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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01780506




Registration number
NCT01780506
Ethics application status
Date submitted
16/01/2013
Date registered
31/01/2013
Date last updated
19/11/2018

Titles & IDs
Public title
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
Scientific 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
Secondary ID [1] 0 0
2012-004458-27
Secondary ID [2] 0 0
GS-US-292-0104
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV 0 0
HIV Infections 0 0
Condition category
Condition code
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - E/C/F/TAF
Treatment: Drugs - E/C/F/TDF
Treatment: Drugs - E/C/F/TDF Placebo
Treatment: Drugs - E/C/F/TAF Placebo

Experimental: E/C/F/TAF (Double-Blind Phase) - E/C/F/TAF plus E/C/F/TDF placebo for 144 weeks

Active comparator: E/C/F/TDF (Double-Blind Phase) - E/C/F/TDF plus E/C/F/TAF placebo for 144 weeks

Experimental: Open-Label Extension Phase - After study unblinding, participants who complete 144 weeks of the study had the option to receive open-label E/C/F/TAF until commercially available, or until Gilead Sciences terminated the study in that country.


Treatment: Drugs: E/C/F/TAF
150/150/200/10 mg FDC tablet administered orally once daily

Treatment: Drugs: E/C/F/TDF
150/150/200/300 mg FDC tablet administered orally once daily

Treatment: Drugs: E/C/F/TDF Placebo
Tablet administered orally once daily

Treatment: Drugs: E/C/F/TAF Placebo
Tablet administered orally once daily
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 48
Timepoint [1] 0 0
Week 48
Secondary outcome [1] 0 0
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Weeks 96 and 144
Timepoint [1] 0 0
Weeks 96 and 144
Secondary outcome [2] 0 0
Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Weeks 48, 96, and 144
Timepoint [2] 0 0
Weeks 48, 96. and 144
Secondary outcome [3] 0 0
Change From Baseline in CD4+ Cell Count at Week 48
Timepoint [3] 0 0
Baseline; Week 48
Secondary outcome [4] 0 0
Change From Baseline in CD4+ Cell Count at Week 96
Timepoint [4] 0 0
Baseline; Week 96
Secondary outcome [5] 0 0
Change From Baseline in CD4+ Cell Count at Week 144
Timepoint [5] 0 0
Baseline; Week 144
Secondary outcome [6] 0 0
Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48
Timepoint [6] 0 0
Baseline; Week 48
Secondary outcome [7] 0 0
Percent Change From Baseline in Hip BMD at Week 96
Timepoint [7] 0 0
Baseline; Week 96
Secondary outcome [8] 0 0
Percent Change From Baseline in Hip BMD at Week 144
Timepoint [8] 0 0
Baseline; Week 144
Secondary outcome [9] 0 0
Percent Change From Baseline in Spine BMD at Week 48
Timepoint [9] 0 0
Baseline; Week 48
Secondary outcome [10] 0 0
Percent Change From Baseline in Spine BMD at Week 96
Timepoint [10] 0 0
Baseline; Week 96
Secondary outcome [11] 0 0
Percent Change From Baseline in Spine BMD at Week 144
Timepoint [11] 0 0
Baseline; Week 144
Secondary outcome [12] 0 0
Change From Baseline in Serum Creatinine at Week 48
Timepoint [12] 0 0
Baseline; Week 48
Secondary outcome [13] 0 0
Change From Baseline in Serum Creatinine at Week 96
Timepoint [13] 0 0
Baseline; Week 96
Secondary outcome [14] 0 0
Change From Baseline in Serum Creatinine at Week 144
Timepoint [14] 0 0
Baseline; Week 144
Secondary outcome [15] 0 0
Percentage of Participants Experiencing Treatment-emergent Proteinuria Through Week 48
Timepoint [15] 0 0
Up to 48 weeks
Secondary outcome [16] 0 0
Percentage of Participants Experiencing Treatment-emergent Proteinuria Through Week 96
Timepoint [16] 0 0
Up to 96 weeks
Secondary outcome [17] 0 0
Percentage of Participants Experiencing Treatment-emergent Proteinuria Through Week 144
Timepoint [17] 0 0
Up to 144 weeks
Secondary outcome [18] 0 0
Percent Change From Baseline in Urine Retinol Binding Protein (RBP) to Creatinine Ratio at Week 48
Timepoint [18] 0 0
Baseline; Week 48
Secondary outcome [19] 0 0
Percent Change From Baseline in Urine RBP to Creatinine Ratio at Week 96
Timepoint [19] 0 0
Baseline; Week 96
Secondary outcome [20] 0 0
Percent Change From Baseline in Urine RBP to Creatinine Ratio at Week 144
Timepoint [20] 0 0
Baseline; Week 144
Secondary outcome [21] 0 0
Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio at Week 48
Timepoint [21] 0 0
Baseline; Week 48
Secondary outcome [22] 0 0
Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio at Week 96
Timepoint [22] 0 0
Baseline; Week 96
Secondary outcome [23] 0 0
Percent Change From Baseline in Urine Beta-2-microglobulin to Creatinine Ratio at Week 144
Timepoint [23] 0 0
Baseline; Week 144

