Open-label Safety Study of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Single-Tablet Regimen in HIV-1 Positive Patients With Mild to Moderate Renal Impairment

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01818596
First received: March 22, 2013
Last updated: March 3, 2014
Last verified: March 2014
  Purpose

This open-label, multicenter, multi-cohort study is to assess the safety, tolerability, and efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) single-tablet regimen (STR) in treatment-naive and treatment-experienced HIV-positive, adult participants with mild to moderate renal impairment.

The primary objective of this study is to evaluate the effect of E/C/F/TAF STR on renal parameters at Week 24. The proportion of subjects achieving virologic response of HIV-1 RNA < 50 copies/mL will also be assessed.

At sites able to conduct the appropriate testing, approximately 30 participants will be enrolled into an intensive pharmacokinetic/pharmacodynamic (PK/PD) substudy to evaluate the PK/PD parameters of the individual components of E/C/F/TAF as well as tenofovir diphosphate (TFV-DP).


Condition Intervention Phase
HIV
HIV Infections
Drug: E/C/F/TAF
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Change from baseline in the estimated glomerular filtration rate (eGFR) at Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]

    eGFR, a measure of blood filtration by the kidney, will be assessed by the following methods:

    • eGFR calculated by the Cockcroft-Gault (CG) formula (eGFR-CG)
    • eGFR calculated by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) method based on Cystatin C (mg/L) and adjusted for age and sex
    • eGFR calculated by the CKD-EPI method based on serum creatinine and adjusted for age, sex, and race


Secondary Outcome Measures:
  • Change from baseline in the eGFR at Week 48 and 96 [ Time Frame: Baseline to Weeks 48 and 96 ] [ Designated as safety issue: No ]

    eGFR will be assessed by the following methods:

    • eGFR-CG based on serum creatinine
    • eGFR-CKD-EPI based on Cystatin C (mg/L) and adjusted for age and sex
    • eGFR-CKD-EPI based on serum creatinine and adjusted for age, sex, and race

  • Plasma PD (true GFR) of E/C/F/TAF for participants enrolled in the PK/PD sub-study [ Time Frame: Weeks 2, 4, 8, and 24 ] [ Designated as safety issue: No ]
    True GFR will be directly measured using iohexol plasma clearance (CLiohexol)

  • Change from baseline in bone and renal biomarkers at Weeks 24, 48, and 96 [ Time Frame: Weeks 24, 48, and 96 ] [ Designated as safety issue: No ]

    Bone biomarkers will be monitored by evaluating dual-energy X-ray absorptiometry (DEXA) scans of the spine and hip, and will include:

    • C-type collagen sequence (CTX)
    • Procollagen type 1 N-terminal propeptide (P1NP)

    Renal biomarkers will include:

    • Retinol binding protein
    • beta-2-microglobulin

  • Incidence of adverse events and graded laboratory abnormalities [ Time Frame: Baseline to Week 96 ] [ Designated as safety issue: No ]
  • Proportion of participants achieving virologic response at Weeks 24, 48, and 96 [ Time Frame: Weeks 24, 48, and 96 ] [ Designated as safety issue: No ]
    Virologic response is defined as HIV-1 RNA < 50 copies/mL using the FDA-defined snapshot analysis algorithm

  • Plasma PK of E/C/F/TAF including Cmax, Tmax, Clast, Tlast, Ctau, λz, AUCtau, and t1/2 for participants enrolled in the PK/PD sub-study [ Time Frame: Weeks 2, 4, and 8 ] [ Designated as safety issue: No ]
    • Cmax is defined as the maximum concentration of drug
    • Tmax is defined as the time of Cmax
    • Clast is defined as the last observable concentration of drug
    • Tlast is defined as the time of Clast
    • Ctau is defined as the observed drug concentration at the end of the dosing interval
    • λz is defined as the terminal elimination rate constant
    • AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval)
    • t1/2 is defined as the estimate of the terminal elimination half-life of the drug

  • TFV-DP concentration in peripheral blood mononuclear cell (PBMC) for participants enrolled in PK/PD sub-study [ Time Frame: Weeks 2, 4, and 8 ] [ Designated as safety issue: No ]

Enrollment: 245
Study Start Date: March 2013
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: July 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 96 weeks.
Drug: E/C/F/TAF
Elvitegravir 150 mg/cobicistat 150 mg/emtricitabine 200 mg/tenofovir alafenamide 10 mg (E/C/F/TAF) single-tablet regimen (STR) administered orally once daily with food

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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 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 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 is complete.

