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 0835 or +27 21 938 0967
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202109678139121 Date of Registration: 29/09/2021
Trial Status: Retrospective registration - This trial was registered after enrolment of the first participant
TRIAL DESCRIPTION
Public title MK8591-022 Oral ISL QM as PrEP in Cisgender Women at High Risk for HIV-1 Infection
Official scientific title MK8591-022 A Phase 3, Randomized, Active-Controlled, Double-blind Clinical Study to Evaluate the Efficacy and Safety of Oral Islatravir Once-Monthly as Preexposure Prophylaxis in Cisgender Women at High Risk for HIV-1 Infection
Brief summary describing the background and objectives of the trial One proven biomedical intervention for the prevention of HIV infection is PrEP. Although clinical study data have demonstrated that the effectiveness of FTC/TDF QD for PrEP is strongly correlated with adherence to daily therapy [Grant, R. M., et al 2010] [Baeten, J. M., et al 2012], adherence to FTC/TDF QD is suboptimal in many individuals at risk for HIV-1 infection [Marrazzo, J. M., et al 2015] [Hojilla, J. C., et al 2018]. Long-acting agents, such as a monthly pill, have the potential to reduce the risk of HIV-1 acquisition without relying on adherence to a daily regimen. In the same way that long-acting reversible contraceptives have provided important options and increased acceptability and uptake of contraception among women [Ross, J. 2013], expanded choices for HIV-1 prevention may increase utilization, adherence, and effectiveness. ISL has the potential to be an effective agent for HIV-1 PrEP due to its potent antiviral activity, long half-life, and favorable safety profile as demonstrated in early-phase clinical studies. The convenience and discretion of monthly oral administration of ISL may facilitate adherence and access to PrEP for women at high risk for HIV-1 infection, ultimately leading to greater effectiveness for HIV-1 prevention than what is currently observed
Type of trial RCT
Acronym (If the trial has an acronym then please provide) Impower 022
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 05/02/2021
Actual trial start date 19/07/2021
Anticipated date of last follow up 05/02/2023
Actual Last follow-up date
Anticipated target sample size (number of participants) 4500
Actual target sample size (number of participants)
Recruitment status Stopped early/ terminated
Publication URL www.msd.co.za
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
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using by using procedures such as coin-tossing or dice-rolling Central randomisation by phone/fax Masking/blinding used Care giver/Provider,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group ISL Parallel Different groups receive different interventions at same time during study 60 mg QM from Visit 2 to (up to) Visit 37 Up to 3 years from the time the participant provides documented Informed Consent/assent through final contact. HIV Preexposure prophylaxis for Cisgender Women at high risk for HIV-1 infection 1125
Control Group Placebo to ISL Parallel Different groups receive different interventions at same time during study 0mg QM from Visit 2 to (up to) visit 37. Up to 3 years from the time the participant provides documented Informed Consent/assent through final contact. FTC/TDF Group: HIV Preexposure prophylaxis for Cisgender Women at high risk for HIV-1 infection 1125 Placebo
Experimental Group FTC TDF Parallel Different groups receive different interventions at same time during study 200/245 mg QD from Visit 2 to 9up to 37) Up to 3 years from the time the participant provides documented Informed Consent/assent through final contact. HIV Preexposure prophylaxis for Cisgender Women at high risk for HIV-1 infection. 1125
Control Group Placebo to FTCTDF Parallel Different groups receive different interventions at same time duringstudy 0mg QD from Visit 2 to (up to) visit 37 Up to 3 years from the time the participant provides documented Informed Consent/assent through final contact. HIV Preexposure prophylaxis for Cisgender Women at high risk for HIV-1 infection. 1125 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
