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Open-label Safety Study of E/C/F/TAF (Genvoya®) in HIV-1 Positive Patients With Mild to Moderate Renal Impairment

2020年2月18日 更新者：Gilead Sciences

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

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.

研究概览

地位

完全的

条件

干预/治疗

研究类型

介入性

注册 (实际的)

252

阶段

  • 第三阶段

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 墨西哥
    • Jalisco
      • Guadalajara、Jalisco、墨西哥、44340
        • Hospital Civil de Guadalajara Dr. Juan I. Menchaca
  • 多明尼加共和国
      • Santo Domingo、多明尼加共和国、99999
        • Instituto Dominicano de Estudios Virologicos (IDEV)
  • 法国
      • Lyon、法国、69004
        • Hôpital de la Croix Rousse
      • Paris、法国、75651
        • GHPS Service des maladies infectieuses et tropicales pavillon Laveran unité de recherche clinique
  • 泰国
      • Bangkok、泰国、10400
        • Faculty of Medicine Ramathibodi Hospital, Mahidol University
      • Bangkok、泰国、10330
        • HIV-NAT, Thai Red Cross AIDS Research Centre
      • Bangkok、泰国、10700
        • Department of Preventive and Social Medicine, Faculty of Medicine, Siriraj Hospital
      • Khon Kaen、泰国、40002
        • Srinagarind Hospital, Khon Kaen University
  • 澳大利亚
    • New South Wales
      • Darlinghurst、New South Wales、澳大利亚、2010
        • Holdsworth House Medical Practice
    • Victoria
      • Melbourne、Victoria、澳大利亚、3004
        • Clinical Research Infectious Diseases Department- Alfred Hospital
      • Prahran、Victoria、澳大利亚、3181
        • Prahran Market Clinic
  • 美国
    • Arizona
      • Phoenix、Arizona、美国、85015
        • Pueblo Family Physicians
      • Phoenix、Arizona、美国、85006
        • Maricopa Integrated Health System - McDowell Clinic
    • Arkansas
      • Little Rock、Arkansas、美国、72207
        • Health For Life Clinic Pllc
    • California
      • Beverly Hills、California、美国、90211
        • Pacific Oaks Medical Group
      • Hayward、California、美国、94545
        • Kaiser Permanente
      • Long Beach、California、美国、90813
        • Long Beach Education and Research Consultants
      • Los Angeles、California、美国、90069
        • Anthony Mills MD, Inc
      • Los Angeles、California、美国、90036
        • Peter J Ruane, MD, Inc
      • Los Angeles、California、美国、90028
        • LA Gay & Lesbian Center - Jeffrey Goodman Special Care Clinic
      • Palm Springs、California、美国、92262
        • Desert Medical Group Inc. dba Desert Oasis Healthcare Medical Group
      • Sacramento、California、美国、95825
        • Kaiser Permanente Medical Group
      • San Francisco、California、美国、94109
        • Metropolis Medical
      • San Francisco、California、美国、94118
        • Kaiser Permanente CTU San Francisco
    • Colorado
      • Aurora、Colorado、美国、80045
        • University of Colorado
      • Denver、Colorado、美国、80206
        • National Jewish Health
    • District of Columbia
      • Washington、District of Columbia、美国、20009
        • Dupont Circle Physician's Group
    • Florida
      • Fort Lauderdale、Florida、美国、33316
        • Gary J. Richmond, MD PA
      • Fort Pierce、Florida、美国、34982
        • Midway Immunology and Research Center
      • Orlando、Florida、美国、32806
        • Idocf/Valuhealthmd
      • Tampa、Florida、美国、33602
