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

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: NCT01797445
• Other study ID #: GS-US-292-0111
• Secondary ID: 2013-000102-37
• Status: Completed
• Phase: Phase 3
• Start date: March 12, 2013
• Est. completion date: October 3, 2018

Study information

• Verified date: October 2019
• 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) in HIV-1 positive, antiretroviral treatment-naive adults.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 872
• Est. completion date: October 3, 2018
• Est. primary completion date: September 19, 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 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 Exclusion Criteria:

• 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.

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
Canada	Clinique Medicale L'actuel	Montreal
Canada	Research Institute of McGill University Health Care	Montreal	Quebec
Canada	Maple Leaf Research	Toronto
Canada	University Health Network/Toronto General Hospital	Toronto
Canada	Spectrum Health Care	Vancouver
Dominican Republic	Instituto Dominicano de Estudios Virologicos--IDEV	Santo Domingo
France	Hopital de la Croix Rousse	Lyon
France	University Hospital of Montpellier (CHU-Gui de Chauliac)	Montpellier
France	Archet 1 CHU de Nice, Department of Infectiology	Nice
France	Hôpital Bichat Claude Bernard	Paris
France	Hopital Pitie Salpetriere	Paris
France	Hopital Saint Antoine	Paris
France	Hopital Tenon	Paris
France	Saint Louis Hospital of Infectious Diseases	Paris
France	CH Tourcoing	Tourcoing
Italy	Universitaria di Bologna-Policlicnico S' Orsola Malpighi	Bologna
Italy	IRCCS Ospedale San Raffaele	Milan
Mexico	Hospital Civil de Guadalajara	Guadalajara
Mexico	Insituto Nacional De Enfermedades Respiratorias "Ismael Cosio Villegas"	Mexico City
Netherlands	Onze Lieve Vrouwe Gasthuis	Amsterdam
Portugal	Serviço de Doenças Infecciosas, HUC-CHUC, EPE	Coimbra
Portugal	Hospital Santo Antonio dos Capuchos	Lisboa
Portugal	Hospital de Santa Maria - CHLN, EPE	Lisbon
Portugal	Centro Hospitalar do Porto - Hospital Joaquim Urbano	Porto
Puerto Rico	Hope Clinical Research	San Juan
Puerto Rico	University of Puerto Rico ACTU	San Juan
Sweden	Karolinska University Hospital, Huddinge	Stockholm
Sweden	Venhalsan / Sodersjukhuset	Stockholm
United Kingdom	Heart Of England NHS Foundation Trust	Birmingham
United Kingdom	Whittall Street Clinic	Birmingham
United Kingdom	Brighton and Sussex University Hospitals NHS Trust	Brighton
United Kingdom	Brownlee Centre, Gartnavel General Hospital	Glasgow
United Kingdom	Barts Health NHS Trust	London
United Kingdom	Chelsea and Westminster	London
United Kingdom	Kings College Hospital	London
United Kingdom	Mortimer Market Centre	London
United Kingdom	Royal Free London NHS Foundation Trust	London
United Kingdom	North Manchester General Hospital	Manchester
United States	Albany Medical College	Albany	New York
United States	Upstate ID Assoc	Albany	New York
United States	Clinical Alliance for Research & Education - Infectious Diseases (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	Georgia Regents University	Augusta	Georgia
United States	University of Colorado	Aurora	Colorado
United States	Central Texas Clinical Research	Austin	Texas
United States	St. Hope Foundation, Inc.	Bellaire	Texas
United States	Be Well Medical Center	Berkley	Michigan
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Community Research Initiative of New England	Boston	Massachusetts
United States	Jacobi Medical Center	Bronx	New York
United States	Montefiore Medical Center	Bronx	New York
United States	University of North Carolina AIDS Clinical Trials Unit	Chapel Hill	North Carolina
United States	Carolinas Medical Center Myer's Park Clinic	Charlotte	North Carolina
United States	Rush University Medical Center, Section of Infectious Diseases	Chicago	Illinois
United States	The Ruth M. Rothstein CORE Center	Chicago	Illinois
United States	North Texas Infectious Diseases Consultants	Dallas	Texas
United States	Southwest Infectious Disease Clinical Research, Inc.	Dallas	Texas
United States	Trinity Health & 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 Health System	Detroit	Michigan
United States	Duke University Medical Center	Durham	North Carolina
United States	Gary J. Richmond,M.D.,P.A.	Fort Lauderdale	Florida
United States	Midway Immunology and Research Center	Fort Pierce	Florida
United States	Tarrant County Infectious Disease Associates	Fort Worth	Texas
United States	East Carolina University The Brody School of Medicine	Greenville	North Carolina
United States	Greenwich Hospital	Greenwich	Connecticut
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	Research Access Network	Houston	Texas
United States	Therapeutic Concepts, PA	Houston	Texas
United States	Rosedale Infectious Disseases	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 Medical Center	Los Angeles	California
United States	Peter J. Ruane, Inc.	Los Angeles	California
United States	University of Southern California AIDS Clinical Trials Group	Los Angeles	California
United States	Mercer University	Macon	Georgia
United States	North Shore University Hospital - Division of Infectious Diseases	Manhasset	New York
United States	AIDS Healthcare Foundation	Miami	Florida
United States	AIDS Healthcare Foundation	Miami Beach	Florida
United States	Hennepin County Medical Center	Minneapolis	Minnesota
United States	Yale University	New Haven	Connecticut
United States	Chelsea Village Medical	New York	New York
United States	Columbia University Medical Center	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Alameda County Medical Center	Oakland	California
United States	Idocf/Valuhealthmd	Orlando	Florida
United States	Orlando Immunology Center	Orlando	Florida
United States	Stanford University	Palo Alto	California
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 Medical Group	Sacramento	California
United States	University of California, Davis Medical Center	Sacramento	California
United States	Central West Clinical Research	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	Kaiser Permanente San Francisco	San Francisco	California
United States	Kaiser Permanente	San Leandro	California
United States	Southwest CARE Center	Santa Fe	New Mexico
United States	Infectious Diseases Associates of NW FL	Sarasota	Florida
United States	Peter Shalit, MD	Seattle	Washington
United States	Infectious Disease Research Institute Inc.	Tampa	Florida
United States	St. Joseph's Comprehensive Research Institute	Tampa	Florida
United States	University of South Florida	Tampa	Florida
United States	Los Angeles Biomedical Research Institute at Harbor - UCLA Medical Center	Torrance	California
United States	Capital Medical Associates, PC	Washington	District of Columbia
United States	Dupont Circle Physicians Group	Washington	District of Columbia
United States	Medical Faculty Associates	Washington	District of Columbia
United States	Whitman-Walker Health	Washington	District of Columbia
United States	Triple O Research Institute PA	West Palm Beach	Florida
United States	The Research Institute	West Springfield	Massachusetts
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Canada,  Dominican Republic,  France,  Italy,  Mexico,  Netherlands,  Portugal,  Puerto Rico,  Sweden,  United Kingdom, 

References & Publications (8)

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 N, Cox S, Das M, McCallister S, Miller MD, Callebaut C. Rare emergence of drug resistance in HIV-1 treatment-naïve patients receiving elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide for 144 weeks. J Clin Virol. 2018 Jun;103:37-42. doi: — 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 Achieving 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 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.	Week 96
Secondary	Percentage of Participants With HIV-1 RNA < 20 Copies/mL at 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.	Weeks 48 and 96
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	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 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	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	Percentage of Participants With 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.	Baseline to Week 48
Secondary	Percentage of Participants With 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.	Baseline to Week 96
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 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