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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01797445
Recruitment Status : Completed
First Posted : February 22, 2013
Results First Posted : January 8, 2016
Last Update Posted : March 2, 2020
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE February 20, 2013
First Posted Date  ICMJE February 22, 2013
Results First Submitted Date  ICMJE December 4, 2015
Results First Posted Date  ICMJE January 8, 2016
Last Update Posted Date March 2, 2020
Actual Study Start Date  ICMJE March 12, 2013
Actual Primary Completion Date September 19, 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 4, 2015)
Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 48 [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: February 20, 2013)
The proportion of subjects who have HIV-1 RNA < 50 copies/mL [ Time Frame: 48 Weeks ]
The primary efficacy endpoint is determined by the achievement of HIV-1 RNA < 50 copies/mL at Week 48
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 1, 2019)
  • Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 [ Time Frame: 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.
  • Percentage of Participants With HIV-1 RNA < 20 Copies/mL at Weeks 48 and 96 [ Time Frame: 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.
  • Change From Baseline in CD4+ Cell Count at Week 48 [ Time Frame: Baseline; Week 48 ]
  • Change From Baseline in CD4+ Cell Count at Week 96 [ Time Frame: Baseline; Week 96 ]
  • Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 [ Time Frame: 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 [ Time Frame: Baseline; Week 96 ]
    Hip BMD was assessed by DXA scan.
  • Percent Change From Baseline in Spine BMD at Week 48 [ Time Frame: Baseline; Week 48 ]
    Spine BMD was assessed by DXA scan.
  • Percent Change From Baseline in Spine BMD at Week 96 [ Time Frame: Baseline; Week 96 ]
    Spine BMD was assessed by DXA scan.
  • Change From Baseline in Serum Creatinine at Week 48 [ Time Frame: Baseline; Week 48 ]
  • Change From Baseline in Serum Creatinine at Week 96 [ Time Frame: Baseline; Week 96 ]
  • Percentage of Participants With Treatment-emergent Proteinuria Through Week 48 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Baseline; Week 48 ]
    Urine RBP is a renal biomarker which is used to detect drug-induced kidney injury.
  • Percent Change From Baseline in Urine RBP to Creatinine Ratio at Week 96 [ Time Frame: 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 [ Time Frame: Baseline; Week 48 ]
    Urine Beta-2-microglobulin 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 96 [ Time Frame: Baseline; Week 96 ]
    Urine Beta-2-microglobulin is a renal biomarker which is used to detect drug-induced kidney injury.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 20, 2013)
  • To determine the safety by the percent change from baseline in hip bone mineral density [ Time Frame: 48 Weeks ]
    To determine the safety of the two treatment regimens as determined by the percent change from baseline in hip bone mineral density at Week 48
  • To determine the safety determined by the change from baseline in serum creatinine at Week 48 [ Time Frame: 48 Weeks ]
    To determine the safety of the two treatment regimens as determined by the change from baseline in serum creatinine at Week 48
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • HIV
  • HIV Infections
Intervention  ICMJE
  • Drug: E/C/F/TAF
    150/150/200/10 mg FDC tablet administered orally once daily
    Other Name: Genvoya®
  • Drug: E/C/F/TDF
    150/150/200/300 mg FDC tablet administered orally once daily
    Other Name: Stribild®
  • Drug: E/C/F/TDF Placebo
    Tablet administered orally once daily
  • Drug: E/C/F/TAF Placebo
    Tablet administered orally once daily
Study Arms  ICMJE
  • Experimental: E/C/F/TAF (Double-Blind)

    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.

    Interventions:
    • Drug: E/C/F/TAF
    • Drug: E/C/F/TDF Placebo
  • Active Comparator: E/C/F/TDF (Double-Blind)

    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.

    Interventions:
    • Drug: E/C/F/TDF
    • Drug: E/C/F/TAF Placebo
  • Experimental: Open-Label 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.
    Intervention: Drug: E/C/F/TAF
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 16, 2015)
872
Original Estimated Enrollment  ICMJE
 (submitted: February 20, 2013)
840
Actual Study Completion Date  ICMJE October 3, 2018
Actual Primary Completion Date September 19, 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Dominican Republic,   France,   Italy,   Mexico,   Netherlands,   Portugal,   Puerto Rico,   Sweden,   United Kingdom,   United States
Removed Location Countries Australia,   Austria,   Belgium,   Brazil,   Germany,   Spain,   Switzerland,   Thailand
 
Administrative Information
NCT Number  ICMJE NCT01797445
Other Study ID Numbers  ICMJE GS-US-292-0111
2013-000102-37 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Time Frame: 18 months after study completion
Access Criteria: A secured external environment with username, password, and RSA code.
URL: https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy
Responsible Party Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Gilead Study Director Gilead Sciences
PRS Account Gilead Sciences
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP