to comply with all study-related treatments, evaluations, and follow-up.</div>\n<div>\n 6. Written informed consent for adult patients and mature minors to continue participation. They will be rescreened for pregnancy and HIV at re-entry.</div>\n
      • principal_exclusion_criteria<div>\n 1. Any known medical condition that would make participation ill-advised (e.g., an acute or chronic infectious disease, HIV, or malignancy).</div>\n<div>\n 2. Acute or chronic severe malnutrition determined by impaired growth parameters as defined by WHO (weight for length/height or height for age >3 z-scores below the median WHO growth standards.</div>\n<div>\n <div>\n 3. Pre-existing severe haematological toxicity (temporary exclusion: potential participants can be re-screened on resolution) defined as follows:</div>\n <div>\n a. Anaemia: Hb <4.0 g/dL</div>\n <div>\n b. Anaemia: Hb <6.0 g/dL with ARC <100 x 109/L</div>\n <div>\n c. Reticulocytopaenia: ARC <80 x 109/L with Hb <7.0 g/dL</div>\n <div>\n d. Thrombocytopaenia: Platelets <80 x 109/L</div>\n <div>\n e. Neutropaenia: ANC <1.0 x 109/L</div>\n <div>\n 4. Blood transfusion within 60 days before enrollment (temporary exclusion)</div>\n <div>\n 5. In the new cohort, children should be hydroxyurea naïve, without any prior treatment exposure.</div>\n</div>\n<p>\n  </p>\n
      • primary_end_points<div>\n Safety endpoints:</div>\n<div>\n 1. The proportion and number of participants with pre-defined dose-limiting haematological laboratory toxicities, including their type and severity.</div>\n<div>\n 2. The number and type of serious bacterial and malarial infections.</div>\n<div>\n Feasibility endpoints</div>\n<div>\n 3. The proportion of PK studies that are successfully completed and provide a calculated daily dose of hydroxyurea between 15-35 mg/kg/day.</div>\n<div>\n Efficacy endpoints</div>\n<div>\n 4. Laboratory measures of efficacy (e.g., fetal haemoglobin, haemoglobin, ARC, WBC, ANC, and bilirubin).</div>\n<div>\n 5. Clinical complications will be captured, including pain, hospitalizations, and other sickle-related events.</div>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic1
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<div>\n The initial phase of the REACH trial has been ongoing since 2013 with the following  staff: </div>\n<div>\n  </div>\n<div>\n Staff: </div>\n<div>\n <div style=\"margin-left:.38in;\">\n •Site PI: Dr. Tom Williams, Med doctor</div>\n <div style=\"margin-left:.38in;\">\n •Study Coordinator: George Mochamah, Ms clinical trials</div>\n <div style=\"margin-left:.38in;\">\n •Study Clinical Officers: Patric Mpwana and Mejuma Mugosi </div>\n <div style=\"margin-left:.38in;\">\n •TCD Examiners: Metrine Tendwa, Jacob Goligo</div>\n <div style=\"margin-left:.38in;\">\n •Phlebotomy: Masudi Nzai, Maureen Sikubali </div>\n <div style=\"margin-left:.38in;\">\n •Data Team: Gideon Nyutu (Data Manager), 3 data Clerks--Ruth Mwarabu, Ruth Sidi, Alphonce Kazungu </div>\n <div style=\"margin-left:.38in;\">\n •Lab Team: Dr. Alex Macharia Phd, Dr. Sophie Uyoga, Johnstone Makale (lab Manager, BSC), 2 lab tech--Brian Tawa, Patric Ombati</div>\n <div style=\"margin-left:.38in;\">\n •Pharmacy: Dr. Jimmy Shangala</div>\n <div style=\"margin-left:.38in;\">\n •Trial monitor: Siti Ndaa-Onsite, Teresa Latham-remote monitor  </div>\n</div>\n<p>\n Available onsite:</p>\n<p>\n 1. Radiology: Kilifi Country Referal Hospital</p>\n<p>\n 2. Labortatory: Collection, processing and storage of biological samples will be done at the Clinical trials Lab, KEMRI </p>\n<p>\n 3. Site Pharmacy: IP will be stored and dispensed at the KEMRI Pharmacy </p>\n<p>\n  </p>\n
      • other_details_explanation<p>\n Based on positive data from clinical trials, an increasing number of patients in resource rich countries (including the US, where the sponsor is based) are now being treated with hydroxyurea. In the first phase of REACH, we conducted a clinical trial to investigate the safety of hydroxyurea as a supportive treatment in children with sickle cell anaemia in Kenya, Angola, Uganda and the DRC. Though our initial results are encouraging, the first phase of the REACH trial did not include a group who were not taking hydroxyurea for comparison with those who take it.</p>\n<p>\n  </p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n 1. Mbale NDA, Uganda</p>\n<p>\n Date of approvals: 4/10/2023,</p>\n<p>\n Number of sites: 1</p>\n<p>\n 2. CEMS Angola</p>\n<p>\n Date of approvals: 19 July 2023</p>\n<p>\n Number of sites: 1</p>\n<p>\n 3. CEFA, DRC</p>\n<p>\n Date of approvals: 17 October 2023</p>\n<p>\n Number of sites: 1</p>\n<p>\n  </p>\n
      • other_details_regulatory_rejected<p>\n n/a</p>\n
      • other_details_regulatory_halted<p>\n n/a</p>\n
      • estimated_duration4 years
      • design_controlled_randomised
      • design_controlled_open
      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
      • design_controlled_cross_over
      • design_controlled_other
      • design_controlled_specify
      • design_controlled_comparator
      • design_controlled_other_medicinal
      • design_controlled_placebo
      • design_controlled_medicinal_other
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKilifi County Referal Hospital
      • single_site_physical_address230-80108
      • single_site_contact_personGeorge Mochamah
      • single_site_telephone0702999037
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states4
      • number_of_sites
      • multi_country_listUganda, Angola, DRC Congo
      • data_monitoring_committeeYes
      • total_enrolment_per_site225
      • total_participants_worldwide900
      • 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_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameThomas
      • investigator1_middle_name
      • investigator1_family_nameWilliams
      • investigator1_qualificationMedical doctor
      • investigator1_professional_addressKEMRI Wellcome Trust, 230, 80-108, Kilifi
      • investigator1_telephone0702909937 or 0742105040
      • investigator1_emailtwilliams@kemri-wellcome.org
      • organisations_transferred_No
      • number_participants225
      • notification<p>\n NO</p>\n
      • approval_date28-06-2024
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted22-04-2024
      • is_child0
      • unsubmitted1
      • initial_date_submitted22-04-2024
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonReviewer comments have been addressed.
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-02-15 12:29:43
      • created2024-04-03 16:26:09
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id1052
        • application_id1392
        • given_nameThomas
        • middle_name
        • family_nameWilliams
        • qualificationMedical doctor
        • professional_addressKEMRI Wellcome Trust, 230, 80-108, Kilifi
        • telephone0702909937 or 0742105040
        • emailtwilliams@kemri-wellcome.org
        • created2024-04-03 16:36:57
        • modified2024-11-18 12:45:46
      • 1(array)
        • id1053
        • application_id1392
        • given_nameRussell
        • middle_name
        • family_name Ware
        • qualificationMedical doctor
        • professional_addressCincinnati Children\'s Hospital Medical Center, USA.
        • telephone1- (513) 803-4597
        • emailRussell.ware@cchmc.org
        • created2024-04-03 17:32:37
        • modified2024-11-18 12:45:46
    • SiteDetail(array)
      • 0(array)
        • id1691
        • application_id1392
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2024-04-03 16:36:57
        • modified2024-11-18 12:45:46
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id736
        • application_id1392
        • sponsorCincinnati Children\'s Hospital Medical Center
        • sponsor_typeResearch Institution
        • contact_personRussell Ware
        • addressUnited States
        • telephone_number1-513-636-4200
        • fax_number
        • cell_number1- (513) 803-4597
        • email_addressRussell.ware@cchmc.org
        • created2024-04-03 16:36:57
        • modified2024-11-18 12:45:46
  • 1(array)
    • Application(array)
      • id554
      • user_id640
      • trial_status_id1
      • abstract_of_study<p>\n This is a Phase II, open label, single arm trial to evaluate the pharmacokinetics, safety, tolerability and efficacy of rilpivirine (RPV, previously known as TMC278) 25 mg once daily (q.d.) or an adjusted dose of RPV (q.d.) in combination with an investigator-selected background regimen containing 2 nucleoside/nucleotide reverse transcriptase inhibitors</p>\n<p>\n (N[t]RTIs) (zidovudine [AZT], abacavir [ABC], or tenofovir disoproxil fumarate [TDF] in combination with lamivudine [3TC] or emtricitabine [FTC], whichever is approved and marketed or considered local standard of care) in antiretroviral (ARV) treatment-naïve adolescents and children aged ≥ 6 to <18 years.</p>\n<p>\n The trial will consist of a screening period of maximum 8 weeks, an initial treatment period of 48 weeks, and a post Week 48 treatment extension period of 4 years. Subjects who withdraw from the trial on or before the Week 48 visit or subjects with ongoing (serious) adverse events ([S]AEs) at the last on-treatment visit in the extension, will be seen for a follow-up visit 4 weeks later. Recruitment and analyses of the initial 48-week treatment period will be structured into 2 age cohorts: Cohort 1, adolescents ≥12 to <18 years of age; Cohort 2, children ≥6 to <12 years of age.</p>\n
      • study_title<div>\n <strong>A Phase II, open label, single arm trial to evaluate the pharmacokinetics, safety, tolerability, and antiviral activity of rilpivirine (TMC278) in antiretroviral-naïve HIV-1 infected adolescents and children aged ≥6 to <18 years</strong></div>\n
      • laymans_summary(null)
      • short_titlePAINT Study
      • protocol_noECCT/16/10/02
      • version_noClinical Trial Protocol Amendment 7.0
      • date_of_protocol18-12-2015
      • study_drugrilpivirine hydrochloride
      • 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_nameEDURANT®
      • product_type_medical_device_name
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressnkisengese@yahoo.co.uk
      • 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_countries1
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd(null)
      • applicant_prev_data(null)
      • applicant_stability_data(null)
      • applicant_analysis_cert(null)
      • applicant_pictorial_sample(null)
      • applicant_gcp_training(null)
      • applicant_dsmb_charter(null)
      • applicant_detailed_budget(null)
      • applicant_indemnity_pi(null)
      • applicant_practice_license(null)
      • applicant_registration_ctr(null)
      • applicant_pan_african(null)
      • applicant_hard_copies(null)
      • applicant_signed_checklist(null)
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantNicodemus Ivuti Kisengese
      • declaration_date126-10-2016
      • declaration_principal_investigatorProfessor Walter Jaoko, KAVI Institute of Clinical Research, College of Health Sciences, University of Nairobi
      • declaration_date226-10-2016
      • placebo_presentNo
      • study_objectives(null)
      • principal_inclusion_criteria<div>\n Subjects who meet all of the following criteria are eligible for this trial:</div>\n<ol>\n <li>\n Cohort 1: Boys or girls, aged ≥12 to <18 years. Cohort 2: Boys or girls, aged ≥6 to <12 years.</li>\n <li>\n Cohort 1: Subject’s weight is ≥32 kg.Cohort 2: Subject’s weight is ≥17 kg.</li>\n <li>\n Subject with documented chronic HIV-1 infection.</li>\n <li>\n Subject willing and able to give consent. In case the subject’s age is below the cut-off age for consent (according to local regulations), their parent/caregiver should be able and willing to give consent, and the subject will be informed about the trial and asked to give positive assent.</li>\n <li>\n Subject can comply with the protocol requirements.</li>\n <li>\n Subject has, prior to screening, never been treated with a therapeutic HIV vaccine or an HIV drug with the exception of a single dose of NVP (Cohort 1) or up to 6 weeks of AZT use (Cohort 2) to prevent MTCT.</li>\n <li>\n HIV-1 plasma viral load at screening ≥500 HIV-1 RNA copies/mL but ≤100,000 HIV-1 RNA copies/mL (assayed by RNA polymerase chain reaction [PCR] standard specimen procedure).  <u>Note</u>: For Cohort 1 Part 1a, subjects with a screening viral load ≥5,000 HIV-1 RNA copies/mL were allowed.<u>  Note:</u> To reassess eligibility, retesting of a screening value that leads to exclusion will be allowed only once during the screening period using an unscheduled visit.</li>\n <li>\n In the judgment of the investigator, it is appropriate to initiate ART based on the subject’s medical condition and taking into account guidelines for the treatment of HIV-1 infection in children of this age group. <u>Note:</u> Most current treatment guidelines recommend considering initiation of ART when CD4+ cell counts are <350 cells/mm³. However, clinical situations may warrant initiating ART with CD4+ cell counts >350 cells/mm³. An example of such situations would include rapidly declining CD4+ cell counts over time.</li>\n <li>\n Results from the screening HIV-1 genotype demonstrate sensitivity to the selected N(t)RTIs.</li>\n <li>\n Subject is able to swallow the RPV tablet as a whole (since the tablet cannot be chewed, broken, or crushed), except when the appropriate RPV dose for the subjects is determined to be <25 mg (only applicable for subjects enrolled after it has been decided that a lower RPV dose is appropriate for subjects up to a certain e.g., age or body weight). In this case an age-appropriate formulation other than the tablet formulation will be provided.</li>\n <li>\n The subject agrees (or their parents/caregivers agree, in case the subject's age is below the cut-off age for consent according to local regulations, in which case the subject is informed and asked to give positive assent) not to start ART before the baseline visit.</li>\n <li>\n General medical condition, in the investigator’s opinion, does not interfere with the assessments and the completion of the trial.</li>\n</ol>\n
      • principal_exclusion_criteria<div>\n Any previous use of ARVs, with the exception of a single dose of NVP (Cohort 1) or up to 6 weeks of AZT use (Cohort 2) to prevent MTCT.</div>\n<div>\n Note: Cohort 1: Subjects who were infected by MTCT are allowed to enter, provided the mother was ARV treatment-naïve at the time of delivery with the exception of</div>\n<div>\n NVP for no more than 3 days.</div>\n
      • primary_end_points<div>\n <span style=\"font-size:14px;\"><strong>Efficacy</strong></span></div>\n<div>\n  </div>\n<div>\n <u>Plasma viral load</u></div>\n<div>\n Throughout the analysis, plasma viral load will be log10 transformed. Plasma viral load reported as <50 HIV-1 RNA copies/mL will be scored as 49 HIV-1 RNA copies/mL, if not otherwise mentioned.</div>\n<div>\n  </div>\n<div>\n <u>Parameters for Part 1:</u></div>\n<ul>\n <li>\n The change in plasma viral load from baseline at Week 2 (Cohort 1 Part 1a, Cohort 2)/Week 4 (Cohort 1 Part 1b).</li>\n</ul>\n<div>\n  </div>\n<div>\n <u>Parameters for Part 2:</u></div>\n<ul>\n <li>\n Proportion of subjects with a viral load <50 and <400 HIV-1 RNA copies/mL at all time points, and time to achieve these;</li>\n <li>\n Proportion of subjects with a decrease from baseline in plasma viral load of 1.0 log10 at Week 12</li>\n <li>\n Change from baseline in log10 viral load;</li>\n <li>\n Time to loss of response.</li>\n</ul>\n<div>\n <span style=\"font-size:14px;\"><strong>Immunology</strong></span></div>\n<div>\n  </div>\n<div>\n <u>Immunology parameter:</u></div>\n<ul>\n <li>\n The change from baseline in CD4+ cell count (absolute and %).</li>\n</ul>\n<div>\n The analysis will be based on observed values and on imputed values using NC = F, i.e., subjects who prematurely discontinued the trial and will have their CD4+ cell count following discontinuation imputed with the baseline value (resulting in a change of 0), and will have LOCF for intermediate missing values.</div>\n<div>\n  </div>\n<div>\n Raw data and changes versus baseline will be descriptively and graphically presented.</div>\n<div>\n  </div>\n<div>\n <u>Resistance Determinations</u></div>\n<div>\n The results of the viral pheno- and genotypes will be evaluated by the Protocol Virologist. Relevant changes in the viral phenotype and genotype will be tabulated and described, particularly for subjects with virologic failure. These changes in viral phenotype and genotype will not be regarded as AEs.</div>\n<div>\n  </div>\n<div>\n Furthermore, phenotypic resistance data, including the fold change in EC50 values, of RPV and other ARVs will be described.</div>\n<div>\n  </div>\n<div>\n <div>\n  </div>\n <div>\n <strong>Safety</strong></div>\n <div>\n  </div>\n <div>\n <u>Adverse Events/HIV-Related Events</u></div>\n <div>\n Type (system organ class, preferred term) and incidence of all AEs and HIV-related events, between the signing of ICF and last trial-related activity, will be tabulated per trial period (i.e., screening, the treatment period and follow-up). Separate tabulations will be made by severity, drug relationship, and outcome of the AEs. Separate tabulations and listings will be made for those subjects who have discontinued the trial for an AE/HIV-related event, or who experienced a grade 3r 4 AE, or an SAE.</div>\n</div>\n<div>\n  </div>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety0
