Safety and Efficacy of a Switch to Doravirine, Tenofovir, Lamivudine (MK-1439A) in Human Immunodeficiency Virus (HIV-1)-Infected Participants Virologically Suppressed on an Anti-retroviral Regimen in Combination With Two Nucleoside Reverse Transcriptase Inhibitors (MK-1439A-024) (DRIVE-SHIFT)

Merck Sharp & Dohme (MSD)

Status and phase: Completed; Phase 3

Conditions: HIV-1 Infection

Treatments: Drug: Baseline regimen of two nucleoside reverse transcriptase inhibitors; Drug: Baseline regimen of cobicistat-boosted elvitegravir; Drug: Baseline regimen of ritonavir- or cobicistat-boosted protease inhibitor; Drug: Doravirine, Tenofovir, Lamivudine; Drug: Baseline regimen of a non-nucleoside reverse transcriptase inhibitor

Study type: Interventional

Funder types: Industry

Identifiers

NCT02397096

1439A-024

MK-1439A-024 (Other Identifier)

2014-005550-18 (EudraCT Number)

Details and patient eligibility

About

The multicenter, open label, randomized study will evaluate the safety and efficacy of a switch to MK-1439A (MK-1439 [doravirine] plus lamivudine and tenofovir disoproxil fumarate) in HIV-1-infected participants virologically suppressed on a protocol-specified antiretroviral regimen. The primary hypothesis is that a switch to doravirine, tenofovir, lamivudine will be non-inferior to continuation of the regimen at Screening for 24 weeks, as assessed by the proportion of participants maintaining HIV-1 ribonucleic acid (RNA) <50 copies/mL. The Base Study results will be based on the first 48 weeks of this ongoing study.

Full description

Three optional study extensions are planned. Study Extension 1 will evaluate safety of the switch to doravirine, tenofovir, lamivudine for an additional 2 years beyond the Base Study. Study Extensions 2 and 3 will evaluate safety of the switch to doravirine, tenofovir, lamivudine until doravirine, tenofovir, lamivudine becomes locally available, or 4 years beyond Study Extension 1, whichever comes first.

Enrollment: 673 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Inclusion Criteria include, but are not limited to:

• Have plasma Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) levels below the limit of quantification (BLoQ) (<40 copies/mL by the Abbott RealTime HIV-1 Assay as determined by the central laboratory) at the screening visit.
• Receiving antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 Nucleoside Reverse Transcriptase Inhibitor (NRTIs) (and no other antiretroviral therapy) continuously for >= 6 months.
• Receiving first or second retroviral regimen (participants receiving a NNRTI at Screening must be on their first retroviral regimen)
• No history of using an experimental NNRTI
• Has a genotype prior to starting his/her initial antiretroviral regimen and no known resistance to any of the study agents
• Not receiving lipid lowering therapy or on a stable dose of lipid lowering therapy at the time of enrollment
• Has the following laboratory values at screening within 30 days prior to the treatment phase of this study: Alkaline phosphatase ≤ 3.0 x upper limit of normal (ULN), Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) ≤ 5.0 x ULN, and Hemoglobin ≥9.0 g/dL (if female) or ≥10.0 g/dL (if male)
• Has a calculated creatinine clearance at the time of screening ≥ 50 mL/min, based on the Cockcroft-Gault equation
• Male or female participant not of reproductive potential or, if of reproductive potential, agrees to avoid becoming pregnant or impregnating a partner while receiving study drug and for 14 days after the last dose of study drug by complying with one of the following: 1) practice abstinence from heterosexual activity, or 2) use acceptable contraception during heterosexual activity
• For inclusion in Study Extension 1 (optional): completed the Week 48 visit; considered to have derived benefit from study participation up to Week 48; considered to be a clinically appropriate candidate for an additional 2 years treatment with study drug
• For inclusion in Study Extension 2 (optional): completed the Week 144 visit; considered to have derived benefit from study participation up to Week 144; considered to be a clinically appropriate candidate for an additional 2 years treatment with study drug
• For inclusion in Study Extension 3 (optional): completed the Week 240 visit; considered to have derived benefit from study participation up to Week 240; considered to be a clinically appropriate candidate for an additional 2 years treatment with study drug

Exclusion criteria

Exclusion Criteria include, but are not limited to:

• Uses recreational or illicit drugs or has a recent history of drug or alcohol abuse or dependence
• Received treatment for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1 such as adefovir, emtricitabine, lamivudine, or tenofovir
• Has documented or known resistance to study drugs including doravirine, lamivudine, and/or tenofovir
• Participated in a study with an investigational compound or device within 30 days or anticipates doing so during the course of this study
• Used systemic immunosuppressive therapy or immune modulators within 30 days or anticipates needing them during the course of this study (short courses of corticosteroids will be allowed)
• Current, active diagnosis of acute hepatitis due to any cause (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 function)
• Has evidence of decompensated liver disease or has liver cirrhosis and a Child-Pugh Class C score or Pugh-Turcotte score >9
• Pregnant, breastfeeding, or expecting to conceive at any time during the study
• Female and is expecting to donate eggs or male and is expecting to donate sperm during the study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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673 participants in 2 patient groups

Immediate Switch to Doravirine, Tenofovir, Lamivudine

Experimental group

Description:

Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a non nucleoside reverse transcriptase inhibitor (NNRTI) (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for \>=6 months with undetectable HIV-1 RNA will switch on Day 1 to doravirine, tenofovir, lamivudine single tablet by mouth once daily for 48 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions

Treatment:

Drug: Baseline regimen of a non-nucleoside reverse transcriptase inhibitor

Drug: Doravirine, Tenofovir, Lamivudine

Drug: Baseline regimen of ritonavir- or cobicistat-boosted protease inhibitor

Drug: Baseline regimen of cobicistat-boosted elvitegravir

Drug: Baseline regimen of two nucleoside reverse transcriptase inhibitors

Delayed Switch to Doravirine, Tenofovir, Lamivudine

Active Comparator group

Description:

Participants receiving continuous antiretroviral therapy with a ritonavir- or cobicistat-boosted protease inhibitor (atazanavir, darunavir, or lopinavir) or cobicistat-boosted elvitegravir or a NNRTI (specifically, efavirenz, nevirapine, or rilpivirine) in combination with 2 NRTIs for \>=6 months with undetectable HIV-1 RNA will continue on this therapy until Week 24, at which time they will switch to doravirine, tenofovir, lamivudine single tablet by mouth once daily for 24 weeks in the Base Study and, optionally, for up to an additional 6 years in the Study Extensions

Treatment:

Drug: Baseline regimen of a non-nucleoside reverse transcriptase inhibitor

Drug: Doravirine, Tenofovir, Lamivudine

Drug: Baseline regimen of ritonavir- or cobicistat-boosted protease inhibitor

Drug: Baseline regimen of cobicistat-boosted elvitegravir

Drug: Baseline regimen of two nucleoside reverse transcriptase inhibitors