Study to Evaluate the Safety and Efficacy of E/C/F/TAF Versus E/C/F/TDF in HIV-1 Positive, Antiretroviral Treatment-Naive Adults
- Conditions
- HIVHIV Infections
- Interventions
- Drug: E/C/F/TAFDrug: E/C/F/TDFDrug: E/C/F/TDF PlaceboDrug: E/C/F/TAF Placebo
- Registration Number
- NCT01797445
- Lead Sponsor
- Gilead Sciences
- Brief Summary
The primary objective of this study is to evaluate the efficacy of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) versus elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF) in HIV-1 positive, antiretroviral treatment-naive adults.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 872
- Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
- Plasma HIV-1 RNA levels ≥ 1,000 copies/mL at screening
- 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
- Screening genotype report must show sensitivity to elvitegravir, emtricitabine, tenofovir DF
- Normal electrocardiogram (ECG)
- Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault formula for creatinine clearance
- Hepatic transaminases (AST and ALT) ≤ 5 × upper limit of normal (ULN)
- Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
- Adequate hematologic function
- Serum amylase ≤ 5 × ULN
- Males and females of childbearing potential must agree to utilize highly effective contraception methods or be non-heterosexually active or 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
- Females who have stopped menstruating for ≥ 12 months but do not have documentation of ovarian hormonal failure must have a serum follicle stimulating hormone (FSH) level at screening within the post-menopausal range based on the Central Laboratory reference range
- Age ≥ 18 years
Key
- A new AIDS-defining condition diagnosed within the 30 days prior to screening
- Hepatitis B surface antigen (HBsAg) positive
- Hepatitis C antibody positive
- Individuals experiencing decompensated cirrhosis
- 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
- History of malignancy within the past 5 years or ongoing malignancy other than cutaneous Kaposi's sarcoma, basal cell carcinoma, or resected, noninvasive cutaneous squamous carcinoma
- Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to baseline
- Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the individual unsuitable for the study or unable to comply with dosing requirements
- Participation in any other clinical trial (including observational trials) without prior approval
- Receiving ongoing therapy with drugs not to be used with elvitegravir, cobicistat, emtricitabine, tenofovir DF, and TAF or participants with any known allergies to the excipients of E/C/F/TDF or E/C/F/TAF
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description E/C/F/TAF (Double-Blind) E/C/F/TAF E/C/F/TAF plus E/C/F/TDF placebo for 144 weeks After 144 weeks, participants will continue to take their blinded study drug until treatment assignments have been unblinded. E/C/F/TAF (Double-Blind) E/C/F/TDF Placebo E/C/F/TAF plus E/C/F/TDF placebo for 144 weeks After 144 weeks, participants will continue to take their blinded study drug until treatment assignments have been unblinded. E/C/F/TDF (Double-Blind) E/C/F/TDF E/C/F/TDF plus E/C/F/TAF placebo for 144 weeks After 144 weeks, participants will continue to take their blinded study drug until treatment assignments have been unblinded. E/C/F/TDF (Double-Blind) E/C/F/TAF Placebo E/C/F/TDF plus E/C/F/TAF placebo for 144 weeks After 144 weeks, participants will continue to take their blinded study drug until treatment assignments have been unblinded. Open-Label E/C/F/TAF E/C/F/TAF After the unblinding visit, in countries where E/C/F/TAF is not commercially available, participants (except in UK) who complete 144 weeks of study will be given the option to receive open-label E/C/F/TAF and attend study visits every 12 weeks until it becomes commercially available, or until Gilead terminates the study in that country.
- Primary Outcome Measures
Name Time Method Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 48 Week 48 The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 48 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.
- Secondary Outcome Measures
Name Time Method Percent Change From Baseline in Urine RBP to Creatinine Ratio at Week 96 Baseline; Week 96 Urine RBP is a renal biomarker which is used to detect drug-induced kidney injury.
Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio at Week 48 Baseline; Week 48 Urine Beta-2-microglobulin is a renal biomarker which is used to detect drug-induced kidney injury.
Percentage of Participants With Treatment-emergent Proteinuria Through Week 48 Baseline to Week 48 Grades 1 (mild), 2 (moderate), and 3 (severe) were the highest treatment-emergent postbaseline grades for urine protein using the dipstick method. The worst postbaseline value is presented for each participant.
Percentage of Participants With Treatment-emergent Proteinuria Through Week 96 Baseline to Week 96 Grades 1 (mild), 2 (moderate), and 3 (severe) were the highest treatment-emergent postbaseline grades for urine protein using the dipstick method. The worst postbaseline value is presented for each participant.
Percent Change From Baseline in Urine Retinol Binding Protein (RBP) to Creatinine Ratio at Week 48 Baseline; Week 48 Urine RBP is a renal biomarker which is used to detect drug-induced kidney injury.
Percent Change From Baseline in Spine BMD at Week 48 Baseline; Week 48 Spine BMD was assessed by DXA scan.
Percent Change From Baseline in Spine BMD at Week 96 Baseline; Week 96 Spine BMD was assessed by DXA scan.