1. Is confirmed HIV-uninfected based on negative HIV-1/HIV-2 test results before randomization. Note: If a positive result is obtained for any HIV test prior to randomization, the participant is not eligible for the study. Additional testing to confirm suspected HIV infection during screening will be performed in accordance with local guidelines. If HIV infection is confirmed, participants will be referred for appropriate care, as necessary. 2. Has been sexually active with a male sexual partner in the 30 days prior to Screening. 3. Is at high risk for HIV-1 infection as defined by a risk score ≥5 using a VOICE risk score tool (ex-US sites) or meets the CDC criteria for PrEP eligibility (US sites). Demographics 4. Was assigned female sex at birth, is cisgender, 16 years to 45 years of age, inclusive, at the time of providing informed consent/assent. Female Participants 5. A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: • Is not a WOCBP OR • Is a WOCBP and using an acceptable contraceptive method, as described in Appendix 5 during the intervention period and for at least 42 days after the last dose (corresponding to the time needed to eliminate any study intervention [approximately 5 terminal halflives]). • A WOCBP must have a negative highly sensitive pregnancy test ([urine or serum] as required by local regulations) within 24 hours before the first dose of study intervention. • If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. • Additional requirements for pregnancy testing during and after study intervention are located in Appendix 2. • The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early 1. Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator. 2. Has active HBV infection (defined as HBsAg-positive or HBV DNA positive) Note: Past HBV infection or previous HBV vaccination (defined as HBsAg-negative and positive for antibody against HBsAg) is not an exclusion criterion. Note: Participants who do not demonstrate immunity to HBV are encouraged to be vaccinated against HBV. 3. Current or chronic history of liver disease (eg, nonalcoholic or alcoholic steatohepatitis) or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome, asymptomatic gallstones, or cholecystectomy), unless the participant has stable liver function tests and no significant hepatic synthetic dysfunction. Note: Hepatic synthetic dysfunction is defined as a serum albumin <2.8 g/dL or an INR >1.7 in the absence of another explanation for the abnormal laboratory value. 4. Has a history of malignancy within 5 years of screening except for adequately-treated basal cell or squamous cell skin cancer, or in situ cervical cancer. 5. Has a history or current evidence of any condition (including active tuberculosis infection), therapy, laboratory abnormality or other circumstance (including drug or alcohol use or dependence) that might, in the opinion of the investigator, confound the results of the study or interfere with the participant’s participation for the full duration of the study, such that it is not in the best interest of the participant to enroll. Prior/Concomitant Therapy 6. Has taken cabotegravir at any time (past or current use) 7. Is currently receiving or is anticipated to require any prohibited therapies outlined in Section 6.5 from 30 days prior to Day 1 through the duration of the study. Note: Participants taking FTC/TDF for PrEP at screening may continue their regimen until the day of randomization. Also, any prior or current HIV PrEP medications taken by the participant, Adolescent: 13 Year(s)-17 Year(s),Adult: 18 Year(s)-44 Year(s),Middle Aged: 45 Year(s)-64 Year(s) 16 Year(s) 45 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 04/05/2021 University of the Witwatersrand Human Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
31 Princess Wales Terrace Johannesburg 2041 South Africa
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 28/05/2021 THE SOUTH AFRICAN MEDICAL RESEARCH COUNCIL
Ethics Committee Address
Street address City Postal code Country
Francie Van Zijl Drive Cape Town 7505 South Africa
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 27/04/2021 Columbia University IRB 2
Ethics Committee Address
Street address City Postal code Country
154 Haven Avenue Columbia 10032 United States of America
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 08/06/2021 Joint Clinical Research Centre Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Plot 101 Lubowa Estates, Off Entebbe Road Kampala 10005 Uganda
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 07/05/2021 The University of North Carolina at Chapel Hill Biomedical IRB
