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

NCT ID: NCT01818596

Last Updated: 2020-03-02

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

252 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-03-27

Study Completion Date

2018-07-18

Brief Summary

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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.

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Detailed Description

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Conditions

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HIV HIV Infections

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

E/C/F/TAF

Intervention Type DRUG

E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food

Interventions

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E/C/F/TAF

E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food

Intervention Type DRUG

Other Intervention Names

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Genvoya®

Eligibility Criteria

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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:


* 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

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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Maricopa Integrated Health System - McDowell Clinic

Phoenix, Arizona, United States

Site Status

Pueblo Family Physicians

Phoenix, Arizona, United States

Site Status

Health for Life Clinic PLLC

Little Rock, Arkansas, United States

Site Status

Pacific Oaks Medical Group

Beverly Hills, California, United States

Site Status

Kaiser Permanente

Hayward, California, United States

Site Status

Long Beach Education and Research Consultants

Long Beach, California, United States

Site Status

LA Gay & Lesbian Center - Jeffrey Goodman Special Care Clinic

Los Angeles, California, United States

Site Status

Peter J Ruane, MD, Inc

Los Angeles, California, United States

Site Status

Anthony Mills MD, Inc

Los Angeles, California, United States

Site Status

Desert Medical Group Inc. dba Desert Oasis Healthcare Medical Group

Palm Springs, California, United States

Site Status

Kaiser Permanente Medical Group

Sacramento, California, United States

Site Status

Metropolis Medical

San Francisco, California, United States

Site Status

Kaiser Permanente CTU San Francisco

San Francisco, California, United States

Site Status

University of Colorado

Aurora, Colorado, United States

Site Status

National Jewish Health

Denver, Colorado, United States

Site Status

Dupont Circle Physician's Group

Washington D.C., District of Columbia, United States

Site Status

Gary J. Richmond, MD PA

Fort Lauderdale, Florida, United States

Site Status

Midway Immunology and Research Center

Ft. Pierce, Florida, United States

Site Status

Idocf/Valuhealthmd

Orlando, Florida, United States

Site Status

University of South Florida

Tampa, Florida, United States

Site Status

Triple O Research Institute, P.A.

West Palm Beach, Florida, United States

Site Status

Rowan Tree Medical, P.A.

Wilton Manors, Florida, United States

Site Status

Infectious Disease Specialists of Atlanta

Decatur, Georgia, United States

Site Status

Mercer University

Macon, Georgia, United States

Site Status

Indiana University School of Medicine

Indianapolis, Indiana, United States

Site Status

Community Research Initiative of New England

Boston, Massachusetts, United States

Site Status

The Research Institute

Springfield, Massachusetts, United States

Site Status

Be Well Medical Center, P.C.

Berkley, Michigan, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

Hennepin County Medical Center

Minneapolis, Minnesota, United States

Site Status

The Kansas City Care Clinic (KC Free Health Clinic)

Kansas City, Missouri, United States

Site Status

Southampton Healthcare, Inc.

