A Phase 3b Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of E/C/F/TAF Fixed Dose Combination (FDC) in HIV-1 Infected Subjects on Chronic Hemodialysis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 55
- 试验地点
- 26
- 主要终点
- GEN Phase: Percentage of Participants Experiencing Treatment-Emergent Grade 3 or Higher Adverse Events Up to Week 48
研究概览
简要总结
The primary objective of this study is to evaluate the safety and tolerability of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) in human immunodeficiency virus (HIV-1) infected adults with end-stage renal disease (ESRD) on chronic hemodialysis (HD).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •Currently on a stable antiretroviral regimen for ≥ 6 consecutive months
- •Plasma HIV-1 ribonucleic acid (RNA) concentrations < 50 copies/mL for ≥ 6 months preceding the screening visit and have HIV-1 RNA < 50 copies/mL at screening
- •No documented history of HIV-1 resistance to elvitegravir (EVG), emtricitabine (FTC), lamivudine (3TC) or tenofovir (TFV) and no history of switching off EVG, FTC, 3TC or TFV due to concern for resistance
- •Cluster determinant 4 (CD4+) T cell count ≥ 200 cells/μL
- •ESRD with estimated glomerular filtration rate (eGFR) < 15 mL/min by Cockcroft-Gault formula for creatinine clearance
- •On chronic HD for ≥ 6 months prior to screening
- •Adequate hematologic function (absolute neutrophil count ≥ 1,000/mm^3; platelets ≥ 50,000/mm^3; hemoglobin ≥ 8.5 g/dL)
排除标准
- •Hepatitis B co-infection
- •Any clinical history, condition, or test result that, in the opinion of the Investigator, would make the individual unsuitable for the study or unable to comply with dosing requirements
- •Administration of other investigational agents (unless approved by Gilead Sciences). Participation in any other clinical trial, including observational trials, without prior approval from the sponsor is prohibited while participating in this trial.
- •History or presence of allergy or intolerance to the study drugs or their components
- •A new acquired immunodeficiency syndrome (AIDS)-defining condition (excluding CD4+ T cell count and percentage criteria) diagnosed within the 30 days prior to screening, with the exception of oropharyngeal candidiasis
- •Received solid organ or bone marrow transplant
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
E/C/F/TAF
Participants will switch their current antiretroviral regimen to E/C/F/TAF and receive treatment for 96 weeks. After Week 96, participants in the United States (US) who wish to participate in the open-label (OL) rollover extension will continue to take E/C/F/TAF FDC until the End of E/C/F/TAF Visit.
干预措施: E/C/F/TAF (Drug)
Open-Label Rollover Extension B/F/TAF
At Week 96 or the End of E/C/F/TAF Visit (whichever occurs last), participants will be given the option to receive open-label bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) for at least 48 weeks.
干预措施: B/F/TAF (Drug)
结局指标
主要结局
GEN Phase: Percentage of Participants Experiencing Treatment-Emergent Grade 3 or Higher Adverse Events Up to Week 48
时间窗: First Dose Date Up to Week 48
Treatment-emergent Adverse Events (TEAE) were defined as AEs with onset dates on or after the study drug start date and no later than 30 days after the permanent discontinuation of the E/C/F/TAF (GEN Phase) study drug or all AEs for participants still on E/C/F/TAF. It also includes the AEs that led to premature discontinuation of E/C/F/TAF study drug. Clinical events and clinically significant laboratory abnormalities were graded according to the GSI Grading Scale for Severity of Adverse Events and Laboratory Abnormalities. Adverse events were graded as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), or Grade 4 (life threatening).
次要结局
- GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 as Defined by the FDA Snapshot Algorithm(Week 96)
- Pharmacokinetic (PK) Parameter: AUCtau of Elvitegravir (EVG), Cobicistat (COBI), Emtricitabine (FTC), and Tenofovir (TFV)(0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4)
- GEN Phase: Percentage of Participants Experiencing Treatment-Emergent Grade 3 or Higher Adverse Events Up to Week 96(First Dose Date Up to Week 96)
- GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24 as Defined by the FDA Snapshot Algorithm(Week 24)
- GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 Using the Missing = Excluded (M = E) Approach(Week 96)
- BVY OL Extension Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 Using the M = E Approach(Week 48 of the BVY OL Extension Phase)
- GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 Using the Missing = Failure (M = F) Approach(Week 96)
- GEN Phase: Change From Baseline in CD4 Percentage at Week 96(Baseline; Week 96)
- GEN Phase: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48 as Defined by the FDA Snapshot Algorithm(Week 48)
- PK Parameter: AUClast of EVG, COBI, FTC, Tenofovir Alafenamide (TAF), and TFV(0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4)
- GEN Phase: Change From Baseline in Cluster Determinant 4+ (CD4+) Cell Count at Week 96(Baseline; Week 96)
- BVY OL Extension Phase: Change From Baseline in CD4+ Cell Count at Week 48(Baseline; Week 48 of the BVY OL Extension Phase)
- PK Parameter: Cmax of EVG, COBI, FTC, TAF, and TFV(0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4)
- PK Parameter: Ctau of EVG, COBI, FTC, and TFV(0.5, 1, 2, 3, 4, 6, 8, and 24 hours postdose at or between Week 2 or Week 4)
- BVY OL Extension Phase: Change From Baseline in CD4 Percentage at Week 48(Baseline; Week 48 of the BVY OL Extension Phase)