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    • Application(array)
      • id730
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      • abstract_of_study<h1>\n Abstract (300 words):</h1>\n<p>\n <strong>Introduction: </strong>Cervical cancer is the leading cause of new cancer cases among women in Kenya representing a substantial burden of disease for women. HPV infection is a necessary cause of cervical cancer and preliminary evidence suggests a single-dose of the HPV vaccine would provide efficacy in excess of 95%,¹ supporting HPV vaccination as a scaleable intervention for cervical cancer prevention. An evidence gap exists on the efficacy and durability of single-dose HPV vaccine among young women in Africa.</p>\n<p>\n  </p>\n<p>\n <strong>Objectives:</strong> The primary objective is to compare immediate, single-dose bivalent (HPV 16/18) and nonavalent (HPV 16/18/31/33/45/52/58/6/11) vaccination (and delayed meningococcal immunization) with delayed HPV vaccination (and immediate meningococcal immunization) among young women age 15-20 years. We will also conduct costing, budget impact, and cost-effectiveness analyses to provide evidence for decision makers</p>\n<p>\n  </p>\n<p>\n <strong>Methods: </strong>Women age 15-20 years old will be randomized to immediate bivalent and delayed meningococcal vaccine (arm 1), immediate nonavalent vaccine and delayed meningococcal vaccine (arm 2), or delayed HPV vaccine and immediate meningococcal vaccine (arm 3) with 36 months of follow-up. The primary study endpoint is persistent vaccine type specific HPV infection at months 18 and 36. The quantitative antibody response will be documented at months 1 and 24 to support immunobridging analyses to girls and adolescents for the single-dose bivalent and nonavalent vaccines. Using the data on persistent infections and health economic models, we will assess the impact on cervical cancer incidence.</p>\n<p>\n  </p>\n<p>\n <strong>Anticipated results: </strong>Our study will evaluate whether or not single-dose vaccination impacts the incidence of persistent HPV infections. Our health economic modeling results will help policy planners assess the long-term costs, benefits and budget impact of single-dose HPV vaccine delivery, in terms of cervical cancer deaths prevented and the costs saved relative to the two or three dose HPV vaccine schedule.</p>\n<p>\n  </p>\n<p>\n  </p>\n
      • study_title<p align=\"center\">\n  </p>\n<p align=\"center\">\n  </p>\n<p align=\"center\">\n <strong>Single-dose HPV catch-up vaccination efficacy: A blinded, randomized study of single-dose HPV vaccination among adolescent girls and young women in Kenya </strong></p>\n
      • laymans_summary<p align=\"center\">\n <strong>LAY STUDY SUMMARY</strong></p>\n<p>\n Cervical cancer is one of the most common type of cancers worldwide. About 90% of all cervical cancers occur among women from low and middle income regions, and eastern Africa has the one of the highest rates of cervical cancer. In Kenya, more than 4,800 women are newly diagnosed with cervical cancer and about 2,500 women die from this condition each year.</p>\n<p>\n  </p>\n<p>\n Cervical cancer is caused by an infection with Human Papillomavirus, also called HPV. HPV is a common infection that affects 80% of adult women and 65-70% of adult men and is usually transmitted through sexual activities. There are over 100 sub-types of HPV. Of these, 13 types are considered high risk because of their potential to cause cancer. While most HPV infections heal on their own and do not cause any illness, some infections can persist in the body. Persistent infection with a high-risk type of HPV could lead to cancer.</p>\n<p>\n  </p>\n<p>\n There are vaccines that can prevent high risk HPV infections and, therefore, cervical cancer. These vaccines are highly effective and safe. Currently, Kenyan Ministry of Health and the World Health Organization recommend vaccinating with two doses of the HPV vaccine. In 2019, the Ministry of Health will begin a national program to vaccinate girls in Standard 4. Additionally, catch up vaccination of girls up to age 14 years will be supported by the Global Alliance for Vaccination & Immunization. However, there are currently no plans to vaccinate adolescents aged 15 and older, who are also at risk for HPV infection. The primary challenge to vaccinating this age group is the cost associated with a 2 dose vaccines schedule. Reducing the vaccine dose to one could address this barrier.</p>\n<p>\n  </p>\n<p>\n The purpose of our study is to learn whether one dose of HPV vaccine is effective in preventing HPV infection in adolescents aged 15-20 years old. Previous studies done in other countries have found that a single dose of HPV vaccine worked just as well as two doses in preventing HPV. Our study will confirm these findings using a gold-standard study design. Several HPV vaccines are available. Our study will determine the efficacy of two HPV vaccines: bivalent and nonavalent vaccines. The bivalent vaccine protects against 2 high risk HPV types and the nonavalent vaccine protects against 7 high risk types and 2 low risk types.</p>\n<p>\n  </p>\n<p>\n At the start of our study, young women will be randomly sorted into three arms. In arm 1, the women will receive the bivalent HPV vaccine. In arm 2, the women will receive the nonvalent vaccine. And in arm 3, the women will receive a meningococcal vaccine. At the end of the study, those in arms 1 and 2 will receive the meningococcal vaccine, while those in arm 3 will receive either the bivalent or nonavalent HPV vaccine. The three arm study structure makes it possible to compare the women who received an HPV vaccine to those who did not receive an HPV vaccine during the study. We chose to use meningococcal vaccine because it is not ethical to use a placebo when the HPV vaccines have been previously shown to be effective. Additionally, the meningococcal vaccine is already part of the recommended vaccination schedule for adolescents in Kenya. Over the course of the study, the participants will be asked to return for follow up visits periodically. During these visits, the study staff will conduct pelvic and physical exams, and take specimen for HPV testing. Other sexual and reproductive health services will also be offered to the participants during follow up visits. </p>\n
      • short_titleSingle-dose HPV catch-up vaccination efficacy: A blinded, randomized study of single-dose HPV vaccination among adolescent girls and young women in Kenya
      • protocol_noECCT/18/10/02
      • version_no1.0
      • date_of_protocol03-08-2018
      • study_drugBivalent Cervarix, Nonavalent Gardasil, MenVeo meningococcal vaccines
      • disease_conditionCervical Cancer
      • product_type_biologicals0
      • product_type_proteins0
      • product_type_immunologicals0
      • product_type_vaccines1
      • product_type_hormones0
      • product_type_toxoid0
      • product_type_chemical1
      • product_type_medical_device0
      • product_type_chemical_nameHuman Pappilloma Virus Vaccine, Meningococcal vaccine
      • product_type_medical_device_nameNone
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressmaricianah@yahoo.com
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
      • applicant_investigators_cv1
      • applicant_signed_declaration1
      • applicant_financial_declaration1
      • applicant_gmp_certificate1
      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
      • applicant_participating_countries0
      • applicant_addendum1
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      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget1
      • applicant_indemnity_pi1
      • applicant_practice_license1
      • applicant_registration_ctr(null)
      • applicant_pan_african1
      • applicant_hard_copies(null)
      • applicant_signed_checklist1
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantProf. Elizabeth Bukusi
      • declaration_date108-10-2018
      • declaration_principal_investigatorDr. Maricianah Onono (Country Director)
      • declaration_date208-10-2018
      • placebo_presentNo
      • study_objectives<p>\n <strong>Primary Objectives:</strong></p>\n<p>\n  </p>\n<ol>\n <li>\n To test the efficacy of immediate single-dose bivalent or nonavalent HPV vaccination to prevent incident persistent HPV 16/18 infection compared to delayed nonavalent HPV vaccination for young women age 15-20 years.  </li>\n</ol>\n<p>\n  </p>\n<ol>\n <li value=\"2\">\n To test the efficacy of immediate single-dose nonavalent HPV vaccination to prevent incident persistent HPV 16/18/31/33/45/52/58 infection compared to delayed nonavalent HPV vaccination for young women age 15-20 years.  </li>\n</ol>\n<p>\n  </p>\n<ol>\n <li value=\"3\">\n  To determine whether vaccine-type HPV antibody responses after single-dose bivalent or nonavalent vaccination are noninferior in 9-14 year old girls versus 15-20 year old young women.</li>\n</ol>\n<p>\n  </p>\n<p>\n <strong>Secondary objectives</strong></p>\n<p>\n  </p>\n<ol>\n <li>\n To assess cost, cost-effectiveness, and budget impact of single-dose HPV vaccination to support implementation strategies for single-dose HPV vaccination following WHO recommendation in high cervical cancer burden settings. </li>\n</ol>\n<p>\n  </p>\n<ol>\n <li value=\"2\">\n To evaluate B-cell markers as a proxy for immune memory following single-dose bivalent and nonavalent vaccination.</li>\n</ol>\n<p>\n <br />\n  </p>\n
      • principal_inclusion_criteria<ul>\n <li>\n Born female</li>\n <li>\n Age 15 to 20 years</li>\n <li>\n HIV-negative</li>\n <li>\n No history of HPV vaccination</li>\n <li>\n Sexually active: history of 1-5 lifetime partners</li>\n <li>\n Resident within study area without plans to move away in the next 36 months</li>\n</ul>\n
      • principal_exclusion_criteria<p>\n Ineligibility criteria for the study are:</p>\n<ul>\n <li>\n Allergies to vaccine components or latex,</li>\n <li>\n Pregnancy</li>\n <li>\n Hysterectomy</li>\n <li>\n Autoimmune, degenerative, and genetic diseases</li>\n <li>\n Investigator discretion</li>\n</ul>\n
      • primary_end_points<p>\n Persistant vaccine type specific HPV infection at months 18 and 36</p>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • scope_therapy0
      • scope_safety0
      • scope_efficacy1
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others1
      • scope_others_specifyCost , Cost effectiveness and Budget impact
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use1
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n (1) The sites have infrastructure that include adequate study space (2) laboratory equipment (3) experienced staff who have been involved in a number of phase 2 and 3 trials. The staff also have experience in behavioral and contraceptive counseling, clinical assessment, pap smear and cervical cancer screening, HIV care and counseling and therefore the study takes advantage of this existing infrastructure (4) high volume flow of young women eligible for the HPV vaccine per protocol and cervical cancer screening within Kisumu town.</p>\n<p>\n 1) Prof. Elizabeth Bukusi MBChB, M.Med, MPH, PhD</p>\n<p>\n 2)Dr. Maricianah Onono MBChB, MSc, PhDc</p>\n<p>\n 3)Dr. Nelly Mugo MBChB, M.Med, MPH</p>\n<p>\n 4)Dr. Betty Njoroge MBChB, MPH</p>\n<p>\n 5)Dr. Ruanne Barnabas MBChB, DPhil</p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n<p>\n  </p>\n
      • other_details_explanation<p>\n Cervical cancer is the leading cause of new cancer cases in Kenyaand HPV infection is a necessary cause of cervical cancer. Single-dose HPV vaccine has high efficacy (>95%) in observational studies but efficacy is not known for catch-up vaccination. This study will therefore contribute evidence on vaccine efficacy in Kenya among 15-20 year olds bridging a gap in primary prevention for this age group.</p>\n
      • other_details_regulatory_notapproved<p>\n None</p>\n
      • other_details_regulatory_approved<p>\n Kenya Medical Research Institute-Scientific and Ethics Review Unit (KEMRI- SERU)</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n Not applicable</p>\n
      • estimated_durationFive years
      • design_controlled_randomisedYes
      • design_controlled_openNo
      • design_controlled_single_blindNo
      • design_controlled_double_blindYes
      • design_controlled_parallel_groupYes
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorMenVeo (Meningococcal vac
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateNo
      • location_of_area
      • single_site_physical_address
      • single_site_contact_person
      • single_site_telephone
      • multiple_sites_member_stateYes
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites3
      • multi_country_list
      • data_monitoring_committeeYes
      • total_enrolment_per_siteKEMRI NAIROBI- 200-350\nKEMRI KISUMU- 750-1000\nKEMRI THIKA PHRD - 750-100
      • total_participants_worldwideUpto 2250
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male0
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameDr. Maricianah
      • investigator1_middle_nameAtieno
      • investigator1_family_nameOnono
      • investigator1_qualificationMBChB, MSc, PhDc
      • investigator1_professional_addressP.O Box 19669- 40123, Kisumu,Kenya
      • investigator1_telephone0732390992
      • investigator1_emailmaricianah@yahoo.com
      • organisations_transferred_No
      • number_participantsUpto 2250
      • notification
      • approval_date19-11-2018
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted26-05-2020
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
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      • quantity_imported(null)
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      • balance_site(null)
      • final_date(null)
      • modified2025-03-28 15:47:47
      • created2018-10-08 10:03:52
      • total_sites(null)
      • ecitizen_invoice(null)
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        • id455
        • application_id730
        • given_nameDr. Nelly
        • middle_nameRwamba
        • family_nameMugo
        • qualificationMBChB, M.Med, MPH
        • professional_addressCentre for Clinical Research, KEMRI P.O Box 54840-00200, Nairobi, Kenya
        • telephone0723914057
        • emailrwamba@csrtkenya.org
        • created2018-10-08 11:52:34
        • modified2020-05-26 14:21:06
      • 1(array)
        • id456
        • application_id730
        • given_nameDr. Maricianah
        • middle_nameAtieno
        • family_nameOnono
        • qualificationMBChB, MSc, PhDc
        • professional_addressP.O Box 19669- 40123, Kisumu,Kenya
        • telephone0732390992
        • emailmaricianah@yahoo.com
        • created2018-10-08 12:01:17
        • modified2020-05-26 14:21:06
      • 2(array)
        • id457
        • application_id730
        • given_nameProf Bukusi
        • middle_nameAnne
        • family_nameBukusi
        • qualificationMBChB, M.Med (ObGyn), MPH,PhD, PGD (Research Ethics), MBE (Research Ethics),
        • professional_addressP.0 Box 614- 40100, Kisumu
        • telephone0720617503
        • emailebukusi@kemri.org
        • created2018-10-08 12:01:17
        • modified2020-05-26 14:21:06
      • 3(array)
        • id458
        • application_id730
        • given_nameDr. Betty
        • middle_nameWanjiru
        • family_nameNjoroge
        • qualificationMBChB, MPH
        • professional_addressCentre for Clinica Research, KEMRI, P.O BOx 54840-00200,Nairobi, Kenya
        • telephoneO722800693
        • emailbwjoroge@gmail.com
        • created2018-10-08 12:01:17
        • modified2020-05-26 14:21:06
      • 4(array)
        • id459
        • application_id730
        • given_nameDr. Ruanne
        • middle_name
        • family_nameBarnabas
        • qualificationMBChB
        • professional_addressInternational Clinical Research Centre Department of Global Health, University of Washington Ninth and Jefferson Building 908 Jefferson, 12th Floor, Room 1225 Seattle, WA 98104
        • telephone+1206 520 3813
        • emailrbarnaba@uw.edu
        • created2018-10-08 12:01:17
        • modified2020-05-26 14:21:06
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        • id578
        • application_id730
        • county_id47
        • site_nameKEMRI NAIROBI
        • physical_addressKEMRI Headquarters, Mbagathi Road, Nairobi
        • contact_detailsP.O Box 54840-00200, Nairobi, Kenya Tel: 0722800693
        • contact_personDr. Betty Njoroge
        • site_capacity(null)
        • misc(null)
        • created2018-10-08 11:52:34
        • modified2020-05-26 14:21:06
        • County(array)
          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
          • modified2012-06-15 10:27:40
      • 1(array)
        • id579
        • application_id730
        • county_id42
        • site_nameKEMRI KISUMU
        • physical_addressLumumba Health centre, CIS building, Agoi Streeet, Kisumu
        • contact_detailsP.O Box 19669-40123, Kisumu, Kenya
        • contact_personDr. Maricianah Onono
        • site_capacity(null)
        • misc(null)
        • created2018-10-08 13:48:19
        • modified2020-05-26 14:21:06
        • County(array)
          • id42
          • county_nameKisumu
          • created2012-06-15 10:27:02
          • modified2012-06-15 10:27:02
      • 2(array)
        • id580
        • application_id730
        • county_id22
        • site_nameKEMRI THIKA PHRD
        • physical_addressSection 9 OAU, Near Thika Nursing Home, Thika
        • contact_detailsP.O Box P.O Box 54840-00200, Nairobi, Kenya Tel: 0723914057
        • contact_personDr. Nelly Mugo
        • site_capacity(null)
        • misc(null)
        • created2018-10-08 13:48:19
        • modified2020-05-26 14:21:06
        • County(array)
          • id22
          • county_nameKiambu
          • created2012-06-15 10:24:37
          • modified2012-06-15 10:24:37
    • Sponsor(array)
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        • id358
        • application_id730
        • sponsorUniversity of Washington
        • sponsor_typeResearch Institution
        • contact_personJosy S Combs
        • addressOffice of sponsored program 4333 Brooklyn Ave NE Box 359472 Seattle
        • telephone_number(206)543-7052
        • fax_number(206)685-1732
        • cell_number(206)543-7052
        • email_addresscombsj@uw.edu
        • created2018-10-08 11:52:34
        • modified2020-05-26 14:21:06
  • 1(array)
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      • user_id66
      • trial_status_id4
      • abstract_of_study<p>\n A PHASE IV RANDOMIZED TRIAL TO EVALUATE THE VIROLOGIC RESPONSE AND PHARMACOKINETICS OF TWO DIFFERENT POTENT REGIMENS IN HIV INFECTED WOMEN INITIATING TRIPLE ANTIRETROVIRAL REGIMENS BETWEEN 28 AND 36 WEEKS OF PREGNANCY FOR THE PREVENTION OF MOTHER-TO-CHILD TRANSMISSION: NICHD P1081</p>\n<p>\n  </p>\n<p style=\"margin-left:99.0pt;\">\n <strong><u>DESIGN</u>:</strong>                Multicenter two arm randomized open-label trial comparing the ability to achieve virologic suppression at delivery, tolerability, and safety.</p>\n<p style=\"margin-left:99.0pt;\">\n  </p>\n<p style=\"margin-left:99.0pt;\">\n <strong><u>SAMPLE SIZE</u>:</strong>     334 evaluable mother-infant pairs (approximately 167 per arm), which is projected to require enrolling approximately 394 mother-infant pairs.</p>\n<p style=\"margin-left:99.0pt;\">\n  </p>\n<p style=\"margin-left:99.0pt;\">\n <strong><u>POPULATION</u>:</strong>     Human Immunodeficiency Virus (HIV)-1 infected pregnant women with a gestational age between 28 and 36 weeks who are antiretroviral (ARV) naïve or have received short-course zidovudine (maximum of 8 weeks) only for prevention of mother-to-child transmission (PMTCT) in previous pregnancies, and their infants.</p>\n<p style=\"margin-left:99.0pt;\">\n  </p>\n<p style=\"margin-left:99.0pt;\">\n <strong><u>STRATIFY BY</u>:</strong>    Gestational age at enrollment (28-30 weeks or 31-33 weeks or 34-36 weeks) and whether the women will use lamivudine/zidovudine or an alternative, locally supplied nucleoside reverse transcriptase inhibitor (NRTI) backbone.</p>\n<p style=\"margin-left:99.0pt;\">\n  </p>\n<p style=\"margin-left:99.0pt;\">\n <strong><u>REGIMEN</u>:</strong>            Antepartum – Participants will be randomized 1:1</p>\n<p style=\"margin-left:99.0pt;\">\n  </p>\n<p style=\"margin-left:99.0pt;\">\n                                  Arm A: Lamivudine 150 mg/zidovudine 300 mg* twice daily (BID) + efavirenz 600 mg every night (QHS).</p>\n<p style=\"margin-left:99.0pt;\">\n  </p>\n<p style=\"margin-left:99.0pt;\">\n                                  Arm B: Lamivudine 150 mg/zidovudine 300 mg* BID + raltegravir 400 mg BID.</p>\n<p style=\"margin-left:99.0pt;\">\n                                  ____________________</p>\n<p style=\"margin-left:99.0pt;\">\n                                  *Alternative, locally supplied NRTI backbone may be used in place of lamivudine/zidovudine with permission of protocol team obtained prior to randomization.</p>\n<p style=\"margin-left:99.0pt;\">\n  </p>\n<p style=\"margin-left:99.0pt;\">\n                                  <u>Active labor</u>:</p>\n<p style=\"margin-left:99.0pt;\">\n                                  All participants will continue to receive study drugs during labor. In addition, in place of the oral fixed dose combination of lamivudine 150 mg/zidovudine 300 mg (or alternative NRTI backbone), participants may receive intravenous zidovudine, other dosing regimens of oral zidovudine, oral lamivudine and/or additional drugs during labor, according to local standard of care/guidelines.</p>\n<p style=\"margin-left:99.0pt;\">\n  </p>\n<p style=\"margin-left:99.0pt;\">\n                                  <u>Infants</u>:</p>\n<p style=\"margin-left:99.0pt;\">\n                                  Infants will receive ARV according to specific local guidelines.</p>\n<p style=\"margin-left:99.0pt;\">\n <strong><u>TREATMENT</u></strong></p>\n<p style=\"margin-left:99.0pt;\">\n <strong><u>DURATION</u>:</strong>          All women will receive their randomized study regimen from study entry through delivery. Women who meet local guidelines for receiving antiretroviral therapy (ART) will continue triple ART after delivery according to local guidelines. These women can receive study supplied drugs for up to 8 weeks after delivery to facilitate the transition to local standard of care for treatment for maternal health and/or prevention of breast milk transmission. Women who do not meet local guidelines for receiving triple ART will stop study supplied drugs immediately after delivery. Women randomized to Arm A (efavirenz) may continue lamivudine/ zidovudine for a period of time after stopping efavirenz at the discretion of the local investigator.</p>\n<p style=\"margin-left:99.0pt;\">\n  </p>\n<p style=\"margin-left:99.0pt;\">\n <strong><u>STUDY </u></strong></p>\n<p style=\"margin-left:99.0pt;\">\n <strong><u>DURATION</u>:</strong>          Women will be followed for 6 months after delivery. Infants will be followed until 6 months of age and may participate in an extension phase: developmental assessment of infants, lasting up to 4 years of age.</p>\n<p style=\"margin-left:99.0pt;\">\n  </p>\n<p>\n <strong><u>OBJECTIVES</u>:       </strong><u>Primary Objectives</u>:</p>\n<p style=\"margin-left:1.45in;\">\n  </p>\n<p style=\"margin-left:1.9in;\">\n 1.                To compare the ability of two triple ARV regimens (one containing efavirenz and the other raltegravir) begun during the third trimester of pregnancy to achieve a viral load of < 200 copies/mL at the time of delivery.</p>\n<p style=\"margin-left:1.9in;\">\n 2.                To compare the safety and tolerability of two triple ARV regimens (one containing efavirenz and the other raltegravir) begun during the third trimester of pregnancy.</p>\n<p style=\"margin-left:1.45in;\">\n  </p>\n<p style=\"margin-left:1.45in;\">\n <u>Secondary Objectives</u>:</p>\n<p style=\"margin-left:1.45in;\">\n  </p>\n<p style=\"margin-left:1.95in;\">\n 1.                  To compare the kinetics of viral decay between the treatment regimens:</p>\n<p style=\"margin-left:2.2in;\">\n a.       Compare decay of plasma and vaginal HIV-1 RNA and DNA between the treatment regimens.</p>\n<p style=\"margin-left:2.2in;\">\n b.      Compare decay of plasma HIV-1 infectivity between the treatment regimens.</p>\n<p style=\"margin-left:131.4pt;\">\n 2.            To compare infant outcomes including stillbirth, premature birth, low birth weight, perinatal HIV transmission, neurodevelopmental outcomes and to compare (in HIV-infected infants) drug resistance between the two treatment regimens.</p>\n<p style=\"margin-left:131.4pt;\">\n 3.            To assess the baseline prevalence and selection of HIV-1 drug-resistance to the study drugs, using standard genotyping and ultrasensitive genotyping methods.</p>\n<p>\n  </p>\n<p>\n  </p>\n<p style=\"margin-left:1.45in;\">\n <u>Exploratory Objectives</u>:</p>\n<p style=\"margin-left:1.45in;\">\n  </p>\n<p style=\"margin-left:1.7in;\">\n 1.      To describe the population pharmacokinetic (PK) parameters of efavirenz and raltegravir during the third trimester of pregnancy and postpartum using sparse sampling and to evaluate potential relationships between PK parameters, pharmacogenomics and viral load changes.</p>\n<p style=\"margin-left:1.7in;\">\n  </p>\n<p style=\"margin-left:1.7in;\">\n 2.      To describe the maternal vaginal and infant nasopharyngeal and oropharyngeal microbiome environment and the potential association with adverse outcome in HIV exposed uninfected children.</p>\n<p>\n  </p>\n
