Effects of Switching From ATRIPLA™ (Efavirenz, Tenofovir, Emtricitabine) to MK-1439A (Doravirine, Tenofovir, Lamivudine) in Virologically-Suppressed Participants (MK-1439A-028)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 2

Conditions: HIV-1; Central Nervous System

Treatments: Drug: Placebo to Doravirine, Tenofovir, Lamivudine; Drug: ATRIPLA^TM; Drug: Doravirine, Tenofovir, Lamivudine - Open-Label; Drug: Placebo to ATRIPLA™; Drug: Doravirine, Tenofovir, Lamivudine - Blinded

Study type: Interventional

Funder types: Industry

Identifiers

NCT02652260

2015-003617-18 (EudraCT Number)

1439A-028

MK-1439A-028 (Other Identifier)

Details and patient eligibility

About

This study aims to evaluate a switch from fixed dose combination (FDC) treatment with ATRIPLA^TM for 12 weeks prior to screening to FDC treatment with Doravirine, Tenofovir, Lamivudine (MK-1439A) in virologically-suppressed, human immunodeficiency virus type 1 (HIV-1)-infected participants. The primary hypothesis is that switching from ATRIPLA^TM to Doravirine, Tenofovir, Lamivudine results in a lower proportion of participants with at least one CNS toxicity of at least Grade 2 intensity at Week 12 than continuation of ATRIPLA^TM treatment.

Enrollment: 86 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• is taking ATRIPLA™, generic versions of ATRIPLA™, or the components of ATRIPLA™ (EFV,TDF plus emtricitabine),
• has documentation of HIV-1 ribonucleic acid (RNA) < 50 copies/mL during the 12 weeks prior to screening while on ATRIPLA™.
• has plasma HIV-1 RNA levels below the limits of quantification (BLoQ) at the screening visit.
• if genotyped prior to starting initial antiretroviral regimen, must have no known resistance to any of the study agents
• has at least one EFV-associated CNS toxicities of Grade 2 or worse intensity both at the time of screening and at Study Day 1
• is highly unlikely to become pregnant or to impregnate a partner
• To be eligible for study extension 1, participants from Immediate Switch Group (ISG) must have completed Study Week 24, and benefited from study participation; participants from Deferred Switch Group (DSG) must have completed Study Week 36, and benefited from study participation as determined by the investigator
• To be eligible for study extension 2, participants from ISG must have completed Study Week 120, and benefited from study participation; participants from DSG must have completed Study Week 132, and benefited from study participation as determined by the investigator

Exclusion criteria

• is a user of recreational or illicit drugs or has had a recent history of drug or alcohol abuse or dependence.
• has ongoing Grade 4 CNS toxicity during screening period that requires a prompt change in ART
• has been treated for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1 including, but not limited to, adefovir, emtricitabine, entecavir, lamivudine or tenofovir.
• has documented or known resistance to study drugs including doravirine, lamivudine, and/or tenofovir
• has participated in, or anticipates participating in a study with an investigational compound/device within 30 days prior to signing informed consent
• has used systemic immunosuppressive therapy or immune modulators or anticipates using them within 30 days prior to this study
• requires or anticipates requiring any of the prohibited medications
• has significant hypersensitivity or other contraindication to any of the components of the study drugs
• has a current (active) diagnosis of acute hepatitis due to any cause.
• has evidence of decompensated liver disease manifested by the presence of or a history of ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy or other signs or symptoms of advanced liver diseases, or has liver cirrhosis and a Child-Pugh Class C score or Pugh-Turcotte (CPT) score > 9.
• is pregnant, breastfeeding, or expecting to conceive.
• female is expecting to donate eggs (at any time during the study) or male is expecting to donate sperm (at any time during the study).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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86 participants in 2 patient groups

Immediate Switch to Doravirine, Tenofovir, Lamivudine

Experimental group

Description:

Participants on a baseline regimen of ATRIPLA™ for at least 12 weeks prior to screening will be switched to blinded doravirine, tenofovir, lamivudine orally, once daily for 12 weeks, followed by open-label doravirine, tenofovir, lamivudine orally, once daily for an additional 12 weeks. Participants who meet eligibility criteria can enter study extension 1 to receive open-label doravirine, tenofovir, lamivudine for an additional 96 weeks. Participants who meet eligibility criteria can enter study extension 2 to receive open-label doravirine, tenofovir, lamivudine, with a maximum total duration of treatment of 216 weeks. Participants who meet eligibility criteria can enter study extension 3 to receive open-label doravirine, tenofovir, lamivudine, with a maximum total duration of treatment of 312 weeks.

Treatment:

Drug: Doravirine, Tenofovir, Lamivudine - Blinded

Drug: Placebo to ATRIPLA™

Drug: Doravirine, Tenofovir, Lamivudine - Open-Label

Deferred Switch to Doravirine, Tenofovir, Lamivudine

Experimental group

Description:

Participants will continue on their ongoing ATRIPLA™ regimen orally, once daily for 12 weeks, followed by open-label doravirine, tenofovir, lamivudine orally, once daily for 24 weeks. Participants who meet eligibility criteria can enter study extension 1 to receive open-label doravirine, tenofovir, lamivudine for an additional 96 weeks. Participants who meet eligibility criteria can enter study extension 2 to receive open-label doravirine, tenofovir, lamivudine, with a maximum total duration of treatment of 228 weeks. Participants who meet eligibility criteria can enter study extension 3 to receive open-label doravirine, tenofovir, lamivudine, with a maximum total duration of treatment of 324 weeks.

Treatment:

Drug: Doravirine, Tenofovir, Lamivudine - Open-Label

Drug: ATRIPLA^TM

Drug: Placebo to Doravirine, Tenofovir, Lamivudine