Dose Ranging, Switch Study of Islatravir (MK-8591) and Ulonivirine (MK-8507) Once-Weekly in Virologically-Suppressed Adults With Human Immunodeficiency Virus Type 1 (HIV-1) [MK-8591-013]

NCT ID: NCT04564547

Last Updated: 2026-01-26

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

161 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-03-09

Study Completion Date

2025-01-30

Brief Summary

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This is a randomized, controlled, double-blind, study to evaluate the safety and tolerability of islatravir (ISL) + ulonivirine based on review of the accumulated safety data, in adult participants with human immunodeficiency virus type 1 (HIV-1) who have been virologically suppressed for ≥6 months on bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) once-daily.

Detailed Description

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Based on laboratory findings of decreased lymphocyte and CD4+ T-cell counts across the islatravir program and as described in protocol amendment 2 (approved 01-Dec-2021), participants in study Part 1 (double-blind treatment period) were unblinded, discontinued all study interventions, and switched to standard of care non-study antiretroviral (ART) therapy. Participants who received ISL + ulonivirine (Groups 1 to 3) may have then entered into an unblinded safety monitoring period and were monitored for ≥6 months. As specified in protocol amendment 2, study Parts 2 and 3 were no longer planned or initiated for any participant.

Conditions

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HIV-1 Infection

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors
In study Part 1 (double-blind treatment period), a double-blinding technique with in-house blinding is used. Ulonivirine, ISL, and BIC/FTC/TAF will be packaged identically relative to their matching placebos so that the 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 the unblinded safety monitoring period, participants, investigators, and Sponsor personnel are unblinded as to the participant's original randomized intervention group.

Study Groups

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Group 1: ISL 20 mg + Ulonivirine 100 mg

Participants receive ISL 20 mg + ulonivirine 100 mg once weekly (QW) and placebo to BIC/FTC/TAF once daily (QD). Following study-wide discontinuation of study intervention, participants may have entered the optional unblinded safety monitoring period and received standard of care non-study ART.

Group Type EXPERIMENTAL

Islatravir

Intervention Type DRUG

ISL capsule taken by mouth.

Ulonivirine

Intervention Type DRUG

Ulonivirine tablet taken by mouth.

Placebo to Ulonivirine

Intervention Type DRUG

Placebo tablet matched to ulonivirine taken by mouth.

Placebo to BIC/FTC/TAF

Intervention Type DRUG

Placebo tablet matched to BIC/FTC/TAF taken by mouth.

Group 2: ISL 20 mg + Ulonivirine 200 mg

Participants receive ISL 20 mg + ulonivirine 200 mg QW and placebo to BIC/FTC/TAF QD. Following study-wide discontinuation of study intervention, participants may have entered the optional unblinded safety monitoring period and received standard of care non-study ART.

Group Type EXPERIMENTAL

Islatravir

Intervention Type DRUG

ISL capsule taken by mouth.

Ulonivirine

Intervention Type DRUG

Ulonivirine tablet taken by mouth.

Placebo to Ulonivirine

Intervention Type DRUG

Placebo tablet matched to ulonivirine taken by mouth.

Placebo to BIC/FTC/TAF

Intervention Type DRUG

Placebo tablet matched to BIC/FTC/TAF taken by mouth.

Group 3: ISL 20 mg + Ulonivirine 400 mg

Participants receive ISL 20 mg + ulonivirine 400 mg QW and placebo to BIC/FTC/TAF QD. Following study-wide discontinuation of study intervention, participants may have entered the optional unblinded safety monitoring period and received standard of care non-study ART.

Group Type EXPERIMENTAL

Islatravir

Intervention Type DRUG

ISL capsule taken by mouth.

Ulonivirine

Intervention Type DRUG

Ulonivirine tablet taken by mouth.

Placebo to BIC/FTC/TAF

Intervention Type DRUG

Placebo tablet matched to BIC/FTC/TAF taken by mouth.

Group 4: BIC/FTC/TAF

Participants receive placebo to ISL + placebo to ulonivirine QW and BIC/FTC/TAF 50 mg/200 mg/25 mg QD.

Group Type ACTIVE_COMPARATOR

BIC/FTC/TAF

Intervention Type DRUG

BIC/FTC/TAF tablet taken by mouth.

Placebo to ISL

Intervention Type DRUG

Placebo capsule matched to ISL taken by mouth.

Placebo to Ulonivirine

Intervention Type DRUG

Placebo tablet matched to ulonivirine taken by mouth.

Interventions

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Islatravir

ISL capsule taken by mouth.

Intervention Type DRUG

Ulonivirine

Ulonivirine tablet taken by mouth.

Intervention Type DRUG

BIC/FTC/TAF

BIC/FTC/TAF tablet taken by mouth.