      • study_title<p align=\"center\" style=\"margin-left:.1in;\">\n <strong>A PHASE IV RANDOMIZED TRIAL TO EVALUATE THE VIROLOGIC RESPONSE AND PHARMACOKINETICS OF TWO DIFFERENT POTENT REGIMENS IN HIV INFECTED WOMEN INITIATING TRIPLE ANTIRETROVIRAL REGIMENS BETWEEN 28 AND 36 WEEKS OF PREGNANCY FOR THE PREVENTION OF MOTHER-TO-CHILD TRANSMISSION: </strong></p>\n<p align=\"center\" style=\"margin-left:.1in;\">\n <strong>NICHD P1081</strong></p>\n
      • laymans_summary(null)
      • short_titleP1081
      • protocol_noECCT/17/08/04
      • version_no3.0
      • date_of_protocol02-04-2015
      • study_drugRaltegravir, Efavirenz, Lamivudine, Zidovudine
      • 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_nameRaltegravir, Efavirenz, Lamivudine, Zidovudine
      • product_type_medical_device_name
      • comparator(null)
      • comparator_name(null)
      • comparator_registered(null)
      • comparator_countries(null)
      • 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_impd(null)
      • applicant_prev_data(null)
      • applicant_stability_data(null)
      • applicant_analysis_cert(null)
      • applicant_pictorial_sample(null)
      • applicant_gcp_training(null)
      • applicant_dsmb_charter(null)
      • applicant_detailed_budget(null)
      • applicant_indemnity_pi(null)
      • applicant_practice_license(null)
      • applicant_registration_ctr(null)
      • applicant_pan_african(null)
      • applicant_hard_copies(null)
      • applicant_signed_checklist(null)
      • statistical_analysis_plan(null)
      • applicant_contractual_agreement(null)
      • declaration_applicantLucy Koech - +254719193275
      • declaration_date101-08-2017
      • declaration_principal_investigatorDr. Frederick Sawe - +254703247902
      • declaration_date201-08-2017
      • placebo_presentNo
      • study_objectives(null)
      • principal_inclusion_criteria<h2>\n 4.1       Inclusion Criteria</h2>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p>\n 4.1.1    Naïve to ART or have received ART with short course zidovudine (maximum of 8 weeks) for PMTCT in previous pregnancies.</p>\n<p>\n 4.1.2    Willingness and ability to sign informed consent. Participant must be of an age to provide legal informed consent as defined by the country in which the participant resides. If not, the informed consent must be signed by a legal guardian<strong>/</strong>parent, as per country guidelines.</p>\n<p>\n 4.1.3    Documentation of HIV-1 infection defined as positive results from <u>two</u> samples collected at <u>different</u> time points. The same method may be used at both time points. All samples tested must be whole blood, serum or plasma. Documentation maybe abstracted from medical records to satisfy these criteria for infection.</p>\n<p>\n The first test may be any of the following:</p>\n<p>\n  </p>\n<p>\n ·         HIV-1/2 Antigen and Antibodies test and confirmed HIV-1 from HIV-1/2 antibody differentiation test</p>\n<p>\n ·         Two rapid antibody tests from different manufacturers or based on different principles and epitopes</p>\n<p>\n ·         One rapid antibody test AND one [enzyme immunoassay OR Western blot OR immunofluorescence OR chemiluminescence]</p>\n<p>\n ·         One enzyme immunoassay AND one [Western blot OR immunofluorescence OR chemiluminescence]</p>\n<p>\n ·         One HIV DNA PCR</p>\n<p>\n ·         One quantitative HIV RNA PCR (above limit of detection)</p>\n<p>\n ·         One qualitative HIV RNA PCR</p>\n<p>\n ·         One HIV culture (prior to August 2009)</p>\n<p>\n ·         One total HIV nucleic acid</p>\n<p>\n If the first test(s) is positive, a second sample must be collected and tested using any of the tests listed above (except for qualitative RNA assays) at a laboratory participating in an appropriate external quality assurance program and either College of American Pathologists/CLIA approved (for US laboratories) or DAIDS-approved (for non-US laboratories).</p>\n<p>\n  </p>\n<p>\n It is strongly recommended that all kits/methods of analysis are Food and Drug Administration (FDA) approved.</p>\n<p>\n  </p>\n<p>\n 4.1.4    Viable pregnancy with gestational age of  ≥ 28 to ≤ 36 weeks based upon menstrual history and/or ultrasound.</p>\n<p>\n             <strong>Note: </strong>If menstrual history is unknown or if there is a discrepancy between menstrual history and ultrasound, determination of gestational age should be based upon best available methodology at each site.</p>\n<p>\n 4.1.5    Participant intends to continue pregnancy.</p>\n<p>\n 4.1.6    Willingness and intent to deliver at the participating clinical site and to be followed for the duration of the study at the site or associated outpatient facility.</p>\n<p>\n 4.1.7    Participant willing to comply with study regimen.</p>\n<p>\n 4.1.8    Participant agrees to use two reliable methods of contraception after delivery if randomized to the efavirenz arm and is sexually active. A barrier method of contraception (condoms, diaphragm, or cervical cap) together with another reliable form of contraception must be used for 4 weeks after stopping efavirenz.</p>\n
      • principal_exclusion_criteria<h2>\n 4.2       Exclusion Criteria</h2>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<p>\n 4.2.1    Active labor defined as onset of regular contractions or cervical dilatation greater than 2cm.</p>\n<p>\n 4.2.2    Use of ART during current pregnancy.</p>\n<p>\n 4.2.3    Chemotherapy for active malignancy.</p>\n<p>\n 4.2.4    HIV genotypic resistance, as defined in Appendix IV, to efavirenz or raltegravir or to NRTIs that will be included in the ART regimen. Note: A lack of HIV drug-resistance test results at the time of enrollment is not exclusionary.</p>\n<p>\n 4.2.5    Serious active opportunistic infection and/or serious bacterial infection including active TB or unstable or severe medical condition within 14 days of study entry.</p>\n<p>\n 4.2.6    Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.</p>\n<p>\n 4.2.7    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 4.2.8    Vomiting or inability to swallow medications due to an active, pre-existing condition that prevents adequate swallowing and absorption of study medication.</p>\n<p>\n 4.2.9    Known allergy/sensitivity to any study drugs or their formulations or sulfonamide allergy.</p>\n<p>\n 4.2.10  The following laboratory values (within 30 days of enrollment):</p>\n<p>\n ·         Hemoglobin ≥ Grade 3</p>\n<p>\n ·         Absolute neutrophil count ≥ Grade 2</p>\n<p>\n ·         Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST) ≥ Grade 2</p>\n<p>\n ·         Serum creatinine ≥ Grade 1</p>\n<p>\n ·         Platelet count ≥ Grade 3</p>\n<p>\n 4.2.11  Evidence of pre-eclampsia (such as persistent diastolic blood pressure > 90 mmHg).</p>\n<p>\n 4.2.12  Receipt of disallowed medications described in Section 4.3.</p>\n
      • primary_end_points<p style=\"margin-left:1.0in;\">\n  </p>\n<h2>\n 8.2       Outcome Measures</h2>\n<p style=\"margin-left:1.0in;\">\n  </p>\n<h3>\n 8.2.1    Primary Outcome Measures</h3>\n<p style=\"margin-left:1.5in;\">\n  </p>\n<p>\n <u>Efficacy</u>:</p>\n<p>\n  </p>\n<p>\n ·         Plasma HIV-1 viral load <200 copies/mL at the delivery visit (or if there is no viral load measurement at the delivery visit, viral load <200 copies/mL within 3 weeks prior to delivery).</p>\n<p>\n  </p>\n<p>\n Evaluable women will be those who have a viral load measurement at the delivery visit or within 3 weeks prior to delivery. Non-evaluable women (missing viral load measurement due to missed visits, specimen or laboratory error) will be excluded from the primary analysis. Sensitivity analyses will be conducted to assess the potential impact of missing evaluations on the conclusions of the study (see Section 8.6 for details).</p>\n<p>\n  </p>\n<p>\n <u>Tolerability until labor and delivery</u>:</p>\n<p>\n  </p>\n<p>\n ·         Discontinuation of efavirenz or raltegravir (whichever was assigned) prior to labor and delivery for any reason (including loss to follow-up) will be considered a treatment failure in this analysis (note: switching any of the NRTIs with continuation of efavirenz or raltegravir will not be considered a treatment failure).</p>\n<p>\n  </p>\n<p>\n Women who received at least one dose of efavirenz or raltegravir will be evaluable for the tolerability analysis.</p>\n<p>\n <u>Safety through week 24 postpartum</u>:</p>\n<p>\n  </p>\n<p>\n ·         Maternal and infant AEs of Grade ≥3 as defined in the DAIDS toxicity table.</p>\n<p>\n  </p>\n<p>\n Women who received at least one dose of a study drug, and their infants will be evaluable for the safety outcome measures.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis0
      • scope_therapy1
      • scope_safety1
      • scope_efficacy1
      • scope_pharmacokinetic1
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use1
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p>\n <span font-size:=\"\" style=\"color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">See the SSA section 24 page 49 WHICH STATES THE KEMRI /WRP CRC ROLES OF STUDY PERSONNEL</span></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 font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Walter Reed Army Institute of Research IRB approved through letter dated: Nov 09 2016</p>\n<p font-size:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n KEMRI SERU approved through letter dated: Nov 15 2016</p>\n
      • other_details_regulatory_rejected<p>\n N/A</p>\n
      • other_details_regulatory_halted<p>\n N/A</p>\n
      • estimated_durationEach study participant will be in the study for up to 28 Weeks. The trial is projected to last 2 years
      • design_controlled_randomised
      • design_controlled_open
      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
      • design_controlled_cross_over
      • design_controlled_other
      • design_controlled_specify
      • design_controlled_comparator
      • design_controlled_other_medicinal
      • design_controlled_placebo
      • design_controlled_medicinal_other
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKenya Medical Research Institute Walter Reed Project Clinical Research Centre.
