Clinical trial NCT01780506: Study to Evaluate the Safety and Efficacy of E/C/F/TAF (Genvoya®) Versus E/C/F/TDF (Stribild®) in HIV-1 Positive, Antiretroviral Treatment-Naive Adults
Official title: A Phase 3, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Versus Elvitegravir/Cobicistat/Emtricitabine/ Tenofovir Disoproxil Fumarate in HIV-1 Positive, Antiretroviral Treatment-Naïve Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV
HIV Infections
Keywords: HIV
Treatment Naive
HIV 1 Infected
Female
Women
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2013-01-31
Enrollment: 872
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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) FDC in HIV-1 positive, antiretroviral treatment-naive adults.


Eligibility criteria: Key Inclusion Criteria:

* 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 disoproxil fumarate (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

Key Exclusion Criteria:

* A new acquired immunodeficiency syndrome (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
* Individuals receiving ongoing therapy with drugs not to be used with elvitegravir, cobicistat, emtricitabine, tenofovir DF, and TAF or individuals with any known allergies to the excipients of E/C/F/TDF or E/C/F/TAF single-tablet regimen tablets

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48
timeFrame: Week 48
Secondary outcomes:
measure: Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 96 and 144
timeFrame: Weeks 96 and 144
measure: Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Weeks 48, 96, and 144
timeFrame: Weeks 48, 96. and 144
measure: Change From Baseline in CD4+ Cell Count at Week 48
timeFrame: Baseline; Week 48
measure: Change From Baseline in CD4+ Cell Count at Week 96
timeFrame: Baseline; Week 96
measure: Change From Baseline in CD4+ Cell Count at Week 144
timeFrame: Baseline; Week 144
measure: Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48
timeFrame: Baseline; Week 48
measure: Percent Change From Baseline in Hip BMD at Week 96
timeFrame: Baseline; Week 96
measure: Percent Change From Baseline in Hip BMD at Week 144
timeFrame: Baseline; Week 144
measure: Percent Change From Baseline in Spine BMD at Week 48
timeFrame: Baseline; Week 48
measure: Percent Change From Baseline in Spine BMD at Week 96
timeFrame: Baseline; Week 96
measure: Percent Change From Baseline in Spine BMD at Week 144
timeFrame: Baseline; Week 144
measure: Change From Baseline in Serum Creatinine at Week 48
timeFrame: Baseline; Week 48
measure: Change From Baseline in Serum Creatinine at Week 96
timeFrame: Baseline; Week 96
measure: Change From Baseline in Serum Creatinine at Week 144
timeFrame: Baseline; Week 144
measure: Percentage of Participants Experiencing Treatment-emergent Proteinuria Through Week 48
timeFrame: Up to 48 weeks
measure: Percentage of Participants Experiencing Treatment-emergent Proteinuria Through Week 96
timeFrame: Up to 96 weeks
measure: Percentage of Participants Experiencing Treatment-emergent Proteinuria Through Week 144
timeFrame: Up to 144 weeks
measure: Percent Change From Baseline in Urine Retinol Binding Protein (RBP) to Creatinine Ratio at Week 48
timeFrame: Baseline; Week 48
measure: Percent Change From Baseline in Urine RBP to Creatinine Ratio at Week 96
timeFrame: Baseline; Week 96
measure: Percent Change From Baseline in Urine RBP to Creatinine Ratio at Week 144
timeFrame: Baseline; Week 144
measure: Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio at Week 48
timeFrame: Baseline; Week 48
measure: Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio at Week 96
timeFrame: Baseline; Week 96
measure: Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio at Week 144
timeFrame: Baseline; Week 144
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: The University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Spectrum Medical Group
state: Arizona
city: Los Angeles
country: United States
facility: Kaiser Permanente Los Angeles
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Los Angeles
country: United States
facility: Peter J. Ruane, MD, Inc.
state: California
city: Los Angeles
country: United States
facility: Anthony Mills MD Inc
state: California
city: Oakland
country: United States
facility: East Bay AIDS Center
state: California
city: Sacramento
country: United States
facility: Kaiser Permanente - Sacramento
state: California
city: San Diego
country: United States
facility: La Playa Medical Group and Clinical Research
state: California
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: Torrance
country: United States
facility: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center
state: California
city: Denver
country: United States
facility: Apex Research, LLC
state: Colorado
city: New Haven
country: United States
facility: Yale University School of Medicine
state: Connecticut
city: Washington
country: United States
facility: Dupont Circle Physicians Group, P.C.
state: District of Columbia
city: Washington
country: United States
facility: Whitman Walker Clinic
state: District of Columbia
city: Washington
country: United States
facility: Capital Medical Associates, P.C.
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Gary Richmond, MD, PA, Inc.
state: Florida
city: Fort Pierce