Cohort 2 (Treatment-naïve)

  • 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 PrEP (pre-exposure prophylaxis), or PEP (post-exposure prophylaxis), 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 subjects 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
  • Female subjects 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
  • Male subjects 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 male subjects must be non-heterosexually active, or practice sexual abstinence
  • Age ≥ 18 years

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. Subjects who are HCV positive, but have a documented negative HCV RNA, are eligible.
  • Hepatitis B surface antigen (HBVsAg) positive
  • Subjects receiving drug treatment for Hepatitis C, or subjects who are anticipated to receive treatment for Hepatitis C during the course of the study
  • Subjects experiencing decompensated cirrhosis (e.g., 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 subject 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
  • Subjects on hemodialysis, other forms of renal replacement therapy, or on treatment for underlying kidney diseases (including prednisolone, and dexamethasone)
  • Subjects receiving ongoing therapy with any medications not to be used with EVG, COBI, FTC, or TAF or subjects with any known allergies to the excipients of E/C/F/TAF STR
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01818596

  Hide Study Locations
Locations
United States, Arizona
Spectrum Medical Group
Phoenix, Arizona, United States, 85012
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
Anthony Mills MD, Inc
Los Angeles, California, United States, 90069
Peter J Ruane, MD, Inc
Los Angeles, California, United States, 90036
LA Gay & Lesbian Center - Jeffrey Goodman Special Care Clinic
Los Angeles, California, United States, 90028
Orange Coast Medical Group
Newport Beach, California, United States, 92663
Desert Medical Group Inc. dba Desert Oasis Healthcare Medical Group
Palm Springs, California, United States, 92262
Palmtree Clinical Research/Eisenhower Medical Center
Palm Springs, California, United States, 92264
Stanford University
Palo Alto, California, United States, 94304
Kaiser Permanente Medical Group
Sacramento, California, United States, 95825
University of California San Diego
San Diego, California, United States, 92103
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, Connecticut
Yale University
New Haven, Connecticut, United States, 06510
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
Broward Health
Fort Lauderdale, Florida, United States, 33311
Midway Immunology and Research Center
Fort Pierce, Florida, United States, 34982
AHF - Kinder Medical Group
Miami, Florida, United States, 33133
University of Miami
Miami, Florida, United States, 33136
AHF South Beach
Miami Beach, Florida, United States, 33139
Orlando Immunology Center
Orlando, Florida, United States, 32803
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
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115
The Research Institute
Springfield, Massachusetts, United States, 01105
United States, Michigan
Be Well Medical Center, P.C.
Berkeley, 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
Central West Clinical Research
St. Louis, Missouri, United States, 63108
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
South Jersey Infectious Disease
Somers Point, New Jersey, United States, 08244
United States, New Mexico
Southwest CARE Center
Sante 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
Montefiore Medical Center
Bronx, New York, United States, 10467
Jacobi Medical Center
Bronx, New York, United States, 10461
Dr Rizwanullah Hameed
Brooklyn, New York, United States, 11203
North Shore University Hospital/Division of Infectious Diseases
Manhasset, New York, United States, 11030
Aids Care
Rochester, New York, United States, 14607
United States, North Carolina
ID Associates - Caromont Medical Group
Gastonia, North Carolina, United States, 28054
United States, Ohio
Summa Health System CARE Center
Akron, Ohio, United States, 44304
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, South Carolina
Medical University of South Carolina
Charleston, South Carolina, United States, 29425
United States, Texas
St. Hope Foundation
