Doravirine/Islatravir (DOR/ISL) in Heavily Treatment-Experienced (HTE) Participants for Human Immunodeficiency Virus Type 1 (HIV-1) Infection (MK-8591A-019)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 3

Conditions: HIV-1 Infection

Treatments: Drug: DOR/ISL; Drug: Placebo to ISL; Drug: Placebo to DOR; Drug: DOR; Drug: ISL

Study type: Interventional

Funder types: Industry

Identifiers

NCT04233216

MK-8591A-019 (Other Identifier)

8591A-019

205243

2019-000588-26 (EudraCT Number)

Details and patient eligibility

About

This is a 2-part, phase 3 clinical study evaluating the antiretroviral activity and safety/tolerability of islatravir (ISL), doravirine (DOR), and a fixed dose combination (FDC) of DOR/ISL (also known as MK-8591A) in heavily treatment-experienced (HTE) participants with human immunodeficiency virus type 1 (HIV-1) infection. It is hypothesized that the percentage of participants receiving DOR/ISL to achieve ≥0.5 log10 decrease in HIV-1 ribonucleic acid (RNA) from study baseline (Day 1) to Day 8 is superior to placebo, each given in combination with failing antiretroviral therapy (ART).

Full description

Part 1 of this study (Day 1 to Day 7) is the double-blind period in which participants receive either ISL, DOR, DOR/ISL, or placebo. Part 2 of this study (Day 8 to Week 97) is the open-label period in which all participants receive DOR/ISL + optimized background therapy (OBT).

Enrollment: 35 patients

Sex: All

Volunteers: No Healthy Volunteers

Inclusion criteria

• Is HIV-1 positive.
• Has been receiving the same baseline ART for ≥3 months prior to signing the Informed Consent Form/Assent Form.
• Weighs ≥35 kg.
• Has at least triple-class resistance (must include nucleoside reverse transcriptase inhibitor [NRTI], non-nucleoside reverse transcriptase inhibitor [NNRTI], and resistance to either protease inhibitor (PI) or integrase strand transfer inhibitor (InSTI), based on central laboratory-based resistance or proviral DNA resistance testing at the Screening Visit, or historical resistance testing within 12 months of screening.
• Has ≤2 fully active antiretroviral drugs remaining among all antiretroviral classes that can be effectively combined to form a viable regimen based on resistance, tolerability, safety, drug access, or acceptability to participant.
• If female, is not pregnant or breastfeeding, and is: 1) not a woman of childbearing potential (WOCBP); 2) a WOCBP and uses an acceptable method of contraception/is abstinent; or 3) a WOCBP and has a negative pregnancy test within 24 hours of the first dose of study medication.

Exclusion criteria

• Has HIV type 2 (HIV-2) infection.
• Has hypersensitivity or other contraindication to any of the components of the study interventions as determined by the investigator.
• Has hepatitis B virus (HBV) co-infection (defined as hepatitis B surface antigen [HBsAg]-positive or HBV deoxyribonucleic acid [DNA] positive) and is not currently being treated for HBV.
• Has a history or current evidence of any condition, therapy (including active TB co-infection), laboratory abnormality or other circumstance (including drug or alcohol abuse or dependence) that might, in the opinion of the investigator, confound the results of the study or interfere with study participation for the full study duration.
• Is taking or is anticipated to require any of the prohibited therapies from the Screening Visit and throughout the study treatment period.
• Is taking DOR as part of his/her current failing antiretroviral regimen.
• Is taking efavirenz (EFV), etravirine, or nevirapine.
• Is currently participating in or has participated in an interventional clinical study with an investigational compound or device from the Screening Visit through the study treatment period.
• Is female and is expecting to conceive or donate eggs at any time during the study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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35 participants in 4 patient groups, including a placebo group

ISL + ART

Experimental group

Description:

HTE participants with HIV-1 infection take ISL 0.75 mg once daily (QD) in combination with failing ART from Day 1 to Day 7; followed by open-label 100 mg DOR/0.75 mg ISL fixed dose combination (FDC) QD + OBT from Day 8 to Week 97.

Treatment:

Drug: ISL

Drug: DOR/ISL

DOR + ART

Experimental group

Description:

HTE participants with HIV-1 infection take DOR 100 mg QD in combination with failing ART from Day 1 to Day 7; followed by open-label 100 mg DOR/0.75 mg ISL FDC QD + OBT from Day 8 to Week 97.

Treatment:

Drug: DOR

Drug: DOR/ISL

DOR/ISL + ART

Experimental group

Description:

HTE participants with HIV-1 infection take 100 mg DOR/0.75 mg ISL FDC QD in combination with failing ART from Day 1 to Day 7; followed by open-label 100 mg DOR/0.75 mg ISL FDC QD + OBT from Day 8 to Week 97.

Treatment:

Drug: DOR/ISL

Placebo + ART

Placebo Comparator group

Description:

HTE participants with HIV-1 infection take placebo QD in combination with failing ART from Day 1 to Day 7; followed by open-label 100 mg DOR/0.75 mg ISL FDC QD + OBT from Day 8 to Week 97.

Treatment:

Drug: Placebo to DOR

Drug: Placebo to ISL

Drug: DOR/ISL