country: United States
facility: Midway Immunology & Research Center, LLC
state: Florida
city: Miami Beach
country: United States
facility: AIDS Healthcare Foundation
state: Florida
city: Miami
country: United States
facility: The Kinder Medical Group
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Orlando
country: United States
facility: IDOCF/ValuHealthMD, LLC
state: Florida
city: Pensacola
country: United States
facility: Infectious Diseases Associates
state: Florida
city: Tampa
country: United States
facility: The University of South Florida
state: Florida
city: Tampa
country: United States
facility: Infectious Disease Research Institute Inc.
state: Florida
city: Tampa
country: United States
facility: St. Joseph's Comprenhensive Research Inisitute
state: Florida
city: Vero Beach
country: United States
facility: AIDS Research and Treatment Center of the Treasure Coast
state: Florida
city: Atlanta
country: United States
facility: AIDS Research Consortium of Atlanta
state: Georgia
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Atlanta
country: United States
facility: Atlanta ID Group, PC
state: Georgia
city: Decatur
country: United States
facility: Infectious Disease Specialist of Atlanta
state: Georgia
city: Macon
country: United States
facility: Mercer University School of Medicine
state: Georgia
city: Honolulu
country: United States
facility: University of Hawaii - Hawaii Center for AIDS
state: Hawaii
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Chicago
country: United States
facility: Ruth M. Rothstein CORE Center
state: Illinois
city: Chicago
country: United States
facility: Howard Brown Health Center
state: Illinois
city: Baltimore
country: United States
facility: Institute of Human Virology, University of Maryland
state: Maryland
city: Boston
country: United States
facility: Community Research Initative
state: Massachusetts
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Framingham
country: United States
facility: Metrowest Medical Center
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Infectious Diseases Clinical Research
state: Massachusetts
city: Berkley
country: United States
facility: Be Well Medical Center
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
city: Saint Louis
country: United States
facility: Central West Clinical Research, Inc.
state: Missouri
city: Saint Louis
country: United States
facility: Southampton Healthcare, Inc.
state: Missouri
city: Hillsborough
country: United States
facility: ID Care
state: New Jersey
city: Newark
country: United States
facility: Saint Michael's Medical Center
state: New Jersey
city: Santa Fe
country: United States
facility: Southwest C.A.R.E. Center
state: New Mexico
city: Albany
country: United States
facility: Albany Medical College
state: New York
city: Albany
country: United States
facility: Upstate Infectious Diseases Associates
state: New York
city: Bronx
country: United States
facility: Jacobi Medical Center
state: New York
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: Flushing
country: United States
facility: New York Hospital Queens
state: New York
city: Manhasset
country: United States
facility: North Shore University Hospital - Division of Infectious Diseases
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Charlotte
country: United States
facility: Infectious Disease Consultants, PA
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Huntersville
country: United States
facility: Rosedale Infectious Diseases
state: North Carolina
city: Akron
country: United States
facility: Summa Health Care Center
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Providence
country: United States
facility: The Miriam Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Columbia
country: United States
facility: University of South Carolina School of Medicine
state: South Carolina
city: Austin
country: United States
facility: Central Texas Clinical Research
state: Texas
city: Bellaire
country: United States
facility: St. Hope Foundation, Inc.
state: Texas
city: Dallas
country: United States
facility: Trinity Health and Wellness Center/AIDS Arms, Inc.
state: Texas
city: Dallas
country: United States
facility: North Texas Infectious Diseases Consultants
state: Texas
city: Fort Worth
country: United States
facility: Tarrant County Infectious Disease Associates
state: Texas
city: Harlingen
country: United States
facility: Garcias' Family Health Group
state: Texas
city: Houston
country: United States
facility: Therapeutic Concepts, PA
state: Texas
city: Houston
country: United States
facility: Gordon E. Crofoot, MD, PA
state: Texas
city: Longview
country: United States
facility: DCOL Center for Clinical Research
state: Texas
city: Annandale
country: United States
facility: Clinical Alliance for Research & Education - Infectious Diseases, LLC (CARE-ID)
state: Virginia
city: Seattle
country: United States
facility: Peter Shalit, MD
state: Washington
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Darlinghurst
country: Australia
facility: Holdsworth House Medical Practice
state: New South Wales
city: Darlington
country: Australia
facility: Taylor Square Private Clinic
state: New South Wales
city: Sydney
country: Australia
facility: East Sydney Doctors
state: New South Wales
city: Sydney
country: Australia
facility: Albion Street Centre