      • single_site_physical_addressOff Hospital Road
      • single_site_contact_personFredrick K Sawe
      • single_site_telephone+254 703 247 902
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states6 Countries
      • number_of_sites
      • multi_country_listUS = 13 Sites\nBrazil = 8 Sites\nArgentina = 2 Sites\nThailand = 2 Sites\nTanzania = 2 Sites\nKenya = 1 Site
      • data_monitoring_committeeYes
      • total_enrolment_per_siteN/A
      • total_participants_worldwide334
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornYes
      • population_infant_and_toddlerYes
      • population_childrenNo
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male0
      • subjects_healthyNo
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenYes
      • subjects_nursing_womenYes
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameFREDRICK
      • investigator1_middle_nameKIPYEGON
      • investigator1_family_nameSAWE
      • investigator1_qualificationMBChB, MMED
      • investigator1_professional_addressP.O. BOX 1357-20200 KERICHO
      • investigator1_telephone(05220)30388/30686
      • investigator1_emailFredrick.Sawe@usamru-k.org
      • organisations_transferred_Yes
      • number_participants100
      • notification
      • approval_date13-11-2017
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted01-08-2017
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reason
      • final_report<p>\n <strong>INTRODUCTION:</strong></p>\n<p>\n  </p>\n<p>\n NICHD P1081 was a multicenter, phase IV, randomized, open-label, trial to evaluate the safety, tolerance, virologic response, pharmacologic and pharmacokinetics of representatives of two different potent ARV classes in HIV infected pregnant women initiating triple ARV regimens for PMTCT. The primary objectives of the study are to compare two triple ARV regimens (one containing efavirenz and the other raltegravir) 1) ability to achieve a viral load of < 200 copies/mL at the time of delivery and 2) safety and tolerability.</p>\n<p>\n  </p>\n<p>\n The participants were 334 (the Kericho site was to enroll 100) evaluable mother-infant pairs (approximately 167 per arm) of HIV infected pregnant women with a gestational age between 20 and 36 weeks who were antiretroviral (ARV) naïve or had received short-course zidovudine (maximum of 8 weeks) only for PMTCT. The participants were to be randomized 1:1 during the antepartum period to:  Arm A that was to use Lamivudine 150 mg/zidovudine 300 mg twice daily (BID) + efavirenz 600 mg every night (QHS) and Arm B that was to use Lamivudine 150 mg/zidovudine 300 mg BID + raltegravir 400 mg BID. The Infants were to receive ARV according to specific local guidelines i.e they were to be started on 12 weeks of infant prophylaxis:- AZT+NVP for 6 weeks, followed by NVP for 6 weeks. Women were to continue receiving triple antiretroviral therapy (ART) after delivery. Women were to be followed for 6 months after delivery. Infants will be followed until 6 months of age .</p>\n<p>\n  </p>\n<p>\n <strong>The study's objectives were as follows:  </strong></p>\n<p>\n <strong>Primary Objective</strong></p>\n<ol>\n <li>\n To compare the ability of two triple ARV regimens (one containing efavirenz and the other raltegravir) begun during the third trimester of pregnancy to achieve a viral load of < 200 copies/mL at the time of delivery.</li>\n <li>\n To compare the safety and tolerability of two triple ARV regimens (one containing efavirenz and the other raltegravir) begun during the third trimester of pregnancy.</li>\n</ol>\n<p style=\"margin-left:.5in;\">\n <strong>Secondary Objectives</strong></p>\n<p style=\"margin-left:.5in;\">\n  </p>\n<ol>\n <li>\n To compare the kinetics of viral decay between the treatment regimens:</li>\n</ol>\n<p style=\"margin-left:.75in;\">\n  a. Compare decay of plasma and vaginal HIV-1 RNA and DNA between the treatment regimens.</p>\n<p style=\"margin-left:.75in;\">\n b. Compare decay of plasma HIV-1 infectivity between the treatment regimens.</p>\n<ol>\n <li value=\"2\">\n To compare infant outcomes including stillbirth, premature birth, low birth weight, perinatal HIV transmission, and to compare (in HIV-infected infants) drug resistance between the two treatment regimens.</li>\n <li value=\"3\">\n To assess the baseline prevalence and selection of HIV-1 drug-resistance to the study drugs, using standard genotyping and ultrasensitive genotyping methods.</li>\n</ol>\n<p style=\"margin-left:.5in;\">\n <strong>Exploratory Objectives</strong></p>\n<p style=\"margin-left:.5in;\">\n To describe the population PK parameters of efavirenz and raltegravir during the third trimester of pregnancy and postpartum using sparse sampling and to evaluate potential relationships between PK parameters, pharmacogenomics and viral load changes.</p>\n<p>\n  </p>\n<p>\n <strong>ENROLLMENT:      </strong>Nil. The study was a multi-center trial and full accrual occurred in other sites.</p>\n<p>\n  </p>\n<p>\n <strong>PRELIMINARY STUDY REPORT:          </strong>None.</p>\n<p>\n  </p>\n<p>\n <strong>LIST OF ABBREVIATIONS AND DEFINITION OF TERMS:   </strong>N/A</p>\n<p>\n  </p>\n<p>\n <strong>ETHICS: </strong>KEMRI SERU approval received. The KEMRI SERU Study Close-Out Approval is attached.</p>\n<p>\n  </p>\n<p>\n <strong>INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE: </strong>The site Principal Investigator was Dr Fredrick Sawe and Study Coordinator was Priscilla Bii.</p>\n<p>\n  </p>\n<p>\n <strong>INVESTIGATIONAL PLAN: N/A</strong></p>\n<p>\n  </p>\n<p>\n <strong>STUDY PATIENTS: None</strong></p>\n<p>\n  </p>\n<p>\n <strong>EFFICACY EVALUATION: N/A</strong></p>\n<p>\n  </p>\n<p>\n <strong>SAFETY EVALUATION: N/A</strong></p>\n<p>\n  </p>\n<p>\n <strong>DISCUSSION AND OVERALL CONCLUSIONS: </strong>The study never accrued any participants at the site.</p>\n<p>\n  </p>\n<p>\n <strong>REFERENCE LIST: </strong>N/A</p>\n<p>\n  </p>\n<p>\n <strong>APPENDICES: </strong>N/A</p>\n<p>\n  </p>\n<p>\n <strong>FUTURE PLANS: </strong>N/A</p>\n<p>\n  </p>\n<p>\n Thank you for your time and review.</p>\n<p>\n  </p>\n
      • implication_results(null)
      • quantity_imported(null)
      • quantity_dispensed(null)
      • quantity_destroyed(null)
      • quantity_exported(null)
      • balance_site(null)
      • final_date(null)
      • modified2019-07-10 14:07:10
      • created2017-01-23 15:48:05
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id376
        • application_id580
        • given_nameFREDRICK
        • middle_nameKIPYEGON
        • family_nameSAWE
        • qualificationMBChB, MMED
        • professional_addressP.O. BOX 1357-20200 KERICHO
        • telephone(05220)30388/30686
        • emailFredrick.Sawe@usamru-k.org
        • created2017-01-23 15:54:00
        • modified2017-08-01 13:12:42
    • SiteDetail(array)
      • 0(array)
        • id473
        • application_id580
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2017-01-23 15:54:00
        • modified2017-08-01 13:12:42
        • County(empty)
    • Sponsor(array)
      • 0(array)
        • id302
        • application_id580
        • sponsorThe Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) and The National Institute of Allergy and Infectious Diseases (NIAID)
        • sponsor_type(null)
        • contact_person
        • addressBoston Medical Center 771 Albany Street Dowling 4N, Room 4111 Boston, MA 02118
        • telephone_number617-414-3754
        • fax_number
        • cell_number617-414-3754
        • email_addressmarkm@bu.edu
        • created2017-01-23 15:54:00
        • modified2017-08-01 13:12:42
  • 2(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
      • scope_pharmacoecomomic0
      • scope_others0
      • 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
      • design_controlled_open
      • design_controlled_single_blind
      • design_controlled_double_blind
      • design_controlled_parallel_group
      • design_controlled_cross_over
      • design_controlled_other
      • design_controlled_specify
      • design_controlled_comparator
      • design_controlled_other_medicinal
      • design_controlled_placebo
      • design_controlled_medicinal_other
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_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
      • subjects_women_child_bearingNo
      • subjects_women_using_contraceptionNo
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentYes
      • subjects_specifychildren
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameWinnie
      • investigator1_middle_name
      • investigator1_family_nameKeter
      • investigator1_qualificationclinical officer
      • investigator1_professional_address1357
      • investigator1_telephone0522030686
      • investigator1_emailwinnie.keter@usamru-k.org
      • organisations_transferred_Yes
      • number_participants20
      • notification
      • approval_date28-03-2017
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted02-03-2020
      • 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)
      • modified2025-02-10 11:30:49
      • created2016-09-15 15:01:46
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
      • 0(array)
        • id358
        • application_id556
        • given_nameLucy
        • middle_name
        • family_nameKoech
        • qualificationMBCHB
        • professional_address1357
        • telephone0522030686
        • emaillucy.koech@usamru-k.org
        • created2016-09-16 12:06:16
        • modified2020-03-02 14:32:58
    • SiteDetail(array)
      • 0(array)
        • id433
        • application_id556
        • county_id(null)
        • site_name
        • physical_address
        • contact_details
        • contact_person
        • site_capacity(null)
        • misc(null)
        • created2016-09-16 12:06:16
        • modified2020-03-02 14:32:58
        • County(empty)
    • Sponsor(array)
      • 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
  • 3(array)
    • Application(array)
      • id574
      • user_id73
      • trial_status_id8
      • 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 HIV-1 care centers in several counties in Kenya, including 12 in Central Kenya (former central and Nairobi province).  It will include a delivery component in which PrEP will be delivered according to Kenyan national guidelines, utilizing the integrated PrEP as a bridge to ART approach. We will conduct monitoring and evaluation activities to 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 ART according 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<p>\n <strong>Design:  </strong>Prospective, open-label cohort study at HIV-1 care centers in Kenya including 12 in central Kenya.  The PrEP as a bridge to ART intervention will be introduced into clinics according to national guidelines in a staged fashion, stratified by clinic size & region (a stepped wedge design).  Follow-up will be for up to 36 months at each care center.</p>\n<p>\n <strong>Population:   </strong>Heterosexual HIV-1 serodiscordant couples, ≥18 years of age, mutually disclosed.  Up to 200 couples per clinic will participate in the prospective open cohort research evaluation.  Up to 200 key delivery informants will participate in qualitative interviews about PrEP delivery.</p>\n