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p>\n This study will be conducted at Kenyatta National Hospital Comprehensive Care Centre (CCC) and at KAVI-Institute of Clinical Research at the University of Nairobi. The two are about 500 metres apart. All the clinical and laboratory work will be conducted at the CCC, while data entry, study monitoring, financial oversight and overall clinical trial management will be provided by KAVI-Institute of Clinical Research. KAVI has a Data Entry Centre with 5 desktop computers with high speed internet connectivity with a personnel consisting of a Data Manager, and 4 Data Entry Clerks, and a well established financial management system managed by a Finance Manager, a Deputy Finance Manager and an Accounts Assistant. The clinical trial monitoring will be performed by KAVI-ICR Internal Monitor. The Principle Investigator will provide the oversee the overall clinical trials management of the trial.</p>\n
      • other_details_explanation<p>\n The trial is conducted in five countries across Africa, USA and Asia. This is to collect more data across different geographic regions.</p>\n
      • other_details_regulatory_notapproved<p>\n There is no regulatory authority that has not granted approval to this study</p>\n<p>\n This stduy has received full ethical approval from Kenyatta National Hospital Ethics Review Committee.</p>\n
      • other_details_regulatory_approved<p>\n Uganda National Council for Science and Technology  has approved 2 sites</p>\n<p>\n Thailand Ministry of Health has approved one site </p>\n<p>\n South Africa Medicines Control Council has approved 3 sites </p>\n<p>\n United States of America has approved 2 sites</p>\n<p>\n India drug regulatory authority has approved one site </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
      • design_controlled_other
      • design_controlled_specify
      • design_controlled_comparator
      • design_controlled_other_medicinal
      • design_controlled_placebo
      • design_controlled_medicinal_other
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states5
      • number_of_sites2
      • multi_country_listUSA\nThailand\nKenya\nUganda\nSouth Africa
      • data_monitoring_committeeYes
      • total_enrolment_per_site6-12
      • total_participants_worldwide56
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenYes
      • population_adolescentYes
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsNo
      • subjects_vulnerable_populationsNo
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameProfessor Walter
      • investigator1_middle_name
      • investigator1_family_nameJaoko
      • investigator1_qualificationMBChB, MTropMed, PhD, PGD (Health Research Ethics)
      • investigator1_professional_addressDepartment of Medical Microbiology, University of Nairobi; P.O Box 19676 Nairobi-00202, Kenya
      • investigator1_telephoneTel: +254 727 555 254
      • investigator1_emailWJaoko@kaviuon.org
      • organisations_transferred_No
      • number_participants6-12
      • notification<p>\n The follwoing dpcuments have been provided as hard copies because they are size is more than allowable to be attached on this portal. </p>\n<ol>\n <li>\n Investigational Material Packaging Agreement version 28 dated 26 May 2016</li>\n <li>\n Rilpivirine Hydrochloride Safety Data Sheet version 1.92, 05 July 2016</li>\n <li>\n Rilpivirine Hydrochloride dispersible tablets 2.5 mg Certificate of Analysis signed 07 September 2015</li>\n <li>\n Rilpivirine (TMC278) granules 2.5mg/gram Certificate of Analysis, approved 30 December 2013</li>\n <li>\n Study Adherence Questionnaire Care Givers addendum 8, version 3.0, 01 Dec 2015 - Swahili version Kenya dated 18 Dec 2015</li>\n <li>\n Study Adherence Questionnaire Care Givers, addendum 8, English version 3.0, 01 December 2015</li>\n <li>\n Study Adherence Questionnaire Child version 2.0 23 May 2012 - Swahili Final version dated 18 Dec 2015</li>\n <li>\n Study Adherence Questionnaire Subject English version 2.0 23 May 2012</li>\n <li>\n Child Trial Map (Swahili version 1.1 08 OCT 2015)</li>\n <li>\n  Child Trial Map (English  version 1.0 08 OCT 2015)</li>\n <li>\n Patient and Parent Information Booklet Swahili version 5.0 08 OCT 2015</li>\n <li>\n Patient and Parent Information Booklet English version 5.0 08 OCT 2015</li>\n <li>\n TMC278TiDP38C213-SWA21 INT-7 Patient and Parent Information Booklet Swahili Version 1.0, 18DEC2015</li>\n <li>\n TMC278TiDP38C213-SWA21 INT-7 Patient and Parent Information Booklet English Version 1.0, 18DEC2015</li>\n <li>\n Medication Diary ( Swahili version 4.0 08 OCT 2015)</li>\n <li>\n Medication Diary ( English  version 4.0 08 OCT 2015)</li>\n <li>\n Taste Test English Version  1.0, 10 Sep 2015</li>\n <li>\n Taste Test Swahili Version  1.0, 23 Nov 2015</li>\n <li>\n Appointment Card English Version 1.0, 09-Sep-2015</li>\n <li>\n Visit completion certificates English version 1.0, 09 Sep 2015</li>\n <li>\n  Birthday Cards English V1.0, 09-Sep-2015</li>\n <li>\n  Subject Emergency Card version 1.0 06 Jul 2011</li>\n <li>\n Picture of Crayons (Swahili version)</li>\n <li>\n Picture of Crayons (English version)</li>\n <li>\n Instructions on how to prepare the study medication at home (<em>Rilpivirine dispersible tablet</em>) version 1.0 dated 10 May 2016 (English and Swahili)</li>\n</ol>\n
      • approval_date13-02-2017
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted27-10-2016
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2020-09-23 08:46:56
      • created2016-09-05 10:54:23
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id356
        • application_id554
        • given_nameProfessor Walter
        • middle_name
        • family_nameJaoko
        • qualificationMBChB, MTropMed, PhD, PGD (Health Research Ethics)
        • professional_addressDepartment of Medical Microbiology, University of Nairobi; P.O Box 19676 Nairobi-00202, Kenya
        • telephoneTel: +254 727 555 254
        • emailWJaoko@kaviuon.org
        • created2016-09-05 11:12:41
        • modified2016-10-27 10:54:51
    • SiteDetail(array)
      • 0(array)
        • id431
        • application_id554
        • county_id47
        • site_nameKAVI Institute of Clinical Research
        • physical_addressDepartment of Medical Microbiology,College of Health Sciences University of Nairobi
        • contact_detailsP.O Box 19676 Nairobi-00202, Kenya Tel: +254 727 555 254
        • contact_personProfessor Walter Jaoko
        • site_capacity(null)
        • misc(null)
        • created2016-09-05 11:12:41
        • modified2016-10-27 10:54:51
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 1(array)
        • id444
        • application_id554
        • county_id35
        • site_nameKenya Medical Research Institute/Walter Reed Project, HIV Program
        • physical_addressHospital Road, Kericho, Kenya
        • contact_detailsP.O Box 1357 - 20200, Hospital Road, Kericho, Kenya Tel: +254 52 30686/+254 52 30388 Mobile: +254 729110124 Fax: +254 52 30662/+254 52 30546
        • contact_personDr. Isaac Tsikhutsu, MBChB, MMED, FPCCM
        • site_capacity(null)
        • misc(null)
        • created2016-10-27 07:08:06
        • modified2016-10-27 10:54:51
        • County(array)
          • id35
          • county_nameKericho
          • created2012-06-15 10:26:16
          • modified2012-06-15 10:26:16
    • Sponsor(array)
      • 0(array)
        • id284
        • application_id554
        • sponsorJanssen Research and Development
        • sponsor_type(null)
        • contact_personLinda Roach
        • addressBuilding 6, Country Club Estates 21 Woodlands Drive Woodmead, 2191, South Africa.
        • telephone_number+27 11 518 7173
        • fax_number+27 11 518 7102/3
        • cell_number+27 71 622 2242 .
        • email_addresslroach@its.jnj.com
        • created2016-09-05 11:12:41
        • modified2016-10-27 10:54:51
  • 2(array)
    • Application(array)
      • id1029
      • user_id622
      • trial_status_id7
      • abstract_of_study<p>\n <strong>PROTOCOL TITLE: A 3-ARM, RANDOMIZED, BLINDED, ACTIVE-CONTROLLED, PHASE II STUDY OF RO7121661, A PD1-TIM3 BISPECIFIC ANTIBODY AND RO7247669, A PD1-LAG3 BISPECIFIC ANTIBODY, COMPARED WITH NIVOLUMAB IN PARTICIPANTS WITH ADVANCED OR METASTATIC SQUAMOUS CELL CARCINOMA OF THE ESOPHAGUS</strong></p>\n<p>\n  </p>\n<p>\n <strong>PROTOCOL NUMBER: </strong>BP42772</p>\n<p>\n <strong>TEST PRODUCT: </strong>RO7121661, RO7247669, Nivolumab</p>\n<p>\n <strong>PHASE: </strong>II</p>\n<p>\n <strong>RATIONALE</strong></p>\n<p>\n Cancer remains a major cause of death worldwide despite several new agents providing survival</p>\n<p>\n benefits to patients. Many cancer indications have a poor prognosis and the management of</p>\n<p>\n most advanced solid tumors remains challenging because of the high rate of tumor recurrence or</p>\n<p>\n the development of distant metastases.</p>\n<p>\n Despite the effectiveness of PD1/L1 checkpoint inhibitor (CPI) therapy in various tumor types</p>\n<p>\n including esophageal squamous-cell carcinoma (ESCC), additional treatment options targeting</p>\n<p>\n immune checkpoints are needed, because the majority of patients eventually progress after an</p>\n<p>\n initial response or fail to respond to PD1/L1 checkpoint blockade.</p>\n<p>\n By targeting both PD1 and TIM3 or LAG3 on dysfunctional tumor-specific T lymphocytes, the</p>\n<p>\n PD1-TIM3 and PD1-LAG3 bispecific antibodies aim to restore an effective anti-tumor</p>\n<p>\n immune-response and provide survival benefit to more patients with cancer than currently</p>\n<p>\n available agents do. PDL1 expression in ESCC ranges from 15% to 83% in tumor cells and from</p>\n<p>\n 13% to 31% in tumor-infiltrated immune cells. Studies with nivolumab, pembrolizumab, and other</p>\n<p>\n PD1 inhibitors demonstrated benefit over chemotherapy in the second-line (2L) ESCC</p>\n<p>\n population leading to market authorizations in that setting (e.g. in the U.S., EU, Japan, South</p>\n<p>\n Korea, and other jurisdictions). Both TIM3 and LAG3 have been shown to be expressed on</p>\n<p>\n tumor-infiltrating lymphocytes in patients with ESCC. RO7121661 and RO7247669 may</p>\n<p>\n therefore have the potential to be a therapeutic option for patients with ESCC.</p>\n<p>\n The purpose of this study is to assess the efficacy of RO7121661 and RO7247669 compared</p>\n<p>\n with nivolumab to address a significant unmet medical need in patients with unresectable</p>\n<p>\n advanced or recurrent ESCC who are refractory or intolerant to one prior line of chemotherapy.</p>\n<p>\n <strong>OBJECTIVES AND ENDPOINTS</strong></p>\n<p>\n <strong>Primary Objective:</strong> To evaluate the efficacy of RO7121661 and RO7247669 compared with nivolumab.</p>\n<p>\n <strong>Primary Endpoint: </strong>OS, defined as the time from randomization to death from any cause</p>\n<p>\n Secondary Objectives:</p>\n<ul>\n <li>\n To evaluate the safety and tolerability of RO7121661and RO7247669 compared with nivolumab.</li>\n <li>\n To evaluate the efficacy of RO7121661 and RO7247669 compared with nivolumab.</li>\n <li>\n To investigate the pharmacokinetics (PK) of RO7121661, RO7247669, and nivolumab.</li>\n <li>\n To evaluate the immune response after administration of RO7121661, RO7247669, and nivolumab.</li>\n <li>\n To assess treatment-induced pharmacodynamic changes (PD Biomarkers) in peripheral blood and tumor microenvironment</li>\n <li>\n To assess baseline characteristics in the tumor microenvironment as predictive biomarkers of response</li>\n</ul>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n <strong>OVERALL DESIGN</strong></p>\n<p>\n <strong>Study Design</strong></p>\n<p>\n This is a Phase II, randomized, blinded, active-controlled, global, multicenter study designed to evaluate the safety and efficacy of RO7121661 and RO7247669, compared with nivolumab in patients with advanced or metastatic ESCC refractory or intolerant to fluoropyrimidine- or taxane- and platinum-based regimen. The study will enroll approximately 255 participants aged ³ 18 years with Eastern Cooperative Oncology Group Performance Status of 0 or 1. Participants will be randomized in a 1:1:1 ratio to receive RO7121661, RO7247669, or nivolumab. Participants will be stratified by previous (neo-)adjuvant chemotherapy, chemoradiotherapy or definitive chemoradiotherapy in curative intention (yes versus no), expression of PDL1 (< 1% versus ³ 1%), and geographic region of the enrolling site (Asia versus Rest of World). Randomization should occur on Day -1 or Day 1after the patient’s eligibility (i.e., inclusion/exclusion criteria) has been confirmed. In the experimental arms, participants will receive RO7121661 or RO7247669 at a fixed dose of 2100 mg administered by IV infusion every 2 weeks (Q2W) on Day 1 of each 14-day cycle. In the active comparator arm, participants will receive nivolumab at a fixed dose of 240 mg administered by IV infusion Q2W on Day 1 of each 14-day cycle. Treatment may be continued as long as participants are experiencing clinical benefit, as assessed by the Investigator, in the absence of unacceptable toxicity or symptomatic deterioration attributed to disease progression after an integrated assessment of radiographic data, biopsy results (if available), and clinical status for a maximum of 24 months. Participants who meet the criteria for disease progression per RECIST v1.1 will be permitted to continue study treatment if they meet all criteria for treatment beyond progression.</p>\n<p>\n Participants will undergo tumor assessments at screening and every 6 weeks (± 7 days) for</p>\n<p>\n 48 weeks following Day 1 of Cycle 1 (D1C1), regardless of treatment delays. After completion of the Week 48 tumor assessment, tumor assessments will be required every 12 weeks (± 7 days) regardless of treatment delays until radiographic disease progression per RECIST v1.1, initiation of a new anti-cancer therapy, withdrawal of consent, death, or study termination by the Sponsor, whichever occurs first. Thus, tumor assessments are to continue according to the schedule in participants who discontinue treatment for reasons other than disease progression or loss of clinical benefit. For participants who continue treatment after progressive disease, tumor assessments are to continue according to schedule until study treatment is discontinued. At the Investigator’s discretion, tumor assessments may be repeated at any time if progressive disease is suspected. Response will be assessed according to RECIST v1.1 and modified RECIST v1.1 for immune-based therapeutics (iRECIST). Objective response at a single timepoint will be determined by the Investigator according to RECIST v1.1. Objective response per iRECIST will be calculated programmatically by the Sponsor based on Investigator assessments of individual lesions at each specified timepoint. All primary imaging data used for tumor assessments may</p>\n<p>\n be collected by the Sponsor; centralized, blinded independent review of response endpoints by an independent review facility may be conducted. The primary comparison of interest are the hazard ratio of OS of each experimental arm compared to nivolumab, assessing the superiority of the experimental arms over the active comparator treatment. The primary comparison of OS will be made regardless of whether participants withdraw from treatment or receive new anti-cancer therapy prior to disease progression. In order not to confound the OS endpoint, crossover from any of the treatment arms to another arm will not be allowed.</p>\n<p>\n  </p>\n<p>\n During the study, participants will be asked to complete patient-reported outcome (PRO) questionnaires at the beginning of the study, during study treatment, at treatment discontinuation, and during survival follow-up. These will assess disease and treatment-related symptoms, as well as functioning and overall health-related quality of life.</p>\n<p>\n During the study, serum samples will be collected to monitor RO7121661, RO7247669, and nivolumab pharmacokinetics (PK) and to detect the presence of antibodies to RO7121661, RO7247669, or nivolumab. Blood samples for PK analysis may be collected at the participant’s home. This specifically applies to days where no other hospital assessments are required—i.e., C1D8 and C5D8.</p>\n<p>\n Participant samples, including archival and fresh tumor tissue, serum, plasma, and blood samples, will also be collected for biomarker assessments. Safety assessments will include the incidence, nature, and severity of AEs, and other protocol-specified tests such as laboratory abnormalities that are deemed critical to the safety evaluation of the study.</p>\n<p>\n After study treatment discontinuation and disease progression per RECIST v1.1, survival follow-up information will be collected by means of telephone calls, participant medical records, and/or clinic visits approximately every 3 months until death, lost to follow-up, or study termination by the Sponsor, whichever occurs first. All participants will be periodically contacted for survival and new anti-cancer therapy information unless the participant requests to be withdrawn from follow-up (this request must be documented in the source documents and signed by the Investigator). If the participant withdraws from the study, study staff may use a public information source (e.g., county records) when permissible to obtain information about survival status.</p>\n<p>\n The IMPs are: RO7121661 (2100 mg Q2W IV), RO7247669 (2100 mg Q2W IV), and nivolumab (240 mg Q2W IV).</p>\n<p>\n <strong>Length of Study</strong></p>\n<p>\n The duration in each period of the study for each participant will be as follows:</p>\n<p>\n · Screening: Days -28 to -1.</p>\n<p>\n · Treatment Period: Cycle 1 Day 1 up to a maximum of 24 months.</p>\n<p>\n · Survival follow-up: 90 (± 7) days after last treatment with study drug; then every</p>\n<p>\n 3 months (± 14 days) until death, loss to follow-up, or study termination by the Sponsor.</p>\n<p>\n <strong>End of Study</strong></p>\n<p>\n The end of the study will occur when all of the following criteria have been met:</p>\n<p>\n · The required number of deaths for the primary analysis of OS has been observed.</p>\n<p>\n · The last participant, last visit has occurred.</p>\n<p>\n <strong>Data Monitoring Committee</strong></p>\n<p>\n A Joint Monitoring Committee (JMC) will review available safety data periodically and make</p>\n<p>\n recommendations regarding study conduct to ensure the safety of patients enrolled in the study.</p>\n<p>\n The JMC will consist of designated Sponsor personnel and independent clinical expert(s) (i.e., expert[s] independent from the Sponsor). The JMC Chair will be a medical oncologist who is neither the Medical Monitor nor associated with the study. Other JMC members will include, but not be limited to, a drug-safety scientist and biostatistician. The responsibility, membership, and communication flow of the JMC is further described in the JMC Charter.</p>\n<p>\n  </p>\n<p>\n <strong>PARTICIPANT POPULATION</strong></p>\n<p>\n The study population consists of male and female participants with advanced or metastatic</p>\n<p>\n ESCC who are not indicated for radical resection and who are refractory or intolerant to</p>\n<p>\n fluoropyrimidine- or taxane- and platinum-based regimen.</p>\n<p>\n  </p>\n<p>\n <strong>Key Inclusion Criteria</strong></p>\n<p>\n · Participants whose major lesion was histologically confirmed ESCC.</p>\n<p>\n · Patients who are not indicated for radical resection and have previously received 1 line of treatment in non-curative intention prior to randomization. The prior line must be either a fluoropyrimidine- and platinum- or a taxane- and platinum-based regimen and patients must have experienced progressive disease after at least 3 cycles or are intolerable to the treatment. Patients who received treatment with curative intent, i.e. patients who underwent a radical resection (R0 resection confirmed) in conjunction with chemotherapy with fluoropyrimidine-/taxane- and platinum-based drugs including neo-adjuvant/adjuvant therapy (± radiotherapy) or patients who were treated with chemo-radiation (including patients who underwent chemo-radiation followed by salvage surgery) are allowed.</p>\n<p>\n · If recurrence was confirmed by imaging or by pathological assessment of a biopsy within 24 weeks after the last dose of the treatment, patients are eligible and do not require an additional line of therapy in the non-curative setting.</p>\n<p>\n · If recurrence occurred later than 24 weeks after the last dose of the treatment, patients need to be exposed to an additional line of fluoropyrimidine-/taxane- and platinum-based drugs in the non-curative setting to be eligible for the study—unless the Investigator considers the patient not eligible for the re-exposure with fluoropyrimidine/taxane and platinum-based drugs.</p>\n<p>\n · The last dose of chemotherapy or the last radiation treatment (whichever occurs later) should be considered for the determination of the timepoint of recurrence after chemo-radiation.</p>\n<p>\n · Radiologically measurable disease according to RECIST v1.1. Previously irradiated lesions should not be counted as target lesions unless clearly progressed after the radiotherapy.</p>\n<p>\n · Eastern Cooperative Oncology Group Performance Status 0-1.</p>\n<p>\n · A life expectancy of ³ 12 weeks.</p>\n<p>\n · Tissue samples must be provided for analysis of PD-L1 tumor positivity using the PDL1 IHC 28-8 pharmDx assay. Testing will be done centrally and results must be obtained prior to stratification.</p>\n<p>\n · Adequate visceral organ functions</p>\n<p>\n · AEs from any prior radiotherapy, chemotherapy, or surgical procedure must have resolved to Grade £ 1, except alopecia (any grade), vitiligo, endocrinopathy managed with replacement therapy, and Grade 2 peripheral neuropathy.</p>\n<p>\n · Adequate contraception</p>\n<p>\n <strong>Key Exclusion Criteria</strong></p>\n<p>\n · Pregnancy, lactation, or breastfeeding.</p>\n<p>\n · Known hypersensitivity to any of the components of RO7121661, RO7247669, or nivolumab, including but not limited to, hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies.</p>\n<p>\n · Patients with significant malnutrition. Patients whose nutrition has been well controlled for ³ 28 days prior to randomization may be enrolled.</p>\n<p>\n · Evidence of complete esophageal obstruction not amenable to treatment.</p>\n<p>\n · Higher risk of bleeding or fistula caused by esophageal lesions invading adjacent organs (aorta or tracheobronchial tree).</p>\n<p>\n · Symptomatic central nervous system (CNS) metastases.</p>\n<p>\n · Spinal cord compression not definitively treated with surgery and/or radiation or without evidence that disease has been clinically stable for ³ 14 days prior to randomization.</p>\n<p>\n · Active or history of carcinomatous meningitis/leptomeningeal disease.</p>\n<p>\n Asymptomatic CNS primary tumors or metastases if they have requirement for steroids</p>\n<p>\n or enzyme-inducing anticonvulsants in the last 28 days prior to randomization.</p>\n<p>\n · Uncontrolled tumor-related pain.</p>\n<p>\n · Patients with an active second malignancy.</p>\n<p>\n · Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results.</p>\n<p>\n · Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent.</p>\n<p>\n · Significant cardiovascular/cerebrovascular disease within 6 months prior to randomization.</p>\n<p>\n · Known active or uncontrolled bacterial, viral, fungal, mycobacterial (including but not limited to tuberculosis [TB] and typical mycobacterial disease), parasitic, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics, except if for tumor fever) within 28 days prior to randomization.</p>\n<p>\n · Known clinically significant liver disease, including alcoholic hepatitis, cirrhosis, and inherited liver disease.</p>\n<p>\n · Major surgical procedure or significant traumatic injury (excluding biopsies) within 28 days prior to randomization, or anticipation of the need for major surgery during the course of the study.</p>\n<p>\n · Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high risk from treatment complications.</p>\n<p>\n · Dementia or altered mental status that would prohibit informed consent.</p>\n<p>\n · Uncontrolled pleural effusion (with the exception of participants with indwelling catheters, e.g., PleurXâ), pericardial effusion, or ascites requiring recurrent drainage procedures (expected to occur once monthly or more frequently).</p>\n<p>\n · Active or history of autoimmune disease or immune deficiency.</p>\n<p>\n · Positive HIV test at screening.</p>\n<p>\n · Positive hepatitis B surface antigen (HBsAg) or positive total hepatitis B core antibody (HBcAb) test at screening. Participants with a positive HBsAg or total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening are eligible.</p>\n<p>\n · Positive hepatitis C virus (HCV) antibody test at screening. Participants with a positive</p>\n<p>\n HCV antibody test followed by a negative HCV RNA test at screening are eligible.</p>\n<p>\n · Prior cancer therapy with any immunomodulatory agents including CPIs (such as anti-PDL1/PD1, anti-CTLA-4, anti-LAG3, anti-TIM3).</p>\n<p>\n · Vaccination with live vaccines within 28 days prior to randomization, or anticipation that a live attenuated vaccine will be required during the study.</p>\n<p>\n · Treatment with therapeutic oral or IV antibiotics within 14 days prior to randomization.</p>\n<p>\n · Concurrent therapy with any other investigational drug (defined as treatment for which there is currently no regulatory authority-approved indication) < 28 days or 5 half-lives of the drug, whichever is shorter, prior to randomization.</p>\n<p>\n · Treatment with immune-modulating and immune suppressive agents/medication</p>\n<p>\n < 5 half-lives or 28 days (whichever is shorter) prior to randomization.</p>\n<p>\n · Regular immunosuppressive therapy (i.e., for organ transplantation, chronic rheumatologic disease).</p>\n<p>\n · Radiotherapy within the last 28 days before start of study drug treatment is not allowed, with the exception of limited palliative radiotherapy.</p>\n<p>\n · Prior treatment with adoptive cell therapies, such as CAR-T therapies.</p>\n<p>\n  </p>\n<p>\n <strong>NUMBER OF PARTICIPANTS</strong></p>\n<p>\n The planned number of enrolled participants is 255, randomized 1:1:1 into 3 arms.</p>\n<p>\n <strong>CONCOMITANT MEDICATIONS</strong></p>\n<p>\n As a general rule, no concomitant medication will be permitted, with the exception of medications to treat AEs, unless the rationale for exception is discussed and clearly documented between the Investigator and the Sponsor. Use of the following therapies is prohibited during the study and for at least 28 days or</p>\n<p>\n 5 half-lives of the drug, whichever is shorter, prior to randomization and during study treatment, unless otherwise specified below:</p>\n<p>\n · Investigational or unlicensed/unapproved agents.</p>\n<p>\n · Therapy intended for the treatment of cancer (including, but not limited to, chemotherapy, hormonal therapy, immunotherapy, and radiotherapy [with the exception of limited palliative radiotherapy], as well as herbal therapy or traditional Chinese medicines with anti-cancer activity in the label), whether Health Authority approved or experimental.</p>\n<p>\n · Chronic use of steroids (inhaled and topical steroids are permitted) at baseline of > 10 mg of prednisone/day (or equivalent). Concurrent high doses of systemic corticosteroids.</p>\n<p>\n · Administration of a live, attenuated vaccine or anticipation that such a live attenuated vaccine will be required during the study.</p>\n<p>\n · Systemic immunostimulatory agents (including, but not limited to, interferons and IL-2) because these agents could potentially increase the risk for autoimmune conditions when given in combination with CPIs.</p>\n<p>\n · Systemic immunosuppressive medications (including, but not limited to, cyclophosphamide, azathioprine, methotrexate, and thalidomide) because these agents could potentially alter the efficacy and safety of the study drug.</p>\n<p>\n · Adoptive cell therapies, such as CAR-T therapies.</p>\n<p>\n  </p>\n
      • study_title<div>\n A 3-ARM, RANDOMIZED, BLINDED, ACTIVE-CONTROLLED, PHASE II STUDY OF RO7121661, A PD1-TIM3 BISPECIFIC ANTIBODY AND RO7247669, A PD1-LAG3 BISPECIFIC ANTIBODY, COMPARED WITH NIVOLUMAB IN PARTICIPANTS WITH ADVANCED OR METASTATIC SQUAMOUS CELL CARCINOMA OF THE ESOPHAGUS</div>\n
      • laymans_summary<p>\n This is a Phase II, randomized, blinded, active-controlled, global, multicenter study designed to evaluate the safety and efficacy of RO7121661 and RO7247669, compared with nivolumab, in patients with advanced or metastatic esophageal squamous-cell carcinoma (ESCC) refractory or intolerant to fluoropyrimidine- or taxane- and platinum-based regimen.</p>\n<p>\n The purpose of this study is to find out what effects, good or bad, RO7121661 and RO7247669, have on ESCC patients as compared to nivolumab.</p>\n<p>\n RO7121661, RO7247669, and nivolumab belong to a group of medicines called cancer immunotherapeutics. They are designed to recognize and kill tumor cells in the body by activating the body’s own immune system, in particular, T-cells (a type of immune cell) against the tumor.</p>\n<p>\n More precisely<strong>, </strong>RO7121661, RO7247669, and nivolumab are antibodies, which block proteins on T-cells, which help keep the body’s immune responses in check. These proteins are called PD1, TIM3, and LAG3. PD1, TIM3, and LAG3 are involved in regulating the body's natural immune response. Tumors can take advantage of this regulation to partially resist or evade the immune system. RO7121661 blocks PD1 and TIM3, RO7247669 blocks PD1 and LAG3, and nivolumab blocks PD1. By blocking these proteins, RO7121661, RO7247669, and nivolumab may help your immune system stop or reverse the growth of tumors.</p>\n<p>\n RO7121661 and RO7247669 are experimental drugs, which means Health Authorities have not approved RO7121661 and RO7247669 for the treatment of esophageal cancer. Nivolumab is approved in some countries for the treatment of cancer including esophageal cancer.</p>\n<p>\n Approximately 255 participants will take part in this study. The participants will be divided into three groups, receiving either RO7121661, RO7247669, or nivolumab. Each group will consist of 85 participants.</p>\n<p>\n The primary study objective is To evaluate the efficacy of RO7121661 and RO7247669 compared with nivolumab and the primary endpoint is overall survival (OS) defined as the time from randomization to death from any cause.</p>\n<p>\n The duration in each period of the study for each participant will be as follows:</p>\n<ul>\n <li>\n Screening: Days -28 to -1.</li>\n <li>\n Treatment Period: Cycle 1 Day 1 up to a maximum of 24 months.</li>\n <li>\n Survival follow-up: 90 (±7) days after last treatment with study drug; then every 3 months (± 14 days) until death, loss to follow-up, or study termination by the Sponsor.</li>\n</ul>\n<p>\n The end of the study will occur when all of the following criteria have been met:</p>\n<ul>\n <li>\n The required number of deaths for the primary analysis of OS has been observed.</li>\n <li>\n The last participant, last visit has occurred.</li>\n</ul>\n<p>\n  </p>\n
      • short_titleTALIOS
      • protocol_noECCT/21/07/02
      • version_no1
      • date_of_protocol08-12-2020
      • study_drugRO7121661, RO7247669, Nivolumab
      • disease_conditionAdvanced or Metastatic Esophageal Squamous Cell Carcinoma
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals1
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorYes
      • comparator_nameNivolumab
      • comparator_registeredyes
      • comparator_countriesCanada, the United States, the European Union, Japan, Taiwan, Israel, Turkey, Australia, Hong Kong, Brazil, South Korea, Mexico, China, Singapore
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addresshuwaida.bulhan@roche.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries(null)
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantDr. Huwaida Bulhan - Roche Kenya Ltd.
