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.: PACTR202109759050023 Date of Approval: 13/09/2021
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title MK8591-024: Oral ISL QM as PrEP in MSM and TGW at High Risk for HIV-1 Infection
Official scientific title 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 Men and Transgender Women Who Have Sex With Men, and Are 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-1 infection is PrEP.In late 2015,the WHO-recommended PrEP as an additional prevention option for people who are HIV-negative and at substantial risk for HIV [World Health Organization 2015].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 daily FTC/TDF is,however,suboptimal in many people at risk for HIV-1 infection [Marrazzo, J.M., et al 2015][Hojilla, J.C., et al 2018].Globally,the risk of acquiring HIV is 26 times higher among MSM than among all adult men [Joint United Nations Programme on HIV/AIDS 2020] and novel strategies to prevent HIV acquisition in this population are urgently needed.Gay men and other MSM accounted for an estimated 17% of new HIV infections globally,including more than half of new HIV infections in western and central Europe, and North America;40% in Latin America;30% in Asia and the Pacific;22% in the Caribbean;22% in eastern Europe and central Asia;18% in the Middle East and North Africa; and 17% in western and central Africa [Joint United Nations Programme on HIV/AIDS 2019].ISL has the potential to be an effective agent for HIV-1 PrEP due to its 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 in cisgender MSM and TGW who are at high risk for HIV-1 infection, ultimately leading to greater effectiveness for HIV-1 prevention than what is currently observed with FTC/TDF or FTC/TAF QD. Such a simplified regimen may also be of particular benefit to adolescents who typically have challenges with adherence.
Type of trial RCT
Acronym (If the trial has an acronym then please provide) Impower 024
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 01/06/2021
Actual trial start date 02/09/2021
Anticipated date of last follow up 30/12/2023
Actual Last follow-up date
Anticipated target sample size (number of participants) 1500
Actual target sample size (number of participants)
Recruitment status Stopped early/ terminated
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 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 60 mg Once Monthly Day 1 through Month 24 After a screening phase of up to 45 days, participants will be in this study for up to 2.5 years from the time the participant provides documented informed consent/assent through the final contact. ISL QM Group: HIV Preexposure prophylaxis for Cisgender men and transgender women who have sex with men, are at least 16 years of age, and are at high risk for HIV-1 infection 500
Control Group Placebo to FTCTDF 0 mg Once Daily Day 1 through Month 24 After a screening phase of up to 45 days, participants will be in this study for up to 2.5 years from the time the participant provides documented informed consent/assent through the final contact. ISL QM Group: HIV Preexposure prophylaxis for Cisgender men and transgender women who have sex with men, are at least 16 years of age, and are at high risk for HIV-1 infection. 250 Active-Treatment of Control Group
Experimental Group FTCTDF 200/245 mg Once Daily Day 1 through Month 24 After a screening phase of up to 45 days, participants will be in this study for up to 2.5 years from the time the participant provides documented informed consent/assent through the final contact. FTC/TDF QD Group: HIV Preexposure prophylaxis for Cisgender men and transgender women who have sex with men, are at least 16 years of age, and are at high risk for HIV-1 infection 250
Control Group Placebo to ISL 0 mg Once Monthly Day 1 through Month 24 After a screening phase of up to 45 days, participants will be in this study for up to 2.5 years from the time the participant provides documented informed consent/assent through the final contact. FTC/TDF QD Group: HIV Preexposure prophylaxis for Cisgender men and transgender women who have sex with men, are at least 16 years of age, and are at high risk for HIV-1 infection 500 Active-Treatment of Control Group
