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) logo

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

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

Trial documents
1

Trial contacts and locations

0

Loading...

Data sourced from clinicaltrials.gov

Clinical trials

Find clinical trialsTrials by location
© Copyright 2024 Veeva Systems