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Purpose

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).

Condition

Eligibility

Eligible Ages
All ages
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 3
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
Double (Participant, Investigator)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
ISL + ART 		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.
  • Drug: ISL
    ISL 0.75 mg capsule taken by mouth.
    Other names:
    • Islatravir
    • MK-8591
  • Drug: DOR/ISL
    100 mg DOR/0.75 mg ISL FDC taken by mouth.
    Other names:
    • Doravirine/Islatravir
    • MK-8591A
Experimental
DOR + ART 		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.
  • Drug: DOR
    DOR 100 mg tablet taken by mouth.
    Other names:
    • Doravirine
    • MK-1439
  • Drug: DOR/ISL
    100 mg DOR/0.75 mg ISL FDC taken by mouth.
    Other names:
    • Doravirine/Islatravir
    • MK-8591A
Experimental
DOR/ISL + ART 		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.
  • Drug: DOR/ISL
    100 mg DOR/0.75 mg ISL FDC taken by mouth.
    Other names:
    • Doravirine/Islatravir
    • MK-8591A
Placebo Comparator
Placebo + ART 		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.
  • Drug: DOR/ISL
    100 mg DOR/0.75 mg ISL FDC taken by mouth.
    Other names:
    • Doravirine/Islatravir
    • MK-8591A
  • Drug: Placebo to ISL
    Placebo capsule matched to ISL taken by mouth.
  • Drug: Placebo to DOR
    Placebo tablet matched to DOR taken by mouth.

More Details

Status
Completed
Sponsor
Merck Sharp & Dohme LLC

Study Contact

Detailed 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).

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.