Phase IIb, Double-Blinded, Multicenter, Randomized Study to Assess the Effect on Central Nervous System (CNS) Toxicity of Switching From ATRIPLA™ (Efavirenz, Tenofovir, Emtricitabine) to MK-1439A (Doravirine, Tenofovir, Lamivudine) in Virologically-Suppressed Subjects.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 86
- 主要终点
- Percentage of Participants With at Least One Central Nervous System (CNS) Toxicity of at Least Grade 2 Intensity at Week 12
研究概览
简要总结
This study aims to evaluate a switch from fixed dose combination (FDC) treatment with ATRIPLA^TM for 12 weeks prior to screening to FDC treatment with Doravirine, Tenofovir, Lamivudine (MK-1439A) in virologically-suppressed, human immunodeficiency virus type 1 (HIV-1)-infected participants. The primary hypothesis is that switching from ATRIPLA^TM to Doravirine, Tenofovir, Lamivudine results in a lower proportion of participants with at least one CNS toxicity of at least Grade 2 intensity at Week 12 than continuation of ATRIPLA^TM treatment.
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 taking ATRIPLA™, generic versions of ATRIPLA™, or the components of ATRIPLA™ (EFV,TDF plus emtricitabine),
- •has documentation of HIV-1 ribonucleic acid (RNA) < 50 copies/mL during the 12 weeks prior to screening while on ATRIPLA™.
- •has plasma HIV-1 RNA levels below the limits of quantification (BLoQ) at the screening visit.
- •if genotyped prior to starting initial antiretroviral regimen, must have no known resistance to any of the study agents
- •has at least one EFV-associated CNS toxicities of Grade 2 or worse intensity both at the time of screening and at Study Day 1
- •is highly unlikely to become pregnant or to impregnate a partner
- •To be eligible for study extension 1, participants from Immediate Switch Group (ISG) must have completed Study Week 24, and benefited from study participation; participants from Deferred Switch Group (DSG) must have completed Study Week 36, and benefited from study participation as determined by the investigator
- •To be eligible for study extension 2, participants from ISG must have completed Study Week 120, and benefited from study participation; participants from DSG must have completed Study Week 132, and benefited from study participation as determined by the investigator
排除标准
- •is a user of recreational or illicit drugs or has had a recent history of drug or alcohol abuse or dependence.
- •has ongoing Grade 4 CNS toxicity during screening period that requires a prompt change in ART
- •has been treated for a viral infection other than HIV-1, such as hepatitis B, with an agent that is active against HIV-1 including, but not limited to, adefovir, emtricitabine, entecavir, lamivudine or tenofovir.
- •has documented or known resistance to study drugs including doravirine, lamivudine, and/or tenofovir
- •has participated in, or anticipates participating in a study with an investigational compound/device within 30 days prior to signing informed consent
- •has used systemic immunosuppressive therapy or immune modulators or anticipates using them within 30 days prior to this study
- •requires or anticipates requiring any of the prohibited medications
- •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.
- •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 >
- •is pregnant, breastfeeding, or expecting to conceive.
- •female is expecting to donate eggs (at any time during the study) or male is expecting to donate sperm (at any time during the study).
研究组 & 干预措施
Immediate Switch to Doravirine, Tenofovir, Lamivudine
Participants on a baseline regimen of ATRIPLA™ for at least 12 weeks prior to screening will be switched to blinded doravirine, tenofovir, lamivudine orally, once daily for 12 weeks, followed by open-label doravirine, tenofovir, lamivudine orally, once daily for an additional 12 weeks. Participants who meet eligibility criteria can enter study extension 1 to receive open-label doravirine, tenofovir, lamivudine for an additional 96 weeks. Participants who meet eligibility criteria can enter study extension 2 to receive open-label doravirine, tenofovir, lamivudine, with a maximum total duration of treatment of 216 weeks. Participants who meet eligibility criteria can enter study extension 3 to receive open-label doravirine, tenofovir, lamivudine, with a maximum total duration of treatment of 312 weeks.
