Clinical trial NCT02652260: Effects of Switching From ATRIPLA™ (Efavirenz, Tenofovir, Emtricitabine) to MK-1439A (Doravirine, Tenofovir, Lamivudine) in Virologically-Suppressed Participants (MK-1439A-028)
Official title: Phase IIb, Double-Blinded, Multicenter, Randomized Study to Assess the Effect on Central Nervous System (CNS) Toxicity of Switching From ATRIPLA™ (Efavirenz, Tenofovir, Emtricitabine) to MK-1439A (Doravirine, Tenofovir, Lamivudine) in Virologically-Suppressed Subjects.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV-1
Central Nervous System
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2016-01-11
Enrollment: 86
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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).

Primary outcomes:
measure: Percentage of Participants With at Least One Central Nervous System (CNS) Toxicity of at Least Grade 2 Intensity at Week 12
timeFrame: Week 12
Secondary outcomes:
measure: Percentage of Participants With at Least One CNS Toxicity of at Least Grade 2 Intensity at Week 4
timeFrame: Week 4
measure: Change From Baseline in CNS Toxicity Score at Week 4
timeFrame: Baseline and Week 4
measure: Change From Baseline in CNS Toxicity Score at Week 12
timeFrame: Baseline and Week 12
measure: 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
timeFrame: Baseline (time of switch) and 24 weeks post-switch
measure: CNS Toxicity Scores at Time of Switch, and at 24 Weeks Post-switch for the Combined Treatment Groups
timeFrame: Baseline (time of switch) and 24 weeks post-switch
measure: Change From Baseline in Fasting Lipids at Week 12
timeFrame: Baseline (study Day 1) and study week 12
measure: Change in Fasting Lipids Between Time of Switch and Week 24 Post-switch for the Combined Treatment Groups
timeFrame: Baseline (time of switch) and 24 weeks post-switch
measure: Percentage of Participants With HIV-1 RNA <50 and <40 Copies/ml at Week 24 Post-switch for the Combined Treatment Groups
timeFrame: 24 weeks post-switch
measure: Change From Time of Switch to Week 24 Post Switch in CD4 T-cell Count for the Combined Treatment Groups
timeFrame: Baseline (time of switch) and 24 weeks post-switch
measure: Number of Participants With One or More Adverse Events (AEs) Through Study Week 12
timeFrame: Up to Week 12
measure: Number of Participants With One or More Drug-related AEs Through Study Week 12
timeFrame: Up to Week 12
measure: Number of Participants With One or More Serious Adverse Events (SAEs) Through Study Week 12
timeFrame: Up to Week 12
measure: Number of Participants With One or More Drug-related SAEs Through Study Week 12
timeFrame: Up to Week 12
measure: Number of Participants Who Discontinued Treatment Due to an AE Through Study Week 12
timeFrame: Up to Week 12
measure: Number of Participants With One or More AEs for the Combined Treatment Groups 24 Weeks After the Switch
timeFrame: 24 weeks post-switch
measure: Number of Participants With One or More Drug-related AEs for the Combined Treatment Groups 24 Weeks After the Switch
timeFrame: 24 weeks post-switch
measure: Number of Participants With One or More SAEs for the Combined Treatment Groups 24 Weeks After the Switch
timeFrame: 24 weeks post-switch
measure: Number of Participants With One or More Drug-related SAEs for the Combined Treatment Groups 24 Weeks After the Switch
timeFrame: 24 weeks post-switch
measure: Number of Participants Who Discontinued Treatment Due to an AE for the Combined Treatment Groups 24 Weeks After the Switch
timeFrame: 24 weeks post-switch
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.