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• applications(array)
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    • Application(array)
      • id575
      • user_id56
      • trial_status_id7
      • abstract_of_study<p>\n The World Health Organization recommends ART at any CD4 count for persons with HIV-1 infection, particularly those with HIV-1 uninfected partners, and PrEP for persons at high risk of HIV-1 acquisition. The Kenya Ministry of Health has developed an ambitious HIV Prevention Revolution Road Map 2030, including provision of ART regardless of CD4 count and PrEP for HIV-1 serodiscordant couples. In July 2016, the Ministry of Health in Kenya released “Guidelines on use of Antiretroviral Drugs for Treating and Preventing HIV infections in Kenya” which recommend initiation of ART for all HIV infected persons irrespective of CD4 count and oral PrEP for HIV-1 uninfected persons with substantial ongoing risk of HIV infection, including HIV discordant couples. Nevertheless, delivery approaches that will catalyze scale-up of PrEP and ART have not been implemented. HIV-1 care in Kenya is principally delivered through public health HIV-1 care centers, thus offering an existing platform for incorporating clinical prevention services for couples. This project will scale-up integrated PrEP and ART for HIV-1 serodiscordant couples in Kenya to 24 HIV-1 care centers in several counties in Central (former central province) and Western (former Nyanza and Western) Kenya. It will include a delivery component in whichPrEP will be delivered according to Kenyan national guidelines, utilizingthe integrated PrEP as a bridge to ART approach. We will conductmonitoring and evaluation activities will identify implementation barriers and solutions, characterize costs, and provide best practices for further scale-up. A research component will establish prospective open cohorts of couples at each clinic, who will be offered PrEP and ARTaccording to Kenyan national guidelines; follow-up in the cohorts will evaluate impact and facilitators and barriers to implementation at levels from the patient to the health system.</p>\n
      • study_title<p>\n Animplementation project to scale-up delivery of antiretroviral-based HIV-1 prevention amongKenyan HIV-1 serodiscordant couples.</p>\n
      • laymans_summary<p>\n Antiretroviral-based HIV-1 prevention strategies – including antiretroviral treatment (ART) to reduce the infectiousness of HIV-1 infected persons and pre-exposure prophylaxis (PrEP) for uninfected persons to prevent HIV-1 acquisition – are among the most promising new approaches for dramatically decreasing HIV-1 spread worldwide. A priority population for implementation of ART and PrEP for HIV-1 prevention is HIV-1 serodiscordant couples (i.e., one member is HIV-1 infected and the other uninfected). In Kenya, heterosexual HIV-1 serodiscordant couples face high risk of HIV-1 transmission and account for a substantial fraction of new infections. Over the past decade, randomized trials and other clinical investigations have definitively demonstrated that both ART and PrEP have high HIV-1 protection efficacy when used by members of HIV-1 serodiscordant couples. A pragmatic, integrated approach to providing ART and PrEP, with ART promoted for the HIV-1 infected partner in all couples and PrEP offered until six months after ART initiation by the HIV-1 infected partner to permit time to achieve virologic suppression (a strategy called “PrEP as a bridge to ART”), resulted in near-elimination of HIV-1 transmission in a demonstration project among HIV-1 serodiscordant couples.</p>\n
      • short_titleThe Partners Scale-Up Project
      • protocol_noECCT/16/12/01
      • version_noVersion 1.1
      • date_of_protocol28-10-2016
      • study_drugEmtricitabine 200Mg/tenofovirdisoproxil fumarate 300Mg(TDF) (TRUVADA)
      • disease_conditionHIV/AIDS
      • 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_nameTruvada
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressaachoka@kemri-ucsf.org
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
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      • declaration_applicantDr. Stella Njuguna, P.O Box 614-40100 Kisumu
      • declaration_date119-12-2016
      • declaration_principal_investigatorProf. ElizabethBukusi, P.O Box 614-40100 Kisumu
      • declaration_date219-12-2016
      • placebo_presentNo
      • study_objectives<p>\n Objective 1: Deliver integrated PrEP and ART for HIV-1 serodiscordant couples at scale in public HIV-1 care centers in Kenya and evaluate program impact. We will introduce the PrEP as a bridge to ART strategy into public HIV-1 care centers according to national guidelines, and we will rigorously evaluate how effectively this strategy is disseminated and implemented. Key endpoints will include: a) proportion of HIV-1 infected persons whose partners are tested for HIV-1, b) rates of PrEP initiation, adherence, and discontinuation by HIV-1 uninfected partners until their HIV-1 infected partners initiate ART and sustain use for six months, c) ART initiation and adherence by HIV-1 infected individuals, d) couples achieving optimized antiretroviral-based prevention coverage (i.e., high adherence to at least one antiretroviral intervention), and e) HIV-1 uninfected partners staying HIV-1 uninfected. Note: Both ART and PrEP have regulatory and normative guidance sanction in Kenya and are not investigational agents. Thus, the research components of this Objective will focus on optimizing their delivery, rather than on research related to the medications themselves.</p>\n<p>\n Objective 2: Assess facilitators and barriers to a) implementation of integrated PrEP and ART in delivery settings and b) optimized PrEP and ART adherence. In parallel with Objective 1, we will conduct mixed-methods assessments of a) PrEP and ART integration at the level of the provider, health center, and health system and b) adherence at the levels of individuals and dyads. We will use this data iteratively to optimize implementation. Adherence to PrEP and ART will be quantified.</p>\n<p>\n Objective 3: Determine efficiency, cost, and cost-effectiveness of the integrated PrEP and ART when delivered in public health clinics. We will conduct time and motion studies to optimize delivery efficiency, define the costs, and model the cost-effectiveness of PrEP as a bridge to ART, in terms of infections averted, disability-adjusted life years saved, and incremental cost-effectiveness over routine HIV-1 care.</p>\n<p>\n Objective 4: Develop operational tools that will expand and support delivery of integrated PrEP and ART at scale and secure buy in from relevant stakeholders to ensure delivery continues to scale up at the national level. As part of the Objective 1 delivery work, and refined through information learned in Objectives 2 and 3, we will develop training materials, clinical delivery products, and assessment tools. We will also coordinate with program and policy stakeholders to optimize supply chain management, commodities, and training regarding PrEP in Kenya. Finally, we will work with government, civil society, clinical providers and community to provide the necessary foundation to further expand integrated delivery of PrEP and ART at a wider scale in Kenya.</p>\n
      • principal_inclusion_criteria<p>\n Eligibility For HIV-1 uninfected members of the couple - Age ≥18 - Able and willing to provide consent for follow-up in the cohort - HIV-1 uninfected based on negative HIV-1 tests, per Kenya national guidelines - Not currently using PrEP For HIV-1 infected members of the couple - Age ≥18 - Able and willing to provide consent for follow-up in the cohort - HIV-1 infected based on positive HIV-1 tests, per Kenya national guidelines - Not currently using ART For key delivery informants - Able and willing to provide consent For both members of the couple - Meet criteria for initiating PrEP as per Kenya national guidelines, including: o HIV-1 infected member not currently using ART, on ART <6 months, or on ART but not virally suppressed based on a viral load test done at the clinic as per Kenya national guidelines or o Trying to conceive</p>\n
      • principal_exclusion_criteria<p>\n Unable to provide consent, both couples are HIV-1 positive or the positive member is on ART, less than 18 years of age and doesnt meet the iclusion criteria above.</p>\n
      • primary_end_points<p>\n Key endpoints will include: a) HIV-1 infected persons whose partner completes HIV-1 testing, b) PrEP initiation and sustained use by HIV-1 uninfected partners through ART initiation and adherence by their infected partner, c) ART initiation and sustained use by HIV-1 infected persons, d) HIV-1 uninfected partners staying HIV-1 uninfected, and e) couples achieving optimized HIV-1 prevention coverage (defined as PrEP with high adherence, ART with viral suppression, or overlap of the two during the bridge period plus no HIV-1 transmission).We will characterizecouples’ risk profiles using our validated risk score [21], which we can use to further predict HIV-1 incidence in the absence of intervention. Finally, in our prior work, retention in prevention services is a strong measure of acceptability and predictor of HIV-1 protection, as loss to follow-up eliminates access to PrEP/ART; we will measure retention in care, as this is also a feasible measure for public health delivery. Finally, our data [43] do not support sexual risk taking in couples but we will analyze for risk compensation and finalize messaging as part of our counseling materials. We will conduct quantitative and qualitative work to assess barriers and facilitators to use of PrEP as a bridge to ART in couples.Adherence to ART and PrEP will be measured through pharmacy refill (i.e., picking up each new supply, which is a feasible measure for an implementation setting), self-report (e.g., frequency, ability, and self-rating, missed doses)[53, 66, 67], and biologic measures (plasma HIV-1 RNA in those on ART and plasma tenofovir in those on PrEP [a random subset plus seroconverters]). Our goal is to understand both execution (i.e., adherence while used) and persistence (i.e., duration of use). We will use multivariable proportional hazards models to assess correlates of time to initiation and generalized estimating equations to assess adherence correlates.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • scope_therapy0
      • scope_safety0
      • scope_efficacy0
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other1
      • trial_other_specifyImplementation sciense
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use1
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p>\n Principal Investigator-1</p>\n<p>\n Co-Principal Investigator-1</p>\n<p>\n Study coordinator-1</p>\n<p>\n Research Assistants-4</p>\n<p>\n Laboratory Technologists-1</p>\n<p>\n Data manager -1</p>\n<p>\n Sample collectors-1</p>\n<p>\n Community health workers-3</p>\n<p>\n Pharmaceutical Technologist- 1</p>\n<p>\n <strong>FACILITIES:</strong></p>\n<p>\n Site pharmacy</p>\n<p>\n Laboratory</p>\n<p>\n Office space</p>\n<p>\n  </p>\n
      • other_details_explanation<p>\n The trial will be conducted in Two sites in Kenya</p>\n
      • other_details_regulatory_notapproved<p>\n NONE</p>\n
      • other_details_regulatory_approved<p>\n UNIVERSITY OF WASHINGTON IRB</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_durationUpto 36 Months
      • 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_countriesNo
      • multiple_member_states
      • number_of_sites2
      • multi_country_list
      • data_monitoring_committeeNo
      • total_enrolment_per_site2400 Per site
      • total_participants_worldwide4800
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsNo
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_name Dr. Stella Njuguna
      • investigator1_middle_name
      • investigator1_family_nameNjuguna
      • investigator1_qualificationB.Pharm/MPH
      • investigator1_professional_addressP.O BOX 614-40100 Kisumu
      • investigator1_telephone+254 722422977
      • investigator1_emailnjugunastella@gmail.com
      • organisations_transferred_No
      • number_participants4800
      • notification
      • approval_date13-02-2017
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted25-02-2020
      • 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)
      • modified2021-03-04 16:06:11
      • created2016-12-09 15:42:19
      • total_sites(null)
      • ecitizen_invoice(null)
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        • id372
        • application_id575
        • given_nameProf. Elizabeth
        • middle_nameAnn
        • family_nameBukusi
        • qualificationBachelor of Medicine and Bachelor of surgery/Master of Medicine inObstetrics and Gynacology
        • professional_addressP.O BOX 614-40100 Kisumu
        • telephone(254) (020) 2722541/ +254 57 2021036
        • emailebukusi@kemri.org
        • created2016-12-09 15:51:50
        • modified2020-02-25 14:50:14
    • SiteDetail(array)
      • 0(array)
        • id468
        • application_id575
        • county_id42
        • site_nameKISUMU SITE
        • physical_addressAGOI STREET
        • contact_detailsP.O Box 614-40100 KISUMU
        • contact_personDr. Stella Njuguna
        • site_capacity(null)
        • misc(null)
        • created2016-12-09 15:51:50
        • modified2020-02-25 14:50:14
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 1(array)
        • id469
        • application_id575
        • county_id22
        • site_nameThika Site
        • physical_addressParrtners in Prevention, Thika
        • contact_detailsP.O Box Thika
        • contact_personDr. Elizabeth Irungu
        • site_capacity(null)
        • misc(null)
        • created2016-12-09 16:23:24
