A Phase 3 Open-Label Study to Evaluate Switching From Optimized Stable Antiretroviral Regimens Containing Darunavir to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide (E/C/F/TAF) Single Tablet Regimen (STR) Plus Darunavir (DRV) in Treatment Experienced HIV-1 Positive Adults
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 158
- 试验地点
- 62
- 主要终点
- Percentage of Participants in Each Treatment Arm in Cohort 2 With HIV-1 RNA < 50 Copies/mL at Week 24
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) plus darunavir (DRV) relative to current antiretroviral regimens (ARV) in virologically suppressed, HIV-1 positive participants with HIV-1 RNA <50 copies/mL at Week 24.
This study consists of 48 weeks of open-label phase followed by an optional Extension Phase in which all the participants will receive E/C/F/TAF+DRV.
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
- •Ability to understand and sign a written informed consent form
- •History of at least two prior antiretroviral regimens, and history of resistance to at least two different classes of antiretroviral agents
- •Plasma HIV-1 RNA levels < 50 copies/mL at screening. Virologically suppressed on the current antiretroviral regimen containing darunavir 600 mg twice a day or 800 mg once daily continuously for ≥ 4 months preceding the screening visit and have maintained documented undetectable plasma HIV-1 RNA levels (< 50 copies/mL) and must have documentation of genotype/phenotype prior to current regimen which shows no darunavir associated resistance mutation.
- •Currently receiving raltegravir, elvitegravir, or dolutegravir (50 mg once daily, but not twice daily), or have never received integrase inhibitor, or have documentation of genotype/phenotype within 12 months prior to current regimen which must show no evidence of resistance to integrase inhibitors
- •Normal 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 (absolute neutrophil count ≥ 1,000/mm^3; platelets ≥ 50,000/mm^3; hemoglobin ≥ 8.5 g/dL)
- •Serum amylase ≤ 5 × ULN (individuals with serum amylase > 5 × ULN will remain eligible if serum lipase is ≤ 5 × ULN)
- •A female individual is eligible to enter the study if it is confirmed that she is:
- •Not pregnant or nursing
- •Of non-childbearing potential (i.e., women who have had a hysterectomy, have had both ovaries removed or medically documented ovarian failure, or are postmenopausal women > 54 years of age with cessation (for ≥ 12 months) of previously occurring menses), or
- •Of childbearing potential and agrees 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 study drug dose.
- •Female individuals 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.
- •Male individuals must agree to utilize a highly effective method of contraception during heterosexual intercourse or be non-heterosexually active, or practice sexual abstinence from first dose throughout the study period and for 30 days following the last study drug dose.
- •Male individuals must agree to refrain from sperm donation from first dose until at least 30 days after the last study drug dose.
排除标准
- •A new AIDS-defining condition diagnosed within the 30 days prior to screening (except CD4 cell count and/or percentage criteria)
- •Hepatitis B surface antigen (HBsAg) positive
- •Individuals receiving drug treatment for Hepatitis C, or individuals who are anticipated to receive treatment for Hepatitis C during the course of the study.
- •Must not have Q151M, T69ins, or > 3 thymidine analogue mutations (TAMS) present on documented historic genotype report
- •Individuals experiencing decompensated cirrhosis
- •Females who are breastfeeding
- •Positive serum pregnancy test
- •Have an implanted defibrillator or pacemaker
- •Current alcohol or substance use that may interfere with individual's study compliance
- •A 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 (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1 visit
- •Any other clinical condition or prior therapy that 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 from the sponsor is prohibited while participating in this trial
- •Individuals receiving ongoing therapy with any of the disallowed medications, including drugs not to be used with elvitegravir, cobicistat, emtricitabine, TAF, or DRV; or individuals with any known allergies to the study drugs.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Cohort 1
Participants will receive E/C/F/TAF FDC + DRV once daily with food for 48 weeks.
Based on safety and efficacy data from Cohort 1 at Week 4, the participants will be randomized into Cohort 2. The participants in Cohort 1 will continue receiving E/C/F/TAF FDC + DRV through 48 weeks.
干预措施: E/C/F/TAF (Drug)
Cohort 1
Participants will receive E/C/F/TAF FDC + DRV once daily with food for 48 weeks.
Based on safety and efficacy data from Cohort 1 at Week 4, the participants will be randomized into Cohort 2. The participants in Cohort 1 will continue receiving E/C/F/TAF FDC + DRV through 48 weeks.
干预措施: DRV (Drug)
Cohort 2, Treatment Group 1
Participants will be randomized to receive E/C/F/TAF FDC+DRV once daily with food for 48 weeks.
干预措施: E/C/F/TAF (Drug)
Cohort 2, Treatment Group 1
Participants will be randomized to receive E/C/F/TAF FDC+DRV once daily with food for 48 weeks.
干预措施: DRV (Drug)
Cohort 2, Treatment Group 2
Participants will be randomized to continue on their baseline DRV-containing ARV regimen for 48 weeks.
干预措施: Baseline DRV- containing ARV regimen (Drug)
结局指标
主要结局
Percentage of Participants in Each Treatment Arm in Cohort 2 With HIV-1 RNA < 50 Copies/mL at Week 24
时间窗: Week 24
The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 24 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
- Change From Baseline in CD4+ Cell Count at Week 48(Baseline; Week 48)
- Percentage of Participants in Each Treatment Arm in Cohort 2 With HIV-1 RNA < 50 Copies/mL at Week 48(Week 48)
- Change From Baseline in CD4+ Cell Count at Week 24(Baseline; Week 24)