干预措施: Doravirine, Tenofovir, Lamivudine - Blinded (Drug)
Immediate Switch to Doravirine, Tenofovir, Lamivudine
Participants on a baseline regimen of ATRIPLA™ for at least 12 weeks prior to screening will be switched to blinded doravirine, tenofovir, lamivudine orally, once daily for 12 weeks, followed by open-label doravirine, tenofovir, lamivudine orally, once daily for an additional 12 weeks. Participants who meet eligibility criteria can enter study extension 1 to receive open-label doravirine, tenofovir, lamivudine for an additional 96 weeks. Participants who meet eligibility criteria can enter study extension 2 to receive open-label doravirine, tenofovir, lamivudine, with a maximum total duration of treatment of 216 weeks. Participants who meet eligibility criteria can enter study extension 3 to receive open-label doravirine, tenofovir, lamivudine, with a maximum total duration of treatment of 312 weeks.
干预措施: Doravirine, Tenofovir, Lamivudine - Open-Label (Drug)
Immediate Switch to Doravirine, Tenofovir, Lamivudine
Participants on a baseline regimen of ATRIPLA™ for at least 12 weeks prior to screening will be switched to blinded doravirine, tenofovir, lamivudine orally, once daily for 12 weeks, followed by open-label doravirine, tenofovir, lamivudine orally, once daily for an additional 12 weeks. Participants who meet eligibility criteria can enter study extension 1 to receive open-label doravirine, tenofovir, lamivudine for an additional 96 weeks. Participants who meet eligibility criteria can enter study extension 2 to receive open-label doravirine, tenofovir, lamivudine, with a maximum total duration of treatment of 216 weeks. Participants who meet eligibility criteria can enter study extension 3 to receive open-label doravirine, tenofovir, lamivudine, with a maximum total duration of treatment of 312 weeks.
干预措施: Placebo to ATRIPLA™ (Drug)
Deferred Switch to Doravirine, Tenofovir, Lamivudine
Participants will continue on their ongoing ATRIPLA™ regimen orally, once daily for 12 weeks, followed by open-label doravirine, tenofovir, lamivudine orally, once daily for 24 weeks. Participants who meet eligibility criteria can enter study extension 1 to receive open-label doravirine, tenofovir, lamivudine for an additional 96 weeks. Participants who meet eligibility criteria can enter study extension 2 to receive open-label doravirine, tenofovir, lamivudine, with a maximum total duration of treatment of 228 weeks. Participants who meet eligibility criteria can enter study extension 3 to receive open-label doravirine, tenofovir, lamivudine, with a maximum total duration of treatment of 324 weeks.
干预措施: Doravirine, Tenofovir, Lamivudine - Open-Label (Drug)
Deferred Switch to Doravirine, Tenofovir, Lamivudine
Participants will continue on their ongoing ATRIPLA™ regimen orally, once daily for 12 weeks, followed by open-label doravirine, tenofovir, lamivudine orally, once daily for 24 weeks. Participants who meet eligibility criteria can enter study extension 1 to receive open-label doravirine, tenofovir, lamivudine for an additional 96 weeks. Participants who meet eligibility criteria can enter study extension 2 to receive open-label doravirine, tenofovir, lamivudine, with a maximum total duration of treatment of 228 weeks. Participants who meet eligibility criteria can enter study extension 3 to receive open-label doravirine, tenofovir, lamivudine, with a maximum total duration of treatment of 324 weeks.
