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Oral ISL QM as PrEP in Cisgender Women at High Risk for HIV-1 Infection (MK-8591-022) (Impower-022)

Primary Purpose

HIV-I, Human Immunodeficiency Virus Type 1, Prophylaxis

Status
Active
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Islatravir
Placebo to FTC/TDF
FTC/TDF
Placebo to ISL
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for HIV-I focused on measuring Preexposure prophylaxis (PrEP), Prevention

Eligibility Criteria

16 Years - 45 Years (Child, Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

  • Confirmed HIV-uninfected based on negative HIV-1/HIV-2 test results before randomization.
  • Sexually active (vaginal and/or anal sex) with a male sexual partner in the 30 days prior to screening.
  • High risk for HIV-1 infection.
  • Not pregnant or breastfeeding, and one of the following conditions applies: Not a woman of childbearing potential (WOCBP) or is a WOCBP and is using an acceptable contraceptive method during the intervention period and for at least 42 days after the last dose.
  • A WOCBP must have a negative pregnancy test within 24 hours prior to the first dose of study intervention.

Exclusion Criteria:

  • Hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator.
  • Findings of chronic hepatitis B virus (HBV) infection or past HBV.
  • Current or chronic history of liver disease.
  • History of malignancy within 5 years of screening except for adequately-treated basal cell or squamous cell skin cancer, or in situ cervical cancer.
  • Past or current use of cabotegravir, lenacapavir, or any other long-acting HIV prevention product.
  • Currently participating in or has participated in an interventional clinical study with an investigational compound or device, within 30 days prior to Day 1.
  • Expecting to conceive or donate eggs at any time during the study.

Sites / Locations

  • University of Alabama at Birmingham-UAB Sexual Health Research Clinic (SHRC) ( Site 0064)
  • MedStar Health Research Institute (MedStar Physician Based R-MedStar Washington Hospital Center ( Si
  • University of Miami Miller School of Medicine-Infectious Disease ( Site 0076)
  • Orlando Immunology Center ( Site 0068)
  • Ponce De Leon Center Grady Health ( Site 0066)
  • The University of Mississippi Medical Center ( Site 0065)
  • KC CARE Health Center-Clinical Trials ( Site 0059)
  • Rutgers New Jersey Medical School-Clinical Research Center ( Site 0071)
  • Bronx Prevention Center ICAP ( Site 0062)
  • The University of North Carolina at Chapel Hill-Medicine ( Site 0056)
  • Prisma Health Richland Hospital-Clinical Research Unit ( Site 0069)
  • Prism Health North Texas, Oak Cliff Health Center ( Site 0070)
  • West Virginia University-Department of Medicine ( Site 0061)
  • Perinatal HIV Research Unit (PHRU)-HIV Prevention CRS ( Site 0023)
  • Wits Reproductive Health and HIV Institute (WRHI)-Wits RHI Ward 21 Clinical Research site ( Site 002
  • Helen Joseph Hospital-Clinical HIV Research Unit ( Site 0020)
  • Setshaba Research Centre ( Site 0016)
  • SA Medical Research Council - Chatsworth Clinical Research Site ( Site 0030)
  • Maternal Adolescent and Child Health Research (MatCH) ( Site 0025)
  • Qhakaza Mbokodo Research Clinic ( Site 0017)
  • Madibeng Centre for Research ( Site 0019)
  • Aurum Institute Klerksdorp CRS ( Site 0029)
  • Aurum Institute - Rustenburg ( Site 0022)
  • MU-JHU Care Limited-Clinic ( Site 0041)

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

ISL QM

FTC/TDF QD

Arm Description

ISL (islatravir) once monthly AND placebo to FTC/TDF (emtricitabine/tenofovir disoproxil) once daily during Part 1.

FTC/TDF (TRUVADA™ or generic product emtricitabine/tenofovir disoproxil) administered once daily in Parts 1, 2, and 3. Placebo to ISL (islatravir) also administered once monthly during Part 1.