        • modified2020-02-25 14:50:14
        • County(array)
          • id22
          • county_nameKiambu
          • created2012-06-15 10:24:37
          • modified2012-06-15 10:24:37
    • Sponsor(array)
      • 0(array)
        • id298
        • application_id575
        • sponsorUniversity of Washington
        • sponsor_typeOthers
        • contact_personJared Beaten
        • addressInternational Clinical Research Center, P.O Box 359927, 325 Ninth Ave, Seattle, WA 98104
        • telephone_number+1-206-520-3808
        • fax_number1-206-520-3808
        • cell_number+1-206-520-3808
        • email_addressjbeaten@uw.edu
        • created2016-12-09 15:51:50
        • modified2020-02-25 14:50:14
  • 1(array)
    • Application(array)
      • id568
      • user_id613
      • trial_status_id5
      • abstract_of_study<p>\n The abstract/synopsis of this protocol is detailed on Page 15 of the protocol attached.</p>\n
      • study_title<p>\n A randomized, obsever-blind, placebo controlled, two-part, Phase 2 study to evaluate the Safety, Tolerability and Immunogenicity of Two prime-boost regimen of the candidate Prophylactic vaccines for Ebola Ad26-ZEBOV and MVA-BN Filo.</p>\n
      • laymans_summary<div>\n The sponsor, in collaboration with Bavarian Nordic GmbH (BN) and Walter Reed Army Institute of Research (WRAIR), is investigating the potential of a prophylactic Ebola vaccine regimen comprised of the following 2 candidate Ebola vaccines: Ad26.ZEBOV is a monovalent vaccine expressing the full length Ebola virus (EBOV, formerly known as Zaire ebolavirus) Mayinga glycoprotein (GP), and is produced in the human cell line PER.C6®. MVA-mBN226B, further referred to as Modified Vaccinia Ankara (MVA)-BN-Filo®, is a multivalent vaccine expressing the Sudan virus (SUDV) GP, the EBOV GP, the Marburg virus (MARV) Musoke GP, and the Tai Forest virus (TAFV, formerly known as Côte d’Ivoire ebolavirus) nucleoprotein (NP), and is produced in chicken embryo fibroblast cells. The EBOV GP expressed by MVA-BN-Filo has 100%</div>\n<div>\n homology to the one expressed by Ad26.ZEBOV.</div>\n<div>\n Two populations will be studied in this protocol: healthy adults and human immunodeficiency virus (HIV)-infected adults, ages 18-70 years inclusive, will be enrolled.</div>\n
      • short_titleRV 456: Vaccines for Ebola Ad26.ZEBOV and MVA-BN-Filo
      • protocol_noECCT/16/11/05
      • version_noApproved version dated 08 March 2016
      • date_of_protocol08-03-2016
      • study_drugEbola Ad26.ZEBOV and MVA-BN-Filo vaccines
      • disease_conditionEbola
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorYes
      • comparator_nameNormal Saline Placebo
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressjosphat.kosgei@usamru-k.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_countries0
      • 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_african0
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantDr Josphat Kosgei
      • declaration_date114-11-2016
      • declaration_principal_investigatorDr Fredrick Sawe
      • declaration_date214-11-2016
      • placebo_presentYes
      • study_objectives<div>\n Primary Objectives</div>\n<div>\n • To assess the safety and tolerability of different vaccination schedules of Ad26.ZEBOV and</div>\n<div>\n MVA-BN-Filo administered intramuscularly (IM) as heterologous prime-boost regimens in healthy</div>\n<div>\n adults and in HIV-infected adults, with Ad26.ZEBOV prime and MVA-BN-Filo boost vaccination</div>\n<div>\n on Days 1 and 29, respectively and MVA-BN-Filo prime and Ad26.ZEBOV boost vaccination on</div>\n<div>\n Days 1 and 15, respectively.</div>\n<div>\n • To assess the immune responses to the EBOV GP (as measured by [enzyme-linked immunosorbent</div>\n<div>\n assay] ELISA antibody concentration) of different vaccination schedules of Ad26.ZEBOV and</div>\n<div>\n MVA-BN-Filo administered IM as heterologous prime-boost regimens in healthy adults and in</div>\n<div>\n HIV-infected adults, with Ad26.ZEBOV prime and MVA-BN-Filo boost vaccination on Days 1 and</div>\n<div>\n 29, respectively and MVA-BN-Filo prime and Ad26.ZEBOV boost vaccination on Days 1 and 15,</div>\n<div>\n respectively.</div>\n
      • principal_inclusion_criteria<p>\n Healthy adults, both HIV negative and positive, aged 18 to 70 years.</p>\n
      • principal_exclusion_criteria<p>\n Recepient of Ebola vaccine previosly.</p>\n<p>\n Has been diagnosed with Ebola virus infection.</p>\n
      • primary_end_points<p>\n Safety, as assessed by adverse events.</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 The site has the capacity to conduct the study, in terms of human resources, infrastructure, experience, emergency facilities. This is well detailed in the Site Specific Addendum attached.</p>\n
      • other_details_explanation<p>\n Not Applicable</p>\n
      • other_details_regulatory_notapproved<p>\n None.</p>\n
      • other_details_regulatory_approved<p>\n KEMRI SERU approved on October 17 2016.</p>\n
      • other_details_regulatory_rejected<p>\n Not Applicable.</p>\n
      • other_details_regulatory_halted<p>\n Not Applicable.</p>\n
      • estimated_duration64 weeks
      • 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_states6
      • number_of_sites2
      • multi_country_listUSA, Kenya, Nigeria, Uganda, Tanzania, Mozambique
      • data_monitoring_committeeYes
      • total_enrolment_per_site100 in Kericho and 50 in Kombewa, Kisumu
      • total_participants_worldwide575
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsNo
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameElizabeth
      • investigator1_middle_nameChebet
      • investigator1_family_nameNgetich
      • investigator1_qualificationBSc (Nursing), CRA
      • investigator1_professional_addressKEMRI/WRP Kericho
      • investigator1_telephone+254 713 603 217
      • investigator1_emailelizabeth.ngetich@usamru-k.org
      • organisations_transferred_Yes
      • number_participants150
      • notification
      • approval_date02-03-2017
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted18-03-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<p>\n This study was a  Randomized, Observer-blind, Placebo-controlled, Two-part, Phase 2 Study to Evaluate the Safety, Tolerability and Immunogenicity of Two Prime-boost Regimens of the Candidate Prophylactic Vaccines for Ebola Ad26.ZEBOV and MVA-BN-Fil. The primary objectives of this study were to  assess the safety and tolerability of different vaccination schedules of Ad26.ZEBOV and MVA-BN-Filo administered intramuscularly (IM) as heterologous prime-boost regimens in healthy adults and in HIV-infected adults, with Ad26.ZEBOV prime and MVA-BN-Filo boost vaccination on Days 1 and 29, respectively and MVA-BN-Filo prime and Ad26.ZEBOV boost vaccination on Days 1 and 15, respectively.</p>\n<p>\n People without HIV (PWOH) and people living with HIV (PLWH) aged 18-70 years were enrolled at six sites in five African countries: Kenya, Mozambique, Nigeria, Tanzania, and Uganda. A CD4+ cell count >200 cells/μL at screening was an eligibility requirement for PLWH, and those with a screening CD4+ cell count >200 to <350 cells/μL must have been on stable antiretroviral therapy (ART; no regimen change in the four weeks preceding screening). All participants provided written informed consent. The RV 456b study enrolled healthy subjects and HIV-infected subjects, both male and female (aged 18 to 70 years inclusive). There are no changes from the anticipated population.</p>\n<p>\n No study-related SAE was reported for the RV 456b during the study. The majority of solicited AEs across all sites were of mild-to-moderate severity in the 14- and 28-day interval groups. Additionally, most solicited AEs were ≤3 days in duration (61% and 91% of solicited local AEs in the vaccine and placebo groups, respectively, and 53% and 50% of solicited systemic AEs, respectively). The most frequent (occurring in >20% of participants) solicited local AEs were injection-site pain and injection-site pruritus, while the most frequent (occurring in >40% of participants) solicited systemic AEs were fatigue, headache, and myalgia. All SAEs were considered unrelated to the study vaccine. No deaths were reported.</p>\n<p>\n  </p>\n
      • implication_results<p>\n This is the first study to demonstrate safety and EBOV GP-specific immunogenicity in PLWH with an Ebola vaccination regimen of MVA-BN-Filo followed by Ad26.ZEBOV 14 days later. These results show that an accelerated vaccination schedule is well tolerated in both PWOH and PLWH and induces a broad array of durable humoral and cellular immune responses. These findings support continued consideration for accelerated regimen development for rapid deployment among outbreak responders and relevant global populations at immediate risk.</p>\n<p>\n The following publications resulted from this study:</p>\n<ul>\n <li>\n Ake, J.A.; Paolino, K.; Hutter, J.N.; Cicatelli, S.B.; Eller, L.A.; Eller, M.A.; Costanzo, M.C.; Paquin-Proulx, D.; Robb, M.L.; Tran, C.L.; et al. <em><strong>Safety and Immunogenicity of an Accelerated Ebola Vaccination Schedule in People with and without Human Immunodeficiency Virus: A Randomized Clinical Tria</strong></em>l. Vaccines 2024, 12, 497. https://doi.org/10.3390/vaccines12050497</li>\n <li>\n Betty Mwesigwa, Fredrick Sawe, Janet Oyieko, Joel Mwakisisile, Edna Viegas, Gideon Akindiran Akintunde, Josphat Kosgei, Afoke Kokogho, Nyanda Ntinginya, Ilesh Jani, Georgi Shukarev, Jay W Hooper, Steven A Kwilas, Lucy A Ward, Janice Rusnak, Callie Bounds, Rachel Overman, Christopher S Badorrek, Leigh Anne Eller, Michael A Eller, Christina S Polyak, Amber Moodley, Chi L Tran, Margaret C Costanzo, David J Leggat, Dominic Paquin-Proulx, Prossy Naluyima, Dickson Nkafu Anumendem, Auguste Gaddah, Kerstin Luhn, Jenny Hendriks, Chelsea McLean, Macaya Douoguih, Hannah Kibuuka, Merlin L Robb, Cynthia Robinson, Julie A Ake, <em><strong>Safety and Immunogenicity of Accelerated Heterologous Two-dose Ebola Vaccine Regimens in Adults With and Without HIV in Africa</strong></em>, Clinical Infectious Diseases, 2024;, ciae215, https://doi.org/10.1093/cid/ciae215</li>\n</ul>\n<p>\n  </p>\n<p>\n  </p>\n
      • quantity_importedFind attached RV 456 Study Product Recovery Reports
      • quantity_dispensedFind attached RV 456 Study Product Recovery Reports
      • quantity_destroyedFind attached RV 456 Study Product Recovery Reports
      • quantity_exportedFind attached RV 456 Study Product Recovery Reports
      • balance_siteFind attached RV 456 Study Product Recovery Reports
      • final_date0000-00-00
      • modified2024-10-17 16:17:40
      • created2016-11-14 06:53:35
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id367
        • application_id568
        • given_nameFredrick
        • middle_nameKipyego
        • family_nameSawe
        • qualificationMBChB, MMED
        • professional_addressKEMRI/WRP Kericho
        • telephone+254 703 247 902
        • emailfredrick.sawe@usamru-k.org
        • created2016-11-14 07:06:27
        • modified2020-03-18 07:52:01
    • SiteDetail(array)
      • 0(array)
        • id447
        • application_id568
        • county_id35
        • site_nameKEMRI/WRP Kericho
        • physical_addressKericho
        • contact_detailsP.O. Box 1357-20200
        • contact_personDr Fredrick Sawe
        • site_capacity(null)
        • misc(null)
        • created2016-11-14 07:06:27
        • modified2020-03-18 07:52:01
        • County(array)
          • id35
          • county_nameKericho
          • created2012-06-15 10:26:16
          • modified2012-06-15 10:26:16
      • 1(array)
        • id448
        • application_id568
        • county_id42
        • site_nameKEMRI/WRP Kombewa, Kisumu
        • physical_addressKombewa
        • contact_details+254 721 996 988
        • contact_personDr Janet Oyieko
        • site_capacity(null)
        • misc(null)
        • created2016-11-14 07:44:29
        • modified2020-03-18 07:52:01
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
    • Sponsor(array)
      • 0(array)
        • id293
        • application_id568
        • sponsorCrucell Holland B.V., a Janssen pharmaceutical company of Johnson & Johnson
        • sponsor_typeIndustry
        • contact_person
        • addressArchimedesweg 4, 2333 CN Leiden, Netherlands
        • telephone_number+31715199100
        • fax_number
        • cell_number+31715199100
        • email_addressJanssenIDVNL@its.jnj.com
        • created2016-11-14 07:06:27
        • modified2020-03-18 07:52:01
  • 2(array)
    • Application(array)
      • id569
      • user_id360
      • trial_status_id7
      • abstract_of_study<p>\n SYNOPSIS A Randomized, Observer-blind, Placebo-controlled, Two-part, Phase 2 Study to Evaluate the Safety, Tolerability and Immunogenicity of Two Prime-boost Regimens of the Candidate Prophylactic Vaccines for Ebola Ad26.ZEBOV and MVA-BN-Filo. The sponsor, in collaboration with Bavarian Nordic (BN) and Walter Reed Army Institute of Research (WRAIR), is investigating the potential of a prophylactic Ebola vaccine regimen comprised of the following 2 candidate Ebola vaccines: Ad26.ZEBOV is a monovalent vaccine expressing the full length Ebola virus (EBOV, formerly known as Zaire ebolavirus) Mayinga glycoprotein (GP), and is produced in the human cell line PER.C6®. MVA-mBN226B, further referred to as Modified Vaccinia Ankara (MVA)-BN-Filo®, is a multivalent vaccine expressing the Sudan virus (SUDV) GP, the EBOV GP, the Marburg virus (MARV) Musoke GP, and the Tai Forest virus (TAFV, formerly known as Côte d’Ivoire ebolavirus) nucleoprotein (NP), and is produced in chicken embryo fibroblast cells. The EBOV GP expressed by MVA-BN-Filo has 100% homology to the one expressed by Ad26.ZEBOV. Two populations will be studied in this protocol: healthy adults and human immunodeficiency virus (HIV)-infected adults, ages 18-70 years inclusive, will be enrolled. Ad26.ZEBOV and MVA-BN-Filo will be evaluated as a heterologous prime-boost regimen. The first schedule to be evaluated is prime vaccination with MVA-BN-Filo followed by a boost with Ad26.ZEBOV 14 days later. In the second schedule, Ad26.ZEBOV is used to prime a filovirus-specific immune response and MVA-BN-Filo is used to boost the immune response 28 days later. The EBOV GP that is currently circulating in West Africa has 97% homology to the EBOV GP used in this vaccine regimen. STUDY RATIONALE • Enlarge the safety and immunogenicity database for the Ad26.ZEBOV/MVA-BN-Filo 1, 29-day prime-boost regimen in healthy adults. • Assess the safety and immunogenicity of Ad26.ZEBOV/MVA-BN-Filo 1, 29-day prime-boost regimen in HIV-infected subjects and determine the effect of vaccination on HIV disease. • Enlarge the safety and immunogenicity database for MVA-BN-Filo/Ad26.ZEBOV 1, 15 day prime-boost regimen in healthy adults and HIV-infected adults.</p>\n<p>\n  </p>\n
