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)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 673
- 主要终点
- Percentage of Participants Maintaining Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) <50 Copies/mL
研究概览
简要总结
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.
详细描述
Two 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 Extension 2 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.
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
- None
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
- •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
排除标准
- •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
研究组 & 干预措施
Immediate Switch to Doravirine, Tenofovir, Lamivudine
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
干预措施: Doravirine, Tenofovir, Lamivudine (Drug)
Immediate Switch to Doravirine, Tenofovir, Lamivudine
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
干预措施: Baseline regimen of ritonavir- or cobicistat-boosted protease inhibitor (Drug)
Immediate Switch to Doravirine, Tenofovir, Lamivudine
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
干预措施: Baseline regimen of cobicistat-boosted elvitegravir (Drug)
Immediate Switch to Doravirine, Tenofovir, Lamivudine
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
干预措施: Baseline regimen of a non-nucleoside reverse transcriptase inhibitor (Drug)
Immediate Switch to Doravirine, Tenofovir, Lamivudine
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
干预措施: Baseline regimen of two nucleoside reverse transcriptase inhibitors (Drug)
Delayed Switch to Doravirine, Tenofovir, Lamivudine
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
干预措施: Doravirine, Tenofovir, Lamivudine (Drug)
Delayed Switch to Doravirine, Tenofovir, Lamivudine
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
干预措施: Baseline regimen of ritonavir- or cobicistat-boosted protease inhibitor (Drug)
Delayed Switch to Doravirine, Tenofovir, Lamivudine
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
干预措施: Baseline regimen of cobicistat-boosted elvitegravir (Drug)
Delayed Switch to Doravirine, Tenofovir, Lamivudine
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
干预措施: Baseline regimen of a non-nucleoside reverse transcriptase inhibitor (Drug)
Delayed Switch to Doravirine, Tenofovir, Lamivudine
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
干预措施: Baseline regimen of two nucleoside reverse transcriptase inhibitors (Drug)
结局指标
主要结局
Percentage of Participants Maintaining Human Immunodeficiency Virus-1 Ribonucleic Acid (HIV-1 RNA) <50 Copies/mL
时间窗: Immediate Switch to MK-1439A arm: Week 48; Delayed Switch to MK-1439A arm: Week 24
The percentage of participants in each arm achieving HIV-1 RNA levels \<50 copies/mL 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
- Mean Change From Baseline in Fasting Low-density Lipoprotein Cholesterol (LDL-C)(Baseline and Week 24)
- Percentage of Participants Experiencing ≥1 Serious Adverse Event (SAE)(Up to 24 weeks)
- Percentage of Participants Maintaining HIV-1 RNA <50 Copies/mL(Week 24)
- Mean Change From Baseline in Fasting Non-high-density Lipoprotein Cholesterol (Non-HDL-C)(Baseline and Week 24)
- Mean Change From Baseline in Cluster of Differentiation (CD4) Cell Counts(Baseline and Week 24)
- Percentage of Participants With HIV-1 RNA >=50 Copies/mL(Immediate Switch to MK-1439A arm: Week 48; Delayed Switch to MK-1439A arm: Week 24)
- Percentage of Participants Maintaining HIV-1 RNA <40 Copies/mL(Immediate Switch to MK-1439A arm: Week 24; Delayed Switch to MK-1439A arm: Week 24)
- Percentage of Participants Experiencing ≥1 Adverse Event (AE)(Up to week 24)
- Percentage of Participants Discontinuing From Study Medication Due to an AE(s)(Up to Week 24)