Outcomes

Primary Outcome Measures

Incidence Rate Per Year of Confirmed HIV-1 Infections
Incidence rate per year of confirmed HIV-1 infections is the number of participants with confirmed HIV-1 infections divided by the total person-years of follow-up time to HIV-1 infection status. The primary analysis will compare the incidence rate per year of confirmed HIV-1 Infections between the ISL QM arm participants and incidence rate per year of confirmed HIV-1 Infections in the FTC/TDF QD arm participants. HIV serology tests and polymerase chain reaction (PCR) tests will be done at pre-specified timepoints to confirm HIV-1 infection.
Percentage of Participants Who Experienced One or More Adverse Events
An adverse event (AE) is any untoward medical occurrence in a study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign, symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Percentage of Participants Who Discontinued Treatment Due to an Adverse Event
An adverse event (AE) is any untoward medical occurrence in a study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign, symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

Secondary Outcome Measures

Incidence Rate per Year of Confirmed HIV-1 Infections Among Participants
Incidence rate per year of confirmed HIV-1 infections is the number of participants with confirmed HIV-1 infections divided by the total person-years of follow-up time to HIV-1 infection status. The secondary analysis will compare the incidence rate per year of confirmed HIV-1 Infections between the ISL QM arm participants and the background incidence rate calculated from screened participants. The background incidence rate will be estimated using tests based on biomarkers that can differentiate "recent" from "nonrecent" infections in the population screened for this study.

Full Information

First Posted
November 23, 2020
Last Updated
October 16, 2023
Sponsor
Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT04644029
Brief Title
Oral ISL QM as PrEP in Cisgender Women at High Risk for HIV-1 Infection (MK-8591-022)
Acronym
Impower-022
Official 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 Women at High Risk for HIV-1 Infection
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 24, 2021 (Actual)
Primary Completion Date
July 18, 2023 (Actual)
Study Completion Date
July 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study will evaluate whether oral islatravir (ISL) is effective in preventing Human Immunodeficiency Virus Type 1 (HIV-1) infection in women at high-risk for HIV-1 infection. The study will compare oral ISL taken once a month with standard-of-care medication for prevention of HIV-1 infection, emtricitabine/tenofovir disoproxil (FTC/TDF), taken once per day. The primary hypothesis is that oral ISL is more effective than FTC/TDF at reducing the incidence rate per year of confirmed HIV-1 infections.
Detailed Description
Based on laboratory findings of decreased lymphocyte and CD4+ T-cell counts across the islatravir program, dosing of blinded study intervention was halted on 13-Dec-2021 and screening and randomization of new participants was ended. Blinded assessments conducted prior to this date are designated as Study Part 1. During Study Part 2, participants from Part 1 have the option to receive daily FTC/TDF while continuing in the study. Study Part 3 was added to unblind each participant's Part 1 study intervention assignment, continue participants on FTC/TDF, and monitor safety.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV-I, Human Immunodeficiency Virus Type 1, Prophylaxis
Keywords
Preexposure prophylaxis (PrEP), Prevention

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Masking Description
In Study Part 1, a double-blinding technique with in-house blinding will be used. ISL and FTC/TDF and FTC/TAF will be packaged identically relative to their matching placebos so that blind is maintained. The participant, the investigator, and Sponsor personnel or delegate(s) who are involved in the study intervention administration or clinical evaluation of the participants are unaware of the intervention assignments. In Study Part 2, sponsor personnel not directly involved with blinded safety monitoring will be unblinded to participants' randomized study intervention in Part 1. In Study Part 3, participants, investigators, and all Sponsor personnel will be unblinded to the participants' original randomized study intervention group.
Allocation
Randomized
Enrollment
730 (Actual)