      • study_title<p>\n A Randomized, Observer-blind, Placebo-controlled, Two part, Phase 2 Study to Evaluate the Safety, Tolerability and Immunogenicity of Two Prime-boost Regimens of the Candidate Prophylactic Vaccines for Ebola Ad26.ZEBOV and MVA-BN-Filo</p>\n
      • laymans_summary<p>\n Ebola virus disease is caused by an infection with a virus known as the Ebolavirus. The disease is characterized by symptoms such as fever, body aches, diarrhoea, bleeding, and vomiting. According to the World Health Organization, the number of people who die among the population having Ebola virus disease ranges from 25% to 90%. Vaccination is one of the most effective ways to prevent illness caused by viruses. A vaccine contains a non-functional part of the virus that is recognized by the body's protective immune system. The body then produces a response that prevents illness if the person is exposed to that virus again. This process is known as an immune response. The investigational treatment consists of a 2 dose vaccine regimen, 1 dose of Ad26.ZEBOV and 1 dose of MVA-BN-Filo vaccine, for the prevention of Ebola virus disease (Zaire ebolavirus species). This combination will be given at 2 different intervals between the 2 vaccine doses. The first schedule will include MVA-BN-Filo as the first dose followed by Ad26.ZEBOV as the second dose. The second schedule will include Ad26.ZEBOV as the first dose followed by MVA-BN-Filo as the second dose. In this study, researchers want to know the safety of the Ebola vaccine regimen in healthy adults and in human immunodeficiency virus (HIV*)-infected adults when administered using different vaccination schedules and interval. In addition, researchers want to understand the immune responses induced by the Ebola vaccine regimen by performing some tests. *HIV infection affects cells of the immune system and decreases their ability to fight infections. Participants can take part in this study if they have never received an Ebola vaccine, have not been diagnosed with Ebola virus disease, and have not travelled to any place where Ebola virus disease was confirmed up to 1 month before the study starts. Participants in the HIV-infected cohort should have a documented HIV infection within 6 months before the study start and be taking medicines for the treatment of HIV infection for the duration of the study. During the study, all participants will go through screening to confirm if they can take part in the study. Once enrolled, participants will be divided into 2 groups, healthy adults and participants with HIV infection between 18 to 70 years of age. All participants will receive either study vaccine (Ad26.ZEBOV, MVA-BN-Filo) or placebo, which does not contain the study vaccine, but looks like it. All vaccines will be given as an injection in the muscle. This study will be conducted in 2 parts: • • In Part 1 performed in the USA, participants will receive MVA-BN-Filo or placebo on Day 1 followed by Ad26.ZEBOV or placebo on Day 15. • • In Part 2 performed in Africa, participants will be further divided into 2 groups. • o Participants in Group 1 will receive Ad26.ZEBOV or placebo on Day 1 followed by MVA-BN-Filo or placebo on Day 29. • o Participants in Group 2 will receive MVA-BN-Filo or placebo on Day 1 followed by Ad26.ZEBOV or placebo on Day 15. During the study, participants will undergo different study assessments and tests. These include blood tests, vital signs (such as pulse, blood pressure, and temperature), electrocardiograms, physical exams, and pregnancy test for women. Any side effects reported by the participants will also be recorded throughout the study. Blood samples will be taken at several time points to understand how many participants responded to the vaccine regimen and to what extent. There will be a follow-up phase up to 1 year after the second dose to monitor the participants’ health and to collect blood samples for immune response assessments. The overall duration of the study will be approximately 3 years.</p>\n
      • short_titleRV456
      • protocol_noECCT/16/11/04
      • version_noAmendment 2
      • date_of_protocol08-03-2016
      • study_drugAd26.ZEBOV and MVA-BN-Filo
      • disease_conditionEBOLA
      • product_type_biologicals1
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device0
      • product_type_chemical_name
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressmargaretodongo@usamru-k.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_letter0
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd0
      • applicant_prev_data0
      • applicant_stability_data0
      • applicant_analysis_cert0
      • applicant_pictorial_sample0
      • applicant_gcp_training0
      • applicant_dsmb_charter0
      • applicant_detailed_budget0
      • applicant_indemnity_pi0
      • applicant_practice_license0
      • applicant_registration_ctr(null)
      • applicant_pan_african0
      • applicant_hard_copies(null)
      • applicant_signed_checklist0
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantSTACEY MAUREEN OKALLO GONDI
      • declaration_date114-11-2016
      • declaration_principal_investigatorDR JANET OYIEKO
      • declaration_date214-11-2016
      • placebo_presentYes
      • study_objectives<p>\n The purpose of this study is to assess the safety, tolerability and immunogenicity of different vaccination schedules of Ad26.ZEBOVand MVA-BN-Filo administered intramuscularly (IM) as 2-dose heterologous regimens in healthy and in HIV-infected adults.</p>\n
      • principal_inclusion_criteria<p>\n 4.1. Inclusion Criteria 4.1.1. Inclusion Criteria for Healthy Adult Subjects Each potential subject must satisfy all of the following criteria to be enrolled in the study. 1. Each subject must sign an ICF indicating that he or she understands the purpose of and procedures required for the study and is willing to participate in the study. In case the subject cannot read or write, the procedures must be explained and informed consent must be witnessed by a literate third party not involved with the conduct of the study. 2. Subject must be a man or woman aged 18 to 70 years of age, inclusive at screening. 3. Subject must be healthy in the investigator’s clinical judgment on the basis of medical history, physical examination and vital signs performed at screening. 4. Subject must be healthy on the basis of clinical laboratory tests and ECG (only in subjects >50 years) performed at screening. If the results of the laboratory screening tests and ECG are outside the institutional normal reference ranges, the subject may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be recorded in the subject's source documents and initialed by the investigator. However, the subject should not be included when hemoglobin is lower than the institutional normal reference range (or below the values in Attachment 3 when that range is not available). Note: The safety laboratory assessments at screening are to be performed within 28 days prior to the prime vaccination and may be repeated if they fall outside this time window. Note: In case of menstruation, urinalysis must be postponed but a result should be available before the prime vaccination. All urinalyses should be collected as freshly voided, mid-stream, clean catch samples obtained after proper cleansing. Note: If laboratory screening tests are out of range and deemed clinically significant, repeat of screening tests is permitted only once using an unscheduled visit during the screening period to assess eligibility. 5. Before randomization (on Day 1), a woman must be either: − Of childbearing potential and practicing a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for subjects participating in clinical studies, beginning at least 28 days prior to vaccination until at least 3 months after the boost vaccination. The sponsor considers the following methods of birth control to be highly effective: established use of oral, injected or implanted hormonal methods of contraception; placement of an intrauterine device or intrauterine system; barrier methods (condom or occlusive cap [diaphragm or cervical/vault caps] with spermicidal foam/gel/film/cream/suppository); male partner sterilization (the vasectomized partner should be the sole partner for that subject). More restrictive measures may be required by the site. Note: Reliance on abstinence or natural family planning are not acceptable birth control methods for sexually active women of child-bearing potential. VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B]) Clinical Protocol VAC52150EBL2003 Amendment 2 49 Status: Approved, Date: 8 March 2016 OR − Not of childbearing potential: postmenopausal (>45 years of age with amenorrhea for at least 2 years) or permanently sterilized (eg, bilateral tubal occlusion [which includes tubal ligation procedures as consistent with local regulations], hysterectomy, bilateral salpingectomy, bilateral oophorectomy); or otherwise be incapable of pregnancy. Note: If the social situation of a woman changes after start of the study (eg, woman who is not heterosexually active becomes active), she must begin a highly effective method of birth control, as described above. 6. A woman of childbearing potential must have a negative urine β-human chorionic gonadotropin (β-hCG) pregnancy test at screening and a negative urine β-hCG pregnancy test immediately prior to each study vaccine administration. Note: If the pregnancy test result is positive, in order to maintain subject confidentiality, the investigator will ensure adequate counseling and follow-up will be made available. 7. A man who is sexually active with a woman of childbearing potential must be willing to use condoms for sexual intercourse beginning prior to prime vaccination until at least 3 months after the boost vaccination, unless a vasectomy was performed more than 1 year prior to screening. 8. Subject must be available and willing to participate for the duration of the study visits and follow-up. 9. Subject must be willing and able to comply with the protocol requirements, including the Prohibitions and Restrictions specified in Section 4.3. 10. Subject must be willing to provide verifiable identification. 11. Subject must have a means to be contacted. 12. Subject must pass the test of understanding (TOU) (passing score: ≥90%) (Attachment 1).</p>\n
      • principal_exclusion_criteria<p>\n 1. Has received any candidate Ebola vaccine. 2. Diagnosed with Ebola virus disease, or prior exposure to EBOV, including travel to epidemic Ebola areas less than 1 month prior to screening. Note: Participation of international volunteers to Ebola operations is allowed, but they should comply with the prohibitions and restrictions as specified in Section 4.3. 3. Has received any experimental candidate Ad26- or MVA-based vaccine in the past or received any other investigational drug or investigational vaccine or used an invasive investigational medical device within 3 months prior to screening. Note: Receipt of any approved vaccinia/smallpox vaccine or Ad-based candidate vaccine other than Ad26 at any time prior to study entry is allowed. 4. Known allergy or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine products (including any of the constituents of the study vaccines [eg, polysorbate 80, ethylenediaminetetraacetic acid (EDTA) or L-histidine for Ad26.ZEBOV vaccine; tris (hydroxymethyl)-amino methane (THAM) for MVA-BN-Filo vaccine]), including known allergy to egg, egg products and aminoglycosides. VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B]) Clinical Protocol VAC52150EBL2003 Amendment 2 51 Status: Approved, Date: 8 March 2016 5. Subject with acute illness (this does not include minor illnesses such as diarrhea or mild upper respiratory tract infection) or body temperature ≥38.0ºC on Day 1 will be excluded from prime vaccination at that time, but may be rescheduled for prime vaccination at a later date. 6. HIV type 1 or type 2 infection. Note: If the HIV test result is positive, in order to maintain subject confidentiality, the investigator will ensure adequate counseling and follow-up will be made available. 7. A woman who is pregnant, breast-feeding or planning to become pregnant while enrolled in the study or within at least 3 months after the boost vaccination. 