NCT01818596已完成3 期
A Phase 3 Open-label Safety Study of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Single-Tablet Regimen in HIV-1 Positive Patients With Mild to Moderate Renal Impairment
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 252
- 试验地点
- 70
- 主要终点
- Change From Baseline in the Estimated Glomerular Filtration Rate Calculated by the Cockcroft-Gault Formula (eGFR_CG) at Week 24
研究概览
简要总结
The primary objective of this study is to evaluate the effect of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) tablet on renal parameters at Week 24 in treatment-naive and treatment-experienced HIV-positive, adults with mild to moderate renal impairment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Cohort 1 (treatment-experienced switch)
- •Must not have a history of known resistance to elvitegravir (EVG), tenofovir disoproxil fumarate (TDF), or emtricitabine (FTC)
- •Plasma HIV-1 RNA concentrations (at least two measurements) at undetectable levels (according to the local assay being used) in the 6 months preceding the screening visit and have HIV-1 RNA < 50 copies/mL at screening
- •Estimated glomerular filtration rate (GFR) 30-69 mL/min according to the Cockcroft-Gault formula for creatinine clearance, using actual weight
- •May be currently enrolled in Gilead studies GS-US-236-0102, GS-US-236-0103, and GS-US-216-0114, but will be eligible to enroll only after the Week 144 visit for that study is complete; or currently receiving Stribild® (STB) or atazanavir (ATV)/cobicistat (COBI) + Truvada (TVD) in Gilead studies GS-US-236-0104 or GS-US-216-0105, but will be eligible to enroll only after the Week 48 visit for that study is complete.
- •Cohort 2 (treatment-naive)
- •Plasma HIV-1 RNA levels ≥ 1,000 copies/mL at screening
- •Screening genotype report provided by Gilead Sciences must show sensitivity to EVG, FTC, and TDF
- •No prior use of any approved or investigational antiretroviral drug for any length of time, except the use for pre-exposure prophylaxis (PrEP), or post-exposure prophylaxis (PEP), up to 6 months prior to screening
- •Estimated GFR 30-69 mL/min according to the Cockcroft Gault formula for creatinine clearance, using actual weight
- •All Cohorts:
- •All individuals must meet all of the following inclusion criteria to be eligible for participation in this study:
- •The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
- •CD4+ count of ≥ 50 cells/μL
- •Stable renal function: serum creatinine measurements to be taken at least once (within three months of screening)
- •Cause of underlying chronic kidney disease (eg hypertension, diabetes) stable, without change in medical management, for 3 months prior to baseline
- •Normal electrocardiogram (ECG)
- •Hepatic transaminases (AST and ALT) ≤ 5 x upper limit of normal (ULN)
- •Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
- •Adequate hematologic function
- •Serum amylase ≤ 5 x ULN
- •Females of childbearing potential must agree to utilize highly effective contraception methods (two separate forms of contraception, one of which must be an effective barrier method, or be non-heterosexually active, practice sexual abstinence) from screening throughout the duration of study treatment and for 30 days following the last dose of study drug
- •Females 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
- •Males must agree to utilize a highly effective method of contraception during heterosexual intercourse throughout the study period and for 30 days following discontinuation of investigational medicinal product. A highly effective method of contraception is defined as two separate forms of contraception, one of which must be an effective barrier method, or males must be non-heterosexually active, or practice sexual abstinence
排除标准
- •A new AIDS-defining condition (excluding CD4 cell count and percentage criteria) diagnosed within the 30 days prior to screening,with the exception of the first two bullet points
- •Hepatitis C virus (HCV) antibody positive. Individuals who are HCV positive, but have a documented negative HCV RNA, are eligible
- •Hepatitis B surface antigen (HBVsAg) 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
- •Individuals experiencing decompensated cirrhosis (eg, ascites, encephalopathy, etc.)
