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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01780506
• Other study ID #: GS-US-292-0104
• Secondary ID: 2012-004458-27
• Status: Completed
• Phase: Phase 3
• Start date: December 26, 2012
• Est. completion date: September 6, 2017

Study information

• Verified date: August 2018
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 872
• Est. completion date: September 6, 2017
• Est. primary completion date: August 26, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV
• HIV Infections

Intervention

Drug:
• E/C/F/TAF
150/150/200/10 mg FDC tablet administered orally once daily
• E/C/F/TDF
150/150/200/300 mg FDC tablet administered orally once daily
• E/C/F/TDF Placebo
Tablet administered orally once daily
• E/C/F/TAF Placebo
Tablet administered orally once daily

Locations

Country	Name	City	State
Australia	Melbourne Sexual Health Clinic	Carlton	Victoria
Australia	Holdsworth House Medical Practice	Darlinghurst	New South Wales
Australia	Taylor Square Private Clinic	Darlington	New South Wales
Australia	Albion Street Centre	Sydney	New South Wales
Australia	East Sydney Doctors	Sydney	New South Wales
Austria	DIAID, Department of Dermatology, Medical University Vienna	Vienna
Austria	Otto-Wagner-Spital, Sozialmedizinisches Zentrum Baumgartner Hoehe	Wien
Belgium	Hôpital Erasme-ULB	Anderlecht	Brussels
Belgium	CHU Saint-Pierre University Hospital	Brussels
Canada	Clinique Medicale Du Quartier Latin	Montreal	Quebec
Canada	Clinique medicale l'Actuel	Montreal	Quebec
Canada	Clinique OPUS	Montreal	Quebec
Canada	The Ottawa Hospital	Ottawa	Ontario
Canada	Maple Leaf Research	Toronto	Ontario
Canada	Sunnybrook Health Science Center	Toronto
Canada	Spectrum Health	Vancouver	British Columbia
Canada	Health Sciences Centre Winnipeg	Winnipeg	Manitoba
Italy	Ospedale San Raffaele	Milano
Japan	National Center for Global Health and Medicine AIDS Clinical Center	Shinjuku-ku, Tokyo
Puerto Rico	HOPE Clinical Research	San Juan
Spain	Hospital Germans Trias i Pujol	Badalona
Spain	Hospital Clinic i Provincial	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Universitari Vall D'Hebron	Barcelona
Spain	University Hospital Bellvitge	Barcelona
Spain	Hospital General Universitario Gregorio Maranon	Madrid
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Complejo Hospitalario Universitario de Santiago (CHUS)	Santiago de Compostela
Switzerland	Universitätsspital Bern	Berne
Switzerland	Centre Hospitalier Universitaire Vaudois	Lausanne
Switzerland	University Hospital, Zurich	Zurich
Thailand	Ramathibodi Hospital, Mahidol University	Bangkok
Thailand	Siriraj Hospital	Bangkok
Thailand	The HIV Netherland Australia Thailand, Thai Red Cross AIDS Research Center (The HIV-NAT)	Bangkok
Thailand	Chiang Mai University	Chiang Mai
Thailand	Khon Kaen University	Khon Kaen
Thailand	Bamrasnaradura Infectious Diseases Institute	Nonthaburi
United Kingdom	Chelsea & Westminster Hospital	London
United States	Summa Health Care Center	Akron	Ohio
United States	Albany Medical College	Albany	New York
United States	Upstate Infectious Diseases Associates	Albany	New York
United States	Clinical Alliance for Research & Education - Infectious Diseases, LLC (CARE-ID)	Annandale	Virginia
United States	AIDS Research Consortium of Atlanta	Atlanta	Georgia
United States	Atlanta ID Group, PC	Atlanta	Georgia
United States	Emory University	Atlanta	Georgia
United States	Central Texas Clinical Research	Austin	Texas
United States	Institute of Human Virology, University of Maryland	Baltimore	Maryland
United States	St. Hope Foundation, Inc.	Bellaire	Texas
United States	Be Well Medical Center	Berkley	Michigan
United States	The University of Alabama at Birmingham	Birmingham	Alabama
United States	Brigham & Women's Hospital	Boston	Massachusetts
United States	Community Research Initative	Boston	Massachusetts
United States	Jacobi Medical Center	Bronx	New York
