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

NCT02652260 | Completed Phase 2 Results

• 3 other identifiers: 1439A-028MK-1439A-0282015-003617-18
• Study Type: interventional
• Target: 86
• Locations: 0 countries
• Sites: N/A

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With at Least One Central Nervous System (CNS) Toxicity of at Least Grade 2 Intensity at Week 12

  A questionnaire was used to solicit for CNS toxicity based on the following 10 events: dizziness; depression/low mood; insomnia/sleeplessness; anxiety/nervousness; confusion; impaired concentration/attention; headache; somnolence/daytime sleepiness; aggressive mood/behavior; and abnormal dreams. Participants were asked to rate the intensity for each of the 10 events as none (Grade 0), mild (Grade 1), moderate (Grade 2), or severe (Grade 3). Mild = symptom is noticeable but does not interfere with normal activities; moderate = symptom has some impact on normal activities; severe = symptom prevents conduct of normal activities. Percentage of participants with at least one CNS toxicity of Grade 2 or higher were recorded, based on the last observation carried forward (LOCF) approach.

  Week 12

Secondary Outcomes (19)

• Percentage of Participants With at Least One CNS Toxicity of at Least Grade 2 Intensity at Week 4

  Week 4

• Change From Baseline in CNS Toxicity Score at Week 4

  Baseline and Week 4

• Change From Baseline in CNS Toxicity Score at Week 12

  Baseline and Week 12

• Percentage of Participants With at Least One CNS Toxicity of at Least Grade 2 Intensity at Time of Switch, and at 24 Weeks Post-switch for the Combined Treatment Groups

  Baseline (time of switch) and 24 weeks post-switch

• CNS Toxicity Scores at Time of Switch, and at 24 Weeks Post-switch for the Combined Treatment Groups

  Baseline (time of switch) and 24 weeks post-switch

Study Arms (2)

Immediate Switch to Doravirine, Tenofovir, Lamivudine

EXPERIMENTAL

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.

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

Deferred Switch to Doravirine, Tenofovir, Lamivudine

EXPERIMENTAL

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.

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

Interventions

Doravirine, Tenofovir, Lamivudine - Blinded 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

Also known as: MK-1439A

Immediate Switch to Doravirine, Tenofovir, Lamivudine

Doravirine, Tenofovir, Lamivudine - Open-Label 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.

Also known as: MK-1439A

Deferred Switch to Doravirine, Tenofovir, Lamivudine; Immediate Switch to Doravirine, Tenofovir, Lamivudine

ATRIPLA^TM 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

Deferred Switch to Doravirine, Tenofovir, Lamivudine

Placebo to ATRIPLA™ DRUG

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

Immediate Switch to Doravirine, Tenofovir, Lamivudine

Placebo to Doravirine, Tenofovir, Lamivudine DRUG

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

Deferred Switch to Doravirine, Tenofovir, Lamivudine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• 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.

  PMID: 33587439 DERIVED

Related Links

• Merck Clinical Trials Information

MeSH Terms

Interventions

doravirine; Tenofovir; Lamivudine

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Zalcitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Dideoxynucleosides

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 8, 2016
• First Posted: January 11, 2016
• Study Start: March 4, 2016
• Primary Completion: August 14, 2018
• Study Completion: February 7, 2024
• Last Updated: February 7, 2025
• Results First Posted: August 29, 2019

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will share