Ethics Committee Address
Street address City Postal code Country
720 Martin Luther King, Jr. Blvd. Chapel Hill 7097 United States of America
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 19/05/2021 University of Zambia Biomedical Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
Ridgeway Campus Lusaka 50110 Zambia
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 30/09/2021 Kenya Medical Research Instistute
Ethics Committee Address
Street address City Postal code Country
K N H Mbagathi Road Nairobi 00100 Kenya
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 25/10/2021 Eswatini Health and Human Research Review Board
Ethics Committee Address
Street address City Postal code Country
Ministry of Health, Mbandzeni House, 3rd Floor, Mbabane, Eswatini Mbabane H100 Swaziland
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 07/12/2021 National Health Sciences Research Committee
Ethics Committee Address
Street address City Postal code Country
1st Floor Lingadzi House, Robert Mugabe Crescent, Private Bag B303, Lilongwe 3, Malawi Lilongwe 0003 Malawi
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome 1. Confirmed HIV-1 infection 2. AEs and AEs leading to discontinuation of study intervention 2 Years
Secondary Outcome Confirmed HIV-1 infection 3 Years
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Setshaba Research Centre 2088 Block H, Soshanguve Pretoria 0152 South Africa
Qhakaza Mbokodo Research Clinic 15 Parklane Ladysmith 3370 South Africa
Desmond Tutu Health Foundation Masiphumelele Guinea-Fowl Road, Sunnydale Cape Town 7906 South Africa
Madibeng Centre for Research 40 Pienaar Street Brits 0250 South Africa
Helen Joseph Hospital Clinical HIV Research Unit 1 Perth Road Johannesburg 2092 South Africa
Emavundleni Research Centre 14 Sonwabile Drive, Nyanga Crossroads Cape Town 7750 South Africa
Aurum Institute Rustenburg 50 Steen Street, Corner Pretorious Rustenburg 0300 South Africa
Perinatal HIV Research Unit HIV Prevention CRS Chris Hani Road, Diepkloof 319 Iq, Soweto Johannesburg 1864 South Africa
MATCH RESEARCH UNIT Commercial City Site 40 Dr AB Xuma Str. Durban 4001 South Africa
WITS REPRODUCTIVE HEALTH AND HIV RESEARCH UNIT WITS RHI 22 Esselen Street Johannesburg 2001 South Africa
KHAYELITSHA CRS 8 Sulani Drive, Khayelitsha Cape Town 7784 South Africa
Aurum Institute Klerksdorp Clinical Research Centre 201 Jade Square Centre Klerksdorp 2571 South Africa
CHATSWORTH CRS 361 RK Khan Circle Durban 4092 South Africa
MUJHU Care Limited Clinic Upper Mulago Hill Road Kampala 10216 Uganda
Kamwala Health Centre UNC Global Projects LLC Kamwala Health Centre Luena Road off Chilimbulu Road Lusaka 10101 Zambia
ICAP Eswatini Prevention Center Family Life Association of Eswatini FLAS-Mbabane, Smuts Street Mbabane H100 Swaziland
Queen Elizabeth Central Hospital Kamuzu Highway, Chipatala Avenue Blantyre 312200 Malawi
FUNDING SOURCES
Name of source Street address City Postal code Country
Bill and Melinda Gates Foundation award ICRC 16th Avenue Midrand 1685 South Africa
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor MSD Pty Ltd. 117 16th Road, Midrand Johannesburg 1685 South Africa Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Scientific Enquiries LG Bekker Linda-Gail.Bekker@hiv-research.org.za +27216506966 Desmond Tutu HIV Foundation
City Postal code Country Position/Affiliation
Cape Town 7925 South Africa National Principal Investigator
Role Name Email Phone Street address
Public Enquiries Zoe Nell zoe.nell@merck.com +270116553307 MSD Pty Ltd
City Postal code Country Position/Affiliation
Midrand 1685 South Africa Clinical Research Director
Role Name Email Phone Street address
Principal Investigator K Ahmed KAhmed@setshaba.org.za +27127992422 SETSHABA RESEARCH CENTRE
City Postal code Country Position/Affiliation
SOSHANGUVE 0152 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator P Kotze plkotze@gmail.com +27366312372 Qhakaza Mbokodo Research Clinic
City Postal code Country Position/Affiliation
Ladysmith 3370 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator K Gill Katherine.gill@hiv-research.org.za +27217855454 Desmond Tutu Health Foundation - Masiphumelele
City Postal code Country Position/Affiliation
Cape Town 7975 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator C Louw clouw@madibengresearch.co.za +27122521140 MADIBENG CENTRE FOR RESEARCH
City Postal code Country Position/Affiliation