        • University of South Florida
      • West Palm Beach、Florida、美国、33401
        • Triple O Research Institute, P.A.
      • Wilton Manors、Florida、美国、33305
        • Rowan Tree Medical, P.A.
    • Georgia
      • Decatur、Georgia、美国、30033
        • Infectious Disease Specialists of Atlanta
      • Macon、Georgia、美国、31210
        • Mercer University
    • Indiana
      • Indianapolis、Indiana、美国、46202
        • Indiana University School of Medicine
    • Massachusetts
      • Boston、Massachusetts、美国、02111
        • Community Research Initiative of New England
      • Springfield、Massachusetts、美国、01105
        • The Research Institute
    • Michigan
      • Berkley、Michigan、美国、48210
        • Be Well Medical Center, P.C.
      • Detroit、Michigan、美国、48202
        • Henry Ford Health System
    • Minnesota
      • Minneapolis、Minnesota、美国、55415
        • Hennepin County Medical Center
    • Missouri
      • Kansas City、Missouri、美国、64111
        • The Kansas City Care Clinic (KC Free Health Clinic)
      • Saint Louis、Missouri、美国、63139
        • Southampton Healthcare, Inc.
    • New Jersey
      • Neptune、New Jersey、美国、07754
        • Jersey Shore University Medical Center
      • Newark、New Jersey、美国、07102
        • Saint Michael's Medical Center
    • New Mexico
      • Santa Fe、New Mexico、美国、87505
        • Southwest CARE Center
    • New York
      • Albany、New York、美国、12208
        • Albany Medical College
      • Albany、New York、美国、12208
        • Upstate Infectious Diseases Associates
      • Bronx、New York、美国、10467
        • Montefiore Medical Center
      • Bronx、New York、美国、10461
        • Jacobi Medical Center
      • Manhasset、New York、美国、11030
        • North Shore University Hospital/Division of Infectious Diseases
      • Rochester、New York、美国、14607
        • Aids Care
    • Ohio
      • Cincinnati、Ohio、美国、45267-0405
        • University of Cincinnati
      • Cleveland、Ohio、美国、44109
        • MetroHealth Medical Center
    • Pennsylvania
      • Philadelphia、Pennsylvania、美国、19107
        • Thomas Jefferson University
      • Philadelphia、Pennsylvania、美国、19104
        • University of PA HIV Clinical Trials Unit
    • Texas
      • Bellaire、Texas、美国、77401
        • St. Hope Foundation
      • Dallas、Texas、美国、75246
        • North Texas Infectious Diseases Consultants, PA
      • Harlingen、Texas、美国、78550
        • Garcias' Family Health Group
      • Houston、Texas、美国、77004
        • Therapeutic Concepts, PA
      • Houston、Texas、美国、77098
        • Gordon E. Crofoot MD, PA
    • Washington
      • Seattle、Washington、美国、98104
        • Peter Shalit, MD
  • 英国
      • Brighton、英国、BN2 1ES
        • Brighton & Sussex University Hospitals NHS Trust
      • London、英国、SE5 9RJ
        • Kings College London
      • London、英国、Sw10 9NH
        • Chelsea and Westminster NHS Foundation Trust Hospital
      • Manchester、英国、M13 0FH
        • Central Manchester University Hospitals Nhs Foundation Trust
  • 荷兰
      • Utrecht、荷兰、3584 CX
        • University Medical Center Utrecht
  • 西班牙
      • Barcelona、西班牙、8907
        • Hospital Universitari de Bellvitge
      • Barcelona、西班牙、8916
        • Germans Trias i Pujol University Hospital
      • Madrid、西班牙、28046
        • Hospital La Paz