8. Presence of significant conditions (eg, history of seizure disorders, (auto)immune disease or deficiency, any spleen disease, active malignancy, ongoing tuberculosis treatment, other systemic infections) or clinically significant findings during screening of medical history, ECG (only in subjects >50 years), physical examination, vital signs or laboratory testing for which, in the opinion of the investigator, participation would not be in the best interest of the subject (eg, compromise the safety or well-being) or that could prevent, limit, or confound the protocol-specified assessments. Note: Subjects who have recently received treatment for acute, uncomplicated malaria are eligible for participation if at least 3 days have elapsed from the conclusion of a standard, recommended course of therapy for malaria; subjects who are acutely ill with malaria at the time of screening should complete therapy and wait an additional 3 days after completion before screening for the study. Note: Subjects with sickle cell trait can be included. 9. History of or underlying liver or renal insufficiency, or significant cardiac, vascular, pulmonary (eg, persistent asthma), gastrointestinal, endocrinic, neurologic, hematologic, rheumatologic, psychiatric or metabolic disturbances or eczema. 10. History of malignancy other than squamous cell or basal cell skin cancer, unless there has been surgical excision that is considered cured. Subjects with malignancies who are currently being treated or are not surgical cures are excluded. 11. Major surgery (per the investigator’s judgment) within the 4 weeks prior to screening or planned major surgery through the course of the study (from screening until completion of the study, see Section 10.1). 12. Post-organ and/or stem cell transplant whether or not with chronic immunosuppressive therapy. 13. Receipt of any disallowed therapies as noted in Section 8 before the planned administration of the prime vaccine on Day 1. 14. Is currently participating in or planning to participate in another clinical study during the study. Note: Participation in an observational clinical study is allowed. VAC52150 (Ad26.ZEBOV/MVA-BN-Filo [MVA-mBN226B]) Clinical Protocol VAC52150EBL2003 Amendment 2 52 Status: Approved, Date: 8 March 2016 15. Donation of a unit of blood within 8 weeks before Day 1 or plan to donate blood until 42-days post-boost. 16. Receipt of blood products or immunoglobulin within 3 months prior to screening and during participation in the study. 17. Current or past abuse of alcohol, recreational or narcotic drugs, which in the investigator’s opinion would compromise the subject’s safety and/or compliance with the study procedures. 18. History of chronic urticaria (recurrent hives). 19. Subject cannot communicate reliably with the investigator. 20. Subject who, in the opinion of the investigator, is unlikely to adhere to the requirements of the study. 21. Employee of the investigator or study site, with direct involvement in the proposed study or other studies under the direction of that investigator or study site, as well as family members of the employees or the investigator.</p>\n
      • primary_end_points<p>\n Primary Endpoints The primary endpoints are: • Safety as determined by: − Adverse events, collected until the 42-day post-boost visit. − Serious adverse events, collected until the end of the study. − Solicited local and systemic adverse events (reactogenicity), collected until 7 days after each vaccination. • Magnitude, kinetics and durability of humoral immune response against the EBOV GP by determining binding antibody levels using ELISA (in ELISA units/mL and/or endpointtiters) until the 21-day post-boost visit.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy0
      • 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 The KEMRI/WRP Kombewa Clinical Research Center(KCRC) is designed for large clinical trials and has a full clinical laboratory including microbiology capability.Over the years the site has carried out vaccine, drug and epidemiologicalThe KCRC has been recognized (report of the George Institute, 2007) as one of the premier sites in Africa to conduct clinical trials.</p>\n
      • other_details_explanation<p>\n N/A</p>\n
      • other_details_regulatory_notapproved<p>\n N/A</p>\n
      • other_details_regulatory_approved<p>\n N/A</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_duration2 YEARS
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorPLACEBO
      • design_controlled_other_medicinalNo
      • design_controlled_placeboYes
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKOMBEWA CLINICAL RESEARCH CENTRE
      • single_site_physical_addressOFF KISUMU BONDO ROAD, OPPOSITE KOMBEWA SUB COUNTY HOSPITAL
      • single_site_contact_personDR JANET OYIEKO
      • single_site_telephoneTEL +25471996988
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_statesNumber countries 6
      • number_of_sites
      • multi_country_listKenya, Uganda, Tanzania, Mozambique, Nigeria, USA
      • data_monitoring_committeeYes
      • total_enrolment_per_siteKombewa Site 50
      • total_participants_worldwide575
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentNo
      • population_above_18Yes
      • population_adultYes
      • population_elderlyYes
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsNo
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameJANET
      • investigator1_middle_name
      • investigator1_family_nameOYIEKO
      • investigator1_qualificationMD, MMed (Paeds)
      • investigator1_professional_addressP.O BOX 54
      • investigator1_telephone+254721996988
      • investigator1_emailjanet.oyieko@usamru-k.org
      • organisations_transferred_No
      • number_participantsKombewa Site 50
      • notification
      • approval_date28-01-2017
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted23-04-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<div>\n This study was conducted in the USA (Part 1) and Africa (Part 2) and evaluated the safety, tolerability and immunogenicity of 2-dose heterologous vaccination regimens using Ad26.ZEBOV (5×1010 vp) and MVABN-Filo (1×108 Inf.U) in HIV-uninfected and HIV-infected adult participants. One regimen consisted of Ad26.ZEBOV on Day 1 (dose 1) followed by MVA-BN-Filo (dose 2) 28 days later (Part 2, Group 1), and one regimen consisted of MVA-BN-Filo on Day 1 (dose 1) followed by Ad26.ZEBOV (dose 2) 14 days later (Part 1 and Part 2, Group 2). Both regimens evaluated in this study were well-tolerated and no safety concerns were identified. Overall, adverse events reported post vaccination were mild in the majority of participants and transient in nature. No deaths or serious adverse events considered to be related to study vaccine were reported. There were no immediate reportable events, and only 1 participant did not receive dose 2 due to an adverse event of transient grade 1 leukocytosis considered possibly related to study vaccine by the investigator. Both regimens used in this study induced binding antibody responses (FANG ELISA) at 21 days post</div>\n<div>\n dose 2 in almost all (96% to 99%) participants in Part 1 and Part 2. Pooled FANG ELISA data for theMVA-BN-Filo, Ad26.ZEBOV 14-day interval schedule in Part 1 and Part 2 were generally similar to those from either study part alone. At 21 days post dose 2, the GMC in HIV-uninfected participants was higher than the GMC in HIV-infected participants. In both groups (HIV-uninfected and HIV-infected), responses were observed until the last assessment 1 year post dose 2, when a difference between the GMCin HIV-uninfected vs. HIV-infected participants was still present for the MVA-BN-Filo, Ad26.ZEBOV</div>\n<div>\n regimen. At 21 days post dose 2 in Part 1, EBOV GP-specific CD4+ T-cell responses were observed in 52% of HIV-uninfected and 39% of HIV-infected participants. EBOV GP-specific CD8+ T-cell responses were observed at this timepoint in 30% of HIV-uninfected and 22% of HIV-infected participants.</div>\n
      • implication_results<div>\n In summary, this is the first study to demonstrate safety and EBOV GP-specific immunogenicity in PLWH with an Ebola vaccination regimen of MVA-BN-Filo followed by</div>\n<div>\n Ad26.ZEBOV 14 days later. These results show that an accelerated vaccination schedule is well tolerated in both PWOH and PLWHand induces a broad array of durable humoral and cellular immune responses. These findings support continued consideration for accelerated regimen development for rapid deployment among outbreak responders and relevant global populations at immediate risk.</div>\n
      • quantity_imported210
      • quantity_dispensed153
      • quantity_destroyed57
      • quantity_exported0
      • balance_site0
      • final_date0000-00-00
      • modified2025-02-17 16:23:33
      • created2016-11-14 11:11:48
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id368
        • application_id569
        • given_nameJANET
        • middle_name
        • family_nameOYIEKO
        • qualificationMD, MMed (Paeds)
        • professional_addressP.O BOX 54
        • telephone+254721996988
        • emailjanet.oyieko@usamru-k.org
        • created2016-11-14 11:31:40
        • modified2020-04-23 12:12:13
    • SiteDetail(array)
      • 0(array)
        • id449
        • application_id569
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2016-11-14 11:31:40
        • modified2020-04-23 12:12:13
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id294
        • application_id569
        • sponsorCrucell Holland B.V.
        • sponsor_typeIndustry
        • contact_personCynthia B. Robinson, MD
        • addressP.O. Box 2048 2301 CA Leiden The Netherlands
        • telephone_number +1 215 793-7681
        • fax_number +1 215 986-1027
        • cell_number +1 215 793-7681
        • email_addressCRobins6@its.jnj.com
        • created2016-11-14 11:31:40
        • modified2020-04-23 12:12:13
  • 3(array)
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      • user_id81
      • trial_status_id5
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style=\"mso-bidi-font-family:\nArial\">COAST overarching objective is to address the key research gaps in the therapeutic use of oxygen in resource-limited setting in order to provide a better evidence base for future management guidelines. <span style=\"color:black;\nmso-bidi-font-weight:bold\">The trial has been designed to address the poor outcomes of children in sub-Saharan Africa, which are associated with high rates of </span>in-hospital mortality 9-10% (for those with oxygen saturations between 80% and 92%) and 26-30% case fatality for those with oxygen saturations <80%, indicating that the current recommendations and/or management strategies are not working in practice. </span></p>\n<p class=\"MsoNormal\" style=\"margin-top:6.0pt\">\n <span style=\"mso-bidi-font-family:\nArial\">Despite over two decades of investment by WHO technologies group aimed at improving systems for delivering oxygen it appears not to have been afforded a high enough priority at both a global and a country level. Although oxygen is a <span class=\"st1\"><span style=\"mso-bidi-font-weight:bold\">basic element of hospital care, </span></span>the poor implementation of current treatment recommendations also <span class=\"st1\"><span style=\"mso-bidi-font-weight:bold\">stems from the lack of availability in many hospitals, or it cannot be used routinely due to unpredictable supply, faulty cylinders or limitations and interruptions of the electricity supply. This has resulted in </span></span>mismatch between supply of, and demand for, oxygen in many rural hospitals in developing countries<span class=\"st1\"><span style=\"mso-bidi-font-weight:bold\">. </span></span>Whilst the health burden of hypoxia, including morbidity, hospital admission and death have been realised, its potential economic burden for treating children with conditions leading to hypoxia is substantial. As a result there are major gaps between current treatment policies and implementation. These largely stem from the lack of relevant research to inform clinical management; consequently current treatment recommendations are based on weak evidence. <span style=\"color:black\">Systematic and policy reviews have indicated the need for formal evaluation of the </span>hypoxaemia threshold for which oxygen should be targeted and how best to administer oxygen.</span></p>\n<p class=\"MsoNormal\" style=\"mso-pagination:none;tab-stops:47.0pt 72.0pt;\nmso-layout-grid-align:none;text-autospace:none\">\n <span style=\"mso-bidi-font-family:\nArial\">COAST aims to provide the relevant evidence for policy makers and health services by evaluating key elements of an integrated management strategy in African hospitals on the basis of clinical effectiveness and costs. </span></p>\n<p class=\"MsoNormal\" style=\"mso-pagination:none;tab-stops:47.0pt 72.0pt;\nmso-layout-grid-align:none;text-autospace:none\">\n <span style=\"mso-bidi-font-family:\nArial\">COAST is a randomised controlled trial designed to </span><span style=\"mso-fareast-font-family:"MS Mincho";mso-bidi-font-family:Arial\">provide the evidence for the most <i style=\"mso-bidi-font-style:normal\">clinically-effective</i> and <i style=\"mso-bidi-font-style:normal\">cost-efficient</i> targeted use of oxygen as a life-saving treatment with respect to the </span><span style=\"mso-bidi-font-family:Arial\">optimal oxygen saturation threshold for treatment and mode of delivery in 4200 African children, aged 2 months to 12 years, presenting to hospital with respiratory distress complicated by hypoxia (defined as oxygen saturation (SaO₂)< 92%).<span style=\"mso-spacerun:yes\">  </span></span></p>\n<p class=\"MsoNormal\" style=\"mso-pagination:none;tab-stops:47.0pt 72.0pt;\nmso-layout-grid-align:none;text-autospace:none\">\n <span style=\"mso-bidi-font-family:\nArial;color:black;mso-bidi-font-weight:bold\">Children will be enrolled at admission to hospital over 2 years from 5 sites in 2 countries (</span><span style=\"mso-bidi-font-family:Arial\">Uganda and Kenya)<span style=\"color:black;\nmso-bidi-font-weight:bold\"> and followed for 28 days.