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]

NCT04564547 | Completed Phase 2 Results DMC FDA Drug

• 5 other identifiers: 8591-013MK-8591-0132024-511041-19-00U1111-1302-98862020-003071-18
• Study Type: interventional
• Target: 161
• Locations: 3 countries
• Sites: 23

Brief Summary

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.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (3)

• 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

Study Arms (4)

Group 1: ISL 20 mg + Ulonivirine 100 mg

EXPERIMENTAL

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: Islatravir; Drug: Ulonivirine; Drug: Placebo to Ulonivirine; Drug: Placebo to BIC/FTC/TAF

Group 2: ISL 20 mg + Ulonivirine 200 mg

EXPERIMENTAL

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: Islatravir; Drug: Ulonivirine; Drug: Placebo to Ulonivirine; Drug: Placebo to BIC/FTC/TAF

Group 3: ISL 20 mg + Ulonivirine 400 mg

EXPERIMENTAL

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: Islatravir; Drug: Ulonivirine; Drug: Placebo to BIC/FTC/TAF

Group 4: BIC/FTC/TAF

ACTIVE COMPARATOR

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

Drug: BIC/FTC/TAF; Drug: Placebo to ISL; Drug: Placebo to Ulonivirine

Interventions

Islatravir DRUG

ISL capsule taken by mouth.

Also known as: MK-8591

Group 1: ISL 20 mg + Ulonivirine 100 mg; Group 2: ISL 20 mg + Ulonivirine 200 mg; Group 3: ISL 20 mg + Ulonivirine 400 mg

Ulonivirine DRUG

Ulonivirine tablet taken by mouth.

Also known as: MK-8507

Group 1: ISL 20 mg + Ulonivirine 100 mg; Group 2: ISL 20 mg + Ulonivirine 200 mg; Group 3: ISL 20 mg + Ulonivirine 400 mg

BIC/FTC/TAF DRUG

BIC/FTC/TAF tablet taken by mouth.

Also known as: BIKTARVY®

Group 4: BIC/FTC/TAF

Placebo to ISL DRUG

Placebo capsule matched to ISL taken by mouth.

Group 4: BIC/FTC/TAF

Placebo to Ulonivirine DRUG

Placebo tablet matched to ulonivirine taken by mouth.

Group 1: ISL 20 mg + Ulonivirine 100 mg; Group 2: ISL 20 mg + Ulonivirine 200 mg; Group 4: BIC/FTC/TAF

Placebo to BIC/FTC/TAF DRUG

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

Group 1: ISL 20 mg + Ulonivirine 100 mg; Group 2: ISL 20 mg + Ulonivirine 200 mg; Group 3: ISL 20 mg + Ulonivirine 400 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (23)

Pueblo Family Physicians ( Site 2702)

Phoenix, Arizona, 85015, United States

Location

Men's Health Foundation ( Site 2710)

Los Angeles, California, 90069, United States

Location

Midway Immunology and Research ( Site 2713)

Ft. Pierce, Florida, 34982, United States

Location

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

West Palm Beach, Florida, 33407, United States

Location

Infectious Disease Specialists Of Atlanta PC ( Site 2704)

Decatur, Georgia, 30033, United States

Location

Chatham County Health Department ( Site 2707)

Savannah, Georgia, 31410, United States

Location

Kansas City CARE Clinic ( Site 2703)

Kansas City, Missouri, 64111, United States

Location

Saint Hope Foundation, Inc. ( Site 2716)

Bellaire, Texas, 77401, United States

Location

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

Fort Worth, Texas, 76104, United States

Location

DCOL Center for Clinical Research ( Site 2715)

Longview, Texas, 75605, United States

Location

CHU de Toulouse - Hopital Purpan ( Site 2302)

Toulouse, Haute-Garonne, 31059, France

Location

Hopital Gui de Chauliac. ( Site 2303)

Montpellier, Herault, 34295, France

Location

CHU Hotel Dieu Nantes ( Site 2310)

Nantes, Loire-Atlantique, 44093, France

Location

Centre Hospitalier Regional du Orleans ( Site 2304)

Orléans, Loiret, 45100, France

Location

Hopital Avicenne ( Site 2305)

Bobigny, Seine-Saint-Denis, 93000, France

Location

Hopital Saint Louis ( Site 2308)

Paris, 75010, France

Location

Hopital Saint-Antoine ( Site 2307)

Paris, 75012, France

Location

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

Paris, Île-de-France Region, 75013, France

Location

Universitaetsspital Zuerich ( Site 2601)

Zuerich, Canton of Aargau, 8091, Switzerland

Location

Universitaetsspital Basel ( Site 2602)

Basel, Canton of Basel-City, 4031, Switzerland

Location

Inselspital Universitaetsspital Bern ( Site 2603)

Bern, Canton of Bern, 3010, Switzerland

Location

Hopitaux Universitaires de Geneve HUG ( Site 2604)

Geneva, Canton of Geneva, 1211, Switzerland

Location

CHUV (centre hospitalier universitaire vaudois) ( Site 2605)

Lausanne, Canton of Vaud, 1011, Switzerland

Location

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Interventions

islatravir; ulonivirine; bictegravir, emtricitabine, tenofovir alafenamide, drug combination

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2020
• First Posted: September 25, 2020
• Study Start: March 9, 2021
• Primary Completion: January 30, 2025
• Study Completion: January 30, 2025
• Last Updated: January 26, 2026
• Results First Posted: January 26, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share

Locations

CH (5); US (10); FR (8)