      • study_title<p align=\"center\" class=\"MediumGrid21\" style=\"text-align:center;line-height:200%\">\n <b><span style=\"font-family:"Arial",sans-serif\">An implementation project to scale-up delivery of antiretroviral-based HIV-1 prevention </span></b><b style=\"line-height: 200%;\"><span style=\"font-family:"Arial",sans-serif\">among Kenyan HIV-1 serodiscordant couples</span></b></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_title The Partners Scale-Up Project
      • protocol_noECCT/16/12/03
      • version_no1.0
      • date_of_protocol24-10-2016
      • study_drugEmtricitabine/Tenofovir Disoproxil Fumarate (Truvada) - Scale-Up Project
      • disease_conditionPrEP for HIV Prevention in Discordant Couples
      • 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_nameEmtricitabine/Tenofovir Disoproxil Fumarate (Truvada)
      • product_type_medical_device_name
      • comparatorNo
      • comparator_name
      • comparator_registered
      • comparator_countries
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressRwamba@csrtkenya.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_addendum0
      • applicant_fees1
      • applicant_complete_form(null)
      • applicant_impd1
      • applicant_prev_data1
      • applicant_stability_data1
      • applicant_analysis_cert1
      • applicant_pictorial_sample1
      • applicant_gcp_training1
      • applicant_dsmb_charter1
      • applicant_detailed_budget0
      • applicant_indemnity_pi1
      • 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_applicantDr. Elizabeth Irungu
      • declaration_date106-12-2016
      • declaration_principal_investigatorDr. Nelly Rwamba Mugo
      • declaration_date206-12-2016
      • placebo_presentNo
      • study_objectives<p style=\"margin-left:1in;\">\n <strong>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.  </strong>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.  <em>Note:</em> <em>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. </em></p>\n<p style=\"margin-left:45pt;\">\n  </p>\n<p style=\"margin-left:1in;\">\n <strong>Objective 2:   Assess facilitators and barriers to a) implementation of integrated PrEP and ART in delivery settings and b) optimized PrEP and ART adherence.  </strong>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 style=\"margin-left:45pt;\">\n  </p>\n<p style=\"margin-left:1in;\">\n <strong>Objective 3:   Determine efficiency, cost, and cost-effectiveness of the integrated PrEP and ART when delivered in public health clinics.  </strong>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 style=\"margin-left:1in;\">\n  </p>\n<p style=\"margin-left:1in;\">\n <strong>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.</strong> 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 <em>Eligibility</em></p>\n<p>\n  </p>\n<p>\n For HIV-1 uninfected members of the couple</p>\n<p style=\"margin-left:.75in;\">\n -       Age ≥18</p>\n<p style=\"margin-left:.75in;\">\n -       Able and willing to provide consent for follow-up in the cohort</p>\n<p style=\"margin-left:1.0in;\">\n -       HIV-1 uninfected based on negative HIV-1 tests, per Kenya national guidelines</p>\n<p style=\"margin-left:.75in;\">\n -       Not currently using PrEP</p>\n<p>\n  </p>\n<p>\n For HIV-1 infected members of the couple</p>\n<p style=\"margin-left:.75in;\">\n -       Age ≥18</p>\n<p style=\"margin-left:.75in;\">\n -       Able and willing to provide consent for follow-up in the cohort</p>\n<p style=\"margin-left:.75in;\">\n -       HIV-1 infected based on positive HIV-1 tests, per Kenya national guidelines</p>\n<p>\n For both members of the couple</p>\n<p style=\"margin-left:.5in;\">\n -       Meet criteria for initiating PrEP as per Kenya national guidelines, including:</p>\n<p style=\"margin-left:1.0in;\">\n 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</p>\n<p style=\"margin-left:1.0in;\">\n o   Trying to conceive</p>\n<p>\n For key delivery informants</p>\n<p style=\"margin-left:.75in;\">\n -       Able and willing to provide consent </p>\n
      • principal_exclusion_criteria<p>\n For both members of the couple:</p>\n<ul>\n <li>\n Unable or unwilling to provide consent for follow up in cohort.</li>\n <li>\n HIV status not mutually disclosed.</li>\n</ul>\n
      • primary_end_points<p>\n a) proportion of HIV-1 infected persons whose partners are tested for HIV-1,</p>\n<p>\n 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,</p>\n<p>\n d) couples achieving optimized antiretroviral-based prevention coverage (i.e., high adherence to at least one antiretroviral intervention), and</p>\n<p>\n e) HIV-1 uninfected partners staying HIV-1 uninfected.</p>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • scope_therapy1
      • scope_safety0
      • scope_efficacy0
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use1
      • design_controlledNo
      • site_capacity(null)
      • staff_numbers<p font-size:=\"\" line-height:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Partners in Health & Research Development (Formerly Partners in Prevention), has 38 full time clinical trial staff (including physicians, nurses, counsellors, pharmacists, social scientists ).</p>\n<p font-size:=\"\" line-height:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Principal Investigator: Dr. Nelly R. Mugo  MBCHB,MMED,MPH</p>\n<p font-size:=\"\" line-height:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Co-Investigator: Dr. Kenneth Ngure  BSc,MPH,MSc,PhD</p>\n<p font-size:=\"\" line-height:=\"\" style=\"margin: 0px 0px 10px; color: rgb(51, 51, 51); font-family: \" trebuchet=\"\">\n Country Lead: Dr. Elizabeth Irungu  MBCHB, MPH</p>\n
      • other_details_explanation<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. 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<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 HIV-1 care centers in several counties in Kenya, including 12 in Central Kenya (former central and Nairobi province).  It will include a delivery component in which PrEP will be delivered according to Kenyan national guidelines, utilizing the integrated PrEP as a bridge to ART approach. </p>\n
      • other_details_regulatory_notapproved<p>\n N/A</p>\n
      • other_details_regulatory_approved<p>\n KEMRI's SERU - 24th November 2016</p>\n<p>\n University of Washington's IRB - 24th May 2016</p>\n<p>\n  </p>\n
      • other_details_regulatory_rejected<p>\n Not applicable</p>\n
      • other_details_regulatory_halted<p>\n Not applicable</p>\n
      • estimated_duration5 years
      • design_controlled_randomised
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      • design_controlled_double_blind
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      • design_controlled_medicinal_specify
      • single_site_member_stateNo
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      • multiple_sites_member_stateYes
      • multiple_countriesNo
      • multiple_member_states
      • number_of_sites12 (Nairobi & Central parts of Kenya)
      • multi_country_list
      • data_monitoring_committeeNo
      • total_enrolment_per_site200
      • total_participants_worldwide4800
      • population_less_than_18_yearsNo
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
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      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsYes
      • subjects_vulnerable_populationsYes
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      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameJared
      • investigator1_middle_nameMurray
      • investigator1_family_nameBaeten
      • investigator1_qualificationMD, PhD
      • investigator1_professional_addressUniversity of Washington, Box 359927; 325 Ninth Avenue, Seattle Washington 98104
      • investigator1_telephone206 520 3808
      • investigator1_emailjbaeten@uw.edu
      • organisations_transferred_Yes
      • number_participants2400 (Nairobi and Central parts of Kenya)
      • notification
      • approval_date04-02-2017
      • submitted1
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      • deleted_date(null)
      • deactivated0
      • date_submitted13-02-2020
      • is_child0
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      • final_report(null)
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      • balance_site(null)
      • final_date(null)
      • modified2021-09-09 12:06:20
      • created2016-12-01 11:27:12
      • total_sites(null)
      • ecitizen_invoice(null)
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      • 0(array)
        • id371
        • application_id574
        • given_nameNelly
        • middle_nameRwamba
        • family_nameMugo
        • qualificationMBChB, MMeD, MPH
        • professional_address19865-00202
        • telephone067-22561, 0723914057
        • emailrwamba@csrtkenya.org
        • created2016-12-02 08:55:08
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    • SiteDetail(array)
      • 0(array)
        • id455
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        • site_nameThika Level 5 Hospital, Ruiru Sub-County Hospital, Kiambu County Hospital, Kikuyu PCEA Hospital
        • physical_addressThika Sub-County, Ruiru, Kiambu, Kikuyu township
        • contact_detailsKiambu
        • contact_personCCC Manager
        • site_capacity(null)
        • misc(null)
        • created2016-12-02 08:55:08
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          • id22
          • county_nameKiambu
          • created2012-06-15 10:24:37
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        • id456
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        • site_nameCoptic Hospital, Mbagathi Hospital, St. Mary\'s Hospital, Pumwani Maternity Hospital
        • physical_addressNgong Road, Off Mbagathi road, Lang\'ata, Carlifonia Eastleigh - Nairobi
        • contact_detailsNairobi
        • contact_personCCC Manager
        • site_capacity(null)
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        • created2016-12-02 15:25:45
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          • id47
          • county_nameNairobi City
          • created2012-06-15 10:27:40
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        • id465
        • application_id574
        • county_id19
        • site_nameNyeri PGH, Karatina Sub-County Hospital,
        • physical_addressNyeri, Karatina
        • contact_detailsNyeri
        • contact_personCCC Manager
        • site_capacity(null)
        • misc(null)
        • created2016-12-02 16:30:21
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          • county_nameNyeri
          • created2012-06-15 10:24:16
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        • id466
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        • site_nameKerugoya County Hospital
        • physical_addressKerugoya
        • contact_detailsKirinyaga
        • contact_personCCC Manager
        • site_capacity(null)
        • misc(null)
        • created2016-12-02 16:36:21
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          • created2012-06-15 10:24:22
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        • site_nameMurang\'a County Hospital
        • physical_addressMurang\'a
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        • created2016-12-02 16:37:20
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        • sponsorUniversity of Washington
        • sponsor_typeResearch Institution
        • contact_personDr. Nelly R. Mugo
        • address19865-00202