United States	Montefiore Medical Center	Bronx	New York
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Infectious Disease Consultants, PA	Charlotte	North Carolina
United States	Howard Brown Health Center	Chicago	Illinois
United States	Northwestern University	Chicago	Illinois
United States	Ruth M. Rothstein CORE Center	Chicago	Illinois
United States	University of South Carolina School of Medicine	Columbia	South Carolina
United States	North Texas Infectious Diseases Consultants	Dallas	Texas
United States	Trinity Health and Wellness Center/AIDS Arms, Inc.	Dallas	Texas
United States	Infectious Disease Specialist of Atlanta	Decatur	Georgia
United States	Apex Research, LLC	Denver	Colorado
United States	Henry Ford Hospital	Detroit	Michigan
United States	Duke University	Durham	North Carolina
United States	New York Hospital Queens	Flushing	New York
United States	Gary Richmond, MD, PA, Inc.	Fort Lauderdale	Florida
United States	Midway Immunology & Research Center, LLC	Fort Pierce	Florida
United States	Tarrant County Infectious Disease Associates	Fort Worth	Texas
United States	Metrowest Medical Center	Framingham	Massachusetts
United States	Garcias' Family Health Group	Harlingen	Texas
United States	ID Care	Hillsborough	New Jersey
United States	University of Hawaii - Hawaii Center for AIDS	Honolulu	Hawaii
United States	Gordon E. Crofoot, MD, PA	Houston	Texas
United States	Therapeutic Concepts, PA	Houston	Texas
United States	Rosedale Infectious Diseases	Huntersville	North Carolina
United States	DCOL Center for Clinical Research	Longview	Texas
United States	Anthony Mills MD Inc	Los Angeles	California
United States	Kaiser Permanente Los Angeles	Los Angeles	California
United States	Peter J. Ruane, MD, Inc.	Los Angeles	California
United States	University of California, Los Angeles	Los Angeles	California
United States	Mercer University School of Medicine	Macon	Georgia
United States	North Shore University Hospital - Division of Infectious Diseases	Manhasset	New York
United States	The Kinder Medical Group	Miami	Florida
United States	AIDS Healthcare Foundation	Miami Beach	Florida
United States	Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Mount Sinai School of Medicine	New York	New York
United States	Saint Michael's Medical Center	Newark	New Jersey
United States	East Bay AIDS Center	Oakland	California
United States	IDOCF/ValuHealthMD, LLC	Orlando	Florida
United States	Orlando Immunology Center	Orlando	Florida
United States	Infectious Diseases Associates	Pensacola	Florida
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Spectrum Medical Group	Phoenix	Arizona
United States	The Miriam Hospital	Providence	Rhode Island
United States	Kaiser Permanente - Sacramento	Sacramento	California
United States	Central West Clinical Research, Inc.	Saint Louis	Missouri
United States	Southampton Healthcare, Inc.	Saint Louis	Missouri
United States	La Playa Medical Group and Clinical Research	San Diego	California
United States	University of California, San Diego	San Diego	California
United States	Southwest C.A.R.E. Center	Santa Fe	New Mexico
United States	Peter Shalit, MD	Seattle	Washington
United States	Baystate Infectious Diseases Clinical Research	Springfield	Massachusetts
United States	Infectious Disease Research Institute Inc.	Tampa	Florida
United States	St. Joseph's Comprenhensive Research Inisitute	Tampa	Florida
United States	The University of South Florida	Tampa	Florida
United States	Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center	Torrance	California
United States	AIDS Research and Treatment Center of the Treasure Coast	Vero Beach	Florida
United States	Capital Medical Associates, P.C.	Washington	District of Columbia
United States	Dupont Circle Physicians Group, P.C.	Washington	District of Columbia
United States	Whitman Walker Clinic	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belgium,  Canada,  Italy,  Japan,  Puerto Rico,  Spain,  Switzerland,  Thailand,  United Kingdom, 