<span style=\"mso-spacerun:yes\">  </span></span>The trial has a pragmatic design, to ensure this encompasses a spectrum of high-risk children, identified largely by clinical criteria, so that the results are applicable to health services in Africa, with limited access to health technologies.</span></p>\n<h2 style=\"margin-top:10.0pt;margin-right:0cm;margin-bottom:6.0pt;margin-left:\n7.1pt;mso-list:none;tab-stops:36.0pt\">\n <a name=\"_Toc437619370\"><span style=\"font-style:normal\">Primary objectives</span></a></h2>\n<p class=\"MsoNormal\">\n To establish whether:</p>\n<p class=\"MsoListParagraphCxSpFirst\" style=\"margin-bottom:10.0pt;mso-add-space:\nauto;text-indent:-18.0pt;line-height:115%;mso-list:l2 level1 lfo2\">\n <span style=\"font-family:Symbol;mso-fareast-font-family:Symbol;mso-bidi-font-family:\nSymbol;mso-bidi-font-weight:bold\"><span style=\"mso-list:Ignore\">·<span style=\"font:7.0pt "Times New Roman"\">       </span></span></span><span style=\"mso-bidi-font-weight:bold\">liberal oxygenation will decrease mortality compared with permissive hypoxia (usual care); and</span></p>\n<p class=\"MsoListParagraphCxSpLast\" style=\"margin-bottom:10.0pt;mso-add-space:\nauto;text-indent:-18.0pt;line-height:115%;mso-list:l2 level1 lfo2\">\n <span style=\"font-family:Symbol;mso-fareast-font-family:Symbol;mso-bidi-font-family:\nSymbol;mso-bidi-font-weight:bold\"><span style=\"mso-list:Ignore\">·<span style=\"font:7.0pt "Times New Roman"\">       </span></span></span><span style=\"mso-bidi-font-weight:bold\">high flow oxygen delivery will decrease mortality compared with low flow oxygen delivery (usual care).</span></p>\n<h2 style=\"margin-top:10.0pt;margin-right:0cm;margin-bottom:6.0pt;margin-left:\n7.1pt;mso-list:none;tab-stops:36.0pt\">\n <a name=\"_Toc437619371\">Secondary objectives</a></h2>\n<p class=\"MsoNormal\">\n The secondary objectives of COAST are:</p>\n<p class=\"MsoListParagraphCxSpFirst\" style=\"margin-bottom:10.0pt;mso-add-space:\nauto;text-indent:-18.0pt;line-height:115%;mso-list:l1 level1 lfo3\">\n <span style=\"font-family:Symbol;mso-fareast-font-family:Symbol;mso-bidi-font-family:\nSymbol\"><span style=\"mso-list:Ignore\">·<span style=\"font:7.0pt "Times New Roman"\">       </span></span></span>to assess the effectiveness in the speed and success of recovery from the initial respiratory failure;</p>\n<p class=\"MsoListParagraphCxSpMiddle\" style=\"margin-bottom:10.0pt;mso-add-space:\nauto;text-indent:-18.0pt;line-height:115%;mso-list:l1 level1 lfo3\">\n <span style=\"font-family:Symbol;mso-fareast-font-family:Symbol;mso-bidi-font-family:\nSymbol\"><span style=\"mso-list:Ignore\">·<span style=\"font:7.0pt "Times New Roman"\">       </span></span></span>to assess safety and quality of life;</p>\n<p class=\"MsoListParagraphCxSpMiddle\" style=\"margin-bottom:10.0pt;mso-add-space:\nauto;text-indent:-18.0pt;line-height:115%;mso-list:l1 level1 lfo3\">\n <span style=\"font-family:Symbol;mso-fareast-font-family:Symbol;mso-bidi-font-family:\nSymbol\"><span style=\"mso-list:Ignore\">·<span style=\"font:7.0pt "Times New Roman"\">       </span></span></span>to determine long-term effects of the delivery strategies; and</p>\n<p class=\"MsoListParagraphCxSpLast\" style=\"margin-bottom:10.0pt;mso-add-space:\nauto;text-indent:-18.0pt;line-height:115%;mso-list:l1 level1 lfo3\">\n <span style=\"font-family:Symbol;mso-fareast-font-family:Symbol;mso-bidi-font-family:\nSymbol\"><span style=\"mso-list:Ignore\">·<span style=\"font:7.0pt "Times New Roman"\">       </span></span></span>to identify whether the additional costs of each of the interventions are proportionate to the health benefits and to inform future widespread implementation in terms of value for money.</p>\n<p class=\"MsoNormal\" style=\"mso-pagination:none;tab-stops:47.0pt 72.0pt;\nmso-layout-grid-align:none;text-autospace:none\">\n <span style=\"mso-bidi-font-family:\nArial\"> </span></p>\n<p class=\"MsoNormal\" style=\"mso-pagination:none;tab-stops:47.0pt 72.0pt;\nmso-layout-grid-align:none;text-autospace:none\">\n <span style=\"mso-bidi-font-family:\nArial\">The trial will have two randomisations:</span></p>\n<p class=\"MsoNormal\" style=\"line-height:12.0pt;mso-pagination:none\">\n <b><span style=\"mso-bidi-font-family:Arial\">R1: For children with a baseline SaO₂<92% but ≥80%, randomisation to l</span></b><span style=\"mso-bidi-font-family:Arial\">iberal oxygenation delivered by either high flow or low flow versus a more conservative strategy (control: no oxygen) </span></p>\n<p class=\"MsoNormal\" style=\"line-height:12.0pt;mso-pagination:none\">\n <b><span style=\"mso-bidi-font-family:Arial\">R2: For children with a baseline SaO₂<80% and for those randomised to liberal oxygenation for R1, </span></b><span style=\"mso-bidi-font-family:Arial;mso-bidi-font-weight:bold\">h</span><span style=\"mso-bidi-font-family:Arial;color:black\">igh flow versus low flow delivery (routine care)</span></p>\n<p class=\"MsoNormal\" style=\"mso-pagination:none;tab-stops:47.0pt 72.0pt;\nmso-layout-grid-align:none;text-autospace:none\">\n <b style=\"mso-bidi-font-weight:\nnormal\"><span style=\"mso-bidi-font-family:Arial\"> </span></b></p>\n<p>\n <b style=\"mso-bidi-font-weight:normal\"><span style=\"font-size:11.0pt;\nline-height:105%;font-family:Calibri;mso-ascii-theme-font:minor-latin;\nmso-fareast-font-family:"ï¼­ï¼³ 明朝";mso-fareast-theme-font:minor-fareast;\nmso-hansi-theme-font:minor-latin;mso-bidi-font-family:Arial;mso-ansi-language:\nEN-GB;mso-fareast-language:EN-GB;mso-bidi-language:AR-SA\">R1 </span></b><span style=\"font-size:11.0pt;line-height:105%;font-family:Calibri;mso-ascii-theme-font:\nminor-latin;mso-fareast-font-family:"ï¼­ï¼³ 明朝";mso-fareast-theme-font:minor-fareast;\nmso-hansi-theme-font:minor-latin;mso-bidi-font-family:Arial;mso-ansi-language:\nEN-GB;mso-fareast-language:EN-GB;mso-bidi-language:AR-SA\">addresses the question of what threshold to give oxygen in children with hypoxia (above a threshold of SaO₂<span style=\"mso-bidi-font-weight:bold\">≥</span>80%); <b style=\"mso-bidi-font-weight:normal\">R2 </b>addresses how best to give oxygen all receiving to oxygen. For <b style=\"mso-bidi-font-weight:normal\">R1</b>, a cut off of <92% assesses a range of saturations that would be consistent with international recommendations for use of oxygen in sick children - providing important additional data about those at a higher threshold than currently recommended by WHO. Children randomised to control will receive low flow oxygen if they ever develop severe hypoxia (SaO₂<80%). All randomisations will be open. </span></p>\n
      • study_title<p>\n Childrens Oxygen Administration Strategies Trial</p>\n
      • laymans_summary<p>\n Lay title<br />\n Optimising and targeting oxygen treatment in sick children: The COAST trial<br />\n What is the problem?<br />\n Although oxygen is a basic element of hospital care, there are no relevant studies to guide which level of oxygen saturation or the best method of how to administer it (low flow or high flow) to improve outcome. In practice many children in low-income countries do not receive oxygen, despite being recommended, owing to the lack of its availability due to the high cost, or supplies that are unpredictable (erratic delivery of cylinders or electricity to power oxygen concentrators) resulting in mismatch between supply and demand. The outcomes of children in sub-Saharan Africa with pneumonia, remains poor with an in-hospital mortality 9-10% (for those with oxygen saturations between 80% and 92%) and 26-30% case fatality for those with oxygen saturations <80%, indicating that the current recommendations and/or management strategies are not working in practice.<br />\n What questions are we trying to answer?<br />\n COAST has been designed to identify which children would benefit from receiving oxygen and what would be the best delivery method. Although oxygen is a basic element of hospital care, this therapy is costly and supplies are inadequate and erratic in African hospitals.<br />\n COAST will address two related questions of oxygen therapy and one about nutrition supplementation:<br />\n 1. Who to give oxygen too?<br />\n We will examine whether or not giving oxygen improves outcomes for children who have a moderately low level of oxygen it is not certain what the best level to provide oxygen is and whether this results in a better outcome – so half of the children will receive oxygen and the other half will not. Children with severe hypoxia (<80%) will all receive oxygen as we are more confident about the benefits of oxygen in this group.<br />\n 2. How best to give oxygen?<br />\n For children receiving oxygen, we will compare whether giving oxygen at a higher flow compared with a lower flow (routine care) improves outcomes. High flow oxygen provides extra pressure to the airways to prevent them from collapsing after every exhalation. This helps reduce the effort of breathing, which is vital when lung infections can often lead to respiratory exhaustion and ultimately respiratory failure in critically sick children with limited access to relevant life support i.e. mechanical ventilation (the majority of hospitals in Africa).<br />\n 3. Nutritional Support<br />\n To establish whether supplementary feeding for 56-days (8 weeks) using Ready to Use Therapeutic Feeds (RUTF) in all children versus usual standard care will improve outcome at 90-days.<br />\n Where is the study taking place?<br />\n The study will take place in 5 hospitals in 2 African countries Kilifi County Hospital and Coast Provincial General Hospital (Kenya) and Mulago (Kampala) Mbale and Soroti Hospitals in Uganda.</p>\n
      • short_titleCOAST
      • protocol_noECCT/16/11/03
      • version_no1.1
      • date_of_protocol15-09-2016
      • study_drugOxygen
      • disease_conditionSevere pneumonia
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines0
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical0
      • product_type_medical_device1
      • product_type_chemical_name
      • product_type_medical_device_nameAirVO2 Nasal Oxygen interface
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressctfuser@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_countries1
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data0
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi0
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantPatricia Njuguna
      • declaration_date110-11-2016
      • declaration_principal_investigatorKathryn Maitland
      • declaration_date210-11-2016
      • placebo_presentNo
      • study_objectives<p>\n Primary objectives</p>\n<p>\n To establish whether:</p>\n<ul>\n <li>\n liberal oxygenation will decrease mortality compared with permissive hypoxia (usual care); and</li>\n <li>\n high flow oxygen delivery will decrease mortality compared with low flow oxygen delivery (usual care).</li>\n <li>\n Supplementing feeds with RUTF will improve anthropometric outcomes at Day 90 and Day 180.</li>\n</ul>\n<p>\n The secondary objectives of COAST are:</p>\n<ul>\n <li>\n to assess the effectiveness in the speed and success of recovery from the initial respiratory failure;</li>\n <li>\n to assess safety and quality of life;</li>\n <li>\n to determine long-term effects of the delivery strategies; and</li>\n <li>\n to identify whether the additional costs of each of the interventions are proportionate to the health benefits and to inform future widespread implementation in terms of value for money.</li>\n</ul>\n<ol>\n <li value=\"1.1\">\n ctives</li>\n</ol>\n
      • principal_inclusion_criteria<p>\n Aged between 28 days to 12 years with a</p>\n<ul>\n <li>\n History of respiratory illness (cough, upper respiratory tract symptom or any respiratory symptoms, e.g. rapid breathing or increase work of breathing)</li>\n <li>\n Hypoxia (pulse oximetry reading of SaO₂ <92% recorded in room air over 5 minutes)</li>\n <li>\n Plus <em>any one of the following</em> signs of severe pneumonia (from 2013 WHO clinical definitions for pneumonia [<a href=\"#_ENREF_55\" title=\", 2013 #71\">55</a>]):</li>\n</ul>\n<ol style=\"list-style-type:lower-alpha;\">\n <li>\n Sign of respiratory distress (any one of):\n <ul style=\"list-style-type:circle;\">\n <li>\n severe lower chest wall in-drawing</li>\n <li>\n use of auxiliary muscles</li>\n <li>\n head nodding</li>\n <li>\n inability to feed because of respiratory problems</li>\n </ul>\n </li>\n <li>\n Suspected pneumonia\n <ul style=\"list-style-type:circle;\">\n <li>\n fast breathing:\n <ul>\n <li>\n age 2–11 months: ≥ 50/minute</li>\n <li>\n age 1–5 years: ≥ 40/minute</li>\n <li>\n age 5-12 years ≥ 30/minute</li>\n </ul>\n </li>\n <li>\n chest auscultation signs:\n <ul>\n <li>\n decreased breath sounds</li>\n <li>\n bronchial breath sounds</li>\n <li>\n crackles</li>\n <li>\n abnormal vocal resonance (decreased over a pleural effusion or empyema, increased over lobar consolidation)</li>\n <li>\n pleural rub</li>\n </ul>\n </li>\n </ul>\n </li>\n <li>\n Signs of pneumonia with a general danger sign:</li>\n</ol>\n<ul style=\"list-style-type:circle;\">\n <li>\n inability to breastfeed or drink</li>\n <li>\n lethargy or unconscious</li>\n <li>\n convulsions</li>\n</ul>\n
      • principal_exclusion_criteria<ul>\n <li>\n Known uncorrected cyanotic heart disease</li>\n <li>\n Assent/consent refusal by parent/carer</li>\n <li>\n Previously recruited to COAST</li>\n <li>\n Already received oxygen for this episode of illness</li>\n</ul>\n
      • primary_end_points<p>\n Primary</p>\n<p>\n 48 hour mortality post randomisation</p>\n<p>\n Secondary</p>\n<ul>\n <li>\n Treatment failure at 48 hours</li>\n <li>\n Survival to 28 days</li>\n <li>\n Neurocognitive sequelae at 28 days</li>\n <li>\n Disability-free survival to 28 days</li>\n <li>\n Time to hypoxia (≥92%) resolution during initial hospital stay</li>\n <li>\n Length of initial hospital stay</li>\n <li>\n Re-admission to hospital by 28 days</li>\n <li>\n Anthropometric status by 28 days</li>\n</ul>\n<p>\n Resolution of neurocognitive sequelae at 90 days (for those with neurocognitive sequelae at 28 days)</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety0
