Safety and Efficacy of a Switch to Doravirine/Islatravir in Participants With HIV-1 (MK-8591A-017)

Merck Sharp & Dohme (MSD)

Status and phase: Active, not recruiting; Phase 3

Conditions: HIV Infection

Treatments: Drug: ART; Drug: DOR/ISL

Study type: Interventional

Funder types: Industry

Identifiers

NCT04223778

205165

MK-8591A-017 (Other Identifier)

2019-000586-20 (EudraCT Number)

8591A-017

Details and patient eligibility

About

This study will evaluate the safety and efficacy of a switch to MK-8591A (a fixed dose combination of doravirine and islatravir) in human immunodeficiency virus -1 (HIV-1)-infected participants virologically suppressed on a protocol-specified background antiretroviral regimen. The primary hypothesis is that a switch to MK-8591A will be non-inferior to continued treatment with baseline antiretroviral therapy (ART) as assessed by the percentage of participants with HIV-1 ribonucleic acid (RNA) ≥50 copies/mL at Week 48.

Enrollment: 672 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Is HIV-1 positive
• Has been receiving continuous, stable oral 2-drug or 3-drug combination (± pharmacokinetic (PK) booster) with documented viral suppression (HIV-1 RNA <50 copies/mL) for ≥3 months prior to signing informed consent and has no history of prior virologic treatment failure on any past or current regimen.
• Female 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 an acceptable contraceptive method, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle; a WOCBP must have a negative highly sensitive pregnancy test ([urine or serum] as required by local regulations) within 24 hours before the first dose of study intervention; if a urine test cannot be confirmed as negative (e.g. an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive

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 an active diagnosis of hepatitis due to any cause, including active Hepatitis B Virus (HBV) co-infection
• 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
• Is taking or is anticipated to require systemic immunosuppressive therapy, immune modulators, or any prohibited therapies
• Is currently taking long-acting cabotegravir-rilpivirine
• 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 virologic resistance to DOR
• Female expects to conceive or donate eggs at any time during the study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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672 participants in 2 patient groups

Doravirine/Islatravir (DOR/ISL)

Experimental group

Description:

Participants who were previously treated with continuous background antiretroviral therapy (ART) will receive DOR/ISL, a fixed dose combination (FDC) of 100 mg doravirine (DOR)/0.75 mg islatravir (ISL) orally once daily for 96 weeks.

Treatment:

Drug: DOR/ISL

Baseline Background Antiretroviral Therapy (ART)

Active Comparator group

Description:

Participants will receive continuous background ART for 48 weeks and DOR/ISL, a FDC of 100 mg DOR/0.75 mg ISL orally once daily for 48 weeks.

Treatment:

Drug: DOR/ISL

Drug: ART