      • declaration_date107-07-2021
      • declaration_principal_investigatorProf. Mansoor Saleh - AgaKhan University Hostpital Nairobi
      • declaration_date207-07-2021
      • placebo_presentNo
      • study_objectives<div class=\"ct-body3\" color:=\"\" font-size:=\"\" helvetica=\"\" line-height:=\"\" sans=\"\" source=\"\" style=\"box-sizing: border-box; font-family: \">\n <p>\n <strong>Primary Objective:</strong></p>\n <p>\n To evaluate the efficacy of RO7121661 and RO7247669 compared with nivolumab.</p>\n <span style=\"font-size:14px;\"><strong><span style=\"color: rgb(34, 34, 34); font-family: Arial, Verdana, sans-serif;\">Secondary Objectives:</span></strong></span></div>\n<ul>\n <li>\n <span style=\"font-size:14px;\">To evaluate the safety and tolerability of RO7121661and RO7247669 compared with nivolumab.</span></li>\n <li>\n <span style=\"font-size:14px;\">To evaluate the efficacy of RO7121661 and RO7247669 compared with nivolumab.</span></li>\n <li>\n <span style=\"font-size:14px;\">To investigate the pharmacokinetics (PK) of RO7121661, RO7247669, and nivolumab.</span></li>\n <li>\n <span style=\"font-size:14px;\">To evaluate the immune response after administration of RO7121661, RO7247669, and nivolumab.</span></li>\n <li>\n <span style=\"font-size:14px;\">To assess treatment-induced pharmacodynamic changes (PD Biomarkers) in peripheral blood and tumor microenvironment</span></li>\n <li>\n <span style=\"font-size:14px;\">To assess baseline characteristics in the tumor microenvironment as predictive biomarkers of response</span></li>\n</ul>\n<div class=\"ct-body3\" color:=\"\" font-size:=\"\" helvetica=\"\" line-height:=\"\" margin-right:=\"\" sans=\"\" source=\"\" style=\"box-sizing: border-box; font-family: \">\n <p style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n  </p>\n</div>\n<p>\n  </p>\n
      • principal_inclusion_criteria<ul font-size:=\"\" helvetica=\"\" margin-bottom:=\"\" sans=\"\" source=\"\" style=\"box-sizing: border-box; margin-top: 1ex; margin-left: 0px; padding-left: 24px; color: rgb(0, 0, 0); font-family: \">\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Major lesion was histologically confirmed esophageal squamous-cell carcinoma (ESCC)</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Patients who have previously received 1 line of treatment with either a fluoropyrimidine- and platinum- or a taxane- and platinum-based regimen in non-curative intention prior to randomization; or patients who received treatment with a fluoropyrimidine-/taxane- and platinum-based regimen in curative intention and had recurrence within 24 weeks after the last dose of the treatment</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Radiologically measurable disease according to RECIST v1.1. Previously irradiated lesions should not be counted as target lesions unless clearly progressed after the radiotherapy</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n A life expectancy of at least (≥)12 weeks</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Tissue samples must be provided for analysis of anti-programmed death ligand-1 (PD-L1) tumor positivity</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Adverse events from any prior radiotherapy, chemotherapy, or surgical procedure must have resolved to Grade ≤1, except alopecia (any grade), vitiligo, endocrinopathy managed with replacement therapy, and Grade 2 peripheral neuropathy</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Adequate cardiovascular, hematological, liver, and renal function</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Serum albumin ≥25 grams per liter (g/L),</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n For participants not receiving therapeutic anticoagulation: prothrombin time (PT) and activated partial thromboplastin time ≤1.5 times (×) the upper limit of normal (ULN); for participants receiving therapeutic anticoagulation: stable anticoagulant regimen</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n A female participant is eligible to participate if she is not pregnant, not breastfeeding, not a woman of childbearing potential (WOCBP), or a WOCBP who agrees to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods during the treatment period and for at least 5 months after the final dose of study drug and have a negative pregnancy test (blood) within the 7 days prior to randomization.</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n A male participant must remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures such as a condom plus an additional contraceptive method and refrain from donating sperm during the treatment period and for at least 5 months after the final dose of study drug</li>\n</ul>\n
      • principal_exclusion_criteria<ul font-size:=\"\" helvetica=\"\" margin-bottom:=\"\" sans=\"\" source=\"\" style=\"box-sizing: border-box; margin-top: 1ex; margin-left: 0px; padding-left: 24px; color: rgb(0, 0, 0); font-family: \">\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Pregnancy, lactation, or breastfeeding</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Known hypersensitivity to any of the components of RO7121661, RO7247669, or nivolumab, including but not limited to, hypersensitivity to Chinese hamster ovary cell products or other recombinant human or humanized antibodies</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Patients with significant malnutrition. Patients whose nutrition has been well controlled for ≥28 days prior to randomization may be enrolled</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Evidence of complete esophageal obstruction not amenable to treatment</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Higher risk of bleeding or fistula caused by esophageal lesions invading adjacent organs (aorta or tracheobronchial tree)</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Symptomatic central nervous system (CNS) metastases</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Spinal cord compression not definitively treated with surgery and/or radiation or without evidence that disease has been clinically stable for ≥14 days prior to randomization</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Active or history of carcinomatous meningitis/leptomeningeal disease</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Asymptomatic CNS primary tumors or metastases if they have requirement for steroids or enzyme inducing anticonvulsants in the last 28 days prior to randomization</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Uncontrolled tumor-related pain. Participants requiring pain medication must be on a stable regimen at study entry</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Active second malignancy (with some exceptions)</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including diabetes mellitus, history of relevant pulmonary disorders, known autoimmune diseases or immune deficiency, or other diseases with ongoing fibrosis (such as scleroderma, pulmonary fibrosis, emphysema, neurofibromatosis, palmar/plantar fibromatosis, etc.).</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Significant cardiovascular/cerebrovascular disease within 6 months prior to randomization</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Known active or uncontrolled bacterial, viral, fungal, mycobacterial (including but not limited to tuberculosis [TB] and typical mycobacterial disease), parasitic, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with intravenous (IV) antibiotics or hospitalization (relating to the completion of the course of antibiotics, except if for tumor fever) within 28 days prior to randomization</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Known clinically significant liver disease, including alcoholic hepatitis, cirrhosis, and inherited liver disease.</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Major surgical procedure or significant traumatic injury (excluding biopsies) within 28 days prior to randomization, or anticipation of the need for major surgery during the course of the study</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high risk from treatment complications</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Dementia or altered mental status that would prohibit informed consent</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (expected to occur once monthly or more frequently)</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Active or history of autoimmune disease or immune deficiency</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Positive human immunodeficiency virus (HIV) test at screening</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Positive hepatitis B surface antigen (HBsAg) or positive total hepatitis B core antibody (HBcAb) test at screening</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Positive hepatitis C virus (HCV) antibody test at screening</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Prior cancer therapy with any immunomodulatory agents including checkpoint inhibitors (CPIs; such as anti-PDL1/PD1, anti-CTLA-4, anti-LAG3, anti-TIM3)</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Vaccination with live vaccines within 28 days prior to randomization, or anticipation that a live attenuated vaccine will be required during the study</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Treatment with therapeutic oral or IV antibiotics within 14 days prior to randomization</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Concurrent therapy with any other investigational drug (defined as treatment for which there is currently no regulatory authority approved indication) 28 days or 5 half-lives of the drug (whichever is shorter) prior to randomization</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Treatment with immune-modulating and immune suppressive agents/medication 5 half-lives or 28 days (whichever is shorter) prior to randomization</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Regular immunosuppressive therapy (i.e., for organ transplantation, chronic rheumatologic disease)</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Radiotherapy within the last 28 days before start of study drug treatment is not allowed, with the exception of limited palliative radiotherapy</li>\n <li style=\"box-sizing: border-box; line-height: 1.6; margin-bottom: 4px; margin-top: 0.7ex;\">\n Prior treatment with adoptive cell therapies, such as chimeric antigen receptor T cells (CAR-T) therapies</li>\n</ul>\n
      • primary_end_points<div class=\"ct-body3\" color:=\"\" font-size:=\"\" helvetica=\"\" line-height:=\"\" sans=\"\" source=\"\" style=\"box-sizing: border-box; font-family: \">\n <span class=\"term\" data-term=\"primary outcome measure\" style=\"box-sizing: border-box; background-position: left bottom; background-size: 4px 1px; background-repeat: repeat-x; transition: background-color 0s ease 0s, all 0.2s ease 0s, box-shadow 0s ease 0s, all 0.2s ease 0s, color 0s ease 0s, all 0.2s ease 0s; border-bottom: 1px dotted; color: rgb(17, 46, 81); cursor: pointer; display: inline;\" tabindex=\"0\" title=\"Show definition\">Primary Outcome Measures </span> :\n <ol style=\"box-sizing: border-box; margin-top: 1ex; margin-bottom: 1ex;\">\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Overall Survival, Defined as the Time from Randomization to Death from Any Cause [ Time Frame: Up to 3 years, 4 months ]</li>\n </ol>\n</div>\n<div class=\"ct-body3\" color:=\"\" font-size:=\"\" helvetica=\"\" line-height:=\"\" margin-right:=\"\" sans=\"\" source=\"\" style=\"box-sizing: border-box; font-family: \">\n <span class=\"term\" data-term=\"secondary outcome measure\" style=\"box-sizing: border-box; background-position: left bottom; background-size: 4px 1px; background-repeat: repeat-x; transition: background-color 0s ease 0s, all 0.2s ease 0s, box-shadow 0s ease 0s, all 0.2s ease 0s, color 0s ease 0s, all 0.2s ease 0s; border-bottom: 1px dotted; color: rgb(17, 46, 81); cursor: pointer; display: inline;\" tabindex=\"0\" title=\"Show definition\">Secondary Outcome Measures </span> :\n <ol style=\"box-sizing: border-box; margin-top: 1ex; margin-bottom: 1ex;\">\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Number of Participants with Adverse Events, Severity Graded According to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0 (NCI-CTCAE v5.0) [ Time Frame: Up to 3 years, 4 months ]</li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Objective Response Rate (ORR), Defined as the Percentage of Participants with a Complete or Partial Response According to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1) [ Time Frame: Up to 3 years, 4 months ]</li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Disease Control Rate (DCR), Defined as the Percentage of Participants with an Objective Response or Stable Disease According to RECIST v1.1 [ Time Frame: Up to 3 years, 4 months ]</li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Duration of Response for Participants with ORR, Defined as the Time from the First Occurrence of a Documented Objective Response to Disease Progression According to RECIST v1.1 or Death from any Cause, Whichever Occurs First [ Time Frame: Up to 3 years, 4 months ]</li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Progression-Free Survival (PFS), Defined as the Time from Randomization to the First Occurrence of Progression as Determined According to RECIST v1.1 or Death from any Cause, Whichever Occurs First [ Time Frame: Up to 3 years, 4 months ]</li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Percentage of Participants Reporting Clinically Meaningful Improvement in Global Health Status/Quality of Life (GHS/QoL), and Emotional and Social Functioning, Defined as a ≥10-Point Increase from Baseline as Measured by the EORTC QLQ-C30 [ Time Frame: Baseline (Day 1 of Cycle 1) and Day 1 of Cycles 4, 7, and 10 (each cycle is 14 days); then every 3 months until treatment discontinuation; and every 3 months during the first year of post-treatment follow-up (up to 3 years) ]\n <div class=\"tr-indent2\" style=\"box-sizing: border-box; line-height: 1.6; clear: both; margin-left: 1em; margin-top: 1ex;\">\n EORTC QLQ-C30 = European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30</div>\n </li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Percentage of Participants Reporting a Clinically Meaningful Improvement in GHS/QoL, and Emotional and Social Functioning, Defined as a ≥10-Point Increase from Baseline as Measured by the EORTC IL97 Questionnaire [ Time Frame: Baseline (Cycle 1 Day 1) and Day 1 of Cycles 2, 3, 5, 6, 8, and 9 (each cycle is 14 days) ]\n <div class=\"tr-indent2\" style=\"box-sizing: border-box; line-height: 1.6; clear: both; margin-left: 1em; margin-top: 1ex;\">\n EORTC IL97 = European Organisation for Research and Treatment of Cancer - Item Library 97</div>\n </li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Percentage of Participants Reporting a Clinically Meaningful Improvement in Dysphagia, Defined as a ≥10-Point Increase from Baseline as Measured by the EORTC QLQ-OES18 [ Time Frame: Baseline (Cycle 1 Day 1) and Day 1 of each subsequent treatment cycle (each cycle is 14 days) until treatment discontinuation; and every 3 months during the first year of post-treatment follow-up (up to 3 years) ]\n <div class=\"tr-indent2\" style=\"box-sizing: border-box; line-height: 1.6; clear: both; margin-left: 1em; margin-top: 1ex;\">\n EORTC QLQ-OES18 = European Organisation for Research and Treatment of Cancer Quality-of-Life Questionnaire for Esophageal Cancer</div>\n </li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Serum Concentrations of RO7121661, RO7247669, and Nivolumab [ Time Frame: Predose and at end of infusion on Day 1 of every treatment cycle and on Day 8 of Cycles 1 and 5 (each cycle is 14 days); and at treatment discontinuation (up to 2 years) ]</li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Area Under the Time-Serum Concentration Curve (AUC) of RO7121661, RO7247669, and Nivolumab [ Time Frame: Predose and at end of infusion on Day 1 of every treatment cycle and on Day 8 of Cycles 1 and 5 (each cycle is 14 days); and at treatment