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory1
      • trial_therapeutic_use0
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n Kenya: KEMRI Wellcome Trust Programme, Kilifi County Hospital (KCH). The clinical programme at KCH is a well-established research centre on the coast of Kenya. It has been the site of several clinical studies on severe malaria including two large phase III trials (AQUAMAT and FEAST). Coast Provincial General Hospital (CPGH) is based in the second largest city in Kenya (Mombasa) and has conducted in collaboration with KWTRP a number of research studies and Phase III clinical trials in children admitted to CPGH .</p>\n<p>\n Uganda: Mulago National Referral Hospital. Mbale Regional Referral Hospital and Soroti Regional Referral Hospital. Mulago, Mbale and Soroti hospitals have annual admissions to the paediatric ward of 18,000, 20,000 and 8000 respectively. There has been considerable research capacity development in the last five years, with these three sites involved in the FEAST trial and currently conducting a large multicentre trial of transfusion trial (TRACT).</p>\n<p>\n The five centres in Africa represent a spectrum of intensity of malaria transmission, from perennial and high (in Mbale and Soroti) to seasonal and meso-endmic (in Kampala, Mombasa and Kilifi). Mulago and CPGH are located within large urban areas, whereas the populations that utilise Mbale, Soroti and Kilifi are more typically rural; however Mbale has a few slum developments within the town.</p>\n<p>\n Central grant funding will be available for participating sites to support infrastructural upgrade to ensure basic life resuscitation, standard medications available and oxygen can be delivered continuously and sufficient staff to run the trial - each centre have 2 clinician, 5 nurses and laboratory staff. Fischer and Paykel have donated sufficient AIRVO machines (5 per site) , tubing and nasal prongs for oxygen administration.</p>\n
      • other_details_explanation<p>\n The trial is in children with  severe pneumonia in low income settings</p>\n
      • other_details_regulatory_notapproved<p>\n not applicable</p>\n
      • other_details_regulatory_approved<p>\n Uganda March 2016</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n None</p>\n
      • estimated_duration30 months
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorHigh Flow Oxygen versus L
      • design_controlled_other_medicinalYes
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherYes
      • design_controlled_medicinal_specifyAirVO oxgen nasal delivery device
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesYes
      • multiple_member_states2 countries 5 sites
      • number_of_sites2
      • multi_country_listUganda (Mbale and Soroti Regional Referral Hospitals) Mulago National Referral Hospital\nKenya (as above)
      • data_monitoring_committeeYes
      • total_enrolment_per_sitePer site a minimum of 400 and maximum of 800
      • total_participants_worldwide4200
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerYes
      • population_childrenYes
      • population_adolescentNo
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationYes
      • subjects_incapable_consentYes
      • subjects_specifyChildren aged 2months-12 years admitted to hospital with severe pneumonia and hypoxia
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_namePatricia
      • investigator1_middle_name
      • investigator1_family_nameNjuguna
      • investigator1_qualificationMMed PhD
      • investigator1_professional_addressKEMRI Wellcome Trust Programme CRG, Kilifi
      • investigator1_telephone254 41 7522063
      • investigator1_emailPNjuguna@kemri-wellcome.org
      • organisations_transferred_Yes
      • number_participants1200 across 2 sites over 3 years
      • notification<p>\n None</p>\n
      • approval_date22-02-2017
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted26-02-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<p>\n The trial was stopped prematurely by the Trial Steering Committee on the grounds of feasibility. Between 14th Feb 2017 and when enrolment ceased 28th Feb 2020, 1842, eligible children were enrolled into the COAST trial and included in all analyses. In the severe hypoxemia stratum, 388 children were enrolled,194 children were randomized to High Flow Nasal Therapy, and 194 to Low Flow Oxygen. In the hypoxemia stratum,1454 children were enrolled and, 363 were randomized to HFNT, 364 to LFO, and 727 to permissive hypoxemia.</p>\n<p>\n At the point of termination, the COAST trial was unable to answer the two specific hypotheses it was designed to address. First, whether liberal oxygenation therapy for children with hypoxemia (SpO2 80–91%) is superior to permissive hypoxemia. Secondly, there were insufficient data to demonstrate that HFNT was superior to LFO.</p>\n<p>\n Across both strata, HFNT administration was also relatively oxygen-sparing, using room air/oxygen blends without any evidence of harm. In the hypoxemia stratum in many cases HFNT was provided on room air, leading to correction of hypoxemia. Although the trial does not provide definitive data to inform treatment guidelines, the knowledge acquired from the trial adds a new level of uncertainty to the liberal use of oxygen as a supportive therapy.</p>\n<p>\n In the case of severe pneumonia, pre-existing evidence demonstrating clear benefits of oxygen therapy was poor hence the trial was both ethically and scientifically sound.</p>\n<p>\n While oxygen, as a supportive therapy, has been considered the standard treatment for pneumonia for a large part of the last century, the recognition of potential oxygen toxicity is relatively recent. In several areas of emergency care and resuscitation, the use of oxygen is now being challenged by emerging evidence from clinical trials, including in pediatric populations and systematic reviews.</p>\n<p>\n Regarding demand on health services, the routine use of pulse oximetry to target oxygen therapy is poorly implemented despite having been recommended by WHO for triage of sick children. Hence, oxygen therapy is generally targeted by non-specific clinical signs that predict hypoxemia poorly, thus exposing large numbers of children without hypoxemia to oxygen therapy, and raising questions over safety, cost, and demand for a constrained health resource. Our findings indicate that hypoxemia in children with severe pneumonia can be corrected without additional oxygen.</p>\n<p>\n Recognizing the resource limitations and costs of oxygen therapy, the protocol incorporated relatively oxygen sparing strategies in the investigational groups (HFNT and permissive hypoxemia) and vital sign monitoring to ensure early weaning in both liberal (HFNT and LFO)</p>\n<p>\n strategies.</p>\n<p>\n COAST trial represents the largest trial of oxygen therapy ever conducted in children and the only multicenter controlled trial.</p>\n<p>\n We, therefore, proposed that HFNT was a feasible alternative source of respiratory support owing to its relative simplicity in implementation, humidification, low risk of nosocomial infection. In addition, the ability to blend both oxygen and room air to deliver positive end-expiratory pressure, thus, limiting exposure to high concentrations of oxygen (and potential toxicity) and with the prospect of reducing costs to health services.</p>\n<p>\n  </p>\n
      • implication_results<p>\n <span style=\"font-size: 9pt; font-family: Arial, sans-serif;\">Our findings supports the need for future trials with similar designs, particularly in settings where access to oxygen and/or mechanical respiratory support are restricted. The scale of the mortality reduction of High Flow Nasal Therapy over Low Flow Oxygen, particularly in severely hypoxaemic children warrants further investigation. Oxygen-sparing strategies potentially offer cost-effective approaches to reducing overall oxygen requirements in overburdened health services and adds to the general findings in critical care that less is more.<o:p></o:p></span></p>\n
      • quantity_importedN/A
      • quantity_dispensedN/A
      • quantity_destroyedN/A
      • quantity_exportedN/A
      • balance_siteN/A
      • final_date0000-00-00
      • modified2024-07-10 15:32:30
      • created2016-11-02 15:20:40
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id366
        • application_id567
        • given_nameKathryn
        • middle_name
        • family_nameMaitland
        • qualificationMBBS FRCP Phd
        • professional_addressImperial College, London
        • telephone+4420 7594 3891
        • emailk.maitland@imperial.ac.uk
        • created2016-11-02 15:21:12
        • modified2020-02-26 10:02:14
    • SiteDetail(array)
      • 0(array)
        • id445
        • application_id567
        • county_id3
        • site_nameKilifi County Hospital
        • physical_addressHospital Grounds, Off Bofa Road, Kilifi, Kenya
        • contact_detailsn/a
        • contact_personStudy PI: Dr Patricia Njuguna
        • site_capacity(null)
        • misc(null)
        • created2016-11-02 15:21:12
        • modified2020-02-26 10:02:14
        • County(array)
          • id3
          • county_nameKilifi
          • created2012-05-31 16:15:49
          • modified2012-05-31 16:15:49
      • 1(array)
        • id446
        • application_id567
        • county_id1
        • site_nameCoast Provincial General Hospital
        • physical_addressBondeni, Kisauni Rd, Mombasa, Kenya
        • contact_detailsn/a
        • contact_personDr Victor Bandika
        • site_capacity(null)
        • misc(null)
        • created2016-11-02 15:40:41
        • modified2020-02-26 10:02:14
        • County(array)
          • id1
          • county_nameMombasa
          • created2012-05-31 16:15:11
          • modified2012-07-09 13:06:23
    • Sponsor(array)
      • 0(array)
        • id292
        • application_id567
        • sponsorImperial College, London
        • sponsor_typeOthers
        • contact_personGary Roper
        • addressJoint Research Office, Sir Alexander Fleming Building, Imperial College, Exhibition Road, London, United Kingdom, SW7 2AZ
        • telephone_number+44(0)2075949484
        • fax_numbern/a
        • cell_numbern/a
        • email_addressgary.roper@imperial.ac.uk
        • created2016-11-02 15:21:12
        • modified2020-02-26 10:02:14
  • 4(array)
    • Application(array)
      • id556
      • user_id613
      • trial_status_id7
      • abstract_of_study<div>\n <p align=\"center\" style=\"margin-left: 196.1pt;\">\n <strong>SCHEMA IMPAACT P1093</strong></p>\n <p>\n  </p>\n <p align=\"center\" style=\"margin-left: 9.1pt;\">\n <strong>P</strong><strong>hase I/II Multi-Center, Open-Label Pharmacokinetic, Safety, Tolerability and Antiviral Activity of Dolutegravir, a Novel Integrase Inhibitor, in Combination Regimens in</strong></p>\n <p align=\"center\" style=\"margin-left: 120.2pt;\">\n <strong>H</strong><strong>IV-1 Infected Infants, Children and Adolescents</strong></p>\n <p>\n  </p>\n <p style=\"margin-left: 149.05pt;\">\n <strong>DE</strong><strong>SIGN:                                </strong>Phase I/II, multi-center, open-label, non-comparative intensive PK and safety study</p>\n <p>\n  </p>\n <p style=\"margin-left: 149.05pt;\">\n <strong>SAMPLE SIZE:                      </strong>Approximately 160 HIV-1 infected infants, children and adolescents to provide a minimum of 120 evaluable* subjects:</p>\n <p style=\"margin-left: 185.05pt;\">\n Stage I – a minimum of 10 subjects, per cohort</p>\n <p style=\"margin-left: 185.05pt;\">\n Stage II – a minimum of 60 evaluable subjects across all cohorts</p>\n <p>\n  </p>\n <p style=\"margin-left: 149.05pt;\">\n *Evaluable is defined as having been treated exclusively on the dose determined to be optimal for a given age cohort and having either completed 24 (or 48) weeks of exposure to the study drug or having been classified as a safety failure, due to a study drug related adverse event occurring during the first 24 (or 48) weeks of treatment.</p>\n <p>\n  </p>\n <p style=\"margin-left: 149.05pt;\">\n <strong>POPULATION:                      </strong>HIV infected infants, children and adolescents aged ≥ 4 weeks to < 18 years of age.</p>\n <p>\n  </p>\n <p style=\"margin-left: 149.05pt;\">\n <strong>STRATIFICATION:              </strong>All subjects enrolled into the study will be stratified at screening into one of nine age specific cohorts as follows:</p>\n <p>\n  </p>\n <p style=\"margin-left: 149.05pt;\">\n <strong>C</strong><strong>ohort I:         </strong>Adolescents ≥ 12 to <18 years of age</p>\n <p align=\"center\" style=\"margin-left: 219.2pt;\">\n (Film-coated Tablets)</p>\n <p>\n  </p>\n <p style=\"margin-left: 149.05pt;\">\n <strong>C</strong><strong>ohort IIA:    </strong>Children ≥ 6 to <12 years of age</p>\n <p align=\"center\" style=\"margin-left: 219.2pt;\">\n (Film-coated Tablets)</p>\n <p>\n  </p>\n <p style=\"margin-left: 149.05pt;\">\n <strong>C</strong><strong>ohort IIB:     </strong>Children ≥ 6 to <12 years of age</p>\n <p style=\"margin-left: 221.05pt;\">\n (Granules for suspension)</p>\n <p style=\"margin-left: 221.05pt;\">\n Note: Dispersible tablets may also be evaluated in this cohort if requested by regulatory authorities.