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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04644029
Recruitment Status : Active, not recruiting
First Posted : November 25, 2020
Last Update Posted : August 17, 2022
Sponsor:
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC

Study Description
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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.

Condition or disease Intervention/treatment Phase
HIV-I Human Immunodeficiency Virus Type 1 Prophylaxis Drug: Islatravir Drug: Placebo to FTC/TDF Drug: FTC/TDF Drug: Placebo to ISL Phase 3

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 730 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
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.
Primary Purpose: Prevention
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
Actual Study Start Date : February 24, 2021
Estimated Primary Completion Date : July 5, 2024
Estimated Study Completion Date : July 5, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: ISL QM
ISL (islatravir) once monthly AND placebo to FTC/TDF (emtricitabine/tenofovir disoproxil) once daily during Part 1.
 Drug: Islatravir
Oral 60 mg tablet administered once monthly during Part 1.
Other Name: MK-8591

Drug: Placebo to FTC/TDF
0 mg tablet administered once daily during Part 1.
Active Comparator: FTC/TDF QD
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.
 Drug: FTC/TDF
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.
Other Names:
  • TRUVADA™
  • Emtricitabine/Tenofovir disoproxil
  • Emtricitabine/Tenofovir disoproxil fumarate

Drug: Placebo to ISL
0 mg tablet administered orally once monthly in Part 1.


Outcome Measures
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Primary Outcome Measures :
  1. Incidence Rate Per Year of Confirmed HIV-1 Infections [ Time Frame: Up to approximately 36 months ]
    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.

  2. Percentage of Participants Who Experienced One or More Adverse Events [ Time Frame: Up to approximately 37 months ]
    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.

  3. Percentage of Participants Who Discontinued Treatment Due to an Adverse Event [ Time Frame: Up to approximately 36 months ]
    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 :
  1. Incidence Rate per Year of Confirmed HIV-1 Infections Among Participants [ Time Frame: Up to approximately 36 months ]
    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.


Eligibility Criteria
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Ages Eligible for Study:   16 Years to 45 Years   (Child, Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Assigned female sex at birth and is cisgender
Accepts Healthy Volunteers:   Yes
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.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04644029


Locations
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Sponsors and Collaborators
Merck Sharp & Dohme LLC
Investigators
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Study Director: Medical Director Merck Sharp & Dohme LLC
More Information
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Responsible Party: Merck Sharp & Dohme LLC
ClinicalTrials.gov Identifier: NCT04644029    
Other Study ID Numbers: 8591-022
MK-8591-022 ( Other Identifier: Merck )
2021-001289-39 ( EudraCT Number )
First Posted: November 25, 2020    Key Record Dates
Last Update Posted: August 17, 2022
Last Verified: August 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
URL: http://engagezone.msd.com/ds_documentation.php

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Merck Sharp & Dohme LLC:
Preexposure prophylaxis (PrEP)
Prevention
Additional relevant MeSH terms:
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Acquired Immunodeficiency Syndrome
HIV Infections
Infections
Immunologic Deficiency Syndromes
Immune System Diseases
Blood-Borne Infections
Communicable Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Slow Virus Diseases
 Genital Diseases
Urogenital Diseases
Tenofovir
Emtricitabine
Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Islatravir
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-HIV Agents
Anti-Retroviral Agents