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
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 769
- 主要终点
- Percentage of Participants Achieving Plasma HIV-1 RNA <50 Copies/mL at Week 48
研究概览
简要总结
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.
详细描述
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.
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 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.
排除标准
- •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-
- •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.
研究组 & 干预措施
Doravirine 100 mg
Double-blind Doravirine 100 mg administered orally (p.o.) once daily (q.d.) + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study. Eligible participants may continue in Study Extension 1 with open-label Doravirine 100 mg administered p.o. q.d. + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o., q.d. for an additional 96 weeks. Eligible participants may continue to receive the Doravirine regimen in Study Extension 2 until Doravirine becomes locally available, or for an additional 96 weeks, whichever comes first. Eligible participants may continue to receive the Doravirine regimen in Study Extension 3 until Doravirine becomes locally available, or for an additional 96 weeks, whichever comes first.
干预措施: Doravirine (Drug)
Doravirine 100 mg
Double-blind Doravirine 100 mg administered orally (p.o.) once daily (q.d.) + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks in the Base Study. Eligible participants may continue in Study Extension 1 with open-label Doravirine 100 mg administered p.o. q.d. + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o., q.d. for an additional 96 weeks. Eligible participants may continue to receive the Doravirine regimen in Study Extension 2 until Doravirine becomes locally available, or for an additional 96 weeks, whichever comes first. Eligible participants may continue to receive the Doravirine regimen in Study Extension 3 until Doravirine becomes locally available, or for an additional 96 weeks, whichever comes first.
干预措施: TRUVADA™ or EPZICOM™/KIVEXA™ (Drug)
Darunavir 800 mg and Ritonavir 100 mg
Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o. q.d. + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks. Eligible participants may continue in Study Extension 1 with open-label Doravirine 100 mg administered p.o. q.d. + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for an additional 96 weeks. Eligible participants may continue to receive the Doravirine regimen in Study Extension 2 until Doravirine becomes locally available, or for an additional 96 weeks, whichever comes first. Eligible participants may continue to receive the Doravirine regimen in Study Extension 3 until Doravirine becomes locally available, or for an additional 96 weeks, whichever comes first.
干预措施: Doravirine (Drug)
Darunavir 800 mg and Ritonavir 100 mg
Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o. q.d. + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks. Eligible participants may continue in Study Extension 1 with open-label Doravirine 100 mg administered p.o. q.d. + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for an additional 96 weeks. Eligible participants may continue to receive the Doravirine regimen in Study Extension 2 until Doravirine becomes locally available, or for an additional 96 weeks, whichever comes first. Eligible participants may continue to receive the Doravirine regimen in Study Extension 3 until Doravirine becomes locally available, or for an additional 96 weeks, whichever comes first.
干预措施: Darunavir (Drug)
Darunavir 800 mg and Ritonavir 100 mg
Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o. q.d. + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks. Eligible participants may continue in Study Extension 1 with open-label Doravirine 100 mg administered p.o. q.d. + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for an additional 96 weeks. Eligible participants may continue to receive the Doravirine regimen in Study Extension 2 until Doravirine becomes locally available, or for an additional 96 weeks, whichever comes first. Eligible participants may continue to receive the Doravirine regimen in Study Extension 3 until Doravirine becomes locally available, or for an additional 96 weeks, whichever comes first.
干预措施: Ritonavir (Drug)
Darunavir 800 mg and Ritonavir 100 mg
Double-blind Darunavir 800 mg and Ritonavir 100 mg administered p.o. q.d. + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for 96 weeks. Eligible participants may continue in Study Extension 1 with open-label Doravirine 100 mg administered p.o. q.d. + investigator selected TRUVADA™ or EPZICOM™/KIVEXA™ administered p.o. q.d. for an additional 96 weeks. Eligible participants may continue to receive the Doravirine regimen in Study Extension 2 until Doravirine becomes locally available, or for an additional 96 weeks, whichever comes first. Eligible participants may continue to receive the Doravirine regimen in Study Extension 3 until Doravirine becomes locally available, or for an additional 96 weeks, whichever comes first.
干预措施: TRUVADA™ or EPZICOM™/KIVEXA™ (Drug)
结局指标
主要结局
Percentage of Participants Achieving Plasma HIV-1 RNA <50 Copies/mL at Week 48
时间窗: Week 48
The percentage of participants in each arm achieving 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 and all missing data were considered treatment failures, regardless of the reason.
次要结局
- Change From Baseline in Mean CD4+ T-cell Count at Week 48(Baseline and Week 48)
- Mean Change From Baseline in Fasting Low Density Lipoprotein Cholesterol (LDL-C) at Week 48(Baseline and Week 48)
- Percentage of Participants With Any Adverse Event(Up to 98 weeks)
- Percentage of Participants Achieving Plasma HIV-1 RNA <50 Copies/mL at Week 96(Week 96)
- Change From Baseline in Mean CD4+ T-cell Count at Week 96(Baseline and Week 96)
- Mean Change From Baseline in Fasting Non-High Density Lipoprotein Cholesterol (Non-HDL-C) at Week 48(Baseline and Week 48)
- Mean Change From Baseline in Fasting High Density Lipoprotein Cholesterol (HDL-C) at Week 48(Baseline and Week 48)
- Mean Change From Baseline in Fasting Total Cholesterol at Week 48(Baseline and Week 48)
- Mean Change From Baseline in Fasting Triglyceride at Week 48(Baseline and Week 48)
- Percentage of Participants With Any Serious Adverse Event(Up to 98 weeks)
- Percentage of Participants With Any Drug-related Adverse Event(Up to 98 weeks)
- Percentage of Participants With Any Drug-related Serious Adverse Event(Up to 98 weeks)
- Percentage of Participants Who Discontinued Study Treatment Due to an Adverse Event(Up to 96 weeks)
- Percentage of Participants Achieving Plasma HIV-1 RNA <40 Copies/mL at Week 48(Week 48)
- Percentage of Participants Achieving Plasma HIV-1 RNA <40 Copies/mL at Week 96(Week 96)