St Louis, Missouri, United States

Site Status

Jersey Shore University Medical Center

Neptune City, New Jersey, United States

Site Status

Saint Michael's Medical Center

Newark, New Jersey, United States

Site Status

Southwest CARE Center

Santa Fe, New Mexico, United States

Site Status

Albany Medical College

Albany, New York, United States

Site Status

Upstate Infectious Diseases Associates

Albany, New York, United States

Site Status

North Shore University Hospital/Division of Infectious Diseases

Manhasset, New York, United States

Site Status

Aids Care

Rochester, New York, United States

Site Status

Jacobi Medical Center

The Bronx, New York, United States

Site Status

Montefiore Medical Center

The Bronx, New York, United States

Site Status

University of Cincinnati

Cincinnati, Ohio, United States

Site Status

MetroHealth Medical Center

Cleveland, Ohio, United States

Site Status

University of PA HIV Clinical Trials Unit

Philadelphia, Pennsylvania, United States

Site Status

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status

St. Hope Foundation

Bellaire, Texas, United States

Site Status

North Texas Infectious Diseases Consultants, PA

Dallas, Texas, United States

Site Status

Garcias' Family Health Group

Harlingen, Texas, United States

Site Status

Therapeutic Concepts, PA

Houston, Texas, United States

Site Status

Gordon E. Crofoot MD, PA

Houston, Texas, United States

Site Status

Peter Shalit, MD

Seattle, Washington, United States

Site Status

Holdsworth House Medical Practice

Darlinghurst, New South Wales, Australia

Site Status

Clinical Research Infectious Diseases Department- Alfred Hospital

Melbourne, Victoria, Australia

Site Status

Prahran Market Clinic

Prahran, Victoria, Australia

Site Status

Instituto Dominicano de Estudios Virologicos (IDEV)

Santo Domingo, , Dominican Republic

Site Status

Hopital de la Croix Rousse

Lyon, , France

Site Status

GHPS Service des maladies infectieuses et tropicales pavillon Laveran unité de recherche clinique

Paris, , France

Site Status

Hospital Civil de Guadalajara Dr. Juan I. Menchaca

Guadalajara, Jalisco, Mexico

Site Status

University Medical Center Utrecht

Utrecht, , Netherlands

Site Status

Hospital Universitari de Bellvitge

Barcelona, , Spain

Site Status

Germans Trias i Pujol University Hospital

Barcelona, , Spain

Site Status

Hospital La Paz

Madrid, , Spain

Site Status

HIV-NAT, Thai Red Cross AIDS Research Centre

Bangkok, , Thailand

Site Status

Faculty of Medicine Ramathibodi Hospital, Mahidol University

Bangkok, , Thailand

Site Status

Department of Preventive and Social Medicine, Faculty of Medicine, Siriraj Hospital

Bangkok, , Thailand

Site Status

Srinagarind Hospital, Khon Kaen University

Khon Kaen, , Thailand

Site Status

Brighton & Sussex University Hospitals NHS Trust

Brighton, , United Kingdom

Site Status

Kings College London

London, , United Kingdom

Site Status

Chelsea and Westminster NHS Foundation Trust Hospital

London, , United Kingdom

Site Status

Central Manchester University Hospitals NHS foundation Trust

Manchester, , United Kingdom

Site Status

Countries

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United States Australia Dominican Republic France Mexico Netherlands Spain Thailand United Kingdom

References

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Pozniak A, Arribas JR, Gathe J, Gupta SK, Post FA, Bloch M, Avihingsanon A, Crofoot G, Benson P, Lichtenstein K, Ramgopal M, Chetchotisakd P, Custodio JM, Abram ME, Wei X, Cheng A, McCallister S, SenGupta D, Fordyce MW; GS-US-292-0112 Study Team. Switching to Tenofovir Alafenamide, Coformulated With Elvitegravir, Cobicistat, and Emtricitabine, in HIV-Infected Patients With Renal Impairment: 48-Week Results From a Single-Arm, Multicenter, Open-Label Phase 3 Study. J Acquir Immune Defic Syndr. 2016 Apr 15;71(5):530-7. doi: 10.1097/QAI.0000000000000908.

Reference Type RESULT
PMID: 26627107 (View on PubMed)

Post FA, Tebas P, Clarke A, Cotte L, Short WR, Abram ME, Jiang S, Cheng A, Das M, Fordyce MW. Brief Report: Switching to Tenofovir Alafenamide, Coformulated With Elvitegravir, Cobicistat, and Emtricitabine, in HIV-Infected Adults With Renal Impairment: 96-Week Results From a Single-Arm, Multicenter, Open-Label Phase 3 Study. J Acquir Immune Defic Syndr. 2017 Feb 1;74(2):180-184. doi: 10.1097/QAI.0000000000001186.

Reference Type RESULT
PMID: 27673443 (View on PubMed)

Other Identifiers

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2013-000516-25

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-292-0112

Identifier Type: -

Identifier Source: org_study_id

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