        • telephone_number0672222561
        • fax_numbern/a
        • cell_number0733629665
        • email_addressrwamba@csrtkenya.org
        • created2016-12-02 08:55:08
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  • 4(array)
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      • id1167
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      • trial_status_id8
      • abstract_of_study<p>\n <strong>Title: </strong>A Multisectoral Strategy to Address Persistent Drivers of the HIV Epidemic in East Africa (SAPPHIRE)</p>\n<p>\n <strong>Sample Size</strong>:</p>\n<p style=\"margin-left:13.5pt;\">\n <strong><em>Phase A</em></strong>:  3,200 participants (2,100 HIV-negative participants, 650 HIV-positive participants, 450 hypertensive participants ≥15 years of age)</p>\n<p style=\"margin-left:13.5pt;\">\n <strong><em>Phase B</em></strong>:  32 communities of ~10,000 persons each, for a total of ~160,000 adults (≥15 years of age)</p>\n<p>\n <strong>Participating Sites</strong>:  44 communities in rural western Kenya and rural western Uganda (12 in Phase A, 32 in Phase B), that: a) are geopolitical units (i.e. parish in Uganda, or sub-location in Kenya) of ~10,000 persons each (5,000 ≥15 years) within the catchment area of government health clinics; b) have HIV prevalence similar to the region using Ministry of Health data; c) have a letter of commitment to the study from the local political leader; and d) are of sufficient distance from each other to avoid contamination.</p>\n<p>\n <strong>Overall Objective</strong>: Our overall objective is to determine to reduce HIV incidence and to improve community health with multi-sector, scalable interventions.</p>\n<p>\n <strong>Primary Objective</strong>: Reduce HIV incidence using innovative strategies for HIV prevention and treatment to simultaneously reach “persistent driver” populations.</p>\n<p>\n <strong>Secondary Objectives:</strong></p>\n<p style=\"margin-left:38.25pt;\">\n 1.    Evaluate and optimize individual intervention component effects, alone (Phase A) and in combination (Phase B), versus control conditions on prevention coverage and HIV viral suppression</p>\n<p style=\"margin-left:38.25pt;\">\n 2.    Assess the effect of the intervention package on other health outcomes (all-cause mortality, tuberculosis, hypertension linkage and control, heavy alcohol use and mother-to-child HIV transmission) in Phase B</p>\n<p style=\"margin-left:38.25pt;\">\n 3.    Evaluate behavioral and other mechanistic pathways for intervention effects on proximal mediators of HIV incidence in Phase B</p>\n<p style=\"margin-left:38.25pt;\">\n 4.    Assess the reach, effectiveness, patient and provider adoption, and fidelity and the maintenance of intervention components in Phase B</p>\n<p style=\"margin-left:38.15pt;\">\n 5.    Use final study data to inform a strategic and sustainable investment model that maximally reduces HIV incidence and improves community health for the combination interventions tested in Phase B</p>\n<p>\n <strong>Study Design</strong>: This study will consist of 2 phases:</p>\n<p style=\"margin-left:36.0pt;\">\n ·         Phase A, in which randomized trials and pilot studies will assess effectiveness, fidelity and cost and improve context-specific “fit” of prevention and treatment interventions. Combining effectiveness with implementation, costing and modelling outcomes, Phase A will optimize intervention packages with context specific adaptations in structured consultation with stakeholders.</p>\n<p style=\"margin-left:36.0pt;\">\n ·         Phase B, which will evaluate the effects of these optimized dynamic prevention and treatment packages, alone and in combination, on prevention coverage, population-level suppression, and HIV incidence, as well as other health outcomes, in a balanced, community randomized 2x2 factorial design.</p>\n<p>\n <strong>Interventions in Phase A</strong>:</p>\n<p style=\"margin-left:36.0pt;\">\n ●     Dynamic Prevention: We are evaluating ways to optimize dynamic prevention delivery with the following interventions: Provision of Dynamic Prevention intervention at 1) outpatient health centers, 2) antenatal/family planning clinics, 3) youth multisector events and  4) via village health workers interacting at households.</p>\n<p style=\"margin-left:36.0pt;\">\n ●     Dynamic Treatment: We are evaluating services to improve HIV and hypertension care in difficult to reach populations: mobile population services; alcohol use intervention for heavy alcohol users, and hypertension interventions.</p>\n<p>\n <strong>Study Endpoints:  </strong></p>\n<p>\n <strong>Phase A: </strong>The primary endpoints in Phase A are: Prevention coverage (uptake and persistence of PrEP or PEP) and viral suppression (HIV RNA <400 c/mL).  For hypertension intervention, the primary endpoints are  linkage to care and hypertension control.</p>\n<p>\n <strong>Phase B</strong>: The primary and secondary endpoints in Phase B are:</p>\n<p style=\"margin-left:36.0pt;\">\n ·         Prevention coverage (uptake and persistence of PrEP and PEP)</p>\n<p style=\"margin-left:36.0pt;\">\n ·         Viral suppression (HIV RNA <400 c/mL)</p>\n<p style=\"margin-left:36.0pt;\">\n ·         HIV incidence (cumulative 3 year)</p>\n<p style=\"margin-left:36.0pt;\">\n ·         Mortality (cumulative 3 year)</p>\n<p style=\"margin-left:36.0pt;\">\n ·         Tuberculosis (annual incidence rate)</p>\n<p style=\"margin-left:36.0pt;\">\n ·         Hypertension control (<140/90 mmHg)</p>\n<p style=\"margin-left:36.0pt;\">\n ·         Heavy alcohol use</p>\n<p style=\"margin-left:36.0pt;\">\n ·         Mother-to-child HIV transmission (infant HIV free survival at 3 years)</p>\n<p>\n  </p>\n<p>\n <strong>Study Duration</strong>: The study’s Phase A and Phase B components will be conducted over a 5-year period.</p>\n<p>\n <strong>Sample Size and Power, Phase A</strong></p>\n<p>\n  </p>\n<p>\n <strong>Dynamic Prevention: </strong>Assuming a standard deviation in covered time of 35% (based on SEARCH), a two-sided hypothesis test (a=0.05), and conservatively ignoring precision gains from stratified randomization and covariate adjustment, a trial with 200 evaluable persons per arm will have 80% power to detect an approximately 10% absolute effect size (corresponding, for example, to an increase in covered time from 30% to 40%). For primary endpoint measurement for the trials at clinics, we will thus enroll up to 300 participants per arm meeting PrEP/PEP eligibility criteria (1,200 total).  We also enroll up to 250 participants per arm from 16 areas serviced by village health workers (total N=500 HIV-negative persons).  For the youth intervention single arm pilots, we will enroll up to 100 persons/pilot-site to examine feasibility in primary analyses and prevention coverage in secondary analyses.</p>\n<p>\n  </p>\n<p>\n <strong>Dynamic Treatment</strong>: Assuming approximately 40% suppression (or 50% linkage in the hypertension trial) in the control arm and a two-sided hypothesis test (a=0.05), a trial of 100 persons per arm will be powered at 80% to detect a 20% increase in suppression (or linkage in the hypertension trial).  For the alcohol intervention trial, we will enroll up to 200 participants living with HIV per arm, for the mobility intervention trial we will enroll 125 participants living with HIV per arm, and for the hypertension linkage intervention we will enroll 125 participants per arm. For the hypertension treatment trial, we will enroll up to 200 participants (100/arm) based on assuming 40% control in the non-intervention group for 80% power to detect an 20% or greater increase in control.   </p>\n<p>\n  </p>\n<p>\n <strong>Sample Size and Power, Phase B</strong>:</p>\n<p>\n Assuming an HIV- Cohort of approximately 1,175 persons per community, 90% follow up, mean 10% prevention covered time in the control arm, within-cluster standard deviation of 35%, and a coefficient of variation (k) of 0.15 (conservatively based on SEARCH), with 16 communities per arm we will be powered at 90% to detect a relative increase in covered time of approximately 24%. Assuming approximately 124 HIV-positive persons with year 3 HIV RNA level measured per community, 70% viral suppression at year 3 in the control arm, and k=0.10 (conservatively based on SEARCH), with 16 communities per arm we will be powered to detect a relative increase in suppression of approximately 15%. Under some but not all scenarios, this design will also have power >80% to detect an effect of combined Dynamic Prevention and Treatment on three-year cumulative HIV incidence compared to standard-of-care. Assuming a 3-year cumulative HIV incidence of 1.7% in the control arm of the study, k= 0.17 (informed by SEARCH), HIV test sensitivity of 95% and specificity of 99.9%, and 90% follow up of the HIV- Cohort (total N ~17,000 in primary analysis), we estimate >80% power to detect a relative reduction of at least 35% in the full intervention (N=8 communities) vs. control (N=8 communities) arms of the study.</p>\n<p style=\"margin-left:36.0pt;\">\n  </p>\n
      • study_title<p align=\"center\" class=\"Default\" style=\"text-align:center\">\n <b><span lang=\"EN-US\" style=\"font-size:16.0pt;font-family:"Arial",sans-serif\">A Multisectoral Strategy to Address Persistent Drivers of the HIV Epidemic in East Africa<o:p></o:p></span></b></p>\n
      • laymans_summary<p>\n <strong>HIV incidence in Sub-Saharan Africa (SSA) remains well above global elimination targets.</strong><strong>¹</strong>Despite an increasingly large, evidence-based toolkit to prevent HIV transmission, there were over 1 million new HIV infections in SSA in 2018.¹We know from SEARCH²and three other recent SSA population-level studies^3-5that reaching (and exceeding) <em><u>the UNAIDS 2020 population-level viral suppression target of 73%</u></em><em><u>⁶</u></em><em><u>is insufficient to achieve epidemic control</u></em> (<strong>Table 1</strong>). We also know that key sub-populations, in particular youth,^{4, 7-10}men,^{2, 4, 10-12}mobile populations,^13-15and persons with heavy alcohol use^{16, 17}continue to fall short of viral suppression targets, putting them at higher risk for HIV complications, mortality, and onward HIV transmission. Finally, pre-exposure prophylaxis (PrEP), an intervention that has reduced incidence in affected populations in some areas where high rates of viral suppression were already present,^{18, 19}has not been effectively deployed in high risk populations (such as young women) in SSA.^{20, 21}To achieve control of the HIV epidemic and mitigate its consequences, <u>we need <strong>new and scalable</strong> interventions to improve delivery of prevention and treatment to <strong>vital segments of the population that contribute to persistence of new infections.</strong></u>  We describe below why previous approaches that were effective for the majority of people in the ART roll-out <u>do not work</u> for subsets of these “persistent-driver” populations, our proposed solutions, and how a multi-component intervention trial can effectively inform stakeholders on programming and resource allocation to accelerate reductions in HIV incidence.