A Randomized, Double-blind Phase 3B Study to Evaluate the Safety and Efficacy of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Versus Ritonavir-Boosted Atazanavir Plus Emtricitabine/Tenofovir Disoproxil Fumarate in HIV-1 Infected, Antiretroviral Treatment-Naïve Women
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 583
- 试验地点
- 99
- 主要终点
- Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 of the Double-Blind Phase as Determined by the US FDA-Defined Snapshot Algorithm
研究概览
简要总结
The primary objective of this study is to evaluate the efficacy of a regimen containing elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) versus ritonavir (RTV)-boosted atazanavir (ATV/r) plus emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) in HIV-1 infected, antiretroviral treatment-naive adult women.
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
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female (at birth), age ≥ 18 years
- •Ability to understand and sign a written informed consent form
- •Plasma HIV-1 RNA levels ≥ 500 copies/mL
- •No prior use of any approved or investigational antiretroviral drug for any length of time
- •Screening genotype report must show sensitivity to emtricitabine (FTC), tenofovir disoproxil fumarate (TDF) and atazanavir (ATV) boosted with ritonavir (RTV)
- •Normal ECG
- •Adequate renal function: Estimated glomerular filtration rate ≥ 70 mL/min according to the Cockcroft Gault formula
- •Hepatic transaminases ≤ 5 x upper limit of normal (ULN)
- •Total bilirubin ≤ 1.5 mg/dL
- •Adequate hematologic function
- •Serum amylase ≤ 5 x ULN
- •Women of childbearing potential must agree to utilize protocol recommended contraception methods or be non-heterosexually active, or practice sexual abstinence from screening throughout the duration of the study period and for 30 days following the last dose of study drug
- •Women 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.
排除标准
- •A new AIDS defining condition diagnosed within the 30 days
- •Females receiving drug treatment for Hepatitis C, or females who are anticipated to receive treatment for Hepatitis C during the course of the study
- •Females experiencing decompensated cirrhosis
- •Females who are breastfeeding
- •Positive serum pregnancy test (female of childbearing potential)
- •Have an implanted defibrillator or pacemaker
- •Have an ECG pulse rate interval ≥ 220 msec
- •Current alcohol or substance use which may potentially interfere with the female's study compliance
- •History of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma
- •Active, serious infections requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline
- •Participation in any other clinical trial without prior approval
- •Any other clinical condition or prior therapy that would make the female unsuitable for the study or unable to comply with the dosing requirements
- •Females receiving ongoing therapy with any disallowed medications, including drugs not to be used with elvitegravir, cobicistat, FTC, TDF, ATV, RTV; or females with any known allergies to the excipients of Stribild® tablets, Truvada® tablets, atazanavir capsules or ritonavir tablets
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
ATV + RTV+ FTC/TDF
ATV + RTV + FTC/TDF + E/C/F/TDF placebo
干预措施: ATV (Drug)
E/C/F/TDF
E/C/F/TDF + ATV placebo + RTV placebo + FTC/TDF placebo
干预措施: E/C/F/TDF (Drug)
E/C/F/TDF
E/C/F/TDF + ATV placebo + RTV placebo + FTC/TDF placebo
干预措施: ATV Placebo (Drug)
E/C/F/TDF
E/C/F/TDF + ATV placebo + RTV placebo + FTC/TDF placebo
干预措施: RTV Placebo (Drug)
E/C/F/TDF
E/C/F/TDF + ATV placebo + RTV placebo + FTC/TDF placebo
干预措施: FTC/TDF Placebo (Drug)
ATV + RTV+ FTC/TDF
ATV + RTV + FTC/TDF + E/C/F/TDF placebo
干预措施: RTV (Drug)
ATV + RTV+ FTC/TDF
ATV + RTV + FTC/TDF + E/C/F/TDF placebo
干预措施: FTC/TDF (Drug)
ATV + RTV+ FTC/TDF
ATV + RTV + FTC/TDF + E/C/F/TDF placebo
干预措施: E/C/F/TDF Placebo (Drug)
Open-Label Extension Phase
After 48 weeks of blinded treatment, participants will continue to take blinded study drug for 12 weeks and return for an unblinding visit at Week 60. Participants who are virologically suppressed at Week 48 during the double-blinded treatment phase will have the option to enter the open-label extension phase. Participants randomized to the E/C/F/TDF arm will continue to receive open-label E/C/F/TDF and participants randomized to the ATV+ RTV + FTC/TDF arm will be re-randomized to receive either open-label elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or open-label ATV + RTV+ FTC/TDF.
干预措施: E/C/F/TDF (Drug)
Open-Label Extension Phase
After 48 weeks of blinded treatment, participants will continue to take blinded study drug for 12 weeks and return for an unblinding visit at Week 60. Participants who are virologically suppressed at Week 48 during the double-blinded treatment phase will have the option to enter the open-label extension phase. Participants randomized to the E/C/F/TDF arm will continue to receive open-label E/C/F/TDF and participants randomized to the ATV+ RTV + FTC/TDF arm will be re-randomized to receive either open-label elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or open-label ATV + RTV+ FTC/TDF.
干预措施: ATV (Drug)
Open-Label Extension Phase
After 48 weeks of blinded treatment, participants will continue to take blinded study drug for 12 weeks and return for an unblinding visit at Week 60. Participants who are virologically suppressed at Week 48 during the double-blinded treatment phase will have the option to enter the open-label extension phase. Participants randomized to the E/C/F/TDF arm will continue to receive open-label E/C/F/TDF and participants randomized to the ATV+ RTV + FTC/TDF arm will be re-randomized to receive either open-label elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or open-label ATV + RTV+ FTC/TDF.
干预措施: RTV (Drug)
Open-Label Extension Phase
After 48 weeks of blinded treatment, participants will continue to take blinded study drug for 12 weeks and return for an unblinding visit at Week 60. Participants who are virologically suppressed at Week 48 during the double-blinded treatment phase will have the option to enter the open-label extension phase. Participants randomized to the E/C/F/TDF arm will continue to receive open-label E/C/F/TDF and participants randomized to the ATV+ RTV + FTC/TDF arm will be re-randomized to receive either open-label elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or open-label ATV + RTV+ FTC/TDF.
干预措施: FTC/TDF (Drug)
Open-Label Extension Phase
After 48 weeks of blinded treatment, participants will continue to take blinded study drug for 12 weeks and return for an unblinding visit at Week 60. Participants who are virologically suppressed at Week 48 during the double-blinded treatment phase will have the option to enter the open-label extension phase. Participants randomized to the E/C/F/TDF arm will continue to receive open-label E/C/F/TDF and participants randomized to the ATV+ RTV + FTC/TDF arm will be re-randomized to receive either open-label elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or open-label ATV + RTV+ FTC/TDF.
干预措施: E/C/F/TAF (Drug)
结局指标
主要结局
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 of the Double-Blind Phase as Determined by the US FDA-Defined Snapshot Algorithm
时间窗: Week 48
The percentage of participants with HIV-1 RNA \< 50 copies/mL at Week 48 of the double-blind phase was analyzed using the snapshot algorithm, which defines a participant'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
- Change in CD4+ Cell Count at Week 48 of the Open-Label Extension Phase(Baseline; Open-Label Extension Week 48)
- Change From Baseline in CD4+ Cell Count at Week 48 of the Double-Blind Phase(Baseline; Week 48)
- Percentage of Participants Receiving STB or ATV+RTV+TVD With HIV-1 RNA < 50 Copies/mL at Week 48 of the Open-Label Extension Phase(Open-Label Extension Week 48)
- Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 for the STB Group as Determined by the US FDA-Defined Snapshot Algorithm(Week 96)