Comparison of Doravirine, Tenofovir, Lamivudine (MK-1439A) and ATRIPLA™ in Treatment-Naive Human Immunodeficiency Virus Type 1 (HIV-1)-Infected Participants (MK-1439A-021)

Human Immunodeficiency Virus (HIV) Clinical Trial

— DRIVE-AHEAD  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02403674
• Other study ID #: 1439A-021
• Secondary ID: MK-1439A-0212014
• Status: Completed
• Phase: Phase 3
• Start date: June 5, 2015
• Est. completion date: September 7, 2023

Study information

• Verified date: September 2023
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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-1439) 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 192 weeks, including a 96-week double-blind period and a 96-week open-label period. The present results are based on the first 48 weeks of this ongoing study.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 734
• Est. completion date: September 7, 2023
• Est. primary completion date: March 20, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Human Immunodeficiency Virus (HIV)
• Immunologic Deficiency Syndromes

Intervention

Drug:
• Doravirine, Tenofovir, Lamivudine
One doravirine, tenofovir, lamivudine tablet taken q.d. by mouth.
• ATRIPLA™
One ATRIPLA™ tablet taken q.d. by mouth
• Placebo
Placebo tablets matched to ATRIPLA® or Doravirine, Tenofovir, Lamivudine.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL at Week 48	The percentage of participants in each arm with HIV-1 RNA levels <50 copies/mL at Week 48 was determined. Plasma HIV-1 RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled according to the US Food and Drug Administration (FDA) "snapshot" approach in which all missing data are considered treatment failures, regardless of the reason.	Week 48
Primary	Percentage of Participants With Tier-1 Neuropsychiatric Adverse Events (AEs)	The percentage of participants in each arm experiencing =1 pre-specified Tier-1 neuropsychiatric AEs was determined. The list of Tier-1 neuropsychiatric AE categories included "dizziness", "sleep disorders and disturbances", and "altered sensorium" (including disturbance in attention).	Up to Week 48
Secondary	Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96	The percentage of participants in each arm with HIV-1 RNA levels <50 copies/mL at Week 96 will be determined. Plasma HIV-1 RNA levels will be quantified with the Abbott RealTime HIV-1 Assay. The US Food and Drug Administration (FDA) "snapshot" approach (i.e., all missing data handled as treatment failures, regardless of the reason) will be used for efficacy analyses.	Week 96
Secondary	Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48	The percentage of participants in each arm with HIV-1 RNA levels <40 copies/mL (including target detected and target not detected) at Week 48 was determined. Plasma HIV RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled according to the US Food and Drug Administration (FDA) "snapshot" approach in which all missing data are considered treatment failures, regardless of the reason.	Week 48
Secondary	Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 96	The percentage of participants in each arm with HIV-1 RNA levels <40 copies/mL (including target detected and target not detected) at Week 96 will be determined. Plasma HIV-1 RNA levels will be quantified with the Abbott RealTime HIV-1 Assay. The US Food and Drug Administration (FDA) "snapshot" approach (i.e., all missing data handled as treatment failures, regardless of the reason) will be used for efficacy analyses.	Week 96
Secondary	Change From Baseline in CD4 Cell Counts at Week 48	The mean change from baseline in CD4 cell counts at Week 48 was assessed using the Observed Failure (OF) approach. With the OF approach, baseline values were carried forward for participants who discontinued prior to Week 48 due to lack of efficacy. Cell counts at Baseline and Week 48 were measured and expressed as cells/mm^3, and percent change was then calculated as [(Baseline counts - Week 48 counts)*100]. CD4 cell counts were quantified by a central laboratory using a commercially available assay.	Baseline (Day 1) and Week 48
Secondary	Change From Baseline in CD4 Cell Counts at Week 96	The mean change from baseline in CD4 cell counts at Week 96 will be assessed using the Observed Failure (OF) approach. With the OF approach, baseline values will be carried forward for participants who discontinued prior to Week 96 due to lack of efficacy. Cell counts at Baseline and Week 96 will be measured and expressed as cells/mm^3, and percent change will then be calculated as [(Baseline counts - Week 96 counts)*100]. CD4 cell counts will be quantified by a central laboratory using a commercially available assay.	Baseline (Day 1) and Week 96
Secondary	Percentage of Participants Experiencing =1 AE	An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.	Up to Week 48
Secondary	Percentage of Participants Discontinuing From Study Medication Due to an AE(s)	An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.	Up to Week 48
Secondary	Percentage of Participants With Tier-2 Neuropsychiatric AEs	The percentage of participants in each arm experiencing =1 pre-specified Tier-2 neuropsychiatric AEs was determined. The list of Tier-2 neuropsychiatric AE categories included "depression and suicide/self-injury" and "psychosis and psychotic disorders".	Up to Week 48
Secondary	Change From Baseline in Fasting LDL-C at Week 48	The mean percent change from baseline in fasting (fast duration of =8 hours) LDL-C levels at Week 48 was determined for each arm. The Last Observation Carry Forward (LOCF) approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy.	Baseline (Day 1) and Week 48
Secondary	Change From Baseline in Fasting Non-HDL-C at Week 48	The mean percent change from baseline in fasting (fast duration of =8 hours) non-HDL-C levels at Week 48 was determined for each arm. The LOCF approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy.	Baseline (Day 1) and Week 48
Secondary	Change From Baseline in Fasting Cholesterol at Week 48	The mean percent change from baseline in fasting (fast duration of =8 hours) cholesterol levels at Week 48 was determined for each arm. The LOCF approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy.	Baseline (Day 1) and Week 48
Secondary	Change From Baseline in Fasting Triglycerides at Week 48	The mean percent change from baseline in fasting (fast duration of =8 hours) triglycerides levels at Week 48 was determined for each arm. The LOCF approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy.	Baseline (Day 1) and Week 48
Secondary	Change From Baseline in Fasting HDL-C at Week 48	The mean percent change from baseline in fasting (fast duration of =8 hours) HDL-C levels at Week 48 was determined for each arm. The LOCF approach was applied to missing data and data collected after a participant initiated lipid-modifying therapy.	Baseline (Day 1) and Week 48
Secondary	Percentage of Participants With HIV-1 RNA Below the Limit of Quantification (BLoQ) at Week 48	The percentage of participants in each arm with HIV-1 RNA levels BLoQ of 40 copies/mL and target not detected at Week 48 was determined. Plasma HIV RNA levels were quantified with the Abbott RealTime HIV-1 Assay. Data were handled as observed.	Week 48
Secondary	Percentage of Participants With HIV-1 RNA BLoQ at Week 96	The percentage of participants in each arm with HIV-1 RNA levels BLoQ of 40 copies/mL and target not detected at Week 96 will be determined. Plasma HIV RNA levels will be quantified with the Abbott RealTime HIV-1 Assay. Data will be handled as observed.	Week 48
Secondary	Plasma Concentration of Doravirine at Week 48	Plasma samples were collected for analysis of doravirine concentration at Week 48. A total of 2 samples were collected: 1 prior to dosing and 1 collected between 0.5 and 2 hours post-dose.	0 hours post-dose and 2 hours post-dose on Week 48

External Links

•   Merck Clinical Trials Information