discontinuation (up to 2 years) ]</li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Maximum Serum Concentrations of RO7121661, RO7247669, and Nivolumab [ Time Frame: Predose and at end of infusion on Day 1 of every treatment cycle and on Day 8 of Cycles 1 and 5 (each cycle is 14 days); and at treatment discontinuation (up to 2 years) ]</li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Total Clearance of RO7121661, RO7247669, and Nivolumab [ Time Frame: Predose and at end of infusion on Day 1 of every treatment cycle and on Day 8 of Cycles 1 and 5 (each cycle is 14 days); and at treatment discontinuation (up to 2 years) ]</li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Volume of Distribution at Steady State of RO7121661, RO7247669, and Nivolumab [ Time Frame: Predose and at end of infusion on Day 1 of every treatment cycle and on Day 8 of Cycles 1 and 5 (each cycle is 14 days); and at treatment discontinuation (up to 2 years) ]</li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Terminal Half-Life of RO7121661, RO7247669, and Nivolumab [ Time Frame: Predose and at end of infusion on Day 1 of every treatment cycle and on Day 8 of Cycles 1 and 5 (each cycle is 14 days); and at treatment discontinuation (up to 2 years) ]</li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Number of Participants with Anti-Drug Antibodies (ADAs) to RO7121661, RO7247669, or Nivolumab at Baseline and During the Study [ Time Frame: Predose at Baseline (Day 1 of Cycle 1) and on Day 1 of Cycles 2, 3, 4, 5, and 7, and then every 3 cycles thereafter (each cycle is 14 days); and at treatment discontinuation (up to 2 years) ]</li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Change from Baseline in the Number of T-cell Subsets by Phenotype and Activation Status (CD4/CD8 HLA-DR+Ki67+) in the Peripheral Blood [ Time Frame: Predose at Baseline (Day 1 of Cycle 1) and on Day 1 of Cycles 2, 3, 5, and 7, and then every 3 cycles thereafter (each cycle is 14 days); and at treatment discontinuation (up to 2 years) ]</li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Change from Baseline in the Number of CD8+ T-cells Infiltrating the Tumor Microenvironment [ Time Frame: Baseline and Day 1 of Cycle 3 (each cycle is 14 days) ]</li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Change from Baseline in the Number of CD8+ T-cells Proliferating (CD8+Ki67+) in the Tumor Microenvironment [ Time Frame: Baseline and Day 1 of Cycle 3 (each cycle is 14 days) ]</li>\n <li style=\"box-sizing: border-box; font-size: 15px; line-height: 1.6; margin-top: 0.7ex;\">\n Baseline PDL1, CD8+PD1+, CD8+TIM3+, and CD8+LAG3+ Expression in the Tumor Microenvironment [ Time Frame: At Baseline ]</li>\n </ol>\n</div>\n<p>\n  </p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n <strong><u>Aga Khan University, Nairobi</u></strong></p>\n<p>\n The study will be conducted at the Aga Khan University, Clinical Research Unit (CRU) which</p>\n<p>\n occupies a newly renovated space located on the 9th Floor of the Doctor’s Park Building, adjacent to the Aga Khan University Hospital, Nairobi and Aga Khan University Centre along 3rd Parklands Avenue Nairobi. </p>\n<p>\n The 4000sq.ft clinical research unit has been designed and equipped for the conduct of Phase 1-3 Clinical trials. The facility comprises of; phlebotomy and triage suites, examination rooms, informed consent booths, investigational product (IP) treatment suite, clinical research pharmacy, clinical research laboratory, research medical records facility and administrative offices. </p>\n<p>\n The CRU conducts ICH-GCP/FDA compliant Clinical Research. The CRU is well- staffed by trained personnel with expertise in the following research related tasks</p>\n<ul>\n <li>\n Clinical Research Nursing: Make CRF entries/resolve queries; Collect medical information; Vital signs; Collect adverse events; Administer IP; Collect lab samples; Participant recruitment and retention.</li>\n <li>\n Pharmacist and Pharmacy Technologist: Investigational Drug Services: Manage IP receipt/return; Prepare and dispense IP; Unblinding procedures.</li>\n <li>\n Regulatory Affairs: Manage submissions to ethics and regulatory authorities. Maintain essential documents.</li>\n <li>\n Contracts and Budgets: Maintain legal and financial documents; Ensure appropriate invoicing to the sponsor; Ensure appropriate processes for research covered procedures versus patients’ standard of care</li>\n <li>\n Data Management: Make CRF entries/resolve queries; Maintain the patients’ research documents</li>\n <li>\n Clinical Research operations: Oversight of AKU’s Clinical Research Unit’s studies and staff; support all research staff with their tasks</li>\n <li>\n Investigators: Obtain Informed Consent; Assess eligibility; Make CRF entries/resolve Queries; Medical decisions/review; Collect medical information; Vital signs; Assess Ordinal Scale; Collect/Assess Adverse Events; Administer IP; Conduct Physical Exam; Collect Lab Samples; Maintain Essential Documents; IP processes</li>\n</ul>\n<p>\n AKUH, N has Outpatient Cancer Care (OCC) as part of our larger Comprehensive Oncology Program. The facility is designed to provide an integrated, patient-centered service across the care cycle from diagnosis through treatment, survivorship and palliative care.</p>\n<p>\n Cancer patients treated at AKUHN have access to psychosocial and support counselling  as part of AKUH, N best practice.  This is not limited to non-study patients and thus will be available to study patients as well. F</p>\n<p>\n The Outpatient Cancer Care also offers streamlined, efficient care by multidisciplinary team of specialists. This coordinated approach allows for all-inclusive care to cancer patients and their families as a one stop service. ​</p>\n<p>\n The AKUH, N approach to care is guided by core principles of Quality, Access, Impact and Relevance and its healthcare practices are of the highest quality, as benchmarked against international standards including accreditation by:</p>\n<ul>\n <li>\n Joint Commission International (JCI)</li>\n <li>\n College of American Pathologists (CAP)</li>\n <li>\n International Quality Assurance 9001:2008</li>\n</ul>\n<p>\n  </p>\n
      • other_details_explanation<p>\n Not Applicable</p>\n
      • other_details_regulatory_notapproved<p>\n 1. Brazil - submission date 08Mar2021</p>\n<p>\n 2. France - submission date 26Apr2021</p>\n<p>\n 3. Italy - submission date 15Mar2021</p>\n<p>\n 4. South Africa - submission date 14May2021</p>\n<p>\n 5. Ukraine - submission date 16Mar2021</p>\n
      • other_details_regulatory_approved<p>\n 1. Belgium - 27May2021 - 2 sites</p>\n<p>\n 2. Czech Republic - 15Jun2021 - 2 sites</p>\n<p>\n 3. Denmark - 02Jun2021 - 2 sites</p>\n<p>\n 4. Germany - 23Jun2021 - 4 sites</p>\n<p>\n 5. Hungary - 17May2021 - 3 sites</p>\n<p>\n 6. South Korea - 04Mar2021 - 5 sites</p>\n<p>\n 7. Poland - 21May2021 -  5 sites</p>\n<p>\n 8. Russia - 25Mar2021 - 5 sites</p>\n<p>\n 9. Singapore - 28May2021 - 2 sites</p>\n<p>\n 10. Spain - 26Feb2021 - 6 sites</p>\n<p>\n 11. Taiwan - 21Apr2021 - 3 sites</p>\n<p>\n 12. Thailand - 02Jun2021 - 3 sites</p>\n<p>\n 13. Turkey - 19Apr2021 - 6 sites</p>\n<p>\n 14. UK - 17May2021 - 6 sites</p>\n<p>\n  </p>\n
      • other_details_regulatory_rejected<p>\n Not Applicable</p>\n
      • other_details_regulatory_halted<p>\n Not Applicable</p>\n
      • estimated_duration3 years (Jun 2021 to August 2024)
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorNivolumab
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states20
      • number_of_sites2
      • multi_country_listKorea, Taiwan, Singapore, Thailand, Germany, UK France, Spain, Italy, Czech Republic, Poland, Hungary, Turkey, Russia, Ukrane, Denmark, Belgium, Brazil, South Africa & Kenya
      • data_monitoring_committeeYes
      • total_enrolment_per_siteAga Khan University, Nairobi - 5-10\nInternational Cancer Institute - 10-20
      • total_participants_worldwide255
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsNo
      • subjects_vulnerable_populationsNo
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameMansoor
      • investigator1_middle_name
      • investigator1_family_nameSaleh
      • investigator1_qualificationProfessor of Hematology and Oncology
      • investigator1_professional_addressAga Khan University, Nairobi, 3rd Parklands Avenue, Nairobi-Kenya
      • investigator1_telephone+254 709 93 1500
      • investigator1_emailmansoor.saleh@aku.edu
      • organisations_transferred_Yes
      • number_participants15-30
      • notification<p>\n Dear ECCT Reviewers, </p>\n<p>\n This is a novel interventional trial for esophageal cancer, which has limited treatment options in Kenya. </p>\n<p>\n To be able to recruit a sizeable number of Kenyan patients in this competitive recruitment study, we would like to submit the relevant protocol and related documents for your review and approval. The lead institution is AgaKhan University Hospital Nairobi, under PI Prof. Mansoor Saleh. The second site is Internatlonal Cancer Institute Eldoret (ICI) under PI Prof Fred Asirwa Chite. Ethics Committee approval through KEMRI SERU for ICI is unforunately still pending at this time point, but expected soon. We are kindly requesting that you begin reviewing the study documentation, pending PPB approval only once the ICI EC approval is supplied. AKUH Nairobi EC approval has been supplied for your review. </p>\n<p>\n We appreciate the consideration.</p>\n<p>\n Sincerely,</p>\n<p>\n Dr. Huwaida Bulhan (Roche Kenya Ltd)</p>\n
      • approval_date01-11-2021
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted16-09-2021
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonThe application has been approved by the experts
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2025-02-04 15:29:06
      • created2021-06-21 14:40:09
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id685
        • application_id1029
        • given_nameFredrick
        • middle_nameChite
        • family_nameAsirwa
        • qualificationProfessor of Hematology and Oncology
        • professional_addressInternational Cancer Institute, Nandi Road 8/10, Eldoret, Kenya, 8088-30100
        • telephone+254 700 522 149
        • emaildirector@intercancer.com
        • created2021-06-21 15:04:04
        • modified2021-09-16 12:06:55
    • SiteDetail(array)
      • 0(array)
        • id947
        • application_id1029
        • county_id47
        • site_nameAga Khan University, Nairobi
        • physical_address3rd Parklands Avenue, Off Limuru Road
        • contact_detailsP.O. Box 30270, Nairobi 00100
        • contact_personProf Mansoor Saleh
        • site_capacity(null)
        • misc(null)
        • created2021-06-21 15:04:04
        • modified2021-09-16 12:06:55
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 1(array)
        • id970
        • application_id1029
        • county_id27
        • site_nameInternational Cancer Institute
        • physical_addressNandi Road 8/10, Eldoret, Kenya, 8088-30100
        • contact_detailsP.O. Box 8088-30100, Eldoret Kenya
        • contact_personProf Fredrick Chite Asirwa
        • site_capacity(null)
        • misc(null)
        • created2021-06-23 11:00:39
        • modified2021-09-16 12:06:55
        • County(array)
          • id27
          • county_nameUasin Gishu
          • created2012-06-15 10:25:15
          • modified2012-06-15 10:25:15
    • Sponsor(array)
      • 0(array)
        • id517
        • application_id1029
        • sponsorHoffmann La Roche
        • sponsor_typeIndustry
        • contact_personHuwaida Bulhan
        • addressThe Atrium, 6th Floor Chaka Road, off Lenana Road P.O. Box 44212-00100 Nairobi, Kenya
        • telephone_number+254 780 888 997
        • fax_number
        • cell_number+254 780 888 997
        • email_addresshuwaida.bulhan@roche.com
        • created2021-06-21 15:04:04
        • modified2021-09-16 12:06:55
  • 3(array)
    • Application(array)
      • id150
      • user_id80
      • trial_status_id7
      • abstract_of_study<div>\n PROTOCOL SUMMARY </div>\n<div>\n  </div>\n<div>\n Phase: II</div>\n<div>\n  </div>\n<div>\n Population: 234 women who are sexually active (>4 episodes of heterosexual intercourse during the past month), HIV-seronegative, 18 to 45 years old, with bacterial vaginosis (BV) and/or vulvovaginal candidiasis (VVC) and/or <em>Trichomonas vaginalis</em> detected by laboratory testing at a screening visit</div>\n<div>\n  </div>\n<div>\n Number of Sites: Four (3 in Kenya and 1 in the U.S.)</div>\n<div>\n  </div>\n<div>\n Study Duration: 24 months for accrual and follow-up </div>\n<div>\n  </div>\n<div>\n Subject Participation Duration: 12 months total (Enrollment to End of Study Evaluation) </div>\n<div>\n  </div>\n<div>\n Description of Agent or Intervention: Intravaginal metronidazole 750 mg plus miconazole 200 mg (coformulated suppositories) versus matching placebo </div>\n<div>\n suppositories nightly for five consecutive nights each month </div>\n<div>\n  </div>\n<div>\n Indication: Treatment for bacterial vaginosis and/or vulvovaginal candidiasis and/or <em>Trichomonas vaginalis </em>infection and/or mixed infections with two or more of these conditions </div>\n<div>\n  </div>\n<div>\n Objectives:</div>\n<div>\n Primary - To evaluate the effect of monthly periodic presumptive treatment (PPT) using topical metronidazole 750 mg with miconazole 200 mg intravaginal suppositories versus matching placebo nightly for five nights each month for reducing the rates of BV by Gram stain (Nugent’s criteria) and VVC (detection on vaginal saline/KOH wet mount plus positive culture on Sabouraud’s agar) in a randomized, double-blind, placebocontrolled trial in sexually active, HIV-seronegative women. The two primary endpoints, BV and VVC, will be analyzed separately. </div>\n<div>\n  </div>\n<div>\n <div>\n Secondary - To evaluate the effect of monthly PPT using topical metronidazole 750 mg with miconazole 200 mg intravaginal suppositories versus matching placebo nightly for five nights each month for reducing the overall rate of vaginal infections (combined endpoint including BV by Gram stain [Nugent’s criteria], VVC [vaginal saline/KOH wet mount plus positive culture on Sabouraud’s agar] and Trichomonas vaginalis infection [nucleic acid amplification based detection]) in a randomized, double-blind, placebo-controlled trial in sexually active, HIV-seronegative women. To evaluate the effect of monthly PPT using topical metronidazole 750 mg with miconazole 200 mg intravaginal suppositories versus matching placebo nightly for five nights each month for reducing the rate of BV by clinical criteria (Amsel’s criteria) in a randomized, double-blind, placebocontrolled trial in sexually active, HIV-seronegative women. </div>\n <div>\n  </div>\n <div>\n Description of Study Design: </div>\n <div>\n The proposed study is a randomized, double-blind, placebocontrolled, two arm clinical trial (N=117 in each arm). </div>\n</div>\n<p>\n  </p>\n
      • study_title<div>\n A Double-blind, Randomized Trial of Monthly Treatment with Metronidazole and Miconazole Co-formulated Suppositories versus Placebo for Preventing Vaginal Infections in HIVSeronegative Women (DMID Protocol Number: 09-0070)</div>\n
      • laymans_summary(null)
      • short_title(null)
      • protocol_noECCT/11/04/01
      • version_no1.0
      • date_of_protocol29-07-2010
      • study_drugIntravaginal metronidazole 750 mg plus miconazole 200 mg (coformulated suppositories)
      • disease_conditionTreatment for bacterial vaginosis and/or vulvovaginal candidiasis and/or Trichomonas vaginalis infection and/or mixed infections
      • 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_nameIntravaginal metronidazole 750 mg plus miconazole 200 mg (coformulated suppositories)
      • product_type_medical_device_name
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressmclell@uw.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_countries0
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd(null)
      • applicant_prev_data(null)
      • applicant_stability_data(null)
      • applicant_analysis_cert(null)
      • applicant_pictorial_sample(null)
      • applicant_gcp_training(null)
