Clinical trial NCT04564547: 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]
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV-1 Infection
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2020-09-25
Enrollment: 161
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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)

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

Primary outcomes:
measure: Percentage of participants with ≥1 adverse event (AE)
timeFrame: Up to ≥96 weeks
measure: Percentage of participants discontinuing study intervention due to AE
timeFrame: Up to ≥96 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Pueblo Family Physicians ( Site 2702)
state: Arizona
city: Los Angeles
country: United States
facility: Men's Health Foundation ( Site 2710)
state: California
city: Fort Pierce
country: United States
facility: Midway Immunology and Research ( Site 2713)
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute, P.A. ( Site 2712)
state: Florida
city: Decatur
country: United States
facility: Infectious Disease Specialists Of Atlanta PC ( Site 2704)
state: Georgia
city: Savannah
country: United States
facility: Chatham County Health Department ( Site 2707)
state: Georgia
city: Kansas City
country: United States
facility: Kansas City CARE Clinic ( Site 2703)
state: Missouri
city: Bellaire
country: United States
facility: Saint Hope Foundation, Inc. ( Site 2716)
state: Texas
city: Fort Worth
country: United States
facility: Texas Centers for Infectious Disease Associates P.A. ( Site 2709)
state: Texas
city: Longview
country: United States
facility: DCOL Center for Clinical Research ( Site 2715)
state: Texas
city: Toulouse
country: France
facility: CHU de Toulouse - Hopital Purpan ( Site 2302)
state: Haute-Garonne
city: Montpellier Cedex 5
country: France
facility: Hopital Gui de Chauliac. ( Site 2303)
state: Herault
city: Paris
country: France
facility: Pitie Salpetriere University Hospital-Infectious Disease - Tropical Diseases ( Site 2306)
state: Ile-de-France
city: Nantes
country: France
facility: CHU Hotel Dieu Nantes ( Site 2310)
state: Loire-Atlantique
city: Orleans
country: France
facility: Centre Hospitalier Regional du Orleans ( Site 2304)
state: Loiret
city: Bobigny
country: France
facility: Hopital Avicenne ( Site 2305)
state: Seine-Saint-Denis
city: Paris
country: France
facility: Hopital Saint Louis ( Site 2308)
city: Paris
country: France
facility: Hopital Saint-Antoine ( Site 2307)
city: Zuerich
country: Switzerland
facility: Universitaetsspital Zuerich ( Site 2601)
state: Aargau
city: Basel
country: Switzerland
facility: Universitaetsspital Basel ( Site 2602)
state: Basel-Stadt
city: Bern
country: Switzerland
facility: Inselspital Universitaetsspital Bern ( Site 2603)
state: Berne
city: Geneva
country: Switzerland
facility: Hopitaux Universitaires de Geneve HUG ( Site 2604)
state: Geneve
city: Lausanne
country: Switzerland
facility: CHUV (centre hospitalier universitaire vaudois) ( Site 2605)
state: Vaud
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References: