A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Versus Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Positive, Antiretroviral Treatment-Naïve Adults
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 872
- 试验地点
- 116
- 主要终点
- Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 48
研究概览
简要总结
The primary objective of this study is to evaluate the efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) versus elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) in HIV-1 positive, antiretroviral treatment-naive adults.
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
- •Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
- •Plasma HIV-1 RNA levels ≥ 1,000 copies/mL at screening
- •No prior use of any approved or investigational antiretroviral drug for any length of time, except the use for pre-exposure prophylaxis (PREP), or post-exposure prophylaxis (PEP) up to 6 months prior to screening
- •Screening genotype report must show sensitivity to elvitegravir, emtricitabine, tenofovir DF
- •Normal electrocardiogram (ECG)
- •Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance
- •Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN)
- •Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
- •Adequate hematologic function
- •Serum amylase ≤ 5 × ULN
- •Males and females of childbearing potential must agree to utilize highly effective contraception methods or be non-heterosexually active or practice sexual abstinence from screening throughout the duration of study treatment and for 30 days following the last dose of study drug
- •Females who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing
- •Females who have stopped menstruating for ≥ 12 months but do not have documentation of ovarian hormonal failure must have a serum follicle stimulating hormone (FSH) level at screening within the post-menopausal range based on the Central Laboratory reference range
- •Age ≥ 18 years
排除标准
- •A new AIDS-defining condition diagnosed within the 30 days prior to screening
- •Hepatitis B surface antigen (HBsAg) positive
- •Hepatitis C antibody positive
- •Individuals experiencing decompensated cirrhosis
- •Females who are breastfeeding
- •Positive serum pregnancy test
- •Have an implanted defibrillator or pacemaker
- •Current alcohol or substance use judged by the Investigator to potentially interfere with study compliance
- •History of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, noninvasive cutaneous squamous carcinoma
- •Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline
- •Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the individual unsuitable for the study or unable to comply with dosing requirements
- •Participation in any other clinical trial (including observational trials) without prior approval
- •Receiving ongoing therapy with drugs not to be used with elvitegravir, cobicistat, emtricitabine, tenofovir DF, and TAF or participants with any known allergies to the excipients of E/C/F/TDF or E/C/F/TAF
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
E/C/F/TAF (Double-Blind)
E/C/F/TAF plus E/C/F/TDF placebo for 144 weeks
After 144 weeks, participants will continue to take their blinded study drug until treatment assignments have been unblinded.
干预措施: E/C/F/TAF (Drug)
E/C/F/TAF (Double-Blind)
E/C/F/TAF plus E/C/F/TDF placebo for 144 weeks
After 144 weeks, participants will continue to take their blinded study drug until treatment assignments have been unblinded.
干预措施: E/C/F/TDF Placebo (Drug)
E/C/F/TDF (Double-Blind)
E/C/F/TDF plus E/C/F/TAF placebo for 144 weeks
After 144 weeks, participants will continue to take their blinded study drug until treatment assignments have been unblinded.
干预措施: E/C/F/TDF (Drug)
E/C/F/TDF (Double-Blind)
E/C/F/TDF plus E/C/F/TAF placebo for 144 weeks
After 144 weeks, participants will continue to take their blinded study drug until treatment assignments have been unblinded.
干预措施: E/C/F/TAF Placebo (Drug)
Open-Label E/C/F/TAF
After the unblinding visit, in countries where E/C/F/TAF is not commercially available, participants (except in UK) who complete 144 weeks of study will be given the option to receive open-label E/C/F/TAF and attend study visits every 12 weeks until it becomes commercially available, or until Gilead terminates the study in that country.
干预措施: E/C/F/TAF (Drug)
结局指标
主要结局
Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 48
时间窗: Week 48
The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 48 was analyzed using the snapshot algorithm, which defines a patient's virologic response status using only the viral load at the predefined time point within an allowed window of time, along with study drug discontinuation status.
次要结局
- Percent Change From Baseline in Spine BMD at Week 48(Baseline; Week 48)
- Percent Change From Baseline in Spine BMD at Week 96(Baseline; Week 96)
- Change From Baseline in Serum Creatinine at Week 96(Baseline; Week 96)
- Percentage of Participants With Treatment-emergent Proteinuria Through Week 48(Baseline to Week 48)
- Percentage of Participants With Treatment-emergent Proteinuria Through Week 96(Baseline to Week 96)
- Percent Change From Baseline in Urine Retinol Binding Protein (RBP) to Creatinine Ratio at Week 48(Baseline; Week 48)
- Percent Change From Baseline in Urine RBP to Creatinine Ratio at Week 96(Baseline; Week 96)
- Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio at Week 48(Baseline; Week 48)
- Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio at Week 96(Baseline; Week 96)
- Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96(Week 96)
- Change From Baseline in CD4+ Cell Count at Week 48(Baseline; Week 48)
- Change From Baseline in CD4+ Cell Count at Week 96(Baseline; Week 96)
- Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Weeks 48 and 96(Weeks 48 and 96)
- Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48(Baseline; Week 48)
- Percent Change From Baseline in Hip BMD at Week 96(Baseline; Week 96)
- Change From Baseline in Serum Creatinine at Week 48(Baseline; Week 48)