- •Females who are breastfeeding
- •Positive serum pregnancy test
- •Have an implanted defibrillator or pacemaker
- •Current alcohol or substance use judged by the Investigator to potentially interfere with study compliance
- •A history of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, 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 baseline
- •Individuals on hemodialysis, other forms of renal replacement therapy, or on treatment for underlying kidney diseases (including prednisolone and dexamethasone)
- •Individuals receiving ongoing therapy with any medications not to be used with EVG, COBI, FTC, or TAF or individuals with any known allergies to the excipients of E/C/F/TAF
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
E/C/F/TAF
Experimental
Participants will receive E/C/F/TAF for 144 weeks. Following Week 144, in countries where E/C/F/TAF is not available (except for the United Kingdom), participants will be given the option to continue in the study and receive E/C/F/TAF for another 48 weeks, or until the product becomes available through an access program, or until Gilead Sciences elects to discontinue the study in that country, whichever comes first.
干预措施: E/C/F/TAF (Drug)
结局指标
主要结局
Change From Baseline in the Estimated Glomerular Filtration Rate Calculated by the Cockcroft-Gault Formula (eGFR_CG) at Week 24
时间窗: Baseline; Week 24
eGFR is a measurement of the kidney's ability to filter blood.
Change From Baseline in eGFR Calculated by the Chronic Kidney Disease Epidemiology Collaboration Method Based on Cystatin C (eGFR_CKD-EPI,cysC) at Week 24
时间窗: Baseline; Week 24
eGFR is a measurement of the kidney's ability to filter blood. The eGFR_CKD-EPI,cysC method is adjusted for age and sex.
Change From Baseline in eGFR Calculated by the CKD-EPI Method Based on Serum Creatinine (eGFR_CKD-EPI,Creatinine) at Week 24
时间窗: Baseline; Week 24
eGFR is a measurement of the kidney's ability to filter blood. The eGFR_CKD-EPI,creatinine method is adjusted for age, race, and sex.
次要结局
- Change From Baseline in Actual GFR (aGFR) of E/C/F/TAF for Participants Enrolled in the PK/PD Substudy(Baseline; Week 2, 4, or 8; Week 24)
- Percentage of Participants Experiencing Adverse Events or Graded Laboratory Abnormalities(Baseline up to Week 240 plus 30 days)
- PK Parameter: Clast of TAF(Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose)
- PK Parameter: Tlast of TAF(Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose)
- Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Weeks 24, 48, 96, and 144(Weeks 24, 48, 96, and 144)
- Percent Change From Baseline in C-type Collagen Sequence (CTX) at Weeks 24 and 48(Baseline; Weeks 24 and 48)
- Percent Change From Baseline in Procollagen Type 1 N-terminal Propeptide (P1NP) at Weeks 24 and 48(Baseline; Weeks 24 and 48)
- Percent Change From Baseline in Retinol Binding Protein (RBP) to Creatinine Ratio (μg/g) at Weeks 24, 48, 96, and 144(Baseline; Weeks 24, 48, 96, and 144)
- PK Parameter: AUCtau of Tenofovir Diphosphate (TFV-DP) in Peripheral Blood Mononuclear Cell (PBMC) for Participants Enrolled in PK/PD Sub-study(Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose)
- Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio (μg/g) at Weeks 24, 48, 96, and 144(Baseline; Weeks 24, 48, 96, and 144)
- Pharmacokinetic (PK) Parameter: Cmax of TAF(Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose)
- PK Parameter: Tmax of TAF(Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose)
- PK Parameter: t1/2 of TAF(Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose)
- PK Parameter: λz of TAF(Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose)
- PK Parameter: AUCtau of TAF(Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose)
- Change From Baseline in eGFR_CKD-EPI,cysC at Weeks 48, 96, and 144(Baseline; Weeks 48, 96, and 144)
- Change From Baseline in the eGFR_CG at Weeks 48, 96, and 144(Baseline; Weeks 48, 96, and 144)
- Change From Baseline in eGFR_CKD-EPI,Creatinine at Weeks 48, 96, and 144(Baseline; Weeks 48, 96, and 144)
研究者
研究点 (70)
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