8. Arms, Groups, and Interventions

Arm Title
ISL QM
Arm Type
Experimental
Arm Description
ISL (islatravir) once monthly AND placebo to FTC/TDF (emtricitabine/tenofovir disoproxil) once daily during Part 1.
Arm Title
FTC/TDF QD
Arm Type
Active Comparator
Arm Description
FTC/TDF (TRUVADA™ or generic product emtricitabine/tenofovir disoproxil) administered once daily in Parts 1, 2, and 3. Placebo to ISL (islatravir) also administered once monthly during Part 1.
Intervention Type
Drug
Intervention Name(s)
Islatravir
Other Intervention Name(s)
MK-8591
Intervention Description
Oral 60 mg tablet administered once monthly during Part 1.
Intervention Type
Drug
Intervention Name(s)
Placebo to FTC/TDF
Intervention Description
0 mg tablet administered once daily during Part 1.
Intervention Type
Drug
Intervention Name(s)
FTC/TDF
Other Intervention Name(s)
TRUVADA™, Emtricitabine/Tenofovir disoproxil, Emtricitabine/Tenofovir disoproxil fumarate
Intervention Description
Each tablet contains 200 mg emtricitabine and 245 mg of tenofovir disoproxil (equivalent to 300 mg tenofovir disoproxil fumarate or 201.22 mg tenofovir disproxil phosphate), administered orally once daily in Parts 1, 2, and 3.
Intervention Type
Drug
Intervention Name(s)
Placebo to ISL
Intervention Description
0 mg tablet administered orally once monthly in Part 1.
Primary Outcome Measure Information:
Title
Incidence Rate Per Year of Confirmed HIV-1 Infections
Description
Incidence rate per year of confirmed HIV-1 infections is the number of participants with confirmed HIV-1 infections divided by the total person-years of follow-up time to HIV-1 infection status. The primary analysis will compare the incidence rate per year of confirmed HIV-1 Infections between the ISL QM arm participants and incidence rate per year of confirmed HIV-1 Infections in the FTC/TDF QD arm participants. HIV serology tests and polymerase chain reaction (PCR) tests will be done at pre-specified timepoints to confirm HIV-1 infection.
Time Frame
Up to approximately 36 months
Title
Percentage of Participants Who Experienced One or More Adverse Events
Description
An adverse event (AE) is any untoward medical occurrence in a study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign, symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Time Frame
Up to approximately 37 months
Title
Percentage of Participants Who Discontinued Treatment Due to an Adverse Event
Description
An adverse event (AE) is any untoward medical occurrence in a study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign, symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.
Time Frame
Up to approximately 36 months
Secondary Outcome Measure Information:
Title
Incidence Rate per Year of Confirmed HIV-1 Infections Among Participants
Description
Incidence rate per year of confirmed HIV-1 infections is the number of participants with confirmed HIV-1 infections divided by the total person-years of follow-up time to HIV-1 infection status. The secondary analysis will compare the incidence rate per year of confirmed HIV-1 Infections between the ISL QM arm participants and the background incidence rate calculated from screened participants. The background incidence rate will be estimated using tests based on biomarkers that can differentiate "recent" from "nonrecent" infections in the population screened for this study.
Time Frame
Up to approximately 36 months

