Clinical trial NCT02403674: Comparison of Doravirine, Tenofovir, Lamivudine (MK-1439A) and ATRIPLA™ in Treatment-Naive Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Participants (MK-1439A-021)
Official title: A Phase III Multicenter, Double-Blind, Randomized, Active Comparator-Controlled Clinical Trial to Evaluate the Safety and Efficacy of MK-1439A Once-Daily Versus ATRIPLA™ Once-Daily in Treatment-Naïve HIV-1 Infected Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Human Immunodeficiency Virus (HIV)
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2015-03-31
Enrollment: 734
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: The purpose of this study is to compare the antiretroviral activity of doravirine, tenofovir, lamivudine (MK-1439A), a single-tablet, once-daily (q.d.) fixed-dose combination (FDC) containing doravirine (MK-1439A) 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg, with ATRIPLA™, a single-tablet FDC containing efavirenz 600 mg + emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg, in treatment-naive participants infected with human immunodeficiency virus (HIV). The primary hypothesis is that doravirine, tenofovir, lamivudine q.d. is non-inferior to ATRIPLA™ q.d. as assessed by the proportion of participants with HIV-1 ribonucleic acid (RNA) \<50 copies/mL (by the Abbott RealTime HIV-1 Assay) at Week 48. This study has a total duration of 384 weeks, including a 96-week double-blind period and an additional 288-week open-label period.

Detailed description: Participants in Australia, Colombia, Guatemala, Honduras, Israel, New Zealand, Peru, Russia, South Africa, and Thailand who are deriving benefit from doravirine, tenofovir, lamivudine are also eligible to continue receiving study drug during additional open-label extensions which will last for 2 years or until drug is available locally, whichever comes first.

Eligibility criteria: Inclusion Criteria:

* Is HIV-1 positive as determined by a positive result on an enzyme-immunoassay, has screening plasma HIV-1 RNA (determined by the central laboratory) ≥1000 copies/mL within 45 days prior to the treatment phase of this study, and has HIV treatment indicated based on physician assessment
* Has never received antiretroviral therapy (ART)
* Is highly unlikely to either become pregnant or impregnate a partner

Exclusion Criteria:

* Has a history or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound results of the study
* Is a user of recreational or illicit drugs or has a recent history of alcohol/drug abuse
* Has been treated for a viral infection other than HIV-1 (e.g., hepatitis B) with an agent that is active against HIV-1
* Has participated in a study with an investigational drug/device within 30 days prior to Screening
* Has used systemic immunosuppressive therapy or immune modulators within 30 days prior to treatment in this study or is anticipated to need them during the course of the study
* Has a current (active) diagnosis of acute hepatitis due to any cause (note: participants with chronic hepatitis B and C may enter the study as long as they fulfill all entry criteria, have stable liver function tests, and have no significant impairment of hepatic synthetic function)
* Is a female who is pregnant, breastfeeding, or expecting to conceive
* Is a female and is expecting to donate eggs or is male and is expecting to donate sperm (investigators will provide appropriate guidance regarding egg and/or sperm donation after completion of the study treatment regimen)
* 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

Primary outcomes:
measure: Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL at Week 48
timeFrame: Week 48
measure: Percentage of Participants With Tier-1 Neuropsychiatric Adverse Events (AEs)
timeFrame: Up to Week 48
Secondary outcomes:
measure: Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96
timeFrame: Week 96
measure: Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48
timeFrame: Week 48
measure: Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 96
timeFrame: Week 96
measure: Change From Baseline in CD4 Cell Counts at Week 48
timeFrame: Baseline (Day 1) and Week 48
measure: Change From Baseline in CD4 Cell Counts at Week 96
timeFrame: Baseline (Day 1) and Week 96
measure: Percentage of Participants Experiencing ≥1 AE
timeFrame: Up to Week 48
measure: Percentage of Participants Discontinuing From Study Medication Due to an AE(s)
timeFrame: Up to Week 48
measure: Percentage of Participants With Tier-2 Neuropsychiatric AEs
timeFrame: Up to Week 48
measure: Change From Baseline in Fasting LDL-C at Week 48
timeFrame: Baseline (Day 1) and Week 48
measure: Change From Baseline in Fasting Non-HDL-C at Week 48
timeFrame: Baseline (Day 1) and Week 48
measure: Change From Baseline in Fasting Cholesterol at Week 48
timeFrame: Baseline (Day 1) and Week 48
measure: Change From Baseline in Fasting Triglycerides at Week 48
timeFrame: Baseline (Day 1) and Week 48
measure: Change From Baseline in Fasting HDL-C at Week 48
timeFrame: Baseline (Day 1) and Week 48
measure: Percentage of Participants With HIV-1 RNA Below the Limit of Quantification (BLoQ) at Week 48
timeFrame: Week 48
measure: Percentage of Participants With HIV-1 RNA BLoQ at Week 96
timeFrame: Week 96
measure: Plasma Concentration of Doravirine at Week 48
timeFrame: 0 hours post-dose and 2 hours post-dose on Week 48
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Orkin C, Squires KE, Molina JM, Sax PE, Sussmann O, Lin G, Kumar S, Hanna GJ, Hwang C, Martin E, Teppler H. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate (TDF) Versus Efavirenz/Emtricitabine/TDF in Treatment-naive Adults With Human Immunodeficiency Virus Type 1 Infection: Week 96 Results of the Randomized, Double-blind, Phase 3 DRIVE-AHEAD Noninferiority Trial. Clin Infect Dis. 2021 Jul 1;73(1):33-42. doi: 10.1093/cid/ciaa822.
citation: Orkin C, Molina JM, Lombaard J, DeJesus E, Rodgers A, Kumar S, Martin E, Hanna G, Hwang C. Once-daily Doravirine in Human Immunodeficiency Virus Type 1-Infected, Antiretroviral-naive Adults: An Integrated Efficacy Analysis. Clin Infect Dis. 2020 Mar 17;70(7):1344-1352. doi: 10.1093/cid/ciz424.
citation: Thompson M, Orkin C, Molina JM, Sax P, Cahn P, Squires K, Xu X, Rodgers A, Kumar S, Teppler H, Martin E, Hanna G, Hwang C. Once-daily Doravirine for Initial Treatment of Adults Living With Human Immunodeficiency Virus-1: An Integrated Safety Analysis. Clin Infect Dis. 2020 Mar 17;70(7):1336-1343. doi: 10.1093/cid/ciz423.
citation: Orkin C, Squires KE, Molina JM, Sax PE, Wong WW, Sussmann O, Kaplan R, Lupinacci L, Rodgers A, Xu X, Lin G, Kumar S, Sklar P, Nguyen BY, Hanna GJ, Hwang C, Martin EA; DRIVE-AHEAD Study Group. Doravirine/Lamivudine/Tenofovir Disoproxil Fumarate is Non-inferior to Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate in Treatment-naive Adults With Human Immunodeficiency Virus-1 Infection: Week 48 Results of the DRIVE-AHEAD Trial. Clin Infect Dis. 2019 Feb 1;68(4):535-544. doi: 10.1093/cid/ciy540.