</p>\n<p>\n <strong>Barriers to effective HIV prevention and treatment outcomes among key, persistent-driver populations fall into three major themes </strong>based on epidemiologic and qualitative data from SEARCH on seroconversions (N=704), PrEP utilization (3,489 starts²²), viral suppression sub-group analyses (N=13,529^{2, 10, 16}), and other published literature. <u>First</u>, the majority of new infections are in youth, and in this growing, at-risk population, <u>social and economic concerns</u> often far outweigh health concerns on a day-to-day basis (individual barriers).^23-26<em><u>There has been insufficient recognition that at any given moment in time, health is not a preeminent concern,</u> particularly for youth. </em>Indeed, poverty itself may increase “present bias” – the tendency  for short term considerations to outweigh long term ones – contributing to decision-making that harms health.^27-30<u>Second</u> and <u>third,</u> <u>lack of flexibility</u> in how prevention and treatment services, respectively, have been offered to people whose needs and behavior vary from mainstream community members (e.g. mobile populations, drinkers) and may be continually changing (systems barriers) have impeded uptake and impact of these services.^31-35</p>\n<p>\n <strong>Modelling and phylogenetic studies suggest that further progress will require simultaneous and coordinated approaches in HIV treatment and prevention among persistent driver populations. </strong>Individual, “narrow” focused interventions (PrEP) for adolescent girls are important, but alone will not reach HIV elimination levels. Persistent driver populations are minority subsets of demographic populations of considerable size (e.g. while men are at elevated risk of non-suppression, most HIV-infected men are suppressed); some of the barriers they face (e.g. inflexible health systems) are shared across the demographic groups and can be integrated into a personalized public health approach that combines i) <u>foundational changes in health care delivery systems</u> that are scalable and affordable (e.g., re-structuring treatment visits for youth to prioritize non-health concerns) with ii) <u>the option to access more intensive services</u> for the targeted group of persons for whom basic one-size-fits all approaches are insufficient (e.g. intensified alcohol counseling for heavy drinkers and “travel packs” for mobile populations). Assumptions that strategies to reach these populations will be prohibitively expensive or too complex for programs to implement are unsubstantiated, and stakeholders need well-designed studies incorporating multiple interventions for persistent driver populations, and integrating intensification based on choice, to understand what works and inform resource allocation as they move beyond the “90-90-90” era towards HIV elimination.    </p>\n<p>\n <strong>To address these barriers for persistent driver populations to increase prevention coverage for HIV- persons and viral suppression for HIV-infected persons, we used <u>the empirically-validated PRECEDE model</u></strong><strong>³⁶</strong>where health decision-making and health-seeking behaviors can be influenced via interventions that predispose, enable, and reinforce desired engagement with prevention and treatment services (see <strong>Section 8</strong>, below for comprehensive description of our PRECEDE intervention framework). </p>\n<p>\n  </p>\n<p>\n <strong><u>Dynamic HIV prevention</u></strong>: Our 3 Dynamic Prevention components address barriers we identified in offering PrEP to >10,000 persons with risk factors for HIV acquisition in the region (Table 2). First, we will engage youth in HIV prevention and reproductive health services by generating demand for these services within existing life skills and vocational programs (BRAC youth development clubs in Uganda and micro-finance clubs in Kenya) via integration of key health and socio-economic services. For youth, embedding HIV services within a broader, multi-sector strategy for individual and community empowerment via economic and social advancement can lead to better decision-making and also increase <u>demand for and engagement with</u> HIV services. Similar approaches have been used in diverse settings and may overcome present bias and other barriers faced by youth living in poverty by generating demand for services while improving future expectations and decision-making via increased opportunity.^37-44Despite a strong evidence base that these interventions can impact self-reported behaviors, and in some cases unintended pregnancies and STIs, and recent encouraging evidence from the DREAMS program (HIV incidence reduction in <u>non-randomized longitudinal analyses</u><u>⁴⁵</u>), there is little rigorous evidence that these interventions can reduce HIV incidence (as noted in a systematic review of income generation interventions for HIV prevention³⁷) or impact biomedical prevention (e.g. PrEP, PEP, condom use) uptake or adherence <u>from randomized studies.</u> We provide a comprehensive review of key completed and ongoing studies in Table 3. Thus our approach to engage young women and men through these <u>existing programs</u> that <u>offer life skills and vocational training opportunities for economic and social advancement, along with embedded HIV and reproductive health education and expedited referrals for HIV prevention is different and complimentary to the DREAMS program and a potentially efficient way to engage youth that has not been rigorously tested.</u></p>\n<p>\n  </p>\n<p>\n <br />\n <strong>HIV prevention services that offer <u>choice</u> of delivery options (PrEP & PEP) and <u>flexibility</u> in their use and <u>location of delivery</u> over time allow for a dynamic, patient-centered model of prevention. This approach is responsive to the reality of an individual’s changing needs, thereby facilitating <u>continued engagement</u>. </strong>In SEARCH, PrEP use declined over time in spite of initial enthusiasm and uptake by early adopters.⁵⁴<em>In multiple settings, poor adherence to PrEP remains its Achilles’ heel.</em><em>^{55, 56}</em>Rather than presenting PrEP in a similar framework to ART (i.e. lifelong use with 100% adherence for efficacy with delivery at HIV clinic), approaches that incorporate flexibility in choice and delivery location, akin to contraception options for women in developed countries, may prove more successful. Indeed, over the past four decades, increased choice in contraception and flexibility in access have been directly associated with increased use.^{57, 58}Framing prevention in the context of healthy choices, rather than an assessment of risk, may also reduce the association of PrEP with “risky” behavior or promiscuity. Offering PEP – an event-driven option that does not require accurate prediction of risk before a potential HIV exposure (akin to a “morning after” pill), and which additionally provides protection for those with less sexual agency – is a critical innovation in flexible access to prevention services. PEP can also act as a “gateway” to PrEP and other prevention modalities (<strong>Figure 1</strong>), providing infrastructure to add new prevention options as they become available (e.g. the PrEP vaginal ring^{59, 60}). </p>\n<p>\n  </p>\n<p>\n <strong><u>Dynamic HIV Treatment</u></strong><strong>: offering choice and flexibility in HIV clinical care and ART access </strong>that is tailored to the needs of key populations – including youth, men, mobile, and heavy alcohol-using populations – may result in <u>increased care engagement and viral suppression rates</u> among these populations, compared to differentiated care models as currently conceptualized. We have identified key barriers and facilitators for engagement in treatment for each of these groups, obtained via quantitative surveys and focus group discussions among persons who have not engaged, dropped out of care or not achieved viral suppression in SEARCH and via existing literature (Table 4).^{33, 61-67}Treatment outcomes are most likely to be effective when these barriers are overcome. For example in youth, using the PRECEDE framework we have piloted our proposed intervention that combines (i) a “life stage” assessment framework that addresses the many dynamic changes in relationships, school and employment present in youth (PREDISPOSING) (ii) flexible clinic access (ENABLING) and (iii) rapid viral load feedback (REINFORCING). Details on treatment interventions for other key driver populations are in the protocol (see Section 8, below).   </p>\n<p>\n  </p>\n<p>\n <strong>The HIV epidemic will unnecessarily claim and continue to adversely affect millions of lives unless we deploy innovative strategies that extend the gains beyond those of universal testing and ART. </strong>Universal ART must be followed by dynamic prevention and treatment paradigms that allow for heterogeneity in patient need and preference, as well as changing preferences over time – while targeting interventions to those at greatest risk of incident and uncontrolled HIV. Furthermore,<strong> <u>HIV cannot be addressed in a vacuum and must be coupled with health services that are seen by community members as a priority</u> - </strong>including evaluation and treatment for diseases such as hypertension,^68-70diabetes,⁷¹and heavy alcohol use⁷², delivered in an environment that harnesses human capital among youth (the largest segment of the population in SSA⁷³). In our proposal, we postulate that within this broader framework, we can successfully reduce HIV incidence, population viral load and mortality, while improving community health outcomes. We will rigorously evaluate these effects and their costs using a 2-stage optimization and factorial cluster randomized design.</p>\n
      • short_titleSAPPHIRE STUDY
      • protocol_noECCT/22/09/04
      • version_no5.0
      • date_of_protocol25-05-2022
      • study_drug Long-acting injectable Cabotegravir (CAB-LA) 600mg
      • 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_nameCabotegravir
      • product_type_medical_device_name
      • comparatorYes
      • comparator_nameTenofovir/Emtricitabine (TDF/FTC)
      • comparator_registeredYes
      • comparator_countriesKenya
      • ecct_not_applicable0
      • ecct_ref_number
      • email_addressebukusi@kemri.org
      • applicant_covering_letter1
      • applicant_protocol1
      • applicant_patient_information1
      • applicant_investigators_brochure1
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      • applicant_signed_declaration1
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      • applicant_indemnity_cover1
      • applicant_opinion_letter1
      • applicant_approval_letter1
      • applicant_statement1
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      • applicant_fees1
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      • 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
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      • applicant_pan_african1
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      • statistical_analysis_plan1
      • applicant_contractual_agreement1
      • declaration_applicantGreshon Rota
      • declaration_date112-09-2022
      • declaration_principal_investigatorElizabeth Bukusi
      • declaration_date212-09-2022
      • placebo_presentNo