      • applicant_dsmb_charter(null)
      • applicant_detailed_budget(null)
      • applicant_indemnity_pi(null)
      • applicant_practice_license(null)
      • applicant_registration_ctr(null)
      • applicant_pan_african(null)
      • applicant_hard_copies(null)
      • applicant_signed_checklist(null)
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantScott McClelland
      • declaration_date128-06-2013
      • declaration_principal_investigatorScott McClelland
      • declaration_date228-06-2013
      • placebo_presentYes
      • study_objectives(null)
      • principal_inclusion_criteria<div>\n • Informed consent obtained and informed consent form (ICF) signed </div>\n<div>\n • Female, aged 18-45 years </div>\n<div>\n • Sexually active with >4 episodes of sex with a male partner during the past month </div>\n<div>\n • HIV-seronegative on both HIV tests in parallel screening </div>\n<div>\n • Presence of BV and/or VVC and/or T. vaginalis infection at screening: </div>\n<ul>\n <li>\n BV: Microscopic criteria (Nugent’s score <u>></u>7) </li>\n <li>\n VVC: Fungal elements (pseudohyphae, blastoconidia, or both) on vaginal saline wet mount plus a positive culture showing yeast on Sabouraud’s agar</li>\n <li>\n <em>T. vaginalis i</em>nfection: Identification of motile trichomonads on vaginal saline wet preparation </li>\n</ul>\n<div>\n • Able and willing to comply with study visit schedule and procedures during the 12-month period of follow-up </div>\n<div>\n • Able and willing to abstain from sex or to use non-latex condoms (provided) for 24 hours following insertion of each vaginal suppository </div>\n<div>\n • Willing to abstain from alcohol during, and for 48 hours after, treatment </div>\n<div>\n • Plan to remain in study area for the next year </div>\n<div>\n • Agree to not participate in other research studies involving drugs, medical devices, or vaginal products for the duration of study</div>\n
      • principal_exclusion_criteria<div>\n • Currently pregnant (positive urine β-hCG) or planning to conceive during the next 12 months (by self-report) </div>\n<div>\n • Currently breastfeeding </div>\n<div>\n • Within first 3 months post-partum </div>\n<div>\n • Current menstruation – women who are currently menstruating may be enrolled following the completion of menses </div>\n<div>\n • History of 4 or more episodes of treatment for any vaginal infection in the past 12 months. This would be a cumulative total, including any treatment for BV and/or VVC and/or TV and/or syndromic. </div>\n<div>\n • History of medical condition that would contraindicate use of the study product: </div>\n<ul>\n <li>\n Porphyria </li>\n <li>\n Epilepsy </li>\n <li>\n Serious liver disease or signs and symptoms consistent with serious liver disease including jaundice, ascites, esophageal varices, encephalopathy, and bleeding disorders </li>\n <li>\n Renal failure </li>\n</ul>\n<div>\n • History of adverse reaction to the study medications (intravaginal metronidazole or miconazole) </div>\n<div>\n • Current use of medication that may interact with the study drug (due to vaginal absorption of study drug): </div>\n<ul>\n <li>\n Warfarin </li>\n <li>\n Phenytoin </li>\n <li>\n Phenobarbital </li>\n <li>\n Disulfiram </li>\n <li>\n Cimetidine </li>\n <li>\n Lithium </li>\n <li>\n Astemizole </li>\n <li>\n Terfenadine </li>\n</ul>\n<div>\n • Current use of oral or intravaginal antifungal medication </div>\n<div>\n • Current use of oral or intravaginal metronidazole, tinidazole, or clindamycin </div>\n<div>\n • Current use of latex diaphragm </div>\n<div>\n • As determined by the investigator, a medical condition or situation exists such that study participation would not be advisable. </div>\n
      • primary_end_points<p>\n This study has two primary endpoints: </p>\n<ol>\n <li>\n BV by Gram stain (Nugent’s criteria)</li>\n <li>\n VVC (detection on vaginal saline/KOH wet mount plus positive culture on Sabouraud’s agar) </li>\n</ol>\n<p>\n The two primary endpoints, BV and VVC, will be analyzed separately.</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_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n  </p>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:640px;\" width=\"480\">\n <tbody>\n <tr>\n <td style=\"width:241px;\">\n <p>\n DMID Protocol Number</p>\n </td>\n <td style=\"width:399px;\">\n <p>\n 09-0070</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;\">\n <p>\n Protocol Title</p>\n </td>\n <td style=\"width:399px;\">\n <p>\n A double-blind randomized trial of monthly treatment with topical metronidazole and miconazole and co-formulated suppositories versus placebo for preventing vaginal infection in HIV-seronegative women</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;\">\n <p>\n Proposed site:</p>\n </td>\n <td style=\"width:399px;\">\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;\">\n <p style=\"margin-left:.25in;\">\n Site-Investigator’s name</p>\n </td>\n <td style=\"width:399px;\">\n <p>\n Prof. Omu Anzala, MB,ChB, PhD</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;\">\n <p style=\"margin-left:.25in;\">\n Name of institution/facility</p>\n </td>\n <td style=\"width:399px;\">\n <p>\n Kenya AIDS Vaccine Initiative (KAVI)</p>\n <p>\n Department of Medical Microbiology</p>\n <p>\n University of Nairobi</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;\">\n <p style=\"margin-left:.25in;\">\n City, state, country</p>\n </td>\n <td style=\"width:399px;\">\n <p>\n Nairobi, Kenya</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;height:23px;\">\n <p style=\"margin-left:.25in;\">\n Email address</p>\n </td>\n <td style=\"width:399px;height:23px;\">\n <p>\n <a href=\"mailto:oanzala@kaviuon.org\">oanzala@kaviuon.org</a></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;height:23px;\">\n <p style=\"margin-left:.25in;\">\n Brief description of site/facility</p>\n </td>\n <td style=\"width:399px;height:23px;\">\n <p>\n KAVI was established in 1999 as a research unit at the Department of Medical Microbiology, College of Health Sciences, University of Nairobi. It comprises of a fully equipped clinic, Pharmacy, community team, IT/Data, advanced research and safety laboratories, administration and finance department.  The research activities are sponsored by International AIDS Vaccine Initiative (IAVI).  KAVI has two sites namely; KAVI-KNH which is mainly a Phase I site where the four clinical trials have been undertaken since 2001and KAVI-Kangemi which is a clinical site devoted to conducting Phase IIB/III vaccine trials (Efficacy trials) and feasibility studies.</p>\n <p>\n  </p>\n <p>\n The KAVI research team is appropriately trained with majority of members having at least 5 years experience in clinical research.         </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;\">\n <p>\n Site-Investigator’s experience:</p>\n </td>\n <td style=\"width:399px;\">\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;height:35px;\">\n <p style=\"margin-left:.25in;\">\n With the protocol topic</p>\n </td>\n <td style=\"width:399px;height:35px;\">\n <p>\n Prof. Anzala managed the KAVI laboratory during the conduct of five HIV vaccine clinical trials; during these studies there was recruitment of high-risk individuals and screening for STIs / genital infections. Additionally, Prof. Anzala previously worked in the nearby Majengo Clinic for over five years, where he gained extensive experience in HIV/STI cohort research.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;height:35px;\">\n <p style=\"margin-left:.25in;\">\n Conducting clinical trials</p>\n </td>\n <td style=\"width:399px;height:35px;\">\n <p>\n Prof. Anzala has been a principal investigator in three clinical studies and is currently the Program Director of KAVI, where he is in charge of three principal investigators of different studies. Before that, he was the Project Director of KAVI for five years.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;\">\n <p>\n Description of clinic facilities and capabilities:</p>\n <p>\n  </p>\n </td>\n <td style=\"width:399px;\">\n <p>\n  </p>\n <p>\n The clinic has an outdoor waiting area, several exam and counseling rooms, an onsite lab, and area for data management and secure data storage.</p>\n <p>\n All the core personnel have experience in all stages of protocol development and implementation. Staff are trained in the ICH-GCP, GCLP, GPP requirements as well as the country specific regulatory requirements. The staff have experience in the US-CFR requirements that govern clinical trials and have all undergone the human subject protection training.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;\">\n <p>\n Description of lab facilities and capabilities:</p>\n <p>\n  </p>\n </td>\n <td style=\"width:399px;\">\n <p>\n The onsite laboratory can support some routine tests, such as vaginal wet mounts and pregnancy testing. Additional samples are collected and transported daily to a central, well-equipped laboratory at the College of Health Sciences.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;\">\n <p>\n Summary of Study Site feasibility:</p>\n </td>\n <td style=\"width:399px;\">\n <p>\n KAVI staff have worked on site for the last 10 years.  They have the experience needed in conducting clinical trials.  KAVI has mapped the site and is able to utilize the experienced community mobilizers in identifying site participants required for these trials.  In addition, KAVI has sufficient infrastructure required to conduct the study.</p>\n <p>\n  </p>\n </td>\n </tr>\n </tbody>\n</table>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\" style=\"width:643px;\" width=\"482\">\n <tbody>\n <tr>\n <td colspan=\"3\" style=\"width:643px;height:19px;\">\n <p>\n <strong>Key Personnel at Proposed Study Site:</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:196px;height:19px;\">\n <p>\n <strong>Title</strong></p>\n </td>\n <td style=\"width:233px;height:19px;\">\n <p>\n <strong>Name</strong></p>\n </td>\n <td style=\"width:214px;height:19px;\">\n <p>\n <strong>Qualification</strong></p>\n </td>\n </tr>\n <tr>\n <td style=\"width:196px;height:19px;\">\n <p>\n Site-Investigator</p>\n </td>\n <td style=\"width:233px;height:19px;\">\n <p>\n Prof. Omu Anzala, MBChB, PhD</p>\n <p>\n  </p>\n <p>\n  </p>\n </td>\n <td style=\"width:214px;height:19px;\">\n <p>\n See above qualifications</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:196px;height:19px;\">\n <p>\n Research clinician(s)</p>\n </td>\n <td style=\"width:233px;height:19px;\">\n <p>\n Dr. Florence Mutua, MBChB, MSc</p>\n <p>\n  </p>\n <p>\n Dr. Rhoda Mutia, MBChB</p>\n <p>\n  </p>\n </td>\n <td style=\"width:214px;height:19px;\">\n <p>\n The research clinicians are very experienced in women’s health and clinical research. They are well trained in screening, enrolling and retaining subjects for research studies.</p>\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:196px;height:20px;\">\n <p>\n Nurse Counselors</p>\n </td>\n <td style=\"width:233px;height:20px;\">\n <p>\n Ms. Janet Muriithi</p>\n <p>\n  </p>\n <p>\n Ms. Jane Odada</p>\n <p>\n  </p>\n </td>\n <td style=\"width:214px;height:20px;\">\n <p>\n Kenya Registered Nurses (KRN) with additional training in counseling. The research nurses are very experienced in women’s health and clinical research.</p>\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:196px;height:20px;\">\n <p>\n Community Mobilizers</p>\n </td>\n <td style=\"width:233px;height:20px;\">\n <p>\n Ms. Rose Mahira</p>\n <p>\n  </p>\n <p>\n Joseph Gachira</p>\n </td>\n <td style=\"width:214px;height:20px;\">\n <p>\n KRN with training in community outreach</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:196px;height:20px;\">\n <p>\n Laboratory Technologists</p>\n </td>\n <td style=\"width:233px;height:20px;\">\n <p>\n Mrs. Kabiru</p>\n <p>\n  </p>\n <p>\n Ms. Susan Odera, Msc</p>\n </td>\n <td style=\"width:214px;height:20px;\">\n <p>\n The laboratory staff have experience with the laboratory procedures required for this study.</p>\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:196px;height:20px;\">\n <p>\n Secretary</p>\n </td>\n <td style=\"width:233px;height:20px;\">\n <p>\n Ms. Christine Obare</p>\n <p>\n  </p>\n </td>\n <td style=\"width:214px;height:20px;\">\n <p>\n Diploma in Secretarial</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:196px;height:20px;\">\n <p>\n Driver</p>\n </td>\n <td style=\"width:233px;height:20px;\">\n <p>\n Mr. Gregory Akoi</p>\n </td>\n <td style=\"width:214px;height:20px;\">\n <p>\n Driving License Class A, B, C & E</p>\n <p>\n  </p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n<p>\n  </p>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td style=\"width:241px;\">\n <p>\n DMID Protocol Number</p>\n </td>\n <td style=\"width:349px;\">\n <p>\n 09-0070</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;\">\n <p>\n Protocol Title</p>\n </td>\n <td style=\"width:349px;\">\n <p align=\"left\">\n A double-blind randomized trial of monthly treatment with topical metronidazole and miconazole and co-formulated suppositories versus placebo for preventing vaginal infection in HIV-seronegative women</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;\">\n <p>\n Proposed site:</p>\n </td>\n <td style=\"width:349px;\">\n <p>\n Korogocho sex workers clinic Nairobi, Kenya</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;\">\n <p style=\"margin-left:.25in;\">\n Site-Investigator’s name</p>\n </td>\n <td style=\"width:349px;\">\n <p>\n Dr. Joshua Kimani</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;\">\n <p style=\"margin-left:.25in;\">\n Name of institution/facility</p>\n </td>\n <td style=\"width:349px;\">\n <p>\n Kenya AIDS Control Project,</p>\n <p>\n College of Health Sciences</p>\n <p>\n University of Nairobi</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;\">\n <p style=\"margin-left:.25in;\">\n City, state, country</p>\n </td>\n <td style=\"width:349px;\">\n <p>\n Nairobi, Kenya</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;height:23px;\">\n <p style=\"margin-left:.25in;\">\n Email address</p>\n </td>\n <td style=\"width:349px;height:23px;\">\n <p>\n jkimani@csrtkenya.org</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;height:23px;\">\n <p style=\"margin-left:.25in;\">\n Brief description of site/facility</p>\n </td>\n <td style=\"width:349px;height:23px;\">\n <p>\n The Korogocho sex workers clinic is housed within a Nairobi City Council owned health clinic. The facility provides primary health care services to about 300,000 Korogocho slum residents and other members of the general population from the surrounding areas.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;\">\n <p>\n Site-Investigator’s experience:</p>\n </td>\n <td style=\"width:349px;\">\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;\">\n <p style=\"margin-left:.25in;\">\n With the protocol topic</p>\n </td>\n <td style=\"width:349px;\">\n <p>\n The site investigator has been involved with targeted interventions for female sex workers in Kenya for the past 15 years. He has also successfully completed three phase III clinical trials. One such trial involved monthly prophylaxis with Azithromycin or placebo to sex workers in Kibera slums an attempt to reduce incident classical STDS and indirectly HIV sero-conversion.  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;height:35px;\">\n <p style=\"margin-left:.25in;\">\n Conducting clinical trials</p>\n </td>\n <td style=\"width:349px;height:35px;\">\n <p>\n The site investigator is GCP trained and formerly a medical director for phase II and III Malaria clinical trials managed by FHI in several countries in Africa.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;\">\n <p>\n Description of clinic facilities and capabilities:</p>\n <p>\n  </p>\n </td>\n <td style=\"width:349px;\">\n <p>\n The facility has ten rooms and three of them are allocated /dedicated to the ongoing ARV/Care and prevention programs targeting female sex workers from the area.</p>\n <p>\n  </p>\n <p>\n The site personnel have the required training and skills to perform all the study specific assessments as per the study protocol.