干预措施: ATRIPLA^TM (Drug)
Deferred Switch to Doravirine, Tenofovir, Lamivudine
Participants will continue on their ongoing ATRIPLA™ regimen orally, once daily for 12 weeks, followed by open-label doravirine, tenofovir, lamivudine orally, once daily for 24 weeks. Participants who meet eligibility criteria can enter study extension 1 to receive open-label doravirine, tenofovir, lamivudine for an additional 96 weeks. Participants who meet eligibility criteria can enter study extension 2 to receive open-label doravirine, tenofovir, lamivudine, with a maximum total duration of treatment of 228 weeks. Participants who meet eligibility criteria can enter study extension 3 to receive open-label doravirine, tenofovir, lamivudine, with a maximum total duration of treatment of 324 weeks.
干预措施: Placebo to Doravirine, Tenofovir, Lamivudine (Drug)
结局指标
主要结局
Percentage of Participants With at Least One Central Nervous System (CNS) Toxicity of at Least Grade 2 Intensity at Week 12
时间窗: Week 12
A questionnaire was used to solicit for CNS toxicity based on the following 10 events: dizziness; depression/low mood; insomnia/sleeplessness; anxiety/nervousness; confusion; impaired concentration/attention; headache; somnolence/daytime sleepiness; aggressive mood/behavior; and abnormal dreams. Participants were asked to rate the intensity for each of the 10 events as none (Grade 0), mild (Grade 1), moderate (Grade 2), or severe (Grade 3). Mild = symptom is noticeable but does not interfere with normal activities; moderate = symptom has some impact on normal activities; severe = symptom prevents conduct of normal activities. Percentage of participants with at least one CNS toxicity of Grade 2 or higher were recorded, based on the last observation carried forward (LOCF) approach.
次要结局
- Percentage of Participants With at Least One CNS Toxicity of at Least Grade 2 Intensity at Week 4(Week 4)
- Change From Baseline in CNS Toxicity Score at Week 4(Baseline and Week 4)
- Change From Baseline in CNS Toxicity Score at Week 12(Baseline and Week 12)
- Percentage of Participants With at Least One CNS Toxicity of at Least Grade 2 Intensity at Time of Switch, and at 24 Weeks Post-switch for the Combined Treatment Groups(Baseline (time of switch) and 24 weeks post-switch)
- CNS Toxicity Scores at Time of Switch, and at 24 Weeks Post-switch for the Combined Treatment Groups(Baseline (time of switch) and 24 weeks post-switch)
- Change From Baseline in Fasting Lipids at Week 12(Baseline (study Day 1) and study week 12)
- Change in Fasting Lipids Between Time of Switch and Week 24 Post-switch for the Combined Treatment Groups(Baseline (time of switch) and 24 weeks post-switch)
- Percentage of Participants With HIV-1 RNA <50 and <40 Copies/ml at Week 24 Post-switch for the Combined Treatment Groups(24 weeks post-switch)
- Change From Time of Switch to Week 24 Post Switch in CD4 T-cell Count for the Combined Treatment Groups(Baseline (time of switch) and 24 weeks post-switch)
- Number of Participants With One or More Adverse Events (AEs) Through Study Week 12(Up to Week 12)
- Number of Participants With One or More Drug-related AEs Through Study Week 12(Up to Week 12)
- Number of Participants With One or More Serious Adverse Events (SAEs) Through Study Week 12(Up to Week 12)
- Number of Participants With One or More Drug-related SAEs Through Study Week 12(Up to Week 12)
- Number of Participants Who Discontinued Treatment Due to an AE Through Study Week 12(Up to Week 12)
- Number of Participants With One or More AEs for the Combined Treatment Groups 24 Weeks After the Switch(24 weeks post-switch)
- Number of Participants With One or More Drug-related AEs for the Combined Treatment Groups 24 Weeks After the Switch(24 weeks post-switch)
- Number of Participants With One or More SAEs for the Combined Treatment Groups 24 Weeks After the Switch(24 weeks post-switch)
- Number of Participants With One or More Drug-related SAEs for the Combined Treatment Groups 24 Weeks After the Switch(24 weeks post-switch)
- Number of Participants Who Discontinued Treatment Due to an AE for the Combined Treatment Groups 24 Weeks After the Switch(24 weeks post-switch)