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]

A Phase 2b, Randomized, Active-Controlled, Double-Blind, Dose-Ranging Clinical Study to Evaluate a Switch to Islatravir (ISL) and MK-8507 Once-Weekly in Adults With HIV-1 Virologically Suppressed on Bictegravir/Emtricitabine/Tenofovir Alafenamide (BIC/FTC/TAF) Once-Daily

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.

Study Overview

• Status: Completed
• Conditions: HIV-1 Infection
• Intervention / Treatment: Drug: Placebo to BIC/FTC/TAF; Drug: Islatravir; Drug: BIC/FTC/TAF; Drug: Placebo to ISL; Drug: Ulonivirine; Drug: Placebo to Ulonivirine

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 161
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Paris, France, 75010
    • Hopital Saint Louis ( Site 2308)
  • Paris, France, 75012
    • Hopital Saint-Antoine ( Site 2307)
  • Haute-Garonne
    • Toulouse, Haute-Garonne, France, 31059
      • CHU de Toulouse - Hopital Purpan ( Site 2302)
  • Herault
    • Montpellier, Herault, France, 34295
      • Hopital Gui de Chauliac. ( Site 2303)
  • Loire-Atlantique
    • Nantes, Loire-Atlantique, France, 44093
      • CHU Hotel Dieu Nantes ( Site 2310)
  • Loiret
    • Orléans, Loiret, France, 45100
      • Centre Hospitalier Regional du Orleans ( Site 2304)
  • Seine-Saint-Denis
    • Bobigny, Seine-Saint-Denis, France, 93000
      • Hopital Avicenne ( Site 2305)
  • Île-de-France Region
    • Paris, Île-de-France Region, France, 75013
      • Pitie Salpetriere University Hospital-Infectious Disease - Tropical Diseases ( Site 2306)
• Switzerland
  • Canton of Aargau
    • Zuerich, Canton of Aargau, Switzerland, 8091
      • Universitaetsspital Zuerich ( Site 2601)
  • Canton of Basel-City
    • Basel, Canton of Basel-City, Switzerland, 4031
      • Universitaetsspital Basel ( Site 2602)
  • Canton of Bern
    • Bern, Canton of Bern, Switzerland, 3010
      • Inselspital Universitaetsspital Bern ( Site 2603)
  • Canton of Geneva
    • Geneva, Canton of Geneva, Switzerland, 1211
      • Hopitaux Universitaires de Geneve HUG ( Site 2604)
  • Canton of Vaud
    • Lausanne, Canton of Vaud, Switzerland, 1011
      • CHUV (centre hospitalier universitaire vaudois) ( Site 2605)
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85015
      • Pueblo Family Physicians ( Site 2702)
  • California
    • Los Angeles, California, United States, 90069
      • Men's Health Foundation ( Site 2710)
  • Florida
    • Ft. Pierce, Florida, United States, 34982
      • Midway Immunology and Research ( Site 2713)
    • West Palm Beach, Florida, United States, 33407
      • Triple O Research Institute, P.A. ( Site 2712)
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Infectious Disease Specialists Of Atlanta PC ( Site 2704)
    • Savannah, Georgia, United States, 31410
      • Chatham County Health Department ( Site 2707)
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • Kansas City CARE Clinic ( Site 2703)
  • Texas
    • Bellaire, Texas, United States, 77401
      • Saint Hope Foundation, Inc. ( Site 2716)
    • Fort Worth, Texas, United States, 76104
      • Texas Centers for Infectious Disease Associates P.A. ( Site 2709)
    • Longview, Texas, United States, 75605
      • DCOL Center for Clinical Research ( Site 2715)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Placebo to BIC/FTC/TAF; Placebo tablet matched to BIC/FTC/TAF taken by mouth.; Drug: Islatravir; ISL capsule taken by mouth.; Other Names: MK-8591; Drug: Ulonivirine; Ulonivirine tablet taken by mouth.; Other Names: MK-8507; Drug: Placebo to Ulonivirine; Placebo tablet matched to ulonivirine taken by mouth.
Experimental: 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.	Drug: Placebo to BIC/FTC/TAF; Placebo tablet matched to BIC/FTC/TAF taken by mouth.; Drug: Islatravir; ISL capsule taken by mouth.; Other Names: MK-8591; Drug: Ulonivirine; Ulonivirine tablet taken by mouth.; Other Names: MK-8507; Drug: Placebo to Ulonivirine; Placebo tablet matched to ulonivirine taken by mouth.
Experimental: 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.	Drug: Placebo to BIC/FTC/TAF; Placebo tablet matched to BIC/FTC/TAF taken by mouth.; Drug: Islatravir; ISL capsule taken by mouth.; Other Names: MK-8591; Drug: Ulonivirine; Ulonivirine tablet taken by mouth.; Other Names: MK-8507
Active Comparator: 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.	Drug: BIC/FTC/TAF; BIC/FTC/TAF tablet taken by mouth.; Other Names: BIKTARVY®; Drug: Placebo to ISL; Placebo capsule matched to ISL taken by mouth.; Drug: Placebo to Ulonivirine; Placebo tablet matched to ulonivirine taken by mouth.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Experienced One or More Adverse Events (AEs) During the Double-Blind Treatment Period +42 Days Post-Blind	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. As pre-specified in the protocol and supplemental statistical analysis plan (sSAP), presented here is the percentage of participants who experienced one or more AEs during the Double-blind Treatment Period and includes the 42 days following the final dose of double-blind study intervention.	Up to approximately 9 months
Percentage of Participants Who Discontinued Study Intervention Due to an AE During the Double-Blind Treatment Period	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. As pre-specified in the protocol and sSAP, presented here is the percentage of participants who discontinued double-blind study intervention due to an AE during the Double-Blind Treatment Period.	Up to approximately 8 months
Percentage of Participants Who Experienced One or More AEs During the Unblinded Safety Monitoring Period	An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. As pre-specified in the protocol and sSAP, presented here is the percentage of participants who experienced one or more AEs during the Unblinded Safety Monitoring Period, beginning 42 days following the final dose of double-blind study intervention.	Up to approximately 37 months

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

Helpful Links

• Merck Clinical Trials Information
• Plain Language Summary

Study record dates

Study Major Dates

• Study Start (Actual): March 9, 2021
• Primary Completion (Actual): January 30, 2025
• Study Completion (Actual): January 30, 2025

Study Registration Dates

• First Submitted: September 21, 2020
• First Submitted That Met QC Criteria: September 21, 2020
• First Posted (Actual): September 25, 2020

Study Record Updates

• Last Update Posted (Actual): January 26, 2026
• Last Update Submitted That Met QC Criteria: January 8, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Nucleic Acid Synthesis Inhibitors; Antiviral Agents; Reverse Transcriptase Inhibitors; Anti-Retroviral Agents; bictegravir, emtricitabine, tenofovir alafenamide, drug combination; islatravir; ulonivirine
• Other Study ID Numbers: 8591-013; MK-8591-013 (Other Identifier: MSD Protocol Number); 2020-003071-18 (EudraCT Number); 2024-511041-19-00 (Registry Identifier: EU CT); U1111-1302-9886 (Registry Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://trialstransparency.msdclinicaltrials.com/pdf/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No