Safety and Efficacy of E/C/F/TAF (Genvoya®) Versus E/C/F/TDF (Stribild®) in HIV-1 Infected, Antiretroviral Treatment-Naive Adults

A Phase 2, Randomized, Double-Blinded Study of the Safety and Efficacy of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Single Tablet Regimen Versus Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Disoproxil Fumarate Single Tablet Regimen in HIV-1 Infected, Antiretroviral Treatment-Naive Adults

The primary objective of this study is to evaluate the efficacy 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) FDC in HIV-1 infected, antiretroviral treatment-naive adults.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Acquired Immunodeficiency Syndrome
• Intervention / Treatment: Drug: E/C/F/TAF; Drug: E/C/F/TDF Placebo; Drug: E/C/F/TDF; Drug: E/C/F/TAF Placebo

• Study Type: Interventional
• Enrollment (Actual): 279
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00909
    • Clinical Research Puerto Rico
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham (UAB)
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Spectrum Medical Group
  • California
    • Beverly Hills, California, United States, 90211
      • AHF Research Center
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente
    • Los Angeles, California, United States, 90036
      • Peter J. Ruane, MD, Inc.
    • Los Angeles, California, United States, 90069
      • Anthony Mills MD, Inc
    • Oakland, California, United States, 94609
      • East Bay AIDS Center
    • Orange, California, United States, 92869
      • St. Joseph Heritage Healthcare
    • Palo Alto, California, United States, 94304
      • Stanford University
    • Sacramento, California, United States, 95825
      • Kaiser Permanente Medical Group
    • San Diego, California, United States, 92103
      • La Playa Medical Group and Clinical Research
    • San Francisco, California, United States, 94107
      • Metropolis Medical
    • San Francisco, California, United States, 94118
      • Kaiser Permanente Medical Group-Clinical Trials Unit
  • Colorado
    • Denver, Colorado, United States, 80220
      • Apex Research, LLC
  • District of Columbia
    • Washington, District of Columbia, United States, 20009
      • Dupont Circle Physician's Group
    • Washington, District of Columbia, United States, 20036
      • Capital Medical Associates, PC
    • Washington, District of Columbia, United States, 20009
      • Whitman-Walker Health
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Gary J. Richmond,M.D.,P.A.
    • Miami Beach, Florida, United States, 33139
      • Wohlfeiler, Piperato and Associates, LLC
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
    • Orlando, Florida, