Safety and Efficacy of a Switch to Doravirine, Tenofovir, Lamivudine (MK-1439A) in Human Immunodeficiency Virus (HIV-1)-Infected Participants Virologically Suppressed on an Anti-retroviral Regimen in Combination With Two Nucleoside Reverse Transcrip

• Status: Active, not recruiting
• Trial end date: 2023-08-26
• Target enrollment: 0
• Participant gender: All

Summary

The multicenter, open label, randomized study will evaluate the safety and efficacy of a switch to MK-1439A (MK-1439 [doravirine] plus lamivudine and tenofovir disoproxil fumarate) in HIV-1-infected participants virologically suppressed on a protocol-specified antiretroviral regimen. The primary hypothesis is that a switch to doravirine, tenofovir, lamivudine will be non-inferior to continuation of the regimen at Screening for 24 weeks, as assessed by the proportion of participants maintaining HIV-1 ribonucleic acid (RNA) <50 copies/mL. The Base Study results will be based on the first 48 weeks of this ongoing study.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Merck Sharp & Dohme Corp.
• Treatments: Atazanavir Sulfate; Cobicistat; Darunavir; Efavirenz; Elvitegravir; HIV Protease Inhibitors; Lamivudine; Lopinavir; Nevirapine; Protease Inhibitors; Reverse Transcriptase Inhibitors; Rilpivirine; Ritonavir; Tenofovir

Criteria

Inclusion Criteria:

• At least 18 years of age on the day of signing the informed consent.

• Understand the study procedures and voluntarily agree to participate by giving written informed consent for the trial.

• Have plasma HIV-1 RNA levels below the limit of quantification (BLoQ) (<40 copies/mL by the Abbott RealTime HIV-1 Assay as determined by the central laboratory) at the screening visit.

• Receiving antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs (and no other antiretroviral therapy) continuously for >= 6 months.

• Receiving first or second retroviral regimen (participants receiving a NNRTI at Screening must be on their first retroviral regimen)

• No history of using an experimental NNRTI

• Has a genotype prior to starting his/her initial antiretroviral regimen and no known resistance to any of the study agents

• Not receiving lipid lowering therapy or on a stable dose of lipid lowering therapy at the time of enrollment

• Has the following laboratory values at screening within 30 days prior to the treatment phase of this study: Alkaline phosphatase ≤ 3.0 x upper limit of normal (ULN), Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) ≤ 5.0 x ULN, and Hemoglobin ≥9.0 g/dL (if female) or ≥10.0 g/dL (if male)

• Has a calculated creatinine clearance at the time of screening ≥ 50 mL/min, based on the Cockcroft-Gault equation

• Male or female participant not of reproductive potential or, if of reproductive potential, agrees to avoid becoming pregnant or impregnating a partner while receiving study drug and for 14 days after the last dose of study drug by complying with one of the following: 1) practice abstinence from heterosexual activity, or 2) use acceptable contraception during heterosexual activity

• For inclusion in Study Extension 1 (optional): completed the Week 48 visit; considered to have derived benefit from study participation up to Week 48; considered to be a clinically appropriate candidate for an additional 2 years treatment with study drug

• For inclusion in Study Extension 2 (optional): completed the Week 144 visit; considered to have derived benefit from study participation up to Week 144; considered to be a clinically appropriate candidate for an additional 2 years treatment with study drug

Exclusion Criteria:

• Uses recreational or illicit drugs or has a recent history of drug or alcohol abuse or dependence

• Received treatment for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1 such as adefovir, emtricitabine, lamivudine, or tenofovir

• Has documented or known resistance to study drugs including doravirine, lamivudine, and/or tenofovir

• Participated in a study with an investigational compound or device within 30 days or anticipates doing so during the course of this study

• Used systemic immunosuppressive therapy or immune modulators within 30 days or anticipates needing them during the course of this study (short courses of corticosteroids will be allowed)

• Current, active diagnosis of acute hepatitis due to any cause (participants with chronic hepatitis B and C may enter the study as long as they fulfill all entry criteria, have stable liver function tests, and have no significant impairment of hepatic function)

• Has evidence of decompensated liver disease or has liver cirrhosis and a Child-Pugh Class C score or Pugh-Turcotte score >9

• Pregnant, breastfeeding, or expecting to conceive at any time during the study

• Female and is expecting to donate eggs or male and is expecting to donate sperm during the study