state: New South Wales
city: Carlton
country: Australia
facility: Melbourne Sexual Health Clinic
state: Victoria
city: Vienna
country: Austria
facility: DIAID, Department of Dermatology, Medical University Vienna
city: Wien
country: Austria
facility: Otto-Wagner-Spital, Sozialmedizinisches Zentrum Baumgartner Hoehe
city: Anderlecht
country: Belgium
facility: Hôpital Erasme-ULB
state: Brussels
city: Brussels
country: Belgium
facility: CHU Saint-Pierre University Hospital
city: Vancouver
country: Canada
facility: Spectrum Health
state: British Columbia
city: Winnipeg
country: Canada
facility: Health Sciences Centre Winnipeg
state: Manitoba
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Maple Leaf Research
state: Ontario
city: Montreal
country: Canada
facility: Clinique Medicale Du Quartier Latin
state: Quebec
city: Montreal
country: Canada
facility: Clinique medicale l'Actuel
state: Quebec
city: Montreal
country: Canada
facility: Clinique OPUS
state: Quebec
city: Toronto
country: Canada
facility: Sunnybrook Health Science Center
city: Milano
country: Italy
facility: Ospedale San Raffaele
city: Shinjuku-ku, Tokyo
country: Japan
facility: National Center for Global Health and Medicine AIDS Clinical Center
city: San Juan
country: Puerto Rico
facility: HOPE Clinical Research
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital Universitari Vall D'Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial
city: Barcelona
country: Spain
facility: University Hospital Bellvitge
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago (CHUS)
city: Berne
country: Switzerland
facility: Universitätsspital Bern
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
city: Zurich
country: Switzerland
facility: University Hospital, Zurich
city: Bangkok
country: Thailand
facility: The HIV Netherland Australia Thailand, Thai Red Cross AIDS Research Center (The HIV-NAT)
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital, Mahidol University
city: Bangkok
country: Thailand
facility: Siriraj Hospital
city: Chiang Mai
country: Thailand
facility: Chiang Mai University
city: Khon Kaen
country: Thailand
facility: Khon Kaen University
city: Nonthaburi
country: Thailand
facility: Bamrasnaradura Infectious Diseases Institute
city: London
country: United Kingdom
facility: Chelsea & Westminster Hospital
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: Sax PE, Wohl D, Yin MT, Post F, DeJesus E, Saag M, Pozniak A, Thompson M, Podzamczer D, Molina JM, Oka S, Koenig E, Trottier B, Andrade-Villanueva J, Crofoot G, Custodio JM, Plummer A, Zhong L, Cao H, Martin H, Callebaut C, Cheng AK, Fordyce MW, McCallister S; GS-US-292-0104/0111 Study Team. Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomised, double-blind, phase 3, non-inferiority trials. Lancet. 2015 Jun 27;385(9987):2606-15. doi: 10.1016/S0140-6736(15)60616-X. Epub 2015 Apr 15.
citation: Arribas JR, Thompson M, Sax PE, Haas B, McDonald C, Wohl DA, DeJesus E, Clarke AE, Guo S, Wang H, Callebaut C, Plummer A, Cheng A, Das M, McCallister S. Brief Report: Randomized, Double-Blind Comparison of Tenofovir Alafenamide (TAF) vs Tenofovir Disoproxil Fumarate (TDF), Each Coformulated With Elvitegravir, Cobicistat, and Emtricitabine (E/C/F) for Initial HIV-1 Treatment: Week 144 Results. J Acquir Immune Defic Syndr. 2017 Jun 1;75(2):211-218. doi: 10.1097/QAI.0000000000001350.
citation: Margot N, Cox S, Das M, McCallister S, Miller MD, Callebaut C. Infrequent development of drug resistance in HIV-1-infected treatment-naive subjects after 96 weeks of treatment with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate. Antivir Ther. 2017;22(5):443-446. doi: 10.3851/IMP3125. Epub 2017 Jan 11.
citation: Margot NA, Kitrinos KM, Fordyce M, McCallister S, Miller MD, Callebaut C. Rare emergence of drug resistance in HIV-1 treatment-naive patients after 48 weeks of treatment with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide. HIV Clin Trials. 2016 Mar;17(2):78-87. doi: 10.1080/15284336.2016.1142731.
citation: Funderburg NT, McComsey GA, Kulkarni M, Bannerman T, Mantini J, Thornton B, Liu HC, Zhang Y, Song Q, Fang L, Dinoso J, Cheng A, McCallister S, Fordyce MW, Das M. Equivalent Decline in Inflammation Markers with Tenofovir Disoproxil Fumarate vs. Tenofovir Alafenamide. EBioMedicine. 2016 Nov;13:321-327. doi: 10.1016/j.ebiom.2016.10.009. Epub 2016 Oct 11.
citation: Wohl D, Oka S, Clumeck N, Clarke A, Brinson C, Stephens J, Tashima K, Arribas JR, Rashbaum B, Cheret A, Brunetta J, Mussini C, Tebas P, Sax PE, Cheng A, Zhong L, Callebaut C, Das M, Fordyce M; GS-US-2,92-01040111 and Study Team. Brief Report: A Randomized, Double-Blind Comparison of Tenofovir Alafenamide Versus Tenofovir Disoproxil Fumarate, Each Coformulated With Elvitegravir, Cobicistat, and Emtricitabine for Initial HIV-1 Treatment: Week 96 Results. J Acquir Immune Defic Syndr. 2016 May 1;72(1):58-64. doi: 10.1097/QAI.0000000000000940.
citation: Custodio JM, Garner W, Callebaut C, Fordyce M, Plummer A, Zhong L, et al. The Pharmacokinetics of Tenofovir and Tenofovir Diphosphate Following Administration of Tenofovir Alafenamide vs Tenofovir Disoproxil Fumarate [Oral Abstract #6]. The 16th International Workshop on Clinical Pharmacology of HIV & Hepatitis Therapy. Washington DC, USA, May 26-28, 2015.