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;\">\n <p>\n Description of lab facilities and capabilities:</p>\n <p>\n  </p>\n </td>\n <td style=\"width:349px;\">\n <p>\n The site laboratory can only support routine tests.  For more advanced laboratory testing, samples routinely collected from the sex workers are transported daily to a central, well-equipped laboratory at the College of Health Sciences. This laboratory built with support from the Canadian Foundation of Innovation (CFI) supports all the diagnostics tests on samples collected from the sex workers programs and results provided to the clinicians in a timely fashion to aid care provision. Hence, the Korogocho health center will only be used as a recruitment, sample collection and follow-up site for the clinical trial.</p>\n <p>\n  </p>\n <p>\n The central laboratory personnel have the required training and skills to perform all the lab tests as per the study protocol.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;\">\n <p>\n Summary of Study Site feasibility:</p>\n </td>\n <td style=\"width:349px;\">\n <p>\n The Korogocho clinic is well placed to execute the study. We have access to a large population of appropriate /suitable clients with incident BV and VVC. The central labs at the College of Health Sciences, University of Nairobi have superb facilities and skilled manpower to support the trial.</p>\n </td>\n </tr>\n </tbody>\n</table>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td colspan=\"3\" style=\"width:590px;\">\n <p>\n Key Personnel at Proposed Study Site:</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:204px;\">\n <p>\n Title</p>\n </td>\n <td style=\"width:190px;\">\n <p>\n Name</p>\n </td>\n <td style=\"width:196px;\">\n <p>\n Qualification</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:204px;\">\n <p>\n Site-Investigator</p>\n </td>\n <td style=\"width:190px;\">\n <p>\n Joshua Kimani, MBChB, MPH</p>\n <p>\n  </p>\n </td>\n <td style=\"width:196px;\">\n <p>\n See above qualifications</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:204px;\">\n <p>\n Study Coordinator/Manager</p>\n </td>\n <td style=\"width:190px;\">\n <p>\n Jessie Kwatampora, MBChB</p>\n <p>\n  </p>\n </td>\n <td style=\"width:196px;\">\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:204px;\">\n <p>\n Research clinician(s)</p>\n </td>\n <td style=\"width:190px;\">\n <p>\n 2 Nurses with either a BSC- Nursing or KRN</p>\n <p>\n  </p>\n </td>\n <td style=\"width:196px;\">\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:204px;\">\n <p>\n Mobilizer</p>\n </td>\n <td style=\"width:190px;\">\n <p>\n BA Social work</p>\n <p>\n  </p>\n </td>\n <td style=\"width:196px;\">\n <p>\n  </p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n<p>\n  </p>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td style=\"width:241px;\">\n <p>\n DMID Protocol Number</p>\n </td>\n <td style=\"width:349px;\">\n <p>\n 09-0070</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;\">\n <p>\n Protocol Title</p>\n </td>\n <td style=\"width:349px;\">\n <p align=\"left\">\n A double-blind randomized trial of monthly treatment with topical metronidazole and miconazole and co-formulated suppositories versus placebo for preventing vaginal infection in HIV-seronegative women</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;\">\n <p>\n Proposed site:</p>\n </td>\n <td style=\"width:349px;\">\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;\">\n <p style=\"margin-left:.25in;\">\n Site-Investigator’s name</p>\n </td>\n <td style=\"width:349px;\">\n <p>\n R. Scott McClelland, MD, MPH</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;\">\n <p style=\"margin-left:.25in;\">\n Name of institution/facility</p>\n </td>\n <td style=\"width:349px;\">\n <p>\n Mombasa HIV/STD Research Site,</p>\n <p>\n Ganjoni Municipal Clinic</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;\">\n <p style=\"margin-left:.25in;\">\n City, state, country</p>\n </td>\n <td style=\"width:349px;\">\n <p>\n Mombasa, Kenya</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;height:23px;\">\n <p style=\"margin-left:.25in;\">\n Email address</p>\n </td>\n <td style=\"width:349px;height:23px;\">\n <p>\n mcclell@u.washington.edu</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;height:23px;\">\n <p style=\"margin-left:.25in;\">\n Brief description of site/facility</p>\n </td>\n <td style=\"width:349px;height:23px;\">\n <p>\n The Mombasa HIV/STD Research Site, established in 1993, is a collaborative effort of the University of Nairobi, the University of Washington (UW), the Kenya Medical Research Institute (KEMRI), the Municipality of Mombasa, the Ministry of Health, Coast Provincial General Hospital (CPGH), The Fred Hutchinson Cancer Research Center (FHCRC) and the US President’s Emergency Program for AIDS Relief. </p>\n <p>\n  </p>\n <p>\n Since 1993, the site has provided VCT to ~8,000 and care to >2,600 at-risk and HIV-positive women enrolled in an ongoing prospective cohort study.  In addition, the site has trained >50 Kenyan researchers and published >100 manuscripts presenting the findings of HIV prevention, treatment, and pathogenesis studies.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;\">\n <p>\n Site-Investigator’s experience:</p>\n </td>\n <td style=\"width:349px;\">\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;height:35px;\">\n <p style=\"margin-left:.25in;\">\n With the protocol topic</p>\n </td>\n <td style=\"width:349px;height:35px;\">\n <p>\n Dr. McClelland is the author of the protocol and has been engaged in research on STIs in women for over 10 years. He is an expert in vaginal infections, women’s health, and HIV/STI epidemiology in Africa.  He has published over 50 peer-reviewed research articles including numerous publications on the epidemiology, prevention, and treatment of bacterial vaginosis, vulvovaginal candidiasis, and trichomoniasis.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;height:387px;\">\n <p style=\"margin-left:.25in;\">\n Conducting clinical trials</p>\n </td>\n <td style=\"width:349px;height:387px;\">\n <p>\n Dr. McClelland has conducted several clinical trials. Most recently, he served as principal investigator for a randomized double-blind, placebo-controlled trial to evaluate the efficacy of monthly oral PPT for reducing the rates of vaginal infections among HIV-seronegative female sex workers (FSW) from Mombasa, Kenya. From May 2003 to November 2005, 378 HIV-seronegative women were screened, of whom 310 (82%) were enrolled and randomly assigned to receive either the intervention regimen (metronidazole 2g plus fluconazole 150mg) or matching placebos as monthly directly observed therapy (DOT).</p>\n <p>\n  </p>\n <p>\n In addition, Dr. McClelland led a randomized, double-blind, placebo-controlled trial that assessed the effect of micronutrient supplementation on cervical and vaginal HIV-1 shedding. From September 1998 to June 2000, 400 women were enrolled in the trial.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;\">\n <p>\n Description of clinic facilities and capabilities:</p>\n <p>\n  </p>\n </td>\n <td style=\"width:349px;\">\n <p>\n The clinic has two fully equipped research examination rooms and four interview/counseling rooms. A separate climate controlled room is available for the storage of pharmaceuticals. The clinic also includes indoor and outdoor waiting areas.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;\">\n <p>\n Description of lab facilities and capabilities:</p>\n <p>\n  </p>\n </td>\n <td style=\"width:349px;\">\n <p>\n The Mombasa STD/HIV Research Site has a clinical laboratory with the ability to perform HIV-1 ELISA, HSV-2 ELISA, cultures for gonorrhea, trichomoniasis and lactobacilli, GenProbe APTIMA Combo2 (CT/GC) detection, microscopy, cryopreservation and storage of samples.</p>\n <p>\n  </p>\n <p>\n All of the laboratory tests specified in the current proposal can be performed at our laboratory.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:241px;\">\n <p>\n Summary of Study Site feasibility:</p>\n </td>\n <td style=\"width:349px;\">\n <p>\n The research staff at the Mombasa STD/HIV Research Site has conducted an ongoing open cohort study of women in this community for 16 years.  The staff is highly experienced in women’s health research and clinical care.  Dr. McClelland and his research team recently completed a similar trial that successfully met it targets for high rates of participant recruitment and retention. </p>\n <p>\n  </p>\n <p>\n We feel that Mombasa STD/HIV Research Site has the physical infrastructure, human resource capacity, and access to the appropriate target population necessary to successfully complete the current trial.  In addition, our laboratory is uniquely suited to provide support not only to the Mombasa site, but for other trial sites in Africa as well. Specifically, our laboratory has the capability and experience with supporting multiple RCT sites for TMA (Gen-Probe) testing for gonorrhea, chlamydia, and trichomoniasis.  The staff’s extensive training and experience with vaginal wet mounts and Gram stains also means that they can provide quality assurance both internally (for Mombasa) and for other participating labs in Africa.</p>\n </td>\n </tr>\n </tbody>\n</table>\n<table border=\"1\" cellpadding=\"0\" cellspacing=\"0\">\n <tbody>\n <tr>\n <td colspan=\"3\" style=\"width:590px;\">\n <p>\n Key Personnel at Proposed Study Site:</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:204px;\">\n <p>\n Title</p>\n </td>\n <td style=\"width:190px;\">\n <p>\n Name</p>\n </td>\n <td style=\"width:196px;\">\n <p>\n Qualification</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:204px;\">\n <p>\n Site-Investigator</p>\n </td>\n <td style=\"width:190px;\">\n <p>\n R. Scott McClelland, MD, MPH</p>\n <p>\n  </p>\n </td>\n <td style=\"width:196px;\">\n <p>\n See above qualifications</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:204px;\">\n <p>\n Co-Investigators</p>\n </td>\n <td style=\"width:190px;\">\n <p>\n Walter Jaoko, MBChB, MMED, PHD</p>\n <p>\n  </p>\n <p>\n Kishorchandra Mandaliya, MBChB</p>\n <p>\n  </p>\n <p>\n Benson Estambale, MBChB, MMED</p>\n <p>\n  </p>\n </td>\n <td style=\"width:196px;\">\n <p>\n The co-investigators have extensive women’s health research experience and have served as co-PI’s on a number of research studies including clinical trials in Mombasa.</p>\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:204px;\">\n <p>\n Study Coordinator/Manager</p>\n </td>\n <td style=\"width:190px;\">\n <p>\n Jennifer Balkus, MPH</p>\n </td>\n <td style=\"width:196px;\">\n <p>\n The study coordinator is experienced in clinical trials and women’s health research.</p>\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:204px;\">\n <p>\n Research clinician(s)</p>\n </td>\n <td style=\"width:190px;\">\n <p>\n Ruth Gitau, MBChB</p>\n <p>\n  </p>\n <p>\n Vernon Mochache, MBChB</p>\n <p>\n  </p>\n <p>\n Linnet N. Masese, MBChB, MPH</p>\n </td>\n <td style=\"width:196px;\">\n <p>\n The research clinicians are very experienced in women’s health and clinical research. They are well trained in screening, enrolling and retaining subjects for research studies.</p>\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:204px;\">\n <p>\n Counselor</p>\n </td>\n <td style=\"width:190px;\">\n <p>\n Francis Kashonga</p>\n </td>\n <td style=\"width:196px;\">\n <p>\n The counselor is very experienced in women’s health and clinical research. He is well trained in screening and enrolling subjects for research studies.</p>\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:204px;\">\n <p>\n Nurses</p>\n </td>\n <td style=\"width:190px;\">\n <p>\n Esther Mutunga</p>\n <p>\n  </p>\n <p>\n Lucy Adala</p>\n <p>\n  </p>\n <p>\n Carol Ngacha</p>\n <p>\n  </p>\n </td>\n <td style=\"width:196px;\">\n <p>\n The research nurses are very experienced in women’s health and clinical research.  They have extensive experience in screening, enrolling and retaining subjects for research studies.</p>\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:204px;\">\n <p>\n Data manager</p>\n </td>\n <td style=\"width:190px;\">\n <p>\n Carol Mwalimu</p>\n <p>\n  </p>\n <p>\n  </p>\n </td>\n <td style=\"width:196px;\">\n <p>\n The data manager is very experienced in providing data management support for clinical research, including randomized controlled trials.</p>\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:204px;\">\n <p>\n Outreach staff</p>\n </td>\n <td style=\"width:190px;\">\n <p>\n George Wanje</p>\n <p>\n  </p>\n <p>\n Jackie Ngina</p>\n <p>\n  </p>\n <p>\n Elizabeth Wanjiku</p>\n <p>\n  </p>\n </td>\n <td style=\"width:196px;\">\n <p>\n The outreach staff are very experienced in recruiting and retaining participants for clinical research studies. </p>\n <p>\n  </p>\n </td>\n </tr>\n <tr>\n <td style=\"width:204px;\">\n <p>\n Laboratory staff</p>\n </td>\n <td style=\"width:190px;\">\n <p>\n Juma Shafi</p>\n <p>\n  </p>\n <p>\n Khamis Mwinyikai</p>\n <p>\n  </p>\n <p>\n Amina Abdalla</p>\n <p>\n  </p>\n <p>\n Emmanuel Kabare</p>\n <p>\n  </p>\n </td>\n <td style=\"width:196px;\">\n <p>\n The laboratory staff have extensive training and experience with the laboratory procedures required for this study.</p>\n </td>\n </tr>\n <tr>\n <td style=\"width:204px;\">\n <p>\n Administrative staff</p>\n </td>\n <td style=\"width:190px;\">\n <p>\n Fatma Mwidadi</p>\n <p>\n  </p>\n <p>\n Jacqueline Dwallo</p>\n </td>\n <td style=\"width:196px;\">\n <p>\n The administrative staff are very experienced in providing administrative support for international clinical research studies.</p>\n <p>\n  </p>\n </td>\n </tr>\n </tbody>\n</table>\n<p>\n  </p>\n
      • other_details_explanation<p class=\"p1\">\n The PVI trial will be conducted in the US as well as in 3 sites in Kenya. At all sites, the trial will include women with high rates of vaginal infections. This is the</p>\n<p class=\"p1\">\n population most likely to benefit from an intervention to reduce vaginal infections. The multisite international trial design is intended to enhance generalizability for</p>\n<p class=\"p1\">\n similar populations of women in a variety of settings.</p>\n
      • other_details_regulatory_notapproved<p>\n All regulatory authorities have granted approval for this study (see section 11.4 below)</p>\n
      • other_details_regulatory_approved<p class=\"p1\">\n Kenyan site approvals: </p>\n<p class=\"p1\">\n The University of Nairobi/Kenyatta National Hospital most recently approved the application for all three Kenyan sites on the following dates: </p>\n<ul>\n <li class=\"p1\">\n Kenya AIDS Vaccine Initative - 14 April 2013</li>\n <li class=\"p1\">\n Kenya AIDS Control Program - 17 March 2013</li>\n <li class=\"p1\">\n Mombasa HIV/STD Research Clinic - 16 March 2013</li>\n</ul>\n<p class=\"p1\">\n The University of Washington Institutional Review Board most recently approved the application for the Mombasa HIV/STD Research Clinic on 07 November 2012.</p>\n<p class=\"p1\">\n The Kenya Pharmacy and Poisons Board approved initial application for this trial on 23 June 2011 and has approved all subsequent progress reports. </p>\n<p class=\"p1\">\n  </p>\n<p class=\"p1\">\n US site approvals: </p>\n<p class=\"p1\">\n The University of Alabama Institutional Review Board most recently approved the University of Alabama site application on 13 June 2013.</p>\n<p class=\"p1\">\n The University of Washington Institutional Review Board most recently approved the  coordinating center application on 12 September 2012.</p>\n<p class=\"p1\">\n The US Food and Drug Administration approved our Investigational New Drug application (IND #110441) on 06 December 2010.</p>\n<p class=\"p1\">\n  </p>\n
      • other_details_regulatory_rejected<p class=\"p1\">\n No regulatory authorities or ethics committees have rejected this protocol.</p>\n
      • other_details_regulatory_halted<p class=\"p1\">\n This trial has not been halted at any stage for any reason.</p>\n
      • estimated_durationWe have allotted 12 months for participant accrual and 12 months of follow-up for each participant; therefore, we estimate the total duration of the trial to be 24 months.