References & Publications (7)

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 Disoprox — View 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 Internati

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 A — View 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 elvitegravi — View Citation

Margot NA, Kitrinos KM, Fordyce M, McCallister S, Miller MD, Callebaut C. Rare emergence of drug resistance in HIV-1 treatment-naïve patients after 48 weeks of treatment with elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide. HIV Clin Trials. 20 — View 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, McCallist — View 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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at 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.	Week 48
Secondary	Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 96 and 144	The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Weeks 96 and 144 were 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.	Weeks 96 and 144
Secondary	Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Weeks 48, 96, and 144	The percentage of participants achieving HIV-1 RNA < 20 copies/mL at Weeks 48, 96, and 144 were 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.	Weeks 48, 96. and 144
Secondary	Change From Baseline in CD4+ Cell Count at Week 48		Baseline; Week 48
Secondary	Change From Baseline in CD4+ Cell Count at Week 96		Baseline; Week 96
Secondary	Change From Baseline in CD4+ Cell Count at Week 144		Baseline; Week 144
Secondary	Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48	Hip BMD was assessed by dual energy x-ray absorptiometry (DXA) scan.	Baseline; Week 48
Secondary	Percent Change From Baseline in Hip BMD at Week 96	Hip BMD was assessed by DXA scan.	Baseline; Week 96
Secondary	Percent Change From Baseline in Hip BMD at Week 144	Hip BMD was assessed by DXA scan.	Baseline; Week 144
Secondary	Percent Change From Baseline in Spine BMD at Week 48	Spine BMD was assessed by DXA scan.	Baseline; Week 48
Secondary	Percent Change From Baseline in Spine BMD at Week 96	Spine BMD was assessed by DXA scan.	Baseline; Week 96
Secondary	Percent Change From Baseline in Spine BMD at Week 144	Spine BMD was assessed by DXA scan.	Baseline; Week 144
Secondary	Change From Baseline in Serum Creatinine at Week 48		Baseline; Week 48
Secondary	Change From Baseline in Serum Creatinine at Week 96		Baseline; Week 96
Secondary	Change From Baseline in Serum Creatinine at Week 144		Baseline; Week 144
Secondary	Percentage of Participants Experiencing Treatment-emergent Proteinuria Through 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.	Up to 48 weeks
Secondary	Percentage of Participants Experiencing Treatment-emergent Proteinuria Through 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.	Up to 96 weeks
Secondary	Percentage of Participants Experiencing Treatment-emergent Proteinuria Through Week 144	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.	Up to 144 weeks
Secondary	Percent Change From Baseline in Urine Retinol Binding Protein (RBP) to Creatinine Ratio at Week 48	Urine RBP is a renal biomarker which is used to detect drug-induced kidney injury.	Baseline; Week 48
Secondary	Percent Change From Baseline in Urine RBP to Creatinine Ratio at Week 96	Urine RBP is a renal biomarker which is used to detect drug-induced kidney injury.	Baseline; Week 96
Secondary	Percent Change From Baseline in Urine RBP to Creatinine Ratio at Week 144	Urine RBP is a renal biomarker which is used to detect drug-induced kidney injury.	Baseline; Week 144
Secondary	Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio at Week 48	Urine Beta-2-microglobulin is a renal biomarker which is used to detect drug-induced kidney injury.	Baseline; Week 48
Secondary	Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio at Week 96	Urine Beta-2-microglobulin is a renal biomarker which is used to detect drug-induced kidney injury.	Baseline; Week 96
Secondary	Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio at Week 144	Urine Beta-2-microglobulin is a renal biomarker which is used to detect drug-induced kidney injury.	Baseline; Week 144