Eligibility
Key inclusion criteria
Key

* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
26/12/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
6/09/2017
Sample size
Target
Accrual to date
Final
872
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Holdsworth House Medical Practice - Darlinghurst
Recruitment hospital [2] 0 0
Taylor Square Private Clinic - Darlington
Recruitment hospital [3] 0 0
East Sydney Doctors - Sydney
Recruitment hospital [4] 0 0
Albion Street Centre - Sydney
Recruitment hospital [5] 0 0
Melbourne Sexual Health Clinic - Carlton
Recruitment postcode(s) [1] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [2] 0 0
2010 - Darlington
Recruitment postcode(s) [3] 0 0
2010 NSW - Sydney
Recruitment postcode(s) [4] 0 0
2010 - Sydney
Recruitment postcode(s) [5] 0 0
3053 - Carlton
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Connecticut
Country [6] 0 0
United States of America
State/province [6] 0 0
District of Columbia
Country [7] 0 0
United States of America
State/province [7] 0 0
Florida
Country [8] 0 0
United States of America
State/province [8] 0 0
Georgia
Country [9] 0 0
United States of America
State/province [9] 0 0
Hawaii
Country [10] 0 0
United States of America
State/province [10] 0 0
Illinois
Country [11] 0 0
United States of America
State/province [11] 0 0
Maryland
Country [12] 0 0
United States of America
State/province [12] 0 0
Massachusetts
Country [13] 0 0
United States of America
State/province [13] 0 0
Michigan
Country [14] 0 0
United States of America
State/province [14] 0 0
Minnesota
Country [15] 0 0
United States of America
State/province [15] 0 0
Missouri
Country [16] 0 0
United States of America
State/province [16] 0 0
New Jersey
Country [17] 0 0
United States of America
State/province [17] 0 0
New Mexico
Country [18] 0 0
United States of America
State/province [18] 0 0
New York
Country [19] 0 0
United States of America
State/province [19] 0 0
North Carolina
Country [20] 0 0
United States of America
State/province [20] 0 0
Ohio
Country [21] 0 0
United States of America
State/province [21] 0 0
Pennsylvania
Country [22] 0 0
United States of America
State/province [22] 0 0
Rhode Island
Country [23] 0 0
United States of America
State/province [23] 0 0
South Carolina
Country [24] 0 0
United States of America
State/province [24] 0 0
Texas
Country [25] 0 0
United States of America
State/province [25] 0 0
Virginia
Country [26] 0 0
United States of America
State/province [26] 0 0
Washington
Country [27] 0 0
United States of America
State/province [27] 0 0
Wisconsin
Country [28] 0 0
Austria
State/province [28] 0 0
Vienna
Country [29] 0 0
Austria
State/province [29] 0 0
Wien
Country [30] 0 0
Belgium
State/province [30] 0 0
Brussels
Country [31] 0 0
Canada
State/province [31] 0 0
British Columbia
Country [32] 0 0
Canada
State/province [32] 0 0
Manitoba
Country [33] 0 0
Canada
State/province [33] 0 0
Ontario
Country [34] 0 0
Canada
State/province [34] 0 0
Quebec
Country [35] 0 0
Canada
State/province [35] 0 0
Toronto
Country [36] 0 0
Italy
State/province [36] 0 0
Milano
Country [37] 0 0
Japan
State/province [37] 0 0
Shinjuku-ku, Tokyo
Country [38] 0 0
Puerto Rico
State/province [38] 0 0
San Juan
Country [39] 0 0
Spain
State/province [39] 0 0
Badalona
Country [40] 0 0
Spain
State/province [40] 0 0
Barcelona
Country [41] 0 0
Spain
State/province [41] 0 0
Madrid
Country [42] 0 0
Spain
State/province [42] 0 0
Santiago de Compostela
Country [43] 0 0
Switzerland
State/province [43] 0 0
Berne
Country [44] 0 0
Switzerland
State/province [44] 0 0
Lausanne
Country [45] 0 0
Switzerland
State/province [45] 0 0
Zurich
Country [46] 0 0
Thailand
State/province [46] 0 0
Bangkok
Country [47] 0 0
Thailand
State/province [47] 0 0
Chiang Mai
Country [48] 0 0
Thailand
State/province [48] 0 0
Khon Kaen
Country [49] 0 0
Thailand
State/province [49] 0 0
Nonthaburi
Country [50] 0 0
United Kingdom
State/province [50] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT01780506
Trial related presentations / publications
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. Erratum In: Lancet. 2016 Apr 30;387(10030):1816. doi: 10.1016/S0140-6736(16)30252-5.
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.
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.
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Gilead Study Director
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01780506