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Key Inclusion Criteria:

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

Key Exclusion Criteria:

  • 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.

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：不适用
  • 介入模型：单组作业
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：E/C/F/TAF
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.
药品：E/C/F/TAF
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food
其他名称：
  • Genvoya®

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Change From Baseline in the Estimated Glomerular Filtration Rate Calculated by the Cockcroft-Gault Formula (eGFR_CG) at Week 24
大体时间：Baseline; Week 24
eGFR is a measurement of the kidney's ability to filter blood.
Baseline; Week 24
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
大体时间：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.
Baseline; Week 24
Change From Baseline in eGFR Calculated by the CKD-EPI Method Based on Serum Creatinine (eGFR_CKD-EPI,Creatinine) at Week 24
大体时间：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.
Baseline; Week 24

次要结果测量

结果测量
措施说明
大体时间
Change From Baseline in Actual GFR (aGFR) of E/C/F/TAF for Participants Enrolled in the PK/PD Substudy
大体时间：Baseline; Week 2, 4, or 8; Week 24
aGFR was directly measured using iohexol plasma clearance (CLiohexol).
Baseline; Week 2, 4, or 8; Week 24
Percent Change From Baseline in C-type Collagen Sequence (CTX) at Weeks 24 and 48
大体时间：Baseline; Weeks 24 and 48
CTX is a biomarker of bone turnover.
Baseline; Weeks 24 and 48
Percent Change From Baseline in Procollagen Type 1 N-terminal Propeptide (P1NP) at Weeks 24 and 48
大体时间：Baseline; Weeks 24 and 48
P1NP is a biomarker of bone turnover.
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
大体时间：Baseline; Weeks 24, 48, 96, and 144
Urine RBP is a renal biomarker which is used to evaluate drug-induced kidney injury.
Baseline; Weeks 24, 48, 96, and 144
Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio (μg/g) at Weeks 24, 48, 96, and 144
大体时间：Baseline; Weeks 24, 48, 96, and 144
Urine beta-2-microglobulin is a renal biomarker which is used to evaluate drug-induced kidney injury.
Baseline; Weeks 24, 48, 96, and 144
Percentage of Participants Experiencing Adverse Events or Graded Laboratory Abnormalities
大体时间：Baseline up to Week 240 plus 30 days
Adverse events (AEs) and graded laboratory abnormalities occurring during the E/C/F/TAF treatment period were summarized across the participant population. A participant was counted once if they had a qualifying event.
Baseline up to Week 240 plus 30 days
Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Weeks 24, 48, 96, and 144
大体时间：Weeks 24, 48, 96, and 144
The percentage of participants achieving HIV-1 RNA < 50 Copies/mL at Weeks 24, 48, 96, and 144 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.
Weeks 24, 48, 96, and 144
Pharmacokinetic (PK) Parameter: Cmax of TAF
大体时间：Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
Cmax is defined as the maximum concentration of drug. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
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
大体时间：Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
Tmax is defined as the time of Cmax. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
PK Parameter: Clast of TAF
大体时间：Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
Clast is defined as the last observable concentration of drug. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
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
大体时间：Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
Tlast is defined as the time of Clast. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
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
大体时间：Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
λz is defined as the terminal elimination rate constant. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
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
大体时间：Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval). Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
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
大体时间：Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
t1/2 is defined as the estimate of the terminal elimination half-life of the drug. Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
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 Tenofovir Diphosphate (TFV-DP) in Peripheral Blood Mononuclear Cell (PBMC) for Participants Enrolled in PK/PD Sub-study
大体时间：Predose, and 5 minutes, 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 8, and 24 hours postdose
TFV-DP is an active phosphorylated metabolite of tenofovir alafenamide. AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval). Blood draws for this outcome may have been at the Week 2, 4, or 8 visit.
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 the eGFR_CG at Weeks 48, 96, and 144
大体时间：Baseline; Weeks 48, 96, and 144
eGFR is a measurement of the kidney's ability to filter blood.
Baseline; Weeks 48, 96, and 144
Change From Baseline in eGFR_CKD-EPI,cysC at Weeks 48, 96, and 144
大体时间：Baseline; Weeks 48, 96, and 144
eGFR is a measurement of the kidney's ability to filter blood. The eGFR_CKD-EPI,cysC method is adjusted for age and sex.
Baseline; Weeks 48, 96, and 144
Change From Baseline in eGFR_CKD-EPI,Creatinine at Weeks 48, 96, and 144
大体时间：Baseline; Weeks 48, 96, and 144
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.
Baseline; Weeks 48, 96, and 144

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Gilead Sciences

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2013年3月27日

初级完成 (实际的)

2014年7月31日

研究完成 (实际的)

2018年7月18日

研究注册日期

首次提交

2013年3月22日

首先提交符合 QC 标准的

2013年3月22日

首次发布 (估计)

2013年3月26日

研究记录更新

最后更新发布 (实际的)

2020年3月2日

上次提交的符合 QC 标准的更新

2020年2月18日

最后验证

2019年6月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • GS-US-292-0112
  • 2013-000516-25 (EudraCT编号)

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

是的

IPD 计划说明

Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy.

IPD 共享时间框架

18 months after study completion

IPD 共享访问标准

A secured external environment with username, password, and RSA code.

IPD 共享支持信息类型

  • 研究方案
  • 树液

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

艾滋病毒感染的临床试验

E/C/F/TAF的临床试验

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赞助者和合作者

医疗条件

药物干预

CROs by country

CROs in Mauritania

条件

罕见疾病

药物干预

膳食补充剂

赞助者/合作者

地点

3
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