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 result before randomization. 2. Is sexually active with male (assigned male sex at birth) or transgender female partners defined as having anal sexual intercourse with a man or TGW at least once in the past month. 3. Is at high risk for sexually acquiring HIV-1 infection based on self-report of at least 1 of the following: Condomless receptive anal intercourse in the 6 months prior to screening occurring outside a mutually monogamous HIV seronegative concordant relationship,More than 5 partners (anal intercourse) in the 6 months prior to screening (regardless of condom use and HIV serostatus, as reported by the enrollee),Any unprescribed stimulant drug use in the 6 months prior to screening,Rectal or urethral gonorrhea or chlamydia or incident syphilis in the 6 months prior to screening.4.Is cisgender male or transgender female (assigned male sex at birth), and ≥16 years of age at the time of providing informed consent/assent. 5.The participant (or legally acceptable representative) has provided documented informed consent /assent for the study. 6.Has no plans to relocate or travel away from the site for ≥4 consecutive weeks during study participation 1. Has hypersensitivity or other contraindication to any component of the study interventions as determined by the investigator. 2. Has active HBV infection (defined as HBsAg-positive or HBV DNA positive). 3. Has known 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 evidence of hepatic synthetic dysfunction. 5. Has a history or current evidence of any condition (including active tuberculosis infection), therapy, laboratory abnormality or other circumstance (including drug or alcohol abuse 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. 6. Has taken cabotegravir at any time (past or current). Is currently receiving or is anticipated to require any prohibited therapies outlined in Section 6.5 of the study protocol from 30 days prior to Day 1 through the duration of the study. Adolescent: 13 Year-18 Year,Adult: 19 Year-44 Year,Middle Aged: 45 Year(s)-64 Year(s) 16 Year(s) 105 Year(s) Both
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 29/04/2021 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 12/07/2021 University of Cape Town Human Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
G50, G Floor, Old Main Building Cape Town 7925 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 24/08/2021 KENYA MEDICAL RESEARCH INSTITUTE SCIENTIFIC AND ETHICS REVIEW UNIT
Ethics Committee Address
Street address City Postal code Country
OFF MBAGATHI ROAD, Nairobi 00200 Kenya
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 1.Frequent testing for HIV acquisition at all scheduled study visits. 2.Safety assessments from consenting visit until the safety follow-up period of 42 days after the last dose of study intervention.
Secondary Outcome Confirmed HIV-1 infection 1.Frequent testing for HIV acquisition at all scheduled study visits. 2.Safety assessments from consenting visit until the safety follow-up period of 42 days after the last dose of study intervention.
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Wits Reproductive Health and HIV Institute Research Centre 7 Esselen Street, Hillbrow Johannesburg 2038 South Africa
Desmond Tutu Health Foundation Clinical Trials Unit Main Road, Observatory Cape Town 7925 South Africa
Perinatal HIV Research Unit HIV Prevention CRS Chris Hani Road, Diepkloof Johannesburg 1864 South Africa
FUNDING SOURCES
Name of source Street address City Postal code Country
MSD Pty Ltd. 117 16th Road, Midrand Johannesburg 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
Public Enquiries Zoe Nell zoe.nell@merck.com +270116553307 MSD Pty Ltd. 117 16th Road, Midrand
City Postal code Country Position/Affiliation
Johannesburg 1685 South Africa Clinical Research Director
Role Name Email Phone Street address
Scientific Enquiries Richard Kaplan richard.kaplan@hivresearch.org.za +27214066958 Desmond Tutu Health Foundation Clinical Trials Unit, J52 Old Main Building, Main Road
City Postal code Country Position/Affiliation
Cape Town 7925 South Africa National Principal Investigator
Role Name Email Phone Street address
Principal Investigator N Ndlovu nkndlovu@wrhi.ac.za +27113585424 Wits RHI Research Centre , 7 Esselen Street
City Postal code Country Position/Affiliation
Johannesburg 2038 South Africa Co Principal Investigator
Role Name Email Phone Street address
Principal Investigator T Palanee Phillips tpalanee@wrhi.ac.za +27113585471 Wits RHI Research Centre, 7 Esselen Street
City Postal code Country Position/Affiliation
Johannesburg 2038 South Africa Co Principal Investigator
Role Name Email Phone Street address
Principal Investigator R Kaplan Richard.Kaplan@hiv-research.org.za +27214066958 Desmond Tutu Health Foundation Clinical Trials Unit,J52 Old Main Building,Groote Schuur Hospital, Main Road
City Postal code Country Position/Affiliation
Cape Town 7925 South Africa Principal Investigator
Role Name Email Phone Street address
Principal Investigator R Panchia panchiar@phru.co.za +27119899711 Perinatal HIV Research Unit,Ground Floor New Nurses Home, West Wing Chris Hani Baragwanath Academic Hospital, Chris Hani Road
City Postal code Country Position/Affiliation
Johannesburg 1864 South Africa 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