Dose Ranging, Switch Study of Islatravir (ISL) and Ulonivirine (MK-8507) Once-Weekly in Virologically-Suppressed Adults With Human Immunodeficiency Virus Type 1 (HIV-1) [MK-8591-013]
- Conditions
- HIV-1 Infection
- Interventions
- Drug: Placebo to ISLDrug: Placebo to UlonivirineDrug: Placebo to BIC/FTC/TAF
- Registration Number
- NCT04564547
- Lead Sponsor
- Merck Sharp & Dohme LLC
- 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.
- Detailed Description
As of protocol amendment 2 (approved 01-Dec-2021), all participants are unblinded and discontinued from study therapy, and will be switched to non-study antiretroviral therapy. Participants who received ISL + ulonivirine will be followed for ≥6 months.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 161
- Is HIV-1 positive with plasma HIV-1 RNA <50 copies/mL at screening
- Has been virologically suppressed on 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 participant is eligible to participate if she is 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)
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group 1: ISL 20 mg + Ulonivirine 100 mg Placebo to Ulonivirine Participants receive ISL 20 mg (Parts 1-3) + ulonivirine 100 mg once weekly (QW) and placebo to BIC/FTC/TAF once daily (QD) \[Part 1\]. Group 1: ISL 20 mg + Ulonivirine 100 mg Placebo to BIC/FTC/TAF Participants receive ISL 20 mg (Parts 1-3) + ulonivirine 100 mg once weekly (QW) and placebo to BIC/FTC/TAF once daily (QD) \[Part 1\]. Group 2: ISL 20 mg + Ulonivirine 200 mg Islatravir Participants receive ISL 20 mg (Parts 1-3) + ulonivirine 200 mg QW and placebo to BIC/FTC/TAF QD (Part 1). Group 2: ISL 20 mg + Ulonivirine 200 mg Ulonivirine Participants receive ISL 20 mg (Parts 1-3) + ulonivirine 200 mg QW and placebo to BIC/FTC/TAF QD (Part 1). Group 1: ISL 20 mg + Ulonivirine 100 mg Islatravir Participants receive ISL 20 mg (Parts 1-3) + ulonivirine 100 mg once weekly (QW) and placebo to BIC/FTC/TAF once daily (QD) \[Part 1\]. Group 1: ISL 20 mg + Ulonivirine 100 mg Ulonivirine Participants receive ISL 20 mg (Parts 1-3) + ulonivirine 100 mg once weekly (QW) and placebo to BIC/FTC/TAF once daily (QD) \[Part 1\]. Group 3: ISL 20 mg + Ulonivirine 400 mg Islatravir Participants receive ISL 20 mg (Parts 1-3) + ulonivirine 400 mg QW and placebo to BIC/FTC/TAF QD (Part 1). Group 2: ISL 20 mg + Ulonivirine 200 mg Placebo to Ulonivirine Participants receive ISL 20 mg (Parts 1-3) + ulonivirine 200 mg QW and placebo to BIC/FTC/TAF QD (Part 1). Group 2: ISL 20 mg + Ulonivirine 200 mg Placebo to BIC/FTC/TAF Participants receive ISL 20 mg (Parts 1-3) + ulonivirine 200 mg QW and placebo to BIC/FTC/TAF QD (Part 1). Group 3: ISL 20 mg + Ulonivirine 400 mg Ulonivirine Participants receive ISL 20 mg (Parts 1-3) + ulonivirine 400 mg QW and placebo to BIC/FTC/TAF QD (Part 1). Group 3: ISL 20 mg + Ulonivirine 400 mg Placebo to BIC/FTC/TAF Participants receive ISL 20 mg (Parts 1-3) + ulonivirine 400 mg QW and placebo to BIC/FTC/TAF QD (Part 1). Group 4: BIC/FTC/TAF BIC/FTC/TAF Participants receive placebo to ISL + placebo to ulonivirine QW (Part 1) and BIC/FTC/TAF 50 mg/200 mg/25 mg QD (Parts 1 and 2). Group 4: BIC/FTC/TAF Placebo to ISL Participants receive placebo to ISL + placebo to ulonivirine QW (Part 1) and BIC/FTC/TAF 50 mg/200 mg/25 mg QD (Parts 1 and 2). Group 4: BIC/FTC/TAF Placebo to Ulonivirine Participants receive placebo to ISL + placebo to ulonivirine QW (Part 1) and BIC/FTC/TAF 50 mg/200 mg/25 mg QD (Parts 1 and 2).
- Primary Outcome Measures
Name Time Method Percentage of participants with ≥1 adverse event (AE) Up to ≥96 weeks The percentage of participants with AEs will be determined.
Percentage of participants discontinuing study intervention due to AE Up to ≥96 weeks The percentage of participants discontinuing due to AEs will be determined.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (23)
Pueblo Family Physicians ( Site 2702)
🇺🇸Phoenix, Arizona, United States
Men's Health Foundation ( Site 2710)
🇺🇸Los Angeles, California, United States
Midway Immunology and Research ( Site 2713)
🇺🇸Fort Pierce, Florida, United States
Triple O Research Institute, P.A. ( Site 2712)
🇺🇸West Palm Beach, Florida, United States
Infectious Disease Specialists Of Atlanta PC ( Site 2704)
🇺🇸Decatur, Georgia, United States
Chatham County Health Department ( Site 2707)
🇺🇸Savannah, Georgia, United States
Kansas City CARE Clinic ( Site 2703)
🇺🇸Kansas City, Missouri, United States
Saint Hope Foundation, Inc. ( Site 2716)
🇺🇸Bellaire, Texas, United States
Texas Centers for Infectious Disease Associates P.A. ( Site 2709)
🇺🇸Fort Worth, Texas, United States
DCOL Center for Clinical Research ( Site 2715)
🇺🇸Longview, Texas, United States
Scroll for more (13 remaining)Pueblo Family Physicians ( Site 2702)🇺🇸Phoenix, Arizona, United States