A Phase 3b, Multicenter, Open-Label Study to Evaluate Switching From a Regimen of Two Nucleos(t)Ide Reverse Transcriptase Inhibitors (NRTI) Plus a Third Agent to a Fixed Dose Combination (FDC) of Bictegravir/Emtricitabine/Tenofovir Alafenamide (B/F/TAF), in Virologically-Suppressed, HIV-1 Infected African American Participants
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 496
- 试验地点
- 81
- 主要终点
- Percentage of Participants Who Had HIV-1 RNA ≥ 50 Copies/mL at Week 24 as Defined by the US FDA-Defined Snapshot Algorithm: Full Analysis Set
研究概览
简要总结
The primary objective of this study is to evaluate the efficacy of switching from a regimen of 2 nucleos(t)Ide reverse transcriptase inhibitors (NRTIs) and a third agent to a fixed dose combination (FDC) of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus continuing their baseline regimen in HIV-1 infected, virologically suppressed African American 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
- 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
- •Self-describes as Black, African American, or mixed race, including Black
- •Currently receiving an antiretrovirals (ARV) regimen other than FDC of B/F/TAF that consists of any two NRTIs + allowed 3rd agent for ≥ 6 months
- •Allowed 3rd agents include any FDA-approved INSTI, with the exception of bictegravir, any FDA-approved NNRTI with the exception of etravirine, protease inhibitors or the CCR5 antagonist, maraviroc
- •If the baseline 3rd agent is dolutegravir, dosing other than 50 mg once daily is excluded
- •Baseline regimens containing investigational drugs or > 2 classes of ARVs are not permitted, with the exception of the pharmacologic enhancers cobicistat (taken with elvitegravir or a PI), or ritonavir (taken with a PI)
- •Have no documented or suspected resistance to INSTIs and no history of virologic failure on an INSTI containing regimen (2 consecutive HIV-1 RNA ≥ 50 copies/mL after achieving <50 copies/mL while on an INSTI-containing regimen)
- •History of 1-2 thymidine analogue mutations (TAMs), M184V/I, and any other RT substitutions are allowed, with the following exceptions: History of 3 or more TAMs (M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E/N/R), T69-insertions, or K65R/E/N in RT will be excluded
- •Documented plasma HIV-1 RNA < 50 copies/mL during treatment with the baseline regimen for a minimum period of 6 months and at least the last two HIV-1 RNA measurements prior to the Screening visit
- •HIV-1 RNA levels < 50 copies/mL at Screening
- •Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance
排除标准
- •History of 3 or more TAMs (M41L, D67N, K70R, L210W, T215F/Y, and K219Q/E/N/R),T69-insertions, or K65R/E/N in RT
- •No desire to switch from current ARVs
- •An opportunistic illness indicative of stage 3 HIV diagnosed within the 30 days prior to screening
- •Participants experiencing decompensated cirrhosis (e.g., ascites, encephalopathy, or variceal bleeding)
- •Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids during the study (eg, corticosteroids, immunoglobulins, and other immune- or cytokine-based therapies)
- •Malignancy within 5 years of screening other than cutaneous Kaposi's sarcoma, completely resected non -melanoma skin cancer (basal cell carcinoma or non-invasive cutaneous squamous carcinoma), or completely resected carcinoma in-situ of the cervix (CIN 3) or anus (AIN 3). A prior malignancy treated with curative therapy and for which there has been no evidence of disease for at least five years prior to screening is allowed
- •Current alcohol or substance use judged by the Investigator to potentially interfere with participant study compliance
- •Active, serious infections (other than HIV-1 infection) requiring antibiotic or antifungal therapy within 30 days prior to Day 1
- •Participation in any other clinical trial, including observational studies, without prior approval from the sponsor is prohibited while participating in this trial
- •Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the participant unsuitable for the study or unable to comply with the dosing requirements
- •Known hypersensitivity to FDC of B/F/TAF tablets, their metabolites, or formulation excipient
- •Females who are pregnant (as confirmed by positive serum pregnancy test)
- •Females who are breastfeeding
- •Acute hepatitis in the 30 days prior to randomization
- •Active tuberculosis infection.