      • study_objectives<h2>\n Primary Objective</h2>\n<p>\n To reduce HIV incidence using innovative strategies for HIV prevention and treatment to simultaneously reach “persistent driver” populations.</p>\n<h2>\n Secondary Objectives</h2>\n<p style=\"margin-left:36.0pt;\">\n 1.    Evaluate and optimize individual intervention component effects, alone (Phase A) and in combination (Phase B), versus control conditions on prevention coverage and HIV viral suppression.</p>\n<p style=\"margin-left:36.0pt;\">\n 2.    Assess the effect of the intervention package on other health outcomes (all-cause mortality, tuberculosis, hypertension control, heavy alcohol use and mother-to-child HIV transmission) in Phase B.</p>\n<p style=\"margin-left:36.0pt;\">\n 3.    Evaluate behavioral and other mechanistic pathways for intervention effects on proximal mediators of HIV incidence in Phase B.</p>\n<p style=\"margin-left:36.0pt;\">\n 4.    Assess the reach, effectiveness, patient and provider adoption, and fidelity and the maintenance of intervention components in Phase B.</p>\n<p style=\"margin-left:36.0pt;\">\n 5.    Use final study data to inform a strategic and sustainable investment model that maximally reduces HIV incidence and improves community health for the combination interventions tested in Phase B.</p>\n
      • principal_inclusion_criteria<p>\n <u>Outpatient and antenatal/FP clinics</u></p>\n<p style=\"margin-left:18.0pt;\">\n 1.     Age ≥15 years</p>\n<p style=\"margin-left:18.0pt;\">\n 2.     HIV-negative</p>\n<p style=\"margin-left:18.0pt;\">\n 3.     Current or anticipated sexual activity with partner(s) with known HIV-infection or unknown HIV status</p>\n<p>\n  </p>\n<p>\n <u>VHT households </u></p>\n<p style=\"margin-left:18.0pt;\">\n 1.     Age <u>></u>15 years</p>\n<p style=\"margin-left:18.0pt;\">\n 2.     HIV-negative</p>\n<p style=\"margin-left:18.0pt;\">\n 3.     Current or anticipated sexual activity with partner(s) with known HIV-infection or unknown HIV status</p>\n<p>\n  </p>\n<p>\n <u>Youth multi-sector interventions</u></p>\n<p style=\"margin-left:18.8pt;\">\n 1.     Age ≥15 to ≤25 years</p>\n<p style=\"margin-left:18.8pt;\">\n 2.     HIV-negative</p>\n<p style=\"margin-left:18.8pt;\">\n 3.     Current or anticipated sexual activity with partner(s) with known HIV-infection or unknown HIV status</p>\n<p style=\"margin-left:36.0pt;\">\n At least one of the following risk factors: School drop-out, prior pregnancy, transactional sex, orphanhood, work in sector associated with higher HIV risk (e.g. boda boda driver), drink alcohol or STI history</p>\n
      • principal_exclusion_criteria<p>\n <u>Outpatient and antenatal/FP clinics</u></p>\n<p style=\"margin-left:18.8pt;\">\n 1.     <15 years of age</p>\n<p style=\"margin-left:18.8pt;\">\n 2.     Unable to provide consent or parental co-consent as per country guidelines</p>\n<p style=\"margin-left:18.8pt;\">\n 3.     Participation in another Phase A RCT intervention component</p>\n<p style=\"margin-left:18.8pt;\">\n  </p>\n<p>\n <u>VHT households </u></p>\n<p style=\"margin-left:18.0pt;\">\n 1       <15 years of age</p>\n<p style=\"margin-left:18.8pt;\">\n 2       unable to provide consent or parental co-consent as per country guidelines</p>\n<p style=\"margin-left:18.8pt;\">\n 3      Participation in another Phase A RCT intervention component</p>\n<p>\n  </p>\n<p>\n <u>Youth multi-sector interventions  </u></p>\n<p style=\"margin-left:18.8pt;\">\n 1.     <15 or >25 years of age</p>\n<p style=\"margin-left:18.8pt;\">\n 2.     Unable to provide consent or parental co-consent as per country guidelines</p>\n<p style=\"margin-left:18.8pt;\">\n 3.     Participation in another Phase A RCT intervention component</p>\n
      • primary_end_points<p>\n <strong>Study Endpoints:  </strong></p>\n<p>\n <strong>Phase A: </strong>The primary endpoints in Phase A are: Prevention coverage (uptake and persistence of PrEP or PEP) and viral suppression (HIV RNA <400 c/mL).  For hypertension intervention, the primary endpoints are  linkage to care and hypertension control.</p>\n<p>\n <strong>Phase B</strong>: The primary and secondary endpoints in Phase B are:</p>\n<p style=\"margin-left:36.0pt;\">\n ·         Prevention coverage (uptake and persistence of PrEP and PEP)</p>\n<p style=\"margin-left:36.0pt;\">\n ·         Viral suppression (HIV RNA <400 c/mL)</p>\n<p style=\"margin-left:36.0pt;\">\n ·         HIV incidence (cumulative 3 year)</p>\n<p style=\"margin-left:36.0pt;\">\n ·         Mortality (cumulative 3 year)</p>\n<p style=\"margin-left:36.0pt;\">\n ·         Tuberculosis (annual incidence rate)</p>\n<p style=\"margin-left:36.0pt;\">\n ·         Hypertension control (<140/90 mmHg)</p>\n<p style=\"margin-left:36.0pt;\">\n ·         Heavy alcohol use</p>\n<p style=\"margin-left:36.0pt;\">\n ·         Mother-to-child HIV transmission (infant HIV free survival at 3 years)</p>\n
      • scope_diagnosis0
      • scope_prophylaxis1
      • scope_therapy1
      • scope_safety0
      • scope_efficacy0
      • scope_pharmacokinetic0
      • scope_pharmacodynamic0
      • scope_bioequivalence0
      • scope_dose_response0
      • scope_pharmacogenetic0
      • scope_pharmacogenomic0
      • scope_pharmacoecomomic0
      • scope_others0
      • scope_others_specify
      • trial_human_pharmacology0
      • trial_administration_humans0
      • trial_bioequivalence_study0
      • trial_other0
      • trial_other_specify
      • trial_therapeutic_exploratory0
      • trial_therapeutic_confirmatory0
      • trial_therapeutic_use1
      • design_controlledYes
      • site_capacity(null)
      • staff_numbers<p>\n Principal Investigator - Prof Elizabeth Bukusi</p>\n<p>\n Co-investigator - Dr. James Ayieko</p>\n<p>\n Pharmacist - Dr. Greshon Rota</p>\n<p>\n Study Coordinators - 1. Freddie Opel, 2. Norton Sang, 3. Marilyn Nyabuti</p>\n<p>\n Study Clinicians - 4 </p>\n<p>\n Study Nurses - 4</p>\n<p>\n Study Administrators - 3</p>\n<p>\n Retention coordinator - 1</p>\n<p>\n Lab coordinator - 1</p>\n<p>\n Lab tech - 3</p>\n<p>\n Pharm tech - 1</p>\n<p>\n Data manager - 1</p>\n<p>\n ICT Coordinator - 1</p>\n<p>\n Research assistants - 6</p>\n<p>\n Study drivers - 4</p>\n<p>\n Human resource manager - 1</p>\n<p>\n  </p>\n<p>\n  </p>\n
      • other_details_explanation<p>\n The study is seeking to address persistent drivers of HIV transmission in Africa so as to reduce rate of HIV infection inorder to achieve the UNAIDS “90-90-90” strategy which calls for 90% of HIV-infected individuals to be diagnosed by 2020, 90% of whom will be on anti-retroviral therapy (ART) and 90% of whom will achieve sustained virologic suppression.</p>\n
      • other_details_regulatory_notapproved<p>\n Uganda National Drug Authority - 26 August 2022</p>\n
      • other_details_regulatory_approved<p>\n None</p>\n
      • other_details_regulatory_rejected<p>\n None</p>\n
      • other_details_regulatory_halted<p>\n None</p>\n
      • estimated_duration5 Years
      • design_controlled_randomisedYes
      • design_controlled_openYes
      • design_controlled_single_blindNo
      • design_controlled_double_blindNo
      • design_controlled_parallel_groupNo
      • design_controlled_cross_overNo
      • design_controlled_otherNo
      • design_controlled_specify
      • design_controlled_comparatorTenofovir/Emtricitabine
      • design_controlled_other_medicinalNo
      • design_controlled_placeboNo
      • design_controlled_medicinal_otherNo
      • design_controlled_medicinal_specify
      • single_site_member_stateYes
      • location_of_areaKEMRI-SEARCH SAPPHIRE
      • single_site_physical_addressSUBA SUBCOUNTY HOSPITAL - SINDO
      • single_site_contact_personJames Ayieko
      • single_site_telephone0720925262
      • multiple_sites_member_stateNo
      • multiple_countriesYes
      • multiple_member_states2
      • number_of_sites
      • multi_country_listUganda and Kenya
      • data_monitoring_committeeYes
      • total_enrolment_per_site1050
      • total_participants_worldwide2100
      • population_less_than_18_yearsYes
      • population_uteroNo
      • population_preterm_newbornNo
      • population_newbornNo
      • population_infant_and_toddlerNo
      • population_childrenNo
      • population_adolescentYes
      • population_above_18Yes
      • population_adultYes
      • population_elderlyNo
      • gender_female1
      • gender_male1
      • subjects_healthyYes
      • subjects_patientsNo
      • subjects_vulnerable_populationsYes
      • subjects_women_child_bearingYes
      • subjects_women_using_contraceptionYes
      • subjects_pregnant_womenNo
      • subjects_nursing_womenNo
      • subjects_emergency_situationNo
      • subjects_incapable_consentNo
      • subjects_specify
      • subjects_othersNo
      • subjects_others_specify
      • investigator1_given_nameElizabeth
      • investigator1_middle_nameAnne
      • investigator1_family_nameBukusi
      • investigator1_qualificationMBChB, M.Med (ObGyn), MPH, PhD, PGD (Research Ethics), MBE (Research Ethics)
      • investigator1_professional_addressP.O Box 54840, Nairobi, Kenya
      • investigator1_telephone0733617503
      • investigator1_emailebukusi@kemri.go.ke
      • organisations_transferred_Yes
      • number_participants1050
      • notification
      • approval_date09-12-2022
      • submitted1
      • deleted0
      • deleted_date(null)
      • deactivated0
      • date_submitted12-09-2022
      • is_child0
      • unsubmitted0
      • initial_date_submitted(null)
      • admin_stopped0
      • admin_stopped_reason(null)
      • approved2
      • approved_reasonThe reviewer queries have been resolved.
      • final_report(null)
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      • quantity_imported(null)
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      • quantity_destroyed(null)
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      • balance_site(null)
      • final_date(null)
      • modified2025-01-30 13:36:20
      • created2022-09-05 15:39:42
      • total_sites(null)
      • ecitizen_invoice(null)
    • InvestigatorContact(array)
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        • id848
        • application_id1167
        • given_nameElizabeth
        • middle_nameAnne
        • family_nameBukusi
        • qualificationMBChB, M.Med (ObGyn), MPH, PhD, PGD (Research Ethics), MBE (Research Ethics)
        • professional_addressP.O Box 54840, Nairobi, Kenya
        • telephone0733617503
        • emailebukusi@kemri.go.ke
        • created2022-09-05 16:04:19
        • modified2022-09-12 14:00:48
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        • id1311
        • application_id1167
        • county_id(null)
        • site_name
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        • contact_person
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        • misc(null)
        • created2022-09-05 16:04:19
        • modified2022-09-12 14:00:48
        • County(empty)
    • Sponsor(array)
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        • id602
        • application_id1167
        • sponsorNational Institutes of Health (NIH)
        • sponsor_typeResearch Institution
        • contact_personPhillip De Biase
        • address9000 Rockville Pike Bethesda, Maryland 20892
        • telephone_number+1-301-496-4000
        • fax_number
        • cell_number+1-301-496-4000
        • email_addressgrantsinfo@nih.gov
        • created2022-09-05 16:04:19
        • modified2022-09-12 14:00:48
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App Constants

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PHP Environment

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