Doravirine/Islatravir (DOR/ISL) in Heavily Treatment-Experienced (HTE) Participants for Human Immunodeficiency Virus Type 1 (HIV-1) Infection (MK-8591A-019)
Condition: HIV-1 Infection
MeSH terms: Infections
Intervention: ISL; DOR; DOR/ISL; Placebo to ISL; Placebo to DOR
Intervention description: ISL 0.75 mg capsule taken by mouth.; DOR 100 mg tablet taken by mouth.; 100 mg DOR/0.75 mg ISL FDC taken by mouth.; Placebo capsule matched to ISL taken by mouth.; Placebo tablet matched to DOR taken by mouth.
Intervention MeSH terms: Islatravir
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 35.0
Sex: All
Healthy volunteers: No

Summary:

      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).
    

Eligibility criteria:

        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.