A Phase 3b, Randomized, Double-Blind Study to Evaluate Switching From a Regimen Consisting of Efavirenz/Emtricitabine/Tenofovir Disoproxil Fumarate (EFV/FTC/TDF) Fixed Dose Combination (FDC) to Emtricitabine/Rilpivirine/ Tenofovir Alafenamide (FTC/RPV/TAF) FDC in Virologically-Suppressed, HIV-1 Infected Subjects
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 881
- 试验地点
- 113
- 主要终点
- Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined 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 non-inferiority of switching to emtricitabine/rilpivirine/tenofovir alafenamide (FTC/RPV/TAF) fixed dose combination (FDC) as compared to continuing the non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen of efavirenz /FTC/tenofovir disoproxil fumarate (EFV/FTC/TDF) FDC in virologically-suppressed HIV-1 infected participants.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
- •Currently receiving EFV/FTC/TDF FDC for ≥ 6 consecutive months preceding the screening visit
- •Documented plasma HIV-1 RNA levels < 50 copies/mL (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is > 50 copies/mL) for ≥ 6 months preceding the screening visit. Unconfirmed virologic elevation of ≥ 50 copies/mL after previously reaching viral suppression (transient detectable viremia, or "blip") and prior to screening is acceptable
- •Have no documented resistance to any of the study agents at any time in the past
- •HIV-1 RNA < 50 copies/mL at the screening visit
- •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)
- •Normal ECG (or if abnormal, determined by the Investigator to be not clinically significant)
- •Adequate renal function: Estimated glomerular filtration rate ≥ 50 mL/min according to the Cockcroft-Gault formula
排除标准
- •Hepatitis B surface antigen (HBsAg) positive
- •Hepatitis C antibody positive with detectable hepatitis C virus (HCV) RNA (individuals who have HCV antibody but no detectable HCV RNA are eligible to enroll)
- •Individuals experiencing or with a medical history of decompensated cirrhosis (e.g., ascites, encephalopathy, etc.)
- •Females who are breastfeeding
- •Positive serum pregnancy test
- •Current alcohol or substance use judged by the Investigator to potentially interfere with the individual's study compliance
- •A history of malignancy within the past 5 years (prior to screening) or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive cutaneous squamous carcinoma. Individuals with cutaneous KS are eligible, but must not have received any systemic therapy for KS within 30 days of Baseline/Day 1 and must not be anticipated to require systemic therapy during the study
- •Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Baseline/Day 1
- •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 from the sponsor is prohibited while participating in this trial
- •Individuals receiving ongoing therapy with any of the disallowed medications listed in the protocol, including drugs not to be used with FTC, RPV and/or TAF; or individuals with any known allergies to the excipients of FTC/RPV/TAF
- •Note: Other protocol defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
FTC/RPV/TAF
FTC/RPV/TAF plus EFV/FTC/TDF placebo for at least 96 weeks.
干预措施: FTC/RPV/TAF (Drug)
FTC/RPV/TAF
FTC/RPV/TAF plus EFV/FTC/TDF placebo for at least 96 weeks.
干预措施: EFV/FTC/TDF Placebo (Drug)
EFV/FTC/TDF
EFV/FTC/TDF plus FTC/RPV/TAF placebo for at least 96 weeks.
干预措施: EFV/FTC/TDF (Drug)
EFV/FTC/TDF
EFV/FTC/TDF plus FTC/RPV/TAF placebo for at least 96 weeks.
干预措施: FTC/RPV/TAF Placebo (Drug)
Open Label Extension Phase
After the Week 96 visit, participants will be given the option to receive open label FTC/RPV/TAF for up to an additional 48 weeks. In countries where FTC/RPV/TAF is not yet commercially available, participants will be given the option to receive open-label FTC/RPV/TAF and attend visits every 12 weeks until FTC/RPV/TAF becomes commercially available, or until Gilead elects to discontinue the study, whichever occurs first.
干预措施: FTC/RPV/TAF (Drug)
结局指标
主要结局
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-defined Snapshot Algorithm
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
- Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Defined by the US FDA-defined Snapshot Algorithm(Week 48)
- Percentage of Participants With HIV-1 RNA ≥ 50 Copies/mL at Week 96 as Defined by the US FDA-defined Snapshot Algorithm(Week 96)
- Change From Baseline in CD4+ Cell Count at Week 96(Baseline; Week 96)
- Percent Change From Baseline in Spine BMD at Week 48(Baseline; Week 48)
- Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48(Baseline; Week 48)
- Change From Baseline in CD4+ Cell Count at Week 48(Baseline; Week 48)
- Percent Change From Baseline in Spine BMD at Week 96(Baseline; Week 96)
- Change From Baseline in HIVSI Score at Week 96(Baseline; Week 96)
- Percent Change From Baseline in Hip BMD at Week 96(Baseline; Week 96)
- Change From Baseline in HIV Symptoms Index Score (HIVSI) at Week 48(Baseline; Week 48)
- Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the US FDA-defined Snapshot(Week 96)