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]

January 8, 2026 updated by: Merck Sharp & Dohme LLC

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

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
161

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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
Time Frame: Up to approximately 9 months
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
Time Frame: Up to approximately 8 months
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
Time Frame: Up to approximately 37 months
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

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Merck Sharp & Dohme LLC

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 9, 2021

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 30, 2025

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 30, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 21, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 21, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 25, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
January 26, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 8, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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