Clinical trial NCT02275780: Safety and Efficacy of Doravirine (MK-1439) in Participants With Human Immunodeficiency Virus 1 (HIV-1) (MK-1439-018)
Official title: A Phase 3 Multicenter, Double-Blind, Randomized, Active Comparator-Controlled Clinical Trial to Evaluate the Safety and Efficacy of Doravirine (MK-1439) 100 mg Once Daily Versus Darunavir 800 mg Once Daily Plus Ritonavir 100 mg Once Daily, Each in Combination With TRUVADA™ or EPZICOM™/KIVEXA™, in Treatment-Naïve HIV-1 Infected Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV-1
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2014-10-27
Enrollment: 769
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: To establish a new treatment option for treatment-naïve participants with HIV-1, the efficacy and safety of doravirine will be determined relative to a protease inhibitor (PI). Participants will receive double-blind treatment during the 96-week Base Study. Eligible participants in either of the Base Study groups will continue to receive the doravirine-containing regimen open label for an additional 96 weeks in the Study Extension 1. Eligible participants who are deriving benefit will continue in Study Extension 2 to receive the doravirine-containing regimen open label until doravirine becomes locally available or for an additional 96 weeks, whichever comes first. The primary hypothesis is that doravirine 100 mg once a day (q.d.) is non-inferior to darunavir/ritonavir (800 mg/100 mg) q.d., each in combination with TRUVADA™ or EPZICOM™/KIVEXA™, as assessed by the proportion of participants with HIV-1 ribonucleic acid (RNA) \<50 copies/mL at Week 48. If non-inferiority is established, then the superiority of doravirine 100 mg q.d. compared to darunavir/ ritonavir (800 mg/100 mg) q.d. will be assessed.

Detailed description: Participants in Australia, Russia, and South Africa who are deriving benefit from MK-1439A are also eligible to continue receiving study drug during Study Extension 3, which will last for 2 years or until drug is available locally, whichever comes first.

Eligibility criteria: Inclusion Criteria:

* Is HIV-1 positive and has HIV treatment indicated based on physician assessment.
* Has received no (0 days of) antiretroviral therapy (ART), including investigational antiretroviral agents.
* Is considered clinically stable with no signs or symptoms of active infection for at least 2 weeks prior to the start of treatment.
* Female is highly unlikely to become pregnant, or male is highly unlikely to impregnate a partner because they are not of reproductive potential, or agree to practice abstinence or use acceptable contraception for up to 14 days after the last dose of study drug.
* Eligibility for the Study Extension 1 at the Week 96 visit: 1) completed the Week 96 visit, 2) derived benefit from participation through Week 96 in the opinion of the investigator, 3) is a clinically-appropriate candidate for an additional 96 weeks of treatment with the Study Extension regimen.
* Eligibility for the Study Extension 2 at the Week 192 visit: 1) completed the Week 192 visit, 2) derived benefit from participation through Week 192 in the opinion of the investigator, 3) is a clinically-appropriate candidate for 96 weeks of treatment with the Study Extension regimen.

Exclusion Criteria:

* Uses or has had a recent history of using recreational or illicit drugs.
* Has been treated for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1.
* Has documented or known resistance to study drugs including doravirine, darunavir, ritonavir, emtricitabine, tenofovir, abacavir and/or lamivudine.
* Has participated in a study with an investigational compound/device within the prior month, or anticipates doing so during this study.
* Has used systemic immunosuppressive therapy or immune modulators within the prior 30 days, or anticipates doing so during this study.
* 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.
* Is pregnant, breastfeeding or expecting to conceive at any time during the study.
* Female who expects to donate eggs, or male who expects to donate sperm at any time during the study.

Primary outcomes:
measure: Percentage of Participants Achieving Plasma HIV-1 RNA <50 Copies/mL at Week 48
timeFrame: Week 48
Secondary outcomes:
measure: Percentage of Participants Achieving Plasma HIV-1 RNA <50 Copies/mL at Week 96
timeFrame: Week 96
measure: Change From Baseline in Mean CD4+ T-cell Count at Week 48
timeFrame: Baseline and Week 48
measure: Change From Baseline in Mean CD4+ T-cell Count at Week 96
timeFrame: Baseline and Week 96
measure: Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48
timeFrame: Baseline and Week 48
measure: Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48
timeFrame: Baseline and Week 48
measure: Mean Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 48
timeFrame: Baseline and Week 48
measure: Mean Change From Baseline in Fasting Total Cholesterol at Week 48
timeFrame: Baseline and Week 48
measure: Mean Change From Baseline in Fasting Triglyceride at Week 48
timeFrame: Baseline and Week 48
measure: Percentage of Participants With Any Adverse Event
timeFrame: Up to 98 weeks
measure: Percentage of Participants With Any Serious Adverse Event
timeFrame: Up to 98 weeks
measure: Percentage of Participants With Any Drug-related Adverse Event
timeFrame: Up to 98 weeks
measure: Percentage of Participants With Any Drug-related Serious Adverse Event
timeFrame: Up to 98 weeks
measure: Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event
timeFrame: Up to 96 weeks
measure: Percentage of Participants Achieving Plasma HIV-1 RNA <40 Copies/mL at Week 48
timeFrame: Week 48
measure: Percentage of Participants Achieving Plasma HIV-1 RNA <40 Copies/mL at Week 96
timeFrame: Week 96
Other outcomes:
Locations:
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Molina JM, Squires K, Sax PE, Cahn P, Lombaard J, DeJesus E, Lai MT, Rodgers A, Lupinacci L, Kumar S, Sklar P, Hanna GJ, Hwang C, Martin EA; DRIVE-FORWARD trial group. Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1 (DRIVE-FORWARD): 96-week results of a randomised, double-blind, non-inferiority, phase 3 trial. Lancet HIV. 2020 Jan;7(1):e16-e26. doi: 10.1016/S2352-3018(19)30336-4. Epub 2019 Nov 15.
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: Molina JM, Squires K, Sax PE, Cahn P, Lombaard J, DeJesus E, Lai MT, Xu X, Rodgers A, Lupinacci L, Kumar S, Sklar P, Nguyen BY, Hanna GJ, Hwang C; DRIVE-FORWARD Study Group. Doravirine versus ritonavir-boosted darunavir in antiretroviral-naive adults with HIV-1 (DRIVE-FORWARD): 48-week results of a randomised, double-blind, phase 3, non-inferiority trial. Lancet HIV. 2018 May;5(5):e211-e220. doi: 10.1016/S2352-3018(18)30021-3. Epub 2018 Mar 25.