Bellaire, Texas, United States, 77401
North Texas Infectious Diseases Consultants, PA
Dallas, Texas, United States, 75246
Tarrant County Infectious Disease Associates
Fort Worth, Texas, United States, 76104
Garcias' Family Health Group
Harlingen, Texas, United States, 78550
Gordon E. Crofoot MD, PA
Houston, Texas, United States, 77098
Therapeutic Concepts, PA
Houston, Texas, United States, 77004
United States, Washington
Peter Shalit, MD
Seattle, Washington, United States, 98104
Australia, New South Wales
Holdsworth House Medical Practice
Darlinghurst, New South Wales, Australia, 2010
Taylor Square Private Clinic
Sydney, New South Wales, Australia, 2010
Australia, Victoria
Clinical Research Infectious Diseases Department- Alfred Hospital
Melbourne, Victoria, Australia, 3004
Prahran Market Clinic
Prahran, Victoria, Australia, 3181
Austria
LKH West, Resistance
Graz, Austria, 8010
Department of Dermatology - Division of Immunology, Allergy and Infectious Diseases
Vienna, Austria, 1090
Otto-Wagner-Spital, Sozialmed. Zentrum Baumgartner Hoehe (site 4143)
Wien, Austria, 1140
Belgium
CHU Saint-Pierre Hospital - Infectious Diseases Department
Brussels, Belgium, 1000
University Hospital Ghent
Ghent, Belgium, 9000
University Hospitals Leuven
Leuven, Belgium, 3000
Brazil
UPCAids-UNICAMP
Campinas, Brazil, 13083-888
Instituto de Pesquisa Clinica Evandro Chagas - IPEC- FIOCRUZ
Rio de Janeiro, Brazil, 21040-360
Faculdade de Medicina do ABC
Santo Andre, Brazil, 09060-650
Instituto de Infectologia emilio Ribas
Sao Paulo, Brazil, 01246-900
Faculdade de Medicina da Universidade de Sao Paulo
Sao Paulo, Brazil, 01246-903
Centro De Referencia E Treinamento DST/AIDS
Sao Paulo, Brazil, 04121-000
Canada, Ontario
Maple Leaf Research
Toronto, Ontario, Canada, M5G1K2
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N3M5
Canada, Quebec
Clinique Medicale du Quartier Latin
Montreal, Quebec, Canada, H2L5B1
Dominican Republic
Instituto Dominicano de Estudios Virologicos (IDEV)
Santo Domingo, Dominican Republic, 99999
France
Hopital de la Croix Rousse
Lyon, France, 69004
Archet 1 CHU Nice
Nice, France, 6200
GHPS Service des maladies infectieuses et tropicales pavillon Laveran unité de recherche clinique
Paris, France, 75651
Germany
UKB,Medizinische Klinik 1, Immunologische Studienambulanz
Bonn, Germany, 53115
Johann Wolfgang Goethe-University Hospital
Frankfurt, Germany, 60590
University of Cologne, Department of Internal Medicine
Koln, Germany, 50937
MUC Research GmbH
München, Germany, 80335
Italy
Luigi Sacco Hospital
Milano, Italy, 20157
Dept of Infectious Diseases
Torino, Italy, 10149
Mexico
Hospital Civil de Guadalajara Dr. Juan I. Menchaca
Guadalajara, Jalisco, Mexico, 44340
Hospital Civil de Guadalajara Fray Antonio Alcalde
Guadalajara, Mexico, 44280
Netherlands
Erasmus MC
Rotterdam, Netherlands, 3000CA
University Medical Center Utrecht
Utrecht, Netherlands, 3584 CX
Puerto Rico
HOPE Clinical Research
San Juan, Puerto Rico, 00909
VA Caribbean Healthcare System
San Juan, Puerto Rico, 00921
Spain
Hospital Universitario Vall D'Hebron
Barcelona, Spain, 8029
Hospital Clinic I Provincial De Barcelona
Barcelona, Spain, 8036
Hospital Universitari de Bellvitge
Barcelona, Spain, 8907
Germans Trias i Pujol University Hospital
Barcelona, Spain, 8916
Hospital La Paz
Madrid, Spain, 28046
Sweden
Department of Infectious Diseases, Karolinska University Hospital
Stockholm, Sweden, 14186
Switzerland
Universitätsklinik für Infektiologie
Bern, Switzerland, 3010
Hospital University Geneva (HUG)
Geneva, Switzerland, 1205
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
Royal Free London NHS Foundation Trust
London, United Kingdom, NW32QG
Central Manchester University Hospitals NHS foundation Trust
Manchester, United Kingdom, M13 0FH
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Marshall Fordyce, MD Gilead Sciences
  More Information

No publications provided

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: March 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Gilead Sciences:
HIV
Treatment Naive
HIV 1 Infected

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Renal Insufficiency
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Kidney Diseases
Urologic Diseases
Tenofovir
Emtricitabine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on April 16, 2014