Clinical Trials

MainTitle

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

This study has been completed
Sponsor
Gilead Sciences


Information provided by (Responsible Party)
Gilead Sciences
ClinicalTrials.gov Identifier
NCT01818596

First received: March 22, 2013
Last updated: February 18, 2020
Last Verified: June 2019
History of Changes
Purpose

Purpose

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.

Condition Intervention Phase
HIV
HIV Infections

Drug : E/C/F/TAF
Phase 3

Study Type: Interventional
Study Design: Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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

Further study details as provided by Gilead Sciences:

Primary Outcome Measures

  • Change From Baseline in the Estimated Glomerular Filtration Rate Calculated by the Cockcroft-Gault Formula (eGFR_CG) at Week 24 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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.
Secondary Outcome Measures:
  • Change From Baseline in Actual GFR (aGFR) of E/C/F/TAF for Participants Enrolled in the PK/PD Substudy [ Time Frame: Baseline; Week 2, 4, or 8; Week 24 ]
    aGFR was directly measured using iohexol plasma clearance (CLiohexol).
  • Percent Change From Baseline in C-type Collagen Sequence (CTX) at Weeks 24 and 48 [ Time Frame: Baseline; Weeks 24 and 48 ]
    CTX is a biomarker of bone turnover.
  • Percent Change From Baseline in Procollagen Type 1 N-terminal Propeptide (P1NP) at Weeks 24 and 48 [ Time Frame: Baseline; Weeks 24 and 48 ]
    P1NP is a biomarker of bone turnover.
  • Percent Change From Baseline in Retinol Binding Protein (RBP) to Creatinine Ratio (μg/g) at Weeks 24, 48, 96, and 144 [ Time Frame: Baseline; Weeks 24, 48, 96, and 144 ]
    Urine RBP is a renal biomarker which is used to evaluate drug-induced kidney injury.
  • Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio (μg/g) at Weeks 24, 48, 96, and 144 [ Time Frame: Baseline; Weeks 24, 48, 96, and 144 ]
    Urine beta-2-microglobulin is a renal biomarker which is used to evaluate drug-induced kidney injury.
  • Percentage of Participants Experiencing Adverse Events or Graded Laboratory Abnormalities [ Time Frame: 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.
  • Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Weeks 24, 48, 96, and 144 [ Time Frame: 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.
  • Pharmacokinetic (PK) Parameter: Cmax of TAF [ Time Frame: 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.
  • PK Parameter: Tmax of TAF [ Time Frame: 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.
  • PK Parameter: Clast of TAF [ Time Frame: 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.
  • PK Parameter: Tlast of TAF [ Time Frame: 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.
  • PK Parameter: λz of TAF [ Time Frame: 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.
  • PK Parameter: AUCtau of TAF [ Time Frame: 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.
  • PK Parameter: t1/2 of TAF [ Time Frame: 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.
  • PK Parameter: AUCtau of Tenofovir Diphosphate (TFV-DP) in Peripheral Blood Mononuclear Cell (PBMC) for Participants Enrolled in PK/PD Sub-study [ Time Frame: 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.
  • Change From Baseline in the eGFR_CG at Weeks 48, 96, and 144 [ Time Frame: Baseline; Weeks 48, 96, and 144 ]
    eGFR is a measurement of the kidney's ability to filter blood.
  • Change From Baseline in eGFR_CKD-EPI,cysC at Weeks 48, 96, and 144 [ Time Frame: 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.
  • Change From Baseline in eGFR_CKD-EPI,Creatinine at Weeks 48, 96, and 144 [ Time Frame: 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.

Enrollment: 252
Study Start Date: March 27, 2013
Study Completion Date: July 18, 2018
Primary Completion Date: July 31, 2014 (Final data collection date for primary outcome measure)

Arms Assigned Interventions
Experimental: 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.
Drug: E/C/F/TAF

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

Other Name: Genvoya®
Eligibility

Eligibility

Ages Eligible for Study: 18 Years and older  
Sexes Eligible for Study: All  
Accepts Healthy Volunteers: No  

Criteria

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.

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01818596

Locations

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

Sponsors and Collaborators

Gilead Sciences

Investigators

Study Director: Gilead Study Director Gilead Sciences
More Information

More Information


Responsible Party: Gilead Sciences  
ClinicalTrials.gov Identifier: NCT01818596   History of Changes  
Other Study ID Numbers: GS-US-292-0112  
  2013-000516-25  
Study First Received: March 22, 2013  
Last Updated: February 18, 2020  
Individual Participant Data    
Plan to Share IPD: Yes  

Studies a U.S. FDA-regulated Drug Product: Yes  
Studies a U.S. FDA-regulated Device Product: No  

Keywords provided by Gilead Sciences:

HIV
HIV-1 Infected
Treatment Experienced
Treatment Naive

Additional relevant MeSH terms:
HIV Infections
Renal Insufficiency
Genvoya

ClinicalTrials.gov processed this data on June 02, 2020
This information is provided by ClinicalTrials.gov.