Brits 0250 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator N Mwelase tmwelase@witshealth.co.za +27112768800 UNIVERSITY OF WITWATERSRAND CLINICAL HIV RESEARCH UNIT, CHRU
City Postal code Country Position/Affiliation
Johannesburg 2196 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator P Macdonald Pippa.macdonald@hiv-research.org.za +27216505869 EMAVUNDLENI RESEARCH CENTRE
City Postal code Country Position/Affiliation
CAPE TOWN 7750 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator R Panchia panchiar@phru.co.za +27119899711 PERINATAL HIV RESEARCH UNIT, CHBAH
City Postal code Country Position/Affiliation
Diepkloof 1864 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator M Jaggernath mjaggernath@mru.ac.za +27310011921 MATCH RESEARCH UNIT, Commercial City Site
City Postal code Country Position/Affiliation
Durban 4001 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator S Delany Moretlwe sdelany@wrhi.ac.za +27113585300 WITS REPRODUCTIVE HEALTH AND HIV RESEARCH UNIT
City Postal code Country Position/Affiliation
Johannesburg 2001 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator A Ward amyward41@gmail.com +27216505530 KHAYELITSHA CRS
City Postal code Country Position/Affiliation
CAPE TOWN 1184 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator R Selepe pselepe@auruminstitute.org +27871351596 Aurum Institute Klerksdorp Clinical Research Centre
City Postal code Country Position/Affiliation
Klerksdorp 2571 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator L Naidoo Logashvari.naidoo@mrc.ac.za +27314014150 CHATSWORTH CRS
City Postal code Country Position/Affiliation
Durban 4027 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator M Senne msenne@auruminstitute.org +27871351575 The Aurum Institute, Clinical Research Centre
City Postal code Country Position/Affiliation
Rustenburg 0300 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator H Nuwagaba Biribonwoha hn2158@cumc.columbia.edu +26876024678 Family Life Association of Eswatini
City Postal code Country Position/Affiliation
Mbabane H100 Swaziland Principal Investigator
Role Name Email Phone Street address
Principal Investigator B Mirembe bgati@mujhu.org +256772881922 MUJHU Care Limited- Clinic
City Postal code Country Position/Affiliation
Kampala 10216 Uganda Principal Investigator
Role Name Email Phone Street address
Principal Investigator M Kasaro margaret.kasaro@unclusaka.org +260963223210 UNC Global Projects LLC Kamwala Health Centre Luena Road off Chilimbulu Road
City Postal code Country Position/Affiliation
Lusaka 10101 Zambia Principal Investigator
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes MSD (Pty) Ltd will make the results available to the University of the Witwatersrand Human Research Ethics Committee,University of Cape Town Human Research Ethics Committee,South African Medical Research Council Human Research Ethics Committee, South African Health Products Regulatory Authority, study sites and participants. The results will be submitted for presentation at scientific meetings and publication in scientific journals as well. Clinical Study Report 6 months after study completion. Regardless of trial outcome,MSD commits to publish the primary and secondary results of its registered trials of marketed products in which treatment is assigned, according to pre-specified plans for data analysis.To the extent scientifically appropriate, MSD seeks to publish the results of other analyses it conducts that are important to patients, physicians,and payers. Some early phase or pilot trials are intended to be hypothesis-generating rather than hypothesis testing; in such cases, publication of results may not be appropriate since the trial may be underpowered and the analyses complicated by statistical issues such as multiplicity. MSD's policy on authorship is consistent with there commendations published by he International Committee of Medical Journal Editors (ICMJE).In summary, authorship should reflect significant contribution to the design and conduct of the trial, performance or interpretation of the analysis,and/or writing of the manuscript.All named authors must be able to defend the trial results and conclusions. MSD funding of a trial will be acknowledged in publications.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
www.msd.co.za No
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Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information