</p>\n <p>\n  </p>\n <p style=\"margin-left: 149.05pt;\">\n <strong>C</strong><strong>ohorts III:    </strong>Children ≥ 2 to < 6 years of age</p>\n <p style=\"margin-left: 221.05pt;\">\n (Granules for suspension)</p>\n <p>\n  </p>\n <p style=\"margin-left: 149.05pt;\">\n <strong>C</strong><strong>ohort III-DT</strong>: Children ≥ 2 to < 6 years of age</p>\n <p align=\"center\" style=\"margin-left: 219.2pt;\">\n (Dispersible Tablets)</p>\n <p>\n  </p>\n <p style=\"margin-left: 149.05pt;\">\n <strong>C</strong><strong>ohort IV</strong>:      Children ≥ 6 months to < 2 years of age</p>\n <p style=\"margin-left: 221.05pt;\">\n (Granules for suspension)</p>\n <p>\n  </p>\n <p style=\"margin-left: 149.05pt;\">\n <strong>C</strong><strong>ohort IV-DT: </strong>Children ≥ 6 months to < 2 years of age</p>\n <p align=\"center\" style=\"margin-left: 219.2pt;\">\n (Dispersible Tablets)</p>\n</div>\n<p>\n  </p>\n<div>\n <p style=\"margin-left: 149.05pt;\">\n <strong>C</strong><strong>ohort V</strong>:        Infants <u>></u> 4 weeks to < 6 months of age</p>\n <p style=\"margin-left: 221.05pt;\">\n (Granules for suspension)</p>\n <p>\n  </p>\n <p style=\"margin-left: 149.05pt;\">\n <strong>C</strong><strong>ohort V-DT: </strong>Infants <u>></u> 4 weeks to < 6 months</p>\n <p align=\"center\" style=\"margin-left: 219.2pt;\">\n (Dispersible Tablets)</p>\n <p>\n  </p>\n <p>\n  </p>\n <p>\n  </p>\n <p style=\"margin-left: 149.05pt;\">\n <strong>REG</strong><strong>IMEN:                            </strong>Three different dolutegravir (DTG) formulations will be evaluated as follows: film-coated tablets; a granule formulation for suspension; and dispersible tablets. The final dose for each formulation and each age cohort will be selected based on real-time PK evaluations and safety to achieve exposure similar to that observed in adults treated with 50 mg QD.</p>\n <p>\n  </p>\n <p style=\"margin-left: 149.05pt;\">\n See Sections 5.0-5.4 for details on DTG drug regimens, formulations, drug supply and handling.</p>\n <p>\n  </p>\n <p style=\"margin-left: 5pt;\">\n <strong>TREAT</strong><strong>MENT DURATION:  </strong>Stages I and II: 48 Weeks</p>\n <p>\n  </p>\n <p style=\"margin-left: 149.05pt;\">\n Long Term Safety Follow-up: All subjects who successfully complete 48 weeks of DTG treatment will continue to receive DTG for a minimum of three years as part of long term safety follow-up. (See Section 6.3 and Appendix IE for details).</p>\n <p>\n  </p>\n <p style=\"margin-left: 149.05pt;\">\n <strong>H</strong><strong>Y</strong><strong>POTHESIS:                      </strong>DTG will be generally well tolerated and demonstrate an acceptable safety profile, adequate PK and antiviral activity when used concurrently with an optimized background therapy (OBT) in HIV-1 infected infants, children and adolescents.</p>\n <p>\n  </p>\n <p style=\"margin-left: 5pt;\">\n <strong>O</strong><strong>B</strong><strong>JECTIVES:</strong></p>\n <p>\n  </p>\n <p style=\"margin-left: 5pt;\">\n <u>PRIMARY OBJECTIVES</u></p>\n <p>\n  </p>\n <p style=\"margin-left: 41pt;\">\n 1.   To select a dose for each formulation of DTG for chronic dosing in infants, children and adolescents that achieves similar exposure to the DTG 50 mg once daily dose in adults.</p>\n <p>\n  </p>\n <p style=\"margin-left: 41pt;\">\n 2.   To determine the safety and tolerability of DTG in HIV-1 infected infants, children and adolescents at 24 and 48 weeks.</p>\n <p>\n  </p>\n <p style=\"margin-left: 41pt;\">\n 3.   To evaluate the steady-state pharmacokinetics of DTG in combination with other antiretrovirals (OBT) in treatment-experienced and/or treatment-naïve HIV-1 infected infants, children and adolescents and to determine the dose of DTG that achieves a targeted AUC24 (primary PK endpoint) and C24h (secondary PK endpoint) in this population.</p>\n <p>\n  </p>\n <p style=\"margin-left: 5pt;\">\n <u>SECONDARY OBJECTIVES</u></p>\n <p>\n  </p>\n <p style=\"margin-left: 41pt;\">\n 1.   To evaluate the antiviral activity of DTG in combination with an OBT by measuring virologic response in infants, children and adolescents at 24 and 48 weeks.</p>\n <p>\n  </p>\n <p style=\"margin-left: 23pt;\">\n 2.   To evaluate the effect on immunologic response from baseline to 24 and 48 weeks.</p>\n</div>\n<p>\n  </p>\n<p style=\"margin-left: 23pt;\">\n 3.   To assess changes in HIV-1 genotype and phenotype to DTG and other components of the OBT</p>\n<p style=\"margin-left: 41pt;\">\n in subjects experiencing virologic failure.</p>\n<p>\n  </p>\n<p style=\"margin-left: 23pt;\">\n 4.   To determine DTG exposure, its variability and clinical covariates that impact DTG disposition</p>\n<p style=\"margin-left: 41pt;\">\n (e.g. age, weight) using intensive and sparse sampling and population pharmacokinetic analysis.</p>\n<p>\n  </p>\n<p style=\"margin-left: 41pt;\">\n 5.   To determine the extended long term (≥48 weeks) safety and tolerability of DTG in HIV-1 infected infants, children and adolescents.</p>\n<p>\n  </p>\n<p style=\"margin-left: 23pt;\">\n 6.   To explore the relationship between DTG exposure and the antiviral activity.</p>\n
      • study_title<p align=\"center\" style=\"margin-left: 4.55pt;\">\n <strong>P</strong><strong>h</strong><strong>ase I/II, Multi-Center, Open-Label Pharmacokinetic, Safety, Tolerability and Antiviral Activity of Dolutegravir, a Novel Integrase Inhibitor, in Combination Regimens in HIV-1 Infected Infants, Children and Adolescents</strong><strong>P</strong><strong>h</strong><strong>ase I/II, Multi-Center, Open-Label Pharmacokinetic, Safety, Tolerability and Antiviral Activity of Dolutegravir, a Novel Integrase Inhibitor, in Combination Regimens in HIV-1 Infected Infants, Children and Adolescents</strong></p>\n
      • laymans_summary<p>\n This is a study enrolling infants, children and adolescents aged >4weeks to <18 years to asses the safety tolerability and antiviral activity of DTG. Participants are followed up for a total duration of 4 years.</p>\n
      • short_titleIMPAACT P1093
      • protocol_noECCT/16/11/02
      • version_noVersion 4.0
      • date_of_protocol13-04-2016
      • study_drugDolutegravir (DTG)
      • 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_nameTivicay
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressjoel.chebon@usamru-k.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_countries0
      • applicant_addendum1
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd0
      • applicant_prev_data0
      • applicant_stability_data0
      • applicant_analysis_cert0
      • applicant_pictorial_sample0
      • applicant_gcp_training0
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi0
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african0
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantJoel Chebon
      • declaration_date119-09-2016
      • declaration_principal_investigatorLucy C. Koech
      • declaration_date219-09-2016
      • placebo_presentNo
      • study_objectives<div>\n <p style=\"margin-left: 5pt;\">\n <u>PRIMARY OBJECTIVES</u></p>\n <p>\n  </p>\n <p style=\"margin-left: 41pt;\">\n 1.   To select a dose for each formulation of DTG for chronic dosing in infants, children and adolescents that achieves similar exposure to the DTG 50 mg once daily dose in adults.</p>\n <p>\n  </p>\n <p style=\"margin-left: 41pt;\">\n 2.   To determine the safety and tolerability of DTG in HIV-1 infected infants, children and adolescents at 24 and 48 weeks.</p>\n <p>\n  </p>\n <p style=\"margin-left: 41pt;\">\n 3.   To evaluate the steady-state pharmacokinetics of DTG in combination with other antiretrovirals (OBT) in treatment-experienced and/or treatment-naïve HIV-1 infected infants, children and adolescents and to determine the dose of DTG that achieves a targeted AUC24 (primary PK endpoint) and C24h (secondary PK endpoint) in this population.</p>\n <p>\n  </p>\n <p style=\"margin-left: 5pt;\">\n <u>SECONDARY OBJECTIVES</u></p>\n <p>\n  </p>\n <p style=\"margin-left: 41pt;\">\n 1.   To evaluate the antiviral activity of DTG in combination with an OBT by measuring virologic response in infants, children and adolescents at 24 and 48 weeks.</p>\n <p>\n  </p>\n <p style=\"margin-left: 23pt;\">\n 2.   To evaluate the effect on immunologic response from baseline to 24 and 48 weeks.</p>\n</div>\n<p>\n  </p>\n<p style=\"margin-left: 23pt;\">\n 3.   To assess changes in HIV-1 genotype and phenotype to DTG and other components of the OBT</p>\n<p style=\"margin-left: 41pt;\">\n in subjects experiencing virologic failure.</p>\n<p>\n  </p>\n<p style=\"margin-left: 23pt;\">\n 4.   To determine DTG exposure, its variability and clinical covariates that impact DTG disposition</p>\n<p style=\"margin-left: 41pt;\">\n (e.g. age, weight) using intensive and sparse sampling and population pharmacokinetic analysis.</p>\n<p>\n  </p>\n<p style=\"margin-left: 41pt;\">\n 5.   To determine the extended long term (≥48 weeks) safety and tolerability of DTG in HIV-1 infected infants, children and adolescents.</p>\n<p>\n  </p>\n<p style=\"margin-left: 23pt;\">\n 6.   To explore the relationship between DTG exposure and the antiviral activity.</p>\n
      • principal_inclusion_criteria<div>\n <p style=\"margin-left: 5pt;\">\n <strong>4.1       Inclusion Criteria</strong></p>\n <p>\n  </p>\n <p>\n  </p>\n <p style=\"margin-left: 41pt;\">\n 4.1.1    Age: ≥ 4 weeks to <strong><</strong>18 years at study entry</p>\n <p>\n  </p>\n <p style=\"margin-left: 41pt;\">\n 4.1.2    Confirmed HIV-1 infection</p>\n <p>\n  </p>\n <p style=\"margin-left: 95pt;\">\n ·    Documentation of HIV-1 infection defined as positive results from <u>two</u> samples collected at <u>different</u> time points. All samples tested must be whole blood, serum or plasma. All test methods should be FDA-approved if available. If FDA-approved methods are not available, test methods should be verified according to GCLP and approved by the IMPAACT central laboratory.</p>\n <p style=\"margin-left: 113pt;\">\n o  Sample #1 may be tested by non-study public or PEPFAR programs.</p>\n <p style=\"margin-left: 131pt;\">\n However, both the result and the assay date must be recorded in the subject’s</p>\n <p style=\"margin-left: 131pt;\">\n chart. Source documentation (patient’s medical record/chart, in-country</p>\n <p style=\"margin-left: 131pt;\">\n Ministry of Health registers, laboratory results, etc.) must be available if requested.</p>\n <p style=\"margin-left: 131pt;\">\n o  Sample #2 must be performed in a CAP/CLIA-approved laboratory (for US sites) or in a laboratory that operate according to GCLP guidelines and participates’ in appropriate external quality assurance program (for non-US sites).</p>\n</div>\n<p>\n  </p>\n<div>\n <p>\n  </p>\n <p style=\"margin-left: 74pt;\">\n <u>4.1.2.1 Acceptable tests when subjects are ≤ 18 months of age</u></p>\n <p>\n  </p>\n <p style=\"margin-left: 74pt;\">\n Sample #1 and Sample #2 may be tested using any of the following:</p>\n <p>\n  </p>\n <p style=\"margin-left: 74pt;\">\n ·    One HIV DNA PCR</p>\n <p style=\"margin-left: 74pt;\">\n ·    One quantitative HIV RNA  PCR (above the limit of detection of the assay)</p>\n <p style=\"margin-left: 74pt;\">\n ·    One qualitative HIV RNA PCR</p>\n <p style=\"margin-left: 74pt;\">\n ·    One total HIV nucleic acid</p>\n <p>\n  </p>\n <p style=\"margin-left: 77pt;\">\n Note: Subjects ≤ 18 months of age can be enrolled on the basis of one positive test result (from Sample #1) if the results from Sample #2 are pending. The HIV RNA test required at screening per the Schedule of Evaluations may serve as Sample #2 and may be</p>\n <p style=\"margin-left: 77pt;\">\n pending at the time of enrollment. However, any subject in whom infection is not confirmed by the results of Sample #2 should discontinue study drug, per Section 6.6 and be followed per Appendix IF.</p>\n <p>\n  </p>\n <p style=\"margin-left: 77pt;\">\n <u>4.1.2.2 Acceptable tests when subjects are > 18 months of age</u></p>\n <p>\n  </p>\n <p style=\"margin-left: 77pt;\">\n Sample #1 may be tested using any of the following:</p>\n <p>\n  </p>\n <p style=\"margin-left: 95pt;\">\n ·    Two rapid antibody tests from different manufacturers or based on different principles and epitopes</p>\n <p style=\"margin-left: 77pt;\">\n ·    One EIA OR Western Blot OR immunofluorescence OR chemiluminescence</p>\n <p style=\"margin-left: 77pt;\">\n ·    One HIV DNA PCR</p>\n <p style=\"margin-left: 77pt;\">\n ·     One quantitative HIV RNA PCR (above the limit of detection of the assay)</p>\n <p style=\"margin-left: 77pt;\">\n ·    One qualitative HIV RNA PCR</p>\n <p style=\"margin-left: 77pt;\">\n ·    One HIV culture (prior to August 2009)</p>\n <p style=\"margin-left: 77pt;\">\n ·    One total HIV nucleic acid</p>\n <p>\n  </p>\n <p style=\"margin-left: 77pt;\">\n Sample #2 may be tested using any of the following:</p>\n <p>\n  </p>\n <p style=\"margin-left: 95pt;\">\n ·    Rapid antibody test. If this option is used in combination with the two tests for Sample #1, at least one of the three rapid antibody tests for Sample #1 must be FDA approved and the third rapid test must be from a third manufacturer or based on a third principle or epitope.</p>\n <p style=\"margin-left: 77pt;\">\n ·    One EIA  OR  Western Blot OR immunofluorescence OR chemiluminescence</p>\n <p style=\"margin-left: 77pt;\">\n ·    One HIV DNA PCR</p>\n <p style=\"margin-left: 77pt;\">\n ·    One quantitative HIV RNA PCR (above the limit of detection of the assay)</p>\n <p style=\"margin-left: 77pt;\">\n ·    One qualitative HIV RNA PCR</p>\n <p style=\"margin-left: 77pt;\">\n ·    One HIV culture (prior to August 2009)</p>\n <p style=\"margin-left: 77pt;\">\n ·    One total HIV nucleic acid</p>\n <p>\n  </p>\n <p>\n  </p>\n <p>\n  </p>\n <p style=\"margin-left: 41pt;\">\n 4.1.3     Subjects must belong to one of the ARV exposure groups below:</p>\n <p>\n  </p>\n <p style=\"margin-left: 77pt;\">\n 4.1.3.1  ARV-treatment experienced (not including receipt of ARVs as prophylaxis or</p>\n <p align=\"center\" style=\"margin-left: 111.2pt;\">\n PMTCT)</p>\n <p>\n  </p>\n <p style=\"margin-left: 113pt;\">\n Previously took ARVs as treatment, but not currently taking ARVs :</p>\n</div>\n<p>\n  </p>\n<div>\n <p>\n  </p>\n <p style=\"margin-left: 149.05pt;\">\n ·    Must have been off treatment ≥ 4 weeks</p>\n <p>\n  </p>\n <p style=\"margin-left: 151.35pt;\">\n OR</p>\n <p>\n  </p>\n <p align=\"center\" style=\"margin-left: 111.2pt;\">\n -    Currently taking ARVs for treatment but failing:</p>\n <p>\n  </p>\n <p style=\"margin-left: 149.05pt;\">\n ·    Must be on an unchanged, failing therapeutic regimen within the 4 to</p>\n <p style=\"margin-left: 167.05pt;\">\n 12 weeks prior to screening (≤1 log drop in HIV-1 RNA within the 4 to 12 weeks prior to screening).