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
Assigned female sex at birth and is cisgender
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Confirmed HIV-uninfected based on negative HIV-1/HIV-2 test results before randomization. Sexually active (vaginal and/or anal sex) with a male sexual partner in the 30 days prior to screening. High risk for HIV-1 infection. Not pregnant or breastfeeding, and one of the following conditions applies: Not a woman of childbearing potential (WOCBP) or is a WOCBP and is using an acceptable contraceptive method during the intervention period and for at least 42 days after the last dose. A WOCBP must have a negative pregnancy test within 24 hours prior to the first dose of study intervention. Exclusion Criteria: Hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator. Findings of chronic hepatitis B virus (HBV) infection or past HBV. Current or chronic history of liver disease. History of malignancy within 5 years of screening except for adequately-treated basal cell or squamous cell skin cancer, or in situ cervical cancer. Past or current use of cabotegravir, lenacapavir, or any other long-acting HIV prevention product. Currently participating in or has participated in an interventional clinical study with an investigational compound or device, within 30 days prior to Day 1. Expecting to conceive or donate eggs at any time during the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
Facility Information:
Facility Name
University of Alabama at Birmingham-UAB Sexual Health Research Clinic (SHRC) ( Site 0064)
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35205
Country
United States
Facility Name
MedStar Health Research Institute (MedStar Physician Based R-MedStar Washington Hospital Center ( Si
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
University of Miami Miller School of Medicine-Infectious Disease ( Site 0076)
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Orlando Immunology Center ( Site 0068)
City
Orlando
State/Province
Florida
ZIP/Postal Code
32803
Country
United States
Facility Name
Ponce De Leon Center Grady Health ( Site 0066)
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30308
Country
United States
Facility Name
The University of Mississippi Medical Center ( Site 0065)
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216
Country
United States
Facility Name
KC CARE Health Center-Clinical Trials ( Site 0059)
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64111
Country
United States
Facility Name
Rutgers New Jersey Medical School-Clinical Research Center ( Site 0071)
City
Newark
State/Province
New Jersey
ZIP/Postal Code
07103
Country
United States
Facility Name
Bronx Prevention Center ICAP ( Site 0062)
City
Bronx
State/Province
New York
ZIP/Postal Code
10451
Country
United States
Facility Name
The University of North Carolina at Chapel Hill-Medicine ( Site 0056)
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States
Facility Name
Prisma Health Richland Hospital-Clinical Research Unit ( Site 0069)
City
Columbia
State/Province
South Carolina
ZIP/Postal Code
29203
Country
United States
Facility Name
Prism Health North Texas, Oak Cliff Health Center ( Site 0070)
City
Dallas
State/Province
Texas
ZIP/Postal Code
75208
Country
United States
Facility Name
West Virginia University-Department of Medicine ( Site 0061)
City
Morgantown
State/Province
West Virginia
ZIP/Postal Code
26506
Country
United States
Facility Name
Perinatal HIV Research Unit (PHRU)-HIV Prevention CRS ( Site 0023)
City
Johannesburg
State/Province
Gauteng
ZIP/Postal Code
1864
Country
South Africa
Facility Name
Wits Reproductive Health and HIV Institute (WRHI)-Wits RHI Ward 21 Clinical Research site ( Site 002
City
Johannesburg
State/Province
Gauteng
ZIP/Postal Code
2000
Country
South Africa
Facility Name
Helen Joseph Hospital-Clinical HIV Research Unit ( Site 0020)
City
Johannesburg
State/Province
Gauteng
ZIP/Postal Code
2092
Country
South Africa
Facility Name
Setshaba Research Centre ( Site 0016)
City
Tshwane
State/Province
Gauteng
ZIP/Postal Code
0152
Country
South Africa
Facility Name
SA Medical Research Council - Chatsworth Clinical Research Site ( Site 0030)
City
Chatsworth
State/Province
Kwazulu-Natal
ZIP/Postal Code
4092
Country
South Africa
Facility Name
Maternal Adolescent and Child Health Research (MatCH) ( Site 0025)
City
Durban
State/Province
Kwazulu-Natal
ZIP/Postal Code
4001
Country
South Africa
Facility Name
Qhakaza Mbokodo Research Clinic ( Site 0017)
City
Ladysmith
State/Province
Kwazulu-Natal
ZIP/Postal Code
3370
Country
South Africa
Facility Name
Madibeng Centre for Research ( Site 0019)
City
Brits
State/Province
North-West
ZIP/Postal Code
0250
Country
South Africa
Facility Name
Aurum Institute Klerksdorp CRS ( Site 0029)
City
Klerksdorp
State/Province
North-West
ZIP/Postal Code
2571
Country
South Africa
Facility Name
Aurum Institute - Rustenburg ( Site 0022)
City
Rustenburg
State/Province
North-West
ZIP/Postal Code
0299
Country
South Africa
Facility Name
MU-JHU Care Limited-Clinic ( Site 0041)
City
Kampala
ZIP/Postal Code
10216
Country
Uganda

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Links:
URL
https://www.merckclinicaltrials.com/
Description
Merck Clinical Trials Information

Learn more about this trial

Oral ISL QM as PrEP in Cisgender Women at High Risk for HIV-1 Infection (MK-8591-022)

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