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
B/F/TAF
Participants will receive B/F/TAF (50/200/25 mg) FDC tablet orally once daily for 48 weeks, without regard to food. At Week 48, participants who wish to continue on B/F/TAF will be given the option to receive B/F/TAF FDC for up to an additional 24 weeks or until they have access to B/F/TAF, whichever occurs first.
干预措施: B/F/TAF (Drug)
Stay on Baseline Regimen (SBR)/ Delayed B/F/TAF
Participants will stay on baseline regimen consisting of 2 NRTIs and a third agent (each taken as prescribed) for 24 weeks with a delayed switch to B/F/TAF (50/200/25 mg) FDC tablet administered orally, once daily until Week 48 without regard to food. At Week 48, participants who wish to continue on B/F/TAF will be given the option to receive B/F/TAF FDC for up to an additional 24 weeks or until they have access to B/F/TAF, whichever occurs first.
干预措施: B/F/TAF (Drug)
Stay on Baseline Regimen (SBR)/ Delayed B/F/TAF
Participants will stay on baseline regimen consisting of 2 NRTIs and a third agent (each taken as prescribed) for 24 weeks with a delayed switch to B/F/TAF (50/200/25 mg) FDC tablet administered orally, once daily until Week 48 without regard to food. At Week 48, participants who wish to continue on B/F/TAF will be given the option to receive B/F/TAF FDC for up to an additional 24 weeks or until they have access to B/F/TAF, whichever occurs first.
干预措施: NRTIs (Drug)
Stay on Baseline Regimen (SBR)/ Delayed B/F/TAF
Participants will stay on baseline regimen consisting of 2 NRTIs and a third agent (each taken as prescribed) for 24 weeks with a delayed switch to B/F/TAF (50/200/25 mg) FDC tablet administered orally, once daily until Week 48 without regard to food. At Week 48, participants who wish to continue on B/F/TAF will be given the option to receive B/F/TAF FDC for up to an additional 24 weeks or until they have access to B/F/TAF, whichever occurs first.
干预措施: Third Agent (Drug)
结局指标
主要结局
Percentage of Participants Who Had HIV-1 RNA ≥ 50 Copies/mL at Week 24 as Defined by the US FDA-Defined Snapshot Algorithm: Full Analysis Set
时间窗: Week 24
The percentage of participants who had HIV-1 RNA ≥ 50 copies/mL at Week 24 was analyzed using the snapshot algorithm, which defined 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
- Percentage of Participants Who Had HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm: Full Analysis Set(Week 48)
- Change From Baseline in CD4+ Cell Count at Week 24: Full Analysis Set(Baseline to Week 24)
- Percentage of Participants Experiencing Treatment-Emergent Graded Laboratory Abnormalities(First B/F/TAF dose date up to Week 72 plus 30 days)
- Percentage of Participants Who Had HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the US FDA-Defined Snapshot Algorithm: Week 24 Per Protocol Analysis Set(Week 24)
- Percentage of Participants Who Had HIV-1 RNA ≥ 50 Copies/mL at Week 48 as Defined by the US FDA-Defined Snapshot Algorithm: Full Analysis Set(Week 48)
- Percentage of Participants Who Had HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the US FDA-Defined Snapshot Algorithm: Full Analysis Set(Week 24)
- Change From Baseline in CD4+ Cell Count at Week 24: Week 24 Per Protocol Analysis Set(Baseline to Week 24)
- Change From Baseline in CD4+ Cell Count at Week 48: Full Analysis Set(Baseline to Week 48)
- Percentage of Participants Experiencing Treatment-Emergent Adverse Events(First B/F/TAF dose date up to Week 72 plus 30 days)