Intervention Type DRUG

Placebo to ISL

Placebo capsule matched to ISL taken by mouth.

Intervention Type DRUG

Placebo to Ulonivirine

Placebo tablet matched to ulonivirine taken by mouth.

Intervention Type DRUG

Placebo to BIC/FTC/TAF

Placebo tablet matched to BIC/FTC/TAF taken by mouth.

Intervention Type DRUG

Other Intervention Names

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MK-8591 MK-8507 BIKTARVY®

Eligibility Criteria

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Inclusion Criteria

* Is HIV-1 positive with plasma human immunodeficiency virus type 1 (HIV-1) RNA \<50 copies/mL at screening
* Has been virologically suppressed on bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) for ≥6 months
* Has a screening CD4+ T-cell count \>200 cells/mm\^3 (completed by the central laboratory)
* Is male or female, at least 18 years of age, at the time of signing the informed consent
* Female participants are eligible to participate if not pregnant or breastfeeding, and at least one of the following conditions applies:

* Is not a woman of childbearing potential (WOCBP)
* Is a WOCBP and using a contraceptive method that is highly effective (with a failure rate of \<1% per year), or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis)

Exclusion Criteria

* Has HIV-2 infection
* Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator
* Has active hepatitis C virus (HCV) coinfection (defined as detectable HCV RNA) or hepatitis B virus (HBV) coinfection (defined as hepatitis B surface antigen \[HBsAg\]-positive or HBV deoxyribonucleic acid \[DNA\] positive)
* Has a current (active) diagnosis of acute hepatitis due to any cause
* Has a history of malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or cutaneous Kaposi's sarcoma
* 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
* Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapies
* Is currently participating in or has participated in a clinical study with an investigational compound or device from 45 days prior to Day 1 through the study treatment period
* Has a documented or known virological resistance to ulonivirine or nucleoside/nucleotide reverse transcriptase inhibitors (NNRTI)
* Is female and expecting to conceive or donate eggs at any time during the study
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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Pueblo Family Physicians ( Site 2702)

Phoenix, Arizona, United States

Site Status

Men's Health Foundation ( Site 2710)

Los Angeles, California, United States

Site Status

Midway Immunology and Research ( Site 2713)

Ft. Pierce, Florida, United States

Site Status

Triple O Research Institute, P.A. ( Site 2712)

West Palm Beach, Florida, United States

Site Status

Infectious Disease Specialists Of Atlanta PC ( Site 2704)

Decatur, Georgia, United States

Site Status

Chatham County Health Department ( Site 2707)

Savannah, Georgia, United States

Site Status

Kansas City CARE Clinic ( Site 2703)

Kansas City, Missouri, United States

Site Status

Saint Hope Foundation, Inc. ( Site 2716)

Bellaire, Texas, United States

Site Status

Texas Centers for Infectious Disease Associates P.A. ( Site 2709)

Fort Worth, Texas, United States

Site Status

DCOL Center for Clinical Research ( Site 2715)

Longview, Texas, United States

Site Status

CHU de Toulouse - Hopital Purpan ( Site 2302)

Toulouse, Haute-Garonne, France

Site Status

Hopital Gui de Chauliac. ( Site 2303)

Montpellier, Herault, France

Site Status

CHU Hotel Dieu Nantes ( Site 2310)

Nantes, Loire-Atlantique, France

Site Status

Centre Hospitalier Regional du Orleans ( Site 2304)

Orléans, Loiret, France

Site Status

Hopital Avicenne ( Site 2305)

Bobigny, Seine-Saint-Denis, France

Site Status

Hopital Saint Louis ( Site 2308)

Paris, , France

Site Status

Hopital Saint-Antoine ( Site 2307)

Paris, , France

Site Status

Pitie Salpetriere University Hospital-Infectious Disease - Tropical Diseases ( Site 2306)

Paris, Île-de-France Region, France

Site Status

Universitaetsspital Zuerich ( Site 2601)

Zuerich, Canton of Aargau, Switzerland

Site Status

Universitaetsspital Basel ( Site 2602)

Basel, Canton of Basel-City, Switzerland

Site Status

Inselspital Universitaetsspital Bern ( Site 2603)

Bern, Canton of Bern, Switzerland

Site Status

Hopitaux Universitaires de Geneve HUG ( Site 2604)

Geneva, Canton of Geneva, Switzerland

Site Status

CHUV (centre hospitalier universitaire vaudois) ( Site 2605)

Lausanne, Canton of Vaud, Switzerland

Site Status

Countries

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United States France Switzerland

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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MK-8591-013

Identifier Type: OTHER

Identifier Source: secondary_id

2024-511041-19-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1302-9886

Identifier Type: REGISTRY

Identifier Source: secondary_id

2020-003071-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

8591-013

Identifier Type: -

Identifier Source: org_study_id

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