Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202311518894272 Date of Registration: 09/11/2023
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title Pharmacology of Tenofovir Disoproxil Fumarate-Emtricitabine (TDF-FTC) Pre-exposure Prophylaxis in Kenyan Cisgender Women
Official scientific title Pharmacology of Tenofovir Disoproxil Fumarate-Emtricitabine (TDF-FTC) Pre-exposure Prophylaxis in Kenyan Cisgender Women
Brief summary describing the background and objectives of the trial African cisgender women are disproportionately affected with HIV and have elevated risk of acquiring HIV in pregnancy. Pre-exposure prophylaxis (PrEP) is an effective HIV prevention strategy, but variable adherence in PrEP clinical trials among African cisgender women and limited pharmacologic data have resulted in lack of clarity about the degree of PrEP use required for HIV protection in cisgender women. For men who have sex with men, the STRAND study defined the adherence levels to PrEP medication and expected drug concentrations arising from varying directly observed therapy (DOT) doses per week. Those thresholds are today being applied to studies of African cisgender women taking PrEP, and cisgender women-specific levels associated with HIV prevention have never been defined. However, recent data from large PrEP studies we have done among African cisgender women ─including Partners PrEP Study and Partners Demonstration Projects conducted at Thika site─, suggest that these levels may not reflect the pharmacology of cisgender women in African settings, in general and particularly in pregnancy. In these studies in African populations, PrEP dosing was not directly observed therapy and no study has established expected PrEP concentrations in African cisgender women with varying frequency of PrEP adherence. Thus, there is an urgent need to define the frequency of adherence and expected blood concentrations of PrEP medications and their relationship to HIV protection in non-pregnant and pregnant cisgender women. The primary objectives: 1) To define the cisgender women-specific expected blood concentrations and dose-proportionality for TFV-DP in DBS and PBMCs using directly observed TDF/FTC therapy at 2, 4, 7 doses per week. 2) To establish a model to predict adherence rate to TDF/FTC by level of TFV-DP in DBS for cisgender women.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Infections and Infestations
Sub-Disease(s) or condition(s) being studied HIV/AIDS
Purpose of the trial Prevention
Anticipated trial start date 01/10/2021
Actual trial start date 27/04/2022
Anticipated date of last follow up 30/06/2023
Actual Last follow-up date
Anticipated target sample size (number of participants) 72
Actual target sample size (number of participants)
Recruitment status Closed to recruitment,follow-up continuing
Publication URL
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Factorial: participants randomly allocated to either no, one, some or all interventions simultaneously Randomised Simple randomization using a randomization table created by a computer software program Allocation was determined by the holder of the sequence who is situated off site Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Control Group 7 DOT doses per week 7 DOT TDF-FTC Doses per week 18 weeks 18 HIV uninfected non-pregnant cisgender women will be randomly assigned to daily DOT TDF/FTC to help differentiate poor and modest from perfect adherence. 18 Dose Comparison
Experimental Group 2 DOT doses per week 2 DOT TDF-FTC doses per week 18 weeks 18 HIV uninfected non-pregnant cisgender women will be randomly assigned to 2 dose DOT TDF/FTC to help differentiate poor and modest from perfect adherence. 18
Experimental Group 4 DOT doses per week 4 TDF-FTC DOT doses per week 18 weeks 18 HIV uninfected non-pregnant cisgender women will be randomly assigned to 4 dose DOT TDF/FTC per week to help differentiate poor and modest from perfect adherence. 18
Experimental Group 7 DOT doses per week pregnant 7 DOT TDF-FTC Doses per week 18 weeks 18 HIV uninfected pregnant cisgender women will be assigned to daily DOT TDF/FTC as an additional contemporaneous cohort to evaluate the impact of pregnancy on blood and cellular drug levels. 18
