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

NCT ID: NCT02652260

Last Updated: 2025-02-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 86 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-04
• Study Completion Date: 2024-02-07

Brief Summary

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.

Conditions

HIV-1; Central Nervous System

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Immediate Switch to Doravirine, Tenofovir, Lamivudine

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.

Group Type: EXPERIMENTAL

Doravirine, Tenofovir, Lamivudine - Blinded

Intervention Type: DRUG

A single tablet FDC containing doravirine 100 mg, lamivudine (3TC) 300 mg and tenofovir disoproxil fumarate (TDF) 300 mg administered orally, once daily for 12 weeks during the Blinded period

Doravirine, Tenofovir, Lamivudine - Open-Label

Intervention Type: DRUG

A single-tablet FDC containing doravirine 100 mg, 3TC 300 mg and TDF 300 mg administered orally, once daily for either 12 or 24 weeks during the Open-Label Period; also an additional 96 weeks during the Open-Label extension period 1; a maximum total duration of treatment of 228 weeks during the Open-Label extension period 2; and a maximum total duration of treatment of 324 weeks during the Open-Label extension period 3.

Placebo to ATRIPLA™

Intervention Type: DRUG

A single placebo to ATRIPLA™ tablet administered orally, once daily for 12 weeks during the Blinded period

Deferred Switch to Doravirine, Tenofovir, Lamivudine

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.

Group Type: EXPERIMENTAL

Doravirine, Tenofovir, Lamivudine - Open-Label

Intervention Type: DRUG

A single-tablet FDC containing doravirine 100 mg, 3TC 300 mg and TDF 300 mg administered orally, once daily for either 12 or 24 weeks during the Open-Label Period; also an additional 96 weeks during the Open-Label extension period 1; a maximum total duration of treatment of 228 weeks during the Open-Label extension period 2; and a maximum total duration of treatment of 324 weeks during the Open-Label extension period 3.

ATRIPLA^TM

Intervention Type: DRUG

A single tablet FDC containing efavirenz (EFV) 600 mg, emtricitabine (FTC) 200 mg, and TDF 300 mg administered orally, once daily for 12 weeks during the Blinded period

Placebo to Doravirine, Tenofovir, Lamivudine

Intervention Type: DRUG

A single placebo to doravirine, tenofovir, lamivudine tablet administered orally, once daily for 12 weeks during the Blinded period

Interventions

Doravirine, Tenofovir, Lamivudine - Blinded

A single tablet FDC containing doravirine 100 mg, lamivudine (3TC) 300 mg and tenofovir disoproxil fumarate (TDF) 300 mg administered orally, once daily for 12 weeks during the Blinded period

Intervention Type: DRUG

Doravirine, Tenofovir, Lamivudine - Open-Label

A single-tablet FDC containing doravirine 100 mg, 3TC 300 mg and TDF 300 mg administered orally, once daily for either 12 or 24 weeks during the Open-Label Period; also an additional 96 weeks during the Open-Label extension period 1; a maximum total duration of treatment of 228 weeks during the Open-Label extension period 2; and a maximum total duration of treatment of 324 weeks during the Open-Label extension period 3.

Intervention Type: DRUG

ATRIPLA^TM

A single tablet FDC containing efavirenz (EFV) 600 mg, emtricitabine (FTC) 200 mg, and TDF 300 mg administered orally, once daily for 12 weeks during the Blinded period

Intervention Type: DRUG

Placebo to ATRIPLA™

A single placebo to ATRIPLA™ tablet administered orally, once daily for 12 weeks during the Blinded period

Intervention Type: DRUG

Placebo to Doravirine, Tenofovir, Lamivudine

A single placebo to doravirine, tenofovir, lamivudine tablet administered orally, once daily for 12 weeks during the Blinded period

Intervention Type: DRUG

Other Intervention Names

MK-1439A; MK-1439A

Eligibility Criteria

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

References

Nelson M, Winston A, Hill A, Mngqibisa R, Bassa A, Orkin C, Rassool M, Rodgers A, Teal V, Kumar S, Teppler H. Efficacy, safety and central nervous system effects after switch from efavirenz/tenofovir/emtricitabine to doravirine/tenofovir/lamivudine. AIDS. 2021 Apr 1;35(5):759-767. doi: 10.1097/QAD.0000000000002804.

Reference Type: DERIVED

PMID: 33587439 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.merckclinicaltrials.com

Merck Clinical Trials Information

Other Identifiers

MK-1439A-028

Identifier Type: OTHER

Identifier Source: secondary_id

2015-003617-18

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1439A-028

Identifier Type: -

Identifier Source: org_study_id