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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01797445
First received: February 20, 2013
Last updated: July 5, 2016
Last verified: July 2016
  Purpose
This study will evaluate the efficacy and safety of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (Genvoya®; E/C/F/TAF) fixed-dose combination (FDC) versus elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (Stribild®; E/C/F/TDF) in HIV-1 positive, antiretroviral treatment-naive adults.

Condition Intervention Phase
HIV
HIV Infections
Drug: E/C/F/TAF
Drug: E/C/F/TDF
Drug: E/C/F/TDF Placebo
Drug: E/C/F/TAF Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Percentage of Participants Achieving HIV-1 RNA < 50 Copies/mL at Week 48 [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 96 [ Time Frame: Week 96 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Change From Baseline in CD4+ Cell Count at Week 96 [ Time Frame: Baseline; Week 96 ] [ Designated as safety issue: No ]
  • Percent Change From Baseline in Hip Bone Mineral Density (BMD) at Week 48 [ Time Frame: Baseline; Week 48 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    Hip BMD was assessed by DXA scan.

  • Percent Change From Baseline in Spine BMD at Week 48 [ Time Frame: Baseline; Week 48 ] [ Designated as safety issue: Yes ]
    Spine BMD was assessed by DXA scan.

  • Percent Change From Baseline in Spine BMD at Week 96 [ Time Frame: Baseline; Week 96 ] [ Designated as safety issue: Yes ]
    Spine BMD was assessed by DXA scan.

  • Change From Baseline in Serum Creatinine at Week 48 [ Time Frame: Baseline; Week 48 ] [ Designated as safety issue: Yes ]
  • Change From Baseline in Serum Creatinine at Week 96 [ Time Frame: Baseline; Week 96 ] [ Designated as safety issue: Yes ]
  • Percentage of Participants With Treatment-emergent Proteinuria Through Week 48 [ Time Frame: Up to 48 weeks ] [ Designated as safety issue: Yes ]
    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: Up to 96 weeks ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    Urine Beta-2-microglobulin is a renal biomarker which is used to detect drug-induced kidney injury.


Enrollment: 872
Study Start Date: January 2013
Estimated Study Completion Date: January 2017
Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: E/C/F/TAF
E/C/F/TAF plus E/C/F/TDF placebo for 144 weeks
Drug: E/C/F/TAF
E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily
Other Name: Genvoya®
Drug: E/C/F/TDF Placebo
E/C/F/TDF placebo tablet administered orally once daily
Active Comparator: E/C/F/TDF
E/C/F/TDF plus E/C/F/TAF placebo for 144 weeks
Drug: E/C/F/TDF
E/C/F/TDF (150/150/200/300 mg) FDC tablet administered orally once daily
Other Name: Stribild®
Drug: E/C/F/TAF Placebo
E/C/F/TAF placebo tablet administered orally once daily

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01797445

  Show 125 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Moupali Das, MD, MPH Gilead Sciences
  More Information

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01797445     History of Changes
Other Study ID Numbers: GS-US-292-0111  2013-000102-37 
Study First Received: February 20, 2013
Results First Received: December 4, 2015
Last Updated: July 5, 2016
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Spain: Spanish Agency of Medicines
Portugal: INFARMED, National Authority of Medicines and Health Products, IP
Austria: Austrian Medicines and Medical Devices Agency
Austria: Federal Office for Safety in Health Care
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Netherlands: Medicines Evaluation Board (MEB)
Italy: The Italian Medicines Agency
Sweden: Medical Products Agency
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Dominican Republic: Consejo Nacional de Bioetica en Salud
Mexico: Federal Commission for Protection Against Health Risks

Keywords provided by Gilead Sciences:
HIV
Treatment Naive
HIV 1 Infected
Women
Female

Additional relevant MeSH terms:
HIV Infections
Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Tenofovir
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on August 24, 2016