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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 734
- 主要终点
- Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL at Week 48
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Doravirine, Tenofovir, Lamivudine
Treatment-naive HIV-infected participants will receive doravirine, tenofovir, lamivudine, a single-tablet FDC containing doravirine 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg, q.d. by mouth for 96 weeks. Participants will also take 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 96 weeks in order to maintain blinding.
干预措施: Doravirine, Tenofovir, Lamivudine (Drug)
Doravirine, Tenofovir, Lamivudine
Treatment-naive HIV-infected participants will receive doravirine, tenofovir, lamivudine, a single-tablet FDC containing doravirine 100 mg + lamivudine 300 mg + tenofovir disoproxil fumarate 300 mg, q.d. by mouth for 96 weeks. Participants will also take 1 placebo tablet matched to ATRIPLA™ q.d. by mouth for 96 weeks in order to maintain blinding.
干预措施: Placebo (Drug)
ATRIPLA™
Treatment-naive HIV-infected participants will receive ATRIPLA™, a single-tablet FDC containing efavirenz 600 mg + emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 96 weeks. Participants will also take 1 placebo tablet matched to doravirine, tenofovir, lamivudine q.d. by mouth for 96 weeks in order to maintain blinding.
干预措施: ATRIPLA™ (Drug)
ATRIPLA™
Treatment-naive HIV-infected participants will receive ATRIPLA™, a single-tablet FDC containing efavirenz 600 mg + emtricitabine 200 mg + tenofovir disoproxil fumarate 300 mg (equivalent to 245 mg tenofovir disoproxil), q.d. by mouth for 96 weeks. Participants will also take 1 placebo tablet matched to doravirine, tenofovir, lamivudine q.d. by mouth for 96 weeks in order to maintain blinding.
干预措施: Placebo (Drug)
结局指标
主要结局
Percentage of Participants With HIV-1 Ribonucleic Acid (RNA) <50 Copies/mL at Week 48
时间窗: 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.
Percentage of Participants With Tier-1 Neuropsychiatric Adverse Events (AEs)
时间窗: Up to Week 48
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).
次要结局
- Percentage of Participants With HIV-1 RNA <50 Copies/mL at Week 96(Week 96)
- Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 48(Week 48)
- Percentage of Participants With HIV-1 RNA <40 Copies/mL at Week 96(Week 96)
- Change From Baseline in CD4 Cell Counts at Week 48(Baseline (Day 1) and Week 48)
- Change From Baseline in CD4 Cell Counts at Week 96(Baseline (Day 1) and Week 96)
- Percentage of Participants Experiencing ≥1 AE(Up to Week 48)
- Percentage of Participants Discontinuing From Study Medication Due to an AE(s)(Up to Week 48)
- Percentage of Participants With Tier-2 Neuropsychiatric AEs(Up to Week 48)
- Change From Baseline in Fasting LDL-C at Week 48(Baseline (Day 1) and Week 48)
- Change From Baseline in Fasting Non-HDL-C at Week 48(Baseline (Day 1) and Week 48)
- Change From Baseline in Fasting Cholesterol at Week 48(Baseline (Day 1) and Week 48)
- Change From Baseline in Fasting Triglycerides at Week 48(Baseline (Day 1) and Week 48)
- Change From Baseline in Fasting HDL-C at Week 48(Baseline (Day 1) and Week 48)
- Percentage of Participants With HIV-1 RNA Below the Limit of Quantification (BLoQ) at Week 48(Week 48)
- Percentage of Participants With HIV-1 RNA BLoQ at Week 96(Week 96)
- Plasma Concentration of Doravirine at Week 48(0 hours post-dose and 2 hours post-dose on Week 48)