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)

• Register: ClinicalTrials.gov
• Last refreshed on: 26 September 2023
• Main ID: NCT02397096
• Date of registration: 18/03/2015
• Prospective Registration: Yes
• Primary sponsor: Merck Sharp & Dohme LLC
• Public title: 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
• Scientific title: A Phase III Multicenter, Open-Label, Randomized Study to Evaluate a Switch to MK-1439A in HIV-1-Infected Subjects Virologically Suppressed on a Regimen of a Ritonavir-boosted Protease Inhibitor and Two Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
• Date of first enrolment: June 9, 2015
• Target sample size: 673
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT02397096
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Argentina, Australia, Austria, Belgium, Canada, Colombia, Denmark, France, Germany, Guatemala, Israel, Italy, Korea, Republic of, Mexico, New Zealand, Peru, Poland, Puerto Rico, Russian Federation, Spain, Switzerland, United Kingdom, United States

Contacts

• Name: Medical Director
• Affiliation: Merck Sharp & Dohme LLC

Key inclusion & exclusion criteria

Inclusion Criteria:

- At least 18 years of age on the day of signing the informed consent.

- Understand the study procedures and voluntarily agree to participate by giving written
informed consent for the trial.

- Have plasma 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
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

Exclusion Criteria:

- 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



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

HIV-1 Infection

Intervention(s)

Drug: Doravirine, Tenofovir, Lamivudine

Drug: Baseline regimen of cobicistat-boosted elvitegravir

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

Drug: Baseline regimen of two nucleoside reverse transcriptase inhibitors

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

Primary Outcome(s)

Percentage of Participants Maintaining Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) <50 Copies/mL [Time Frame: Immediate Switch to MK-1439A arm: Week 48; Delayed Switch to MK-1439A arm: Week 24]

Secondary Outcome(s)

Mean Change From Baseline in Fasting Low-density Lipoprotein Cholesterol (LDL-C) [Time Frame: Baseline and Week 24]

Percentage of Participants With HIV-1 RNA >=50 Copies/mL [Time Frame: Immediate Switch to MK-1439A arm: Week 48; Delayed Switch to MK-1439A arm: Week 24]

Mean Change From Baseline in Cluster of Differentiation (CD4) Cell Counts [Time Frame: Immediate Switch to MK-1439A arm: Baseline and Week 48; Delayed Switch to MK-1439A arm: Baseline and Week 24]

Percentage of Participants Maintaining HIV-1 RNA <40 Copies/mL [Time Frame: Immediate Switch to MK-1439A arm: Week 24; Delayed Switch to MK-1439A arm: Week 24]

Percentage of Participants Experiencing =1 Serious Adverse Event (SAE) [Time Frame: Up to 24 weeks]

Mean Change From Baseline in Cluster of Differentiation (CD4) Cell Counts [Time Frame: Baseline and Week 24]

Mean Change From Baseline in Fasting Non-high-density Lipoprotein Cholesterol (Non-HDL-C) [Time Frame: Baseline and Week 24]

Percentage of Participants Discontinuing From Study Medication Due to an AE(s) [Time Frame: Up to Week 24]

Percentage of Participants Experiencing =1 Adverse Event (AE) [Time Frame: Up to week 24]

Percentage of Participants Maintaining HIV-1 RNA <40 Copies/mL [Time Frame: Immediate Switch to MK-1439A arm: Week 48; Delayed Switch to MK-1439A arm: Week 24]

Percentage of Participants Maintaining HIV-1 RNA <50 Copies/mL [Time Frame: Week 24]

Secondary ID(s)

1439A-024

MK-1439A-024

2014-005550-18

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 03/04/2019
• URL: https://clinicaltrials.gov/ct2/show/results/NCT02397096