Change From Baseline in Serum Creatinine at Week 96 Baseline; Week 96 Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio at Week 96 Baseline; Week 96 Urine Beta-2-microglobulin is a renal biomarker which is used to detect drug-induced kidney injury.
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 Week 96 The percentage of participants achieving HIV-1 RNA \< 50 copies/mL at Week 96 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.
Change From Baseline in CD4+ Cell Count at Week 48 Baseline; Week 48 Change From Baseline in CD4+ Cell Count at Week 96 Baseline; Week 96 Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Weeks 48 and 96 Weeks 48 and 96 The percentage of participants achieving HIV-1 RNA \< 20 copies/mL at Weeks 48 and 96 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.
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 Baseline; Week 48 Hip BMD was assessed by dual energy x-ray absorptiometry (DXA) scan.
Percent Change From Baseline in Hip BMD at Week 96 Baseline; Week 96 Hip BMD was assessed by DXA scan.
Change From Baseline in Serum Creatinine at Week 48 Baseline; Week 48
Trial Locations
- Locations (116)
Kaiser Permanente - Los Angeles Medical Center
🇺🇸Los Angeles, California, United States
AIDS Research Consortium of Atlanta
🇺🇸Atlanta, Georgia, United States
Mercer University
🇺🇸Macon, Georgia, United States
Community Research Initiative of New England
🇺🇸Boston, Massachusetts, United States
Rush University Medical Center, Section of Infectious Diseases
🇺🇸Chicago, Illinois, United States
Research Access Network
🇺🇸Houston, Texas, United States
Stanford University
🇺🇸Palo Alto, California, United States
Peter J. Ruane, Inc.
🇺🇸Los Angeles, California, United States
Emory University
🇺🇸Atlanta, Georgia, United States
Infectious Diseases Associates of NW FL
🇺🇸Sarasota, Florida, United States
Dupont Circle Physicians Group
🇺🇸Washington, District of Columbia, United States
Whitman-Walker Health
🇺🇸Washington, District of Columbia, United States
Anthony Mills MD Inc
🇺🇸Los Angeles, California, United States
Triple O Research Institute PA
🇺🇸West Palm Beach, Florida, United States
Be Well Medical Center
🇺🇸Berkley, Michigan, United States
North Shore University Hospital - Division of Infectious Diseases
🇺🇸Manhasset, New York, United States
Midway Immunology and Research Center
🇺🇸Fort Pierce, Florida, United States
Medical Faculty Associates
🇺🇸Washington, District of Columbia, United States
Central West Clinical Research
🇺🇸Saint Louis, Missouri, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
North Texas Infectious Diseases Consultants
🇺🇸Dallas, Texas, United States
Atlanta ID Group, PC
🇺🇸Atlanta, Georgia, United States
Los Angeles Biomedical Research Institute at Harbor - UCLA Medical Center
🇺🇸Torrance, California, United States
Southwest Infectious Disease Clinical Research, Inc.
🇺🇸Dallas, Texas, United States
Albany Medical College
🇺🇸Albany, New York, United States
Therapeutic Concepts, PA
🇺🇸Houston, Texas, United States
ID Care
🇺🇸Hillsborough, New Jersey, United States
The Ruth M. Rothstein CORE Center
🇺🇸Chicago, Illinois, United States
Archet 1 CHU de Nice, Department of Infectiology
🇫🇷Nice, France
Chelsea Village Medical
🇺🇸New York, New York, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Gordon E. Crofoot, MD, PA
🇺🇸Houston, Texas, United States
Carolinas Medical Center Myer's Park Clinic
🇺🇸Charlotte, North Carolina, United States
Clinique Medicale L'actuel
🇨🇦Montreal, Canada
Southampton Healthcare, Inc.
🇺🇸Saint Louis, Missouri, United States
Spectrum Health Care
🇨🇦Vancouver, Canada
University of Alabama at Birmingham
🇺🇸Birmingham, Alabama, United States
Spectrum Medical Group
🇺🇸Phoenix, Arizona, United States
Kaiser Permanente
🇺🇸San Leandro, California, United States
Kaiser Permanente San Francisco
🇺🇸San Francisco, California, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
APEX Research LLC
🇺🇸Denver, Colorado, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Capital Medical Associates, PC
🇺🇸Washington, District of Columbia, United States
Greenwich Hospital
🇺🇸Greenwich, Connecticut, United States
St. Hope Foundation, Inc.
🇺🇸Bellaire, Texas, United States
Hennepin County Medical Center
🇺🇸Minneapolis, Minnesota, United States
Jacobi Medical Center
🇺🇸Bronx, New York, United States
Southwest CARE Center
🇺🇸Santa Fe, New Mexico, United States
Clinical Alliance for Research & Education - Infectious Diseases (CARE-ID)
🇺🇸Annandale, Virginia, United States
Peter Shalit, MD
🇺🇸Seattle, Washington, United States
Trinity Health & Wellness Center / AIDS Arms, Inc.
🇺🇸Dallas, Texas, United States
East Carolina University The Brody School of Medicine
🇺🇸Greenville, North Carolina, United States
Infectious Disease Specialist of Atlanta
🇺🇸Decatur, Georgia, United States
Tarrant County Infectious Disease Associates
🇺🇸Fort Worth, Texas, United States
Maple Leaf Research
🇨🇦Toronto, Canada
Alameda County Medical Center
🇺🇸Oakland, California, United States
La Playa Medical Group and Clinical Research
🇺🇸San Diego, California, United States
University of Southern California AIDS Clinical Trials Group
🇺🇸Los Angeles, California, United States
Gary J. Richmond,M.D.,P.A.
🇺🇸Fort Lauderdale, Florida, United States
University of Hawaii - Hawaii Center for AIDS
🇺🇸Honolulu, Hawaii, United States
The Research Institute
🇺🇸West Springfield, Massachusetts, United States
Georgia Regents University
🇺🇸Augusta, Georgia, United States
Upstate ID Assoc
🇺🇸Albany, New York, United States
Rosedale Infectious Disseases
🇺🇸Huntersville, North Carolina, United States
DCOL Center for Clinical Research
🇺🇸Longview, Texas, United States
Research Institute of McGill University Health Care
🇨🇦Montreal, Quebec, Canada
University Health Network/Toronto General Hospital
🇨🇦Toronto, Canada
Hopital de la Croix Rousse
🇫🇷Lyon, France
University Hospital of Montpellier (CHU-Gui de Chauliac)
🇫🇷Montpellier, France
Saint Louis Hospital of Infectious Diseases
🇫🇷Paris, France
Hôpital Bichat Claude Bernard
🇫🇷Paris, France
Hopital Tenon
🇫🇷Paris, France
Hopital Saint Antoine
🇫🇷Paris, France
CH Tourcoing
🇫🇷Tourcoing, France
IRCCS Ospedale San Raffaele
🇮🇹Milan, Italy
Hopital Pitie Salpetriere
🇫🇷Paris, France
Hospital Civil de Guadalajara
🇲🇽Guadalajara, Mexico
Universitaria di Bologna-Policlicnico S' Orsola Malpighi
🇮🇹Bologna, Italy
Insituto Nacional De Enfermedades Respiratorias "Ismael Cosio Villegas"
🇲🇽Mexico City, Mexico
Onze Lieve Vrouwe Gasthuis
🇳🇱Amsterdam, Netherlands
Serviço de Doenças Infecciosas, HUC-CHUC, EPE
🇵🇹Coimbra, Portugal
Hospital de Santa Maria - CHLN, EPE
🇵🇹Lisbon, Portugal
Hospital Santo Antonio dos Capuchos
🇵🇹Lisboa, Portugal
University of Puerto Rico ACTU
🇵🇷San Juan, Puerto Rico
Karolinska University Hospital, Huddinge
🇸🇪Stockholm, Sweden
Centro Hospitalar do Porto - Hospital Joaquim Urbano
🇵🇹Porto, Portugal
Venhalsan / Sodersjukhuset
🇸🇪Stockholm, Sweden
Barts Health NHS Trust
🇬🇧London, United Kingdom
Brighton and Sussex University Hospitals NHS Trust
🇬🇧Brighton, United Kingdom
Heart Of England NHS Foundation Trust
🇬🇧Birmingham, United Kingdom
Whittall Street Clinic
🇬🇧Birmingham, United Kingdom
Brownlee Centre, Gartnavel General Hospital
🇬🇧Glasgow, United Kingdom
Kings College Hospital
🇬🇧London, United Kingdom
Chelsea and Westminster
🇬🇧London, United Kingdom
Mortimer Market Centre
🇬🇧London, United Kingdom
North Manchester General Hospital
🇬🇧Manchester, United Kingdom
Instituto Dominicano de Estudios Virologicos--IDEV
🇩🇴Santo Domingo, Dominican Republic
Weill Cornell Medical College
🇺🇸New York, New York, United States
The Miriam Hospital
🇺🇸Providence, Rhode Island, United States
Hope Clinical Research
🇵🇷San Juan, Puerto Rico
University of California, Davis Medical Center
🇺🇸Sacramento, California, United States
Kaiser Permanente Medical Group
🇺🇸Sacramento, California, United States
University of Colorado
🇺🇸Aurora, Colorado, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Orlando Immunology Center
🇺🇸Orlando, Florida, United States
Idocf/Valuhealthmd
🇺🇸Orlando, Florida, United States
University of South Florida
🇺🇸Tampa, Florida, United States
Infectious Disease Research Institute Inc.
🇺🇸Tampa, Florida, United States
St. Joseph's Comprehensive Research Institute
🇺🇸Tampa, Florida, United States
University of North Carolina AIDS Clinical Trials Unit
🇺🇸Chapel Hill, North Carolina, United States
Wake Forest University Health Sciences
🇺🇸Winston-Salem, North Carolina, United States
Central Texas Clinical Research
🇺🇸Austin, Texas, United States
Royal Free London NHS Foundation Trust
🇬🇧London, United Kingdom
Montefiore Medical Center
🇺🇸Bronx, New York, United States
AIDS Healthcare Foundation
🇺🇸Miami, Florida, United States