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Inclusion criteria for the pregnant cohort -Age ≥18 and ≤30 years -HIV uninfected -Has an active smart phone -Normal renal function (GFR >60ml/min) -Hepatitis B surface Ag negative -High risk for HIV -Pregnant at 13-26 weeks of gestation -Willing to use DOT and come to clinic daily for DOT PrEP for 8 weeks -Willing to have home visits/video streaming if clinic visit not feasible Inclusion criteria for the non- pregnant cohort -Age ≥18 and ≤30 years -HIV uninfected -Has an active smart phone -Normal renal function (GFR >60ml/min) -Hepatitis B surface Ag negative -Low risk for HIV -Not pregnant or breastfeeding -Willing to be randomized to non-daily PrEP and come to clinic frequently for DOT PrEP -Willing to have home visits/video streaming if clinic visit not feasible Exclusion criteria for pregnant women -Inability to give informed consent -HIV positive test at screening or suspected acute HIV infection in the opinion of the clinician -Concomitant medications taken within 30 days of enrollment: aminoglycosides, ganciclovir/valganciclovir, chronic high-dose acyclovir/valacyclovir (>800mg acyclovir or > 500mg valacyclovir for >7 days), cyclosporine, amphotericin B, foscarnet, and cidofovir, and products with same or similar active ingredients as the study medications including TAF®, ATRIPLA®, COMPLERA®, EMTRIVA®, VIREAD®; or drugs containing lamivudine or adefovir, which are close analogs of FTC and tenofovir, respectively. -Current or past use of PrEP (pre-exposure prophylaxis) -Not willing to have home visit -Sickle cell anemia, chronic bleeding, blood transfusion within the past 120 days (excluding for chronic illness) or other blood dyscrasias -Fetus has a known or suspected major congenital anomaly defined by fetal ultrasound. Exclusion criteria for non-pregnant women -Inability to give informed consent -HIV positive test at screening or suspected acute HIV infection in the opinion of the clinician -Concomitant medications taken within 30 days of enrollment: aminoglycosides, ganciclovir/valganciclovir, chronic high-dose acyclovir/valacyclovir (>800mg acyclovir or > 500mg valacyclovir for >7 days), cyclosporine, amphotericin B, foscarnet, and cidofovir, and products with same or similar active ingredients as the study medications including TAF®, ATRIPLA®, COMPLERA®, EMTRIVA®, VIREAD®; or drugs containing lamivudine or adefovir, which are close analogs of FTC and tenofovir, respectively. -Current or past use of PrEP (pre-exposure prophylaxis) -pregnancy/plan to become pregnant in the next 6 months/unwillingness to use birth control Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year 18 Year(s) 30 Year(s) Female
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 19/07/2022 SERU KEMRI
Ethics Committee Address
Street address City Postal code Country
54840-00200, NAIROBI, Kenya Nairobi 00202 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome -Benchmark concentrations of TFV-DP in DBS and PBMCs, and the dosing frequency (i.e., doses per week) required to generate them. The goal is to quantify the effects of dose on steady state TFV-DP in DBS and PBMC based on an incomplete block design. We will use the observed week 8 concentrations for the dose-proportionality model. Week 8 is approximately 90% of steady state (3.3 * 17-day half-life = 8 weeks). Day 4, weeks 1, 2, 3, 4, 5, 6, 7 and 8
Secondary Outcome -Examine models to predict non-daily adherence based on TFV/FTC and TFV-DP in DBS. We will first consider a saturated model allowing a separate mean for each dose/adherence group. The results will then be compared to a reduced model with a class variable indicating non-daily dosing groups” or 100% dosing (that is, the effect of “non-daily dosing” adherence does not differ by dose groups). Day 4, weeks 1, 2, 3, 4, 5, 6, 7 and 8
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
KEMRI CCR PHRD OAU Road, Thika Section 9 Thika 00200 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
US National Institute of Health 10 Center Drive Bethesda, MD 20892 Washington United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor University of Washington 1410 NE Campus Parkway Seatlle United States of America University
COLLABORATORS
Name Street address City Postal code Country
University of Washington 1410 NE Campus Parkway Seattle United States of America
Kenya Medical Research Institute Mbagathi Way Nairobi Kenya
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Kenneth Mugwanya mugwanya@uw.edu 2065203886 325 Ninth Avenue Box 359927
City Postal code Country Position/Affiliation
Seattle United States of America Assistant Professor Global Health University of Washington
Role Name Email Phone Street address
Scientific Enquiries Nelly Mugo rwamba@uw.edu +254733629665 OAU Road, Thika Section 9
City Postal code Country Position/Affiliation
Thika Kenya Site Principal Investigator
Role Name Email Phone Street address
Public Enquiries Nina Ouko akelo@pipsthika.org +254720608741 OAU Road, Thika Section 9
City Postal code Country Position/Affiliation
Thika Kenya study lead clinician
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes The Principal Investigators commit to share this data once the study is completed and published Study Protocol IPD will be shared after study completion and results published. After data analyses, the PIs will seek to publish the study results in publicly accessible sites and journals. The PIs are ready and willing to circulate the published data to individuals who may reach out to them, individually.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information