</p>\n <p>\n  </p>\n <p style=\"margin-left: 149.05pt;\">\n NOTE: Dose adjustments for growth or formula substitutions (i.e. switching from single agent to fixed dose combination) are permitted during this 4 to 12 week period. Substitutions of one ARV within the same class for toxicity or tolerability management, or discontinuation of ARVs are also allowed within the 4 to 12 weeks period.</p>\n <p>\n  </p>\n <p align=\"center\" style=\"margin-left: 165.2pt;\">\n OR</p>\n <p>\n  </p>\n <p style=\"margin-left: 131pt;\">\n -    For subjects < 2 years of age, initiated ARVs for treatment < 4 weeks prior to screening.</p>\n <p>\n  </p>\n <p style=\"margin-left: 77pt;\">\n 4.1.3.2  ARV treatment naive (no exposure to ARVs for treatment; could have received</p>\n <p style=\"margin-left: 113pt;\">\n ARVs for prophylaxis or PMTCT)</p>\n <p style=\"margin-left: 149.05pt;\">\n ·    Age < 2 years</p>\n <p>\n  </p>\n <p style=\"margin-left: 89pt;\">\n 4.1.4        If an infant has received NVP as prophylaxis to prevent mother to child transmission (PMTCT), he or she must have <strong>not </strong>received NVP for at least 14 days prior to enrollment into Stage I or II.</p>\n <p>\n  </p>\n <p align=\"center\" style=\"margin-left: 39.2pt;\">\n 4.1.5    HIV-1 RNA viral load greater than 1,000 copies/mL of plasma at screening</p>\n <p>\n  </p>\n <p style=\"margin-left: 77pt;\">\n NOTE: For subjects enrolling into cohorts IV, IV-DT, V, and V-DT, the HIV RNA test performed at screening may be pending at the time of enrollment. If the screening HIV RNA is ≤ 1000 c/mL, the subject should discontinue study drug, per Section 6.6 and be followed per Appendix IF.</p>\n <p>\n  </p>\n <p style=\"margin-left: 77pt;\">\n 4.1.6     Demonstrated ability or willingness to swallow assigned study medications. NOTE: Film coated tablets MAY NOT be crushed or dissolved. Dispersible tablets MAY NOT be cut and must be used in five milligram intervals.</p>\n <p>\n  </p>\n <p align=\"center\" style=\"margin-left: 39.2pt;\">\n 4.1.7    Parent or legal guardian able and willing to provide signed informed consent.</p>\n <p>\n  </p>\n <p style=\"margin-left: 77pt;\">\n 4.1.8    Female subjects who are of child bearing potential and who are engaging in sexual activity that could lead to pregnancy, must use two adequate birth control methods while on study and for two weeks after stopping study drug. Hormonal birth control alone (e.g., pills, shots, or slow release inserts placed under/on the skin) would not be considered adequate. An effective, medically accepted barrier method of contraception (e.g., female/male condoms, diaphragm or cervical cap with a cream or gel that kills sperm (excluding nonoxydyl-9), intrauterine device [IUD], others) also must be used during the</p>\n</div>\n<p>\n  </p>\n<p style=\"margin-left: 77pt;\">\n study. Condoms are recommended because their appropriate use is the only contraception method effective for preventing HIV-1 transmission.</p>\n<p>\n  </p>\n<p style=\"margin-left: 72.6pt;\">\n 4.1.9   Males engaging in sexual activity that could lead to HIV-1 transmission must use a condom.</p>\n<p>\n  </p>\n<p style=\"margin-left: 41pt;\">\n 4.1.10 Optimized background therapy (OBT):</p>\n<p>\n  </p>\n<p style=\"margin-left: 90.6pt;\">\n ·    Subjects aged ≥2 years of age (Cohorts I, II, III, and III-DT) must have available at least one fully active drug for the OBT to enroll. Historical genotypes obtained within 1 year of screening will be considered by the Protocol Team for determination of fully active drugs if screening genotype testing is inconclusive.</p>\n<p style=\"margin-left: 90.6pt;\">\n ·    Subjects < 2 years of age (Cohorts IV, IV-DT, V, and V-DT) can enroll if genotype testing has been obtained with results pending.</p>\n<p>\n  </p>\n<p style=\"margin-left: 90.6pt;\">\n Note: Subjects enrolled with genotype results pending but found to have no active drugs per genotype performed at screening should discontinue study drug, per Section</p>\n<p style=\"margin-left: 90.6pt;\">\n 6.6 and be followed per Appendix IF. However, such subjects who have a > 1 log drop in HIV RNA by 4 weeks can continue study drug with approval by the Protocol Team.</p>\n
      • principal_exclusion_criteria<div>\n <p style=\"margin-left: 5pt;\">\n <strong>4.2       Exclusion Criteria</strong></p>\n <p>\n  </p>\n <p>\n  </p>\n <p style=\"margin-left: 36.6pt;\">\n 4.2.1    Presence of any active AIDS defining opportunistic infection</p>\n <p>\n  </p>\n <p style=\"margin-left: 36.6pt;\">\n 4.2.2    At enrollment, subject < 3.0 kg</p>\n <p>\n  </p>\n <p style=\"margin-left: 72.6pt;\">\n 4.2.3    Known ≥ Grade 3 of any of the following laboratory toxicities within 30 days prior to study entry: neutrophil count, hemoglobin, platelets, AST, ALT, lipase, serum creatinine and total bilirubin. A single repeat within the 30 days is allowed for eligibility determination. NOTE: ≥ Grade 3 total bilirubin is allowable, if the subject is on ATV.</p>\n <p>\n  </p>\n <p style=\"margin-left: 72.6pt;\">\n 4.2.4    ANY known Grade 4 laboratory toxicities within 30 days prior to study entry. NOTE: Grade 4 total bilirubin is allowable, if the subject is on ATV.</p>\n <p>\n  </p>\n <p style=\"margin-left: 36.6pt;\">\n 4.2.5    The following liver toxicities within 30 days prior to study entry: ALT > 3x ULN <u>AND</u></p>\n <p style=\"margin-left: 72.6pt;\">\n direct bilirubin is > 2x ULN</p>\n <p>\n  </p>\n <p style=\"margin-left: 72.6pt;\">\n 4.2.6    Any prior history of malignancy, with the exception of localized malignancies such as squamous cell or basal cell carcinoma of the skin</p>\n <p>\n  </p>\n <p style=\"margin-left: 36.6pt;\">\n 4.2.7    Clinical or symptomatic evidence of pancreatitis, as determined by the clinician</p>\n <p>\n  </p>\n <p style=\"margin-left: 72.6pt;\">\n 4.2.8    Use of any disallowed medications at time of screening (see Section 4.3.2 for a complete list of disallowed medications)</p>\n <p>\n  </p>\n <p style=\"margin-left: 36.6pt;\">\n 4.2.9    Known history of exposure to integrase inhibitor treatment by the subject or subject’s</p>\n <p style=\"margin-left: 72.6pt;\">\n mother prior to delivery/cessation of breast feeding</p>\n <p>\n  </p>\n <p style=\"margin-left: 36.6pt;\">\n 4.2.10   Known resistance to an integrase inhibitor</p>\n</div>\n<p>\n  </p>\n<p style=\"margin-left: 36.6pt;\">\n 4.2.11   Women who are pregnant or breastfeeding.</p>\n<p>\n  </p>\n<p style=\"margin-left: 72.6pt;\">\n 4.2.12   Subject is currently participating in or has participated in a study with a compound or device that is not commercially available within 30 days of signing informed consent, unless permission from both Protocol Teams is granted</p>\n<p>\n  </p>\n<p style=\"margin-left: 72.6pt;\">\n 4.2.13   Subject is unlikely to adhere to the study procedures, keep appointments, or is planning to relocate during the study to a non-IMPAACT study site</p>\n<p>\n  </p>\n<p style=\"margin-left: 72.6pt;\">\n 4.2.14   Any clinically significant diseases (other than HIV infection) or clinically significant findings during the screening medical history or physical examination that, in the investigator’s opinion, would compromise the outcome of this study</p>\n<p>\n  </p>\n<p style=\"margin-left: 72.6pt;\">\n 4.2.15   Subject has used, or anticipates using, chronic systemic immunosuppressive agents or systemic interferon (e.g. for treatment of HCV infection) within 30 days prior to beginning DTG study treatment. Systemic corticosteroids (e.g. prednisone or equivalent up to 2 mg/kg/day) for replacement therapy or short courses (≤30 days) are permitted. (See disallowed medications Section 4.3.2)</p>\n<p>\n  </p>\n<p style=\"margin-left: 72.6pt;\">\n 4.2.16   Any condition that would, in the opinion of the site investigator, place the subject at an unacceptable risk of injury or render the subject unable to meet the requirements of the protocol.</p>\n<p>\n  </p>\n<p style=\"margin-left: 72.6pt;\">\n 4.2.17   Active TB disease and/or requirement for treatment that includes rifampin at the time of the screening visit. However, subjects who need rifampin treatment while on DTG will be allowed to continue in P1093 provided the DTG dose is adjusted according to Section</p>\n<p style=\"margin-left: 72.6pt;\">\n 6.1.8.</p>\n
      • primary_end_points<p style=\"margin-left: 41pt;\">\n 8.2.1    Primary Endpoints:</p>\n<p>\n  </p>\n<p style=\"margin-left: 77pt;\">\n 8.2.1.1  Toxicity through Week 24</p>\n<p style=\"margin-left: 113pt;\">\n ·    All adverse events or lab toxicities of Grade 3 or higher severity</p>\n<p style=\"margin-left: 131pt;\">\n ·    Adverse events or lab toxicities of Grade 3 or higher severity judged to be at least possibly attributable to the study medication</p>\n<p style=\"margin-left: 113pt;\">\n ·    Termination from treatment due to a drug-related adverse event</p>\n<p style=\"margin-left: 113pt;\">\n ·    Death</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy0
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic1
      • scope_bioequivalence0
      • scope_dose_response1
      • scope_pharmacogenetic1
      • scope_pharmacogenomic0
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      • scope_others_specify
      • trial_human_pharmacology1
      • 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 See the SSA APPEDIX 1 WHICH STATES THE KEMRI /WRP CRC ROLES OF STUDY PERSONNEL</p>\n
      • other_details_explanation<p>\n N/A</p>\n
      • other_details_regulatory_notapproved<p>\n N/A</p>\n
      • other_details_regulatory_approved<p>\n Walter Reed Army Institute of Research IRB approved through letter dated: Aug 10 2016</p>\n<p>\n KEMRI SERU approved through letter dated: Aug 18 2016</p>\n
      • other_details_regulatory_rejected
      • other_details_regulatory_halted
      • estimated_duration After been on study for 48 weeks, all participants shall enter long term followup phase for 3 years.
      • design_controlled_randomised
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      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
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      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKENYA MEDICAL RESEARCH INSTITUTE/WALTER REED PROJECT HIV PROGRAME
      • single_site_physical_addressHospital Road P.O Box 1357 - 20200 Kericho
      • single_site_contact_personLucy Koech
      • single_site_telephone254522030686
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states5
      • number_of_sites
      • multi_country_listKenya, USA, Haiti, Thailand, South Africa
      • data_monitoring_committeeYes
      • total_enrolment_per_site20
      • total_participants_worldwide100
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerYes
      • population_childrenYes
      • population_adolescentYes
      • population_above_18No
      • population_adultNo
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyNo
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
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      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
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      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameWinnie
      • investigator1_middle_name
      • investigator1_family_nameKeter
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      • investigator1_emailwinnie.keter@usamru-k.org
      • organisations_transferred_Yes
      • number_participants20
      • notification
      • approval_date28-03-2017
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      • date_submitted02-03-2020
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      • final_date(null)
      • modified2025-02-10 11:30:49
      • created2016-09-15 15:01:46
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
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        • application_id556
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        • middle_name
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        • telephone0522030686
        • emaillucy.koech@usamru-k.org
        • created2016-09-16 12:06:16
        • modified2020-03-02 14:32:58
    • SiteDetail(array)
      • 0(array)
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        • county_id(null)
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        • created2016-09-16 12:06:16
        • modified2020-03-02 14:32:58
        • County(empty)
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      • 0(array)
        • id286
        • application_id556
        • sponsorNational Institute of Allergy and Infectious Diseases
        • sponsor_typeOthers
        • contact_personEllen Townley
        • addressMaternal Adolescent Pediatric Branch HJF DAIDS, DAIDS/NIAD/NIH 5601 Fischers Lane Room 8B37
        • telephone_number2402924784
        • fax_number2406273465
        • cell_number2402924784
        • email_addressellen.townley@nih.gov
        • created2016-09-16 12:06:16
        • modified2020-03-02 14:32:58
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PHP Environment

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