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPlacebo
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states2
      • number_of_sites3
      • multi_country_listKenya (3 sites)\nUSA (1 site)
      • data_monitoring_committeeYes
      • total_enrolment_per_siteKenya AIDS Vaccine Initiative - Kangemi = 59\nKenya AIDS Control Program - Korogocho = 59\nMombasa HIV/STD Research Clinic = 58
      • total_participants_worldwide234
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male0
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameRaymond
      • investigator1_middle_nameScott
      • investigator1_family_nameMcClelland
      • investigator1_qualificationMD, MPH
      • investigator1_professional_addressUniversity of Washington, Box 359909, 325 9th Ave, Seattle, WA, USA, 98104
      • investigator1_telephone+1 206 543-4278
      • investigator1_emailmcclell@uw.edu
      • organisations_transferred_Yes
      • number_participants176
      • notification<p>\n Attached are all progress reports and letters submitted to KPPB since the study received inital approval in 2011. </p>\n
      • approval_date23-06-2011
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted28-06-2013
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report(null)
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2014-02-05 20:54:44
      • created2013-06-07 18:56:12
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id96
        • application_id150
        • given_nameRaymond
        • middle_nameScott
        • family_nameMcClelland
        • qualificationMD, MPH
        • professional_addressUniversity of Washington, Box 359909, 325 9th Ave, Seattle, WA, USA, 98104
        • telephone+1 206 543-4278
        • emailmcclell@uw.edu
        • created2013-06-07 19:12:02
        • modified2013-06-28 23:10:20
    • SiteDetail(array)
      • 0(array)
        • id120
        • application_id150
        • county_id47
        • site_nameKenya AIDS Vaccine Initiative
        • physical_addressUniversity of Nairobi
        • contact_details+254 20 2725404
        • contact_personProf. Omu Anzala
        • site_capacity(null)
        • misc(null)
        • created2013-06-07 19:12:02
        • modified2013-06-28 23:10:20
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 1(array)
        • id121
        • application_id150
        • county_id47
        • site_nameKenya AIDS Control Program
        • physical_addressUniversity of Nairobi
        • contact_details254 20 2713179 or 254 733 7197 11
        • contact_personDr. Joshua Kimani
        • site_capacity(null)
        • misc(null)
        • created2013-06-07 19:33:50
        • modified2013-06-28 23:10:20
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 2(array)
        • id122
        • application_id150
        • county_id1
        • site_nameMombasa HIV/STD Research Clinic
        • physical_addressGanjoni Municipal Clinic, Mnazi Moja Road
        • contact_details+254 053 8015597
        • contact_personDr. Scott McClelland
        • site_capacity(null)
        • misc(null)
        • created2013-06-07 19:33:50
        • modified2013-06-28 23:10:20
        • County(array)
          • id1
          • county_nameMombasa
          • created2012-05-31 16:15:11
          • modified2012-07-09 13:06:23
    • Sponsor(array)
      • 0(array)
        • id77
        • application_id150
        • sponsorUS National Institutes of Health, Department of Microbiology and Infectious Disease
        • sponsor_type(null)
        • contact_personPeter Wolff
        • addressDMID/NIAID/NIH/DHHS, 6610 Rockledge Drive Room 3111, Bethesda, MD, USA 20892
        • telephone_number+1 301 451-3741
        • fax_number
        • cell_number+1 301 451-3741
        • email_addresspwolff@niaid.nih.gov
        • created2013-06-07 19:12:02
        • modified2013-06-28 23:10:20
  • 4(array)
    • Application(array)
      • id619
      • user_id546
      • trial_status_id5
      • abstract_of_study<div>\n Disease Burden</div>\n<div>\n According to the WHO (2015) Malaria is one of the most important infectious diseases which threatens about 3.2 billion people; almost half of the world’s population. Plasmodium falciparum (P. falciparum) malaria is a major cause of morbidity and mortality in Africa. Siaya County in Western Kenya is holoendemic for malaria. At the Siaya Hospital outpatient department alone, data abstraction shows 2000-4000 cases of uncomplicated malaria seen at the facility annually.</div>\n<div>\n  </div>\n<div>\n <div>\n Available remedies</div>\n <div>\n Artemisinin-based combination therapies (ACTs) such as Coartem®/Riamet® and Eurartesim®, are current standard-of-care for P. falciparum malaria. Artemisinin produces rapid clearance of parasitemia and resolution of symptoms by reducing parasite number by 100- to 1000-fold per asexual cycle of the parasite. Artemisinin and its derivatives are rapidly eliminated. It is therefore given in combination with 4-aminoquinoline drugs which have a longer half-life. This requires a three day course of treatment.</div>\n <div>\n  </div>\n <div>\n Emergence of resistance</div>\n <div>\n Recent studies showed that artemisinin resistance extends over more of Southeast Asia than had previously been known, and is now present close to the border with India (Menard et al 2016). If widespread artemisinin drug resistance was to occur, malaria pharmacotherapy would be severely impaired. This finding signifies that spread of resistance is inevitable, thus there is urgent need for new antimalarials with new mechanism of actions (Tun et al 2015).</div>\n <div>\n  </div>\n <div>\n Secondly, evidence suggests that compliance to this 3-day regimen is low, thereby reducing</div>\n <div>\n Treatment effectiveness. New drug combinations are required. Particularly, effective single dose combination treatments will likely improve effectiveness; reduce likelihood of development of drug resistance.</div>\n <div>\n  </div>\n <div>\n  </div>\n <div>\n  </div>\n</div>\n<div>\n  </div>\n
      • study_title<div>\n A Phase 2 interventional, multicenter, randomized <span style=\"font-size: 12px;\">open-label study to determine the effective and tolerable </span><span style=\"font-size: 12px;\">dose of KAF156 and Lumefantrine Solid Dispersion </span><span style=\"font-size: 12px;\">Formulation in combination, given once daily for 1, 2 and </span><span style=\"font-size: 12px;\">3-days to adults and children with uncomplicated </span><span style=\"font-size: 12px;\">Plasmodium falciparum malaria.</span></div>\n<div>\n  </div>\n<div>\n  </div>\n
      • laymans_summary<p>\n A phase 2 interventional, multicentre, randomized open-label study to determine the effective and tolerable dose of KAF156 and Lumefantrine and 3-days to adults and children with uncomplicated <em>plasmodium falciparum</em> malaria</p>\n
      • short_titleEfficacy and safety of KAF156 in combination with LUM-SDF in adults and children with uncomplicated Plasmodium falciparum malaria
      • protocol_noECCT/17/08/03
      • version_no02
      • date_of_protocol14-02-2017
      • study_drugKAF156 plus Lumefantrine vs Coartem®
      • disease_conditionUncomplicated Plasmodium Falciparum Malaria
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_name2-Amino-1-[2-(4- fluoro-phenyl)-3-(4-fluoro-phenyl)amino)-8,8- dimethyl-5,6-dihydro-imidazo[1,2-a]pyrazin- 7(8H)-yl)-ethanone diphosphate
      • product_type_medical_device_name
      • comparatorNo
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      • comparator_registered
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      • ecct_not_applicable0
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      • email_addresstsang@kemricdc.org
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      • declaration_applicantDr Tony Sang
      • declaration_date127-07-2017
      • declaration_principal_investigatorDr Grace Kaguthi (PI)
      • declaration_date227-07-2017
      • placebo_presentNo
      • study_objectives<p>\n <strong>Primary Objective</strong></p>\n<ul>\n <li>\n To determine the effective doses of KAF156 combined with LUM-SDF given daily over 1, 2 or 3 days for treatment of uncomplicated malaria caused by <em>P.falciparum</em>.</li>\n</ul>\n<p>\n  </p>\n<p>\n <strong>Secondary Objectives</strong></p>\n<ul>\n <li>\n To evaluate the safety and tolerability of KAF156/LUM-SDF.</li>\n <li>\n To further assess the effect of treatment with KAF156/LUM-SDF by assessing uncorrected ACPR and corrected ACPR at additional time points, as well as fever- and parasite clearance times.</li>\n <li>\n To assess the key PK parameters of KAF156 and lumefantrine.</li>\n</ul>\n<p>\n  </p>\n<p>\n <strong>Exploratory Objectives</strong></p>\n<ul>\n <li>\n To explore the effect of pharmacokinetic parameters on key efficacy and safety parameters.</li>\n <li>\n To explore the effect of KAF156/LUM-SDF on gametocytes and transmission-blocking potential.</li>\n <li>\n To further explore the effect of treatment with KAF156/LUM-SDF by assessing parasite reduction ratio and the parasite clearance estimator.</li>\n <li>\n To examine the relationship between parasite genotypes of interest and parasite clearance kinetics/efficacy.</li>\n</ul>\n
      • principal_inclusion_criteria<ul>\n <li>\n PK Run-in Part and Part A: male and female patients ≥ 12 years and with a body weight ≥ 35.0 kg. Part B: after determining the effective/tolerated doses and <span style=\"font-size: 12px;\">regimens in adolescent and adult patients, male and female patients ≥ 2 and < 12 years and with a body weight ≥ 10.0 kg will be included.</span></li>\n <li>\n Microscopic confirmation of P. falciparum by Giemsa-stained thick and thin films.</li>\n <li>\n P. falciparum parasitaemia of more than 1000 and less than 150 000 parasites/μL at the time of pre-screening (i.e., Study Visit 1).</li>\n <li>\n Axillary temperature ≥ 37.5 ºC or oral/tympanic/rectal temperature ≥ 38.3 ºC; or similar history of fever during the previous 24 hours (history of fever must be documented).</li>\n <li>\n Written informed consent must be obtained before any assessment is performed. If the patient is unable to read and write, then a witnessed consent according to local ethical standards is permitted. Patients < 18 years old, who are capable of providing assent, must provide assent with parental/legal guardian consent or as per local ethical guidelines.</li>\n</ul>\n
      • principal_exclusion_criteria<ul>\n <li>\n Mixed  Plasmodium infections.</li>\n <li>\n Signs and symptoms of severe malaria according to  WHO  (World Health Organization) 2015 criteria unless characterized by high parasitaemia only.</li>\n <li>\n Patients with concurrent febrile illnesses (e.g., typhoid fever).</li>\n <li>\n Severe vomiting, defined as more than 3 times in the 24 hours prior to inclusion in the study or  severe diarrhea defined as more than 3 watery stools per day.</li>\n <li>\n Pregnant or nursing (lactating) women.</li>\n <li>\n Clinically relevant abnormalities of electrolyte balance which require correction, e.g., hypokalemia, hypocalcemia  or hypomagnesemia.</li>\n <li>\n <div>\n Anemia (Hemoglobin level < 8 g/dL).</div>\n </li>\n <li>\n <div>\n <span style=\"font-size: 12px;\">Patients with prior antimalarial therapy or antibiotics with </span><span style=\"font-size: 12px;\">antimalarial activity within minimum of their five (5) plasma </span><span style=\"font-size: 12px;\">half-lives (or within 4 weeks of screening if half-life is </span><span style=\"font-size: 12px;\">unknown).</span></div>\n </li>\n <li>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-size: 12px;\">History or family history of long QT syndrome or sudden cardiac </span><span style=\"font-size: 12px;\">death, or any other clinical condition known to prolong the QTc </span><span style=\"font-size: 12px;\">(heart rate-corrected QT) interval, such as history of symptomatic </span><span style=\"font-size: 12px;\">cardiac arrhythmias, clinically relevant bradycardia or severe </span><span style=\"font-size: 12px;\">heart disease.</span></span></div>\n </li>\n <li>\n <div>\n <span style=\"font-size: 12px;\"><span style=\"font-size: 12px;\"><span style=\"font-size: 12px;\">Any surgical or medical condition which might significantly alter <span style=\"font-size: 12px;\">the absorption, distribution, metabolism, or excretion of drugs, or </span><span style=\"font-size: 12px;\">which may jeopardize the patient in case of participation in the </span><span style=\"font-size: 12px;\">study. The investigator should make this determination in </span><span style=\"font-size: 12px;\">consideration of the patient’s medical history and/or clinical or </span><span style=\"font-size: 12px;\">laboratory evidence of any of the following:</span></span></span></span></div>\n <ul>\n <li>\n AST/ALT > 2 x the upper limit of normal range (ULN), <span style=\"font-size: 12px;\">regardless of the level of total bilirubin</span></li>\n <li>\n AST/ALT > 1.5 and ≤ 2 x ULN and total bilirubin is > ULN</li>\n <li>\n Total bilirubin > 2 x ULN, regardless of the level of <span style=\"font-size: 12px;\">AST/ALT</span></li>\n </ul>\n </li>\n</ul>\n<div>\n  </div>\n
      • primary_end_points<ul>\n <li>\n PCR-corrected adequate clinical and <span style=\"font-size: 12px;\">parasitological response (ACPR) at Day </span><span style=\"font-size: 12px;\">29 (i.e., 28 days post-dose) in Parts A </span><span style=\"font-size: 12px;\">and B.</span></li>\n <li>\n Assessments of KAF156 exposure in <span style=\"font-size: 12px;\">the PK Run-in cohort to understand the </span><span style=\"font-size: 12px;\">impact of LUM-SDF on KAF156 </span><span style=\"font-size: 12px;\">exposure.</span></li>\n</ul>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic1
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
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      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory1
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n The Siaya Hospital outpatient department sees between 300 and 500 confirmed malaria cases every month aged 6 months to up to 70 years. There are no anticipated challenges to accruing the required sample size. There is also capacity to meet protocol safety monitoring by availability of ECG machine, reliable and reproducible laboratories and availability of trained and experienced microscopists to review slides.</p>\n<p>\n The investigative team comprises a pool of clinical research staff experienced in quality and regulatory requirements, informed consent (five nurses, two clinicians, one medical officer, pharmacist and pharmaceutical technologist) and two data specialist, two laboratory technologists, three QA staff, as well as an administrative staff: drivers and administrative assistants. Siaya site will recruit between 70 and 100 patients. </p>\n
      • other_details_explanation<p>\n Trial will be conducted in the applicants country.</p>\n
      • other_details_regulatory_notapproved<p>\n N/A</p>\n
      • other_details_regulatory_approved<p>\n KEMRI Scientifc Ethics Review Unit approved the study on <span style=\"font-size: 12px;\">21 Jun 2017</span></p>\n<p>\n Number of Kenyan sites  2</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration43 Days per subject
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorArtemether-lumefantrine (
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKEMRI Siaya
      • single_site_physical_addressSiaya County Referral Hospital
      • single_site_contact_personDr Grace Kiringa
      • single_site_telephone+254729489743
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states9
      • number_of_sites
      • multi_country_listKenya, Uganda,Mozambique, Gabon, Burkina Faso, Vietnam, Thailand, Gambia, Mali
      • data_monitoring_committeeYes
      • total_enrolment_per_siteSite will recruit a total of between 70- 100 patients in part A and part B.
      • total_participants_worldwideThe plan is to enroll and treat 12 patients in PK Run-in Part and randomize approximately 500 patients in Parts A and B (325 in Part A and up to 175 in Part B) in approximately 15 sites in Africa and Asia.
      • 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
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameVidelis
      • investigator1_middle_nameKenya Medical Research Institute (KEMRI)Research Collaboration Campus, Off Busia Road, Kisian, Kenya.P.O Box 1578-40100
      • investigator1_family_nameNduba
      • investigator1_qualificationPHD in Epidemiology
      • investigator1_professional_addressKEMRI / CRDR
      • investigator1_telephone+254 (0) 724522474
      • investigator1_emailvnduba@gmail.com
      • organisations_transferred_No
      • number_participantsCompetitive
      • notification
      • approval_date02-10-2017
      • submitted1
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      • deleted_date(null)
      • deactivated0
      • date_submitted28-07-2020
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      • approved2
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      • quantity_destroyed(null)
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      • balance_site(null)
      • final_date(null)
      • modified2022-03-10 16:36:10
      • created2017-07-20 11:13:09
      • total_sites(null)
      • ecitizen_invoice(null)
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        • professional_addressKenya Medical Research Institute (KEMRI)Research Collaboration Campus, Off Busia Road, Kisian, Kenya.P.O Box 1578-40100
        • telephone+254(0) 729489743
        • emailskiringa@gmail.com
        • created2017-07-20 12:12:15
        • modified2020-07-28 17:41:59
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        • created2017-07-20 12:12:15
        • modified2020-07-28 17:41:59
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        • id318
        • application_id619
        • sponsorNovartis Pharma AG
        • sponsor_typeIndustry
        • contact_personHavana Chikoto
        • addressLichtstrasse 35, CH4056, Basel, Switzerland
        • telephone_number+41 61 324 1111
        • fax_number
        • cell_number+41 61 324 1111
        • email_addresshavana.chikoto@novartis.com
        • created2017-07-20 12:12:15
        • modified2020-07-28 17:41:59
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