A Switch to Doravirine/Islatravir (DOR/ISL) in Participants With Human Immunodeficiency Virus Type 1 (HIV-1) Who Are Virologically Suppressed on Antiretroviral Therapy (ART) (MK-8591A-051)

Merck Sharp & Dohme (MSD)

Status and phase: Active, not recruiting; Phase 3

Conditions: HIV-1 Infection

Treatments: Drug: DOR/ISL; Drug: ART

Study type: Interventional

Funder types: Industry

Identifiers

NCT05631093

8591A-051

2022-502127-22 (EudraCT Number)

MK-8591A-051 (Other Identifier)

jRCT2031220698 (Registry Identifier)

Details and patient eligibility

About

The primary objectives of this study are to evaluate the safety and tolerability of a switch to Doravirine/Islatravir (DOR/ISL) compared with continued baseline antiretroviral therapy (ART), through Week 48; and to evaluate the antiretroviral activity of a switch to DOR/ISL compared with continued baseline ART at Week 48. The primary hypothesis is that DOR/ISL is non-inferior to continued baseline ART, as assessed by the percentage of participants with HIV-1 ribonucleic acid (RNA) ≥50 copies/mL at Week 48, with a margin of 4 percentage points used to define non-inferiority.

Enrollment: 501 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Is HIV-1 positive with plasma HIV-1 RNA <50 copies/mL at screening
• Has been receiving continuous, stable oral 2-drug or 3-drug combination (± PK booster) ART with documented viral suppression (HIV-1 RNA <50 copies/mL) for ≥3 consecutive months prior to providing documented informed consent and has no history of prior virologic treatment failure on any past or current regimen
• Female is not a participant of childbearing potential (POCBP); or if a POCBP uses an acceptable contraceptive method or abstains from penile-vaginal intercourse as their preferred and usual lifestyle; has a negative highly sensitive pregnancy test; and whose medical history, menstrual history, and recent sexual activity has been reviewed by the investigator

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 a diagnosis of an active acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within 30 days prior to screening
• Has active hepatitis B virus (HBV) infection
• Has chronic hepatitis C virus (HCV) infection consistent with cirrhosis
• Has a ≤5 years prior history of malignancy
• Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or strong and moderate cytochrome P450 3A (CYP3A ) inducers
• Has taken long-acting HIV therapy at any time
• Is currently participating in or has participated in a clinical study and received (or is receiving) an investigational compound or device from 45 days prior to Day 1 through the study treatment period
• Has a documented or known virologic resistance to DOR

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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501 participants in 2 patient groups

ART + DOR/ISL

Active Comparator group

Description:

Participants with HIV-1 that has been virologically suppressed for ≥3 consecutive months on a stable oral ART are first treated with standard of care (SOC) ART for 48 weeks, followed by 96 weeks of treatment with DOR/ISL Participants will have the option to continue in an optional study extension and receive DOR/ISL for up to an additional 96 weeks or until DOR/ISL is commercially accessible (whichever comes first).

Treatment:

Drug: ART

Drug: DOR/ISL

DOR/ISL

Experimental group

Description:

Participants with HIV-1 that has been virologically suppressed for ≥3 consecutive months on a stable oral ART are treated with DOR/ISL for 144 weeks. Participants will have the option to continue in an optional study extension and receive DOR/ISL for up to an additional 96 weeks or until DOR/ISL is commercially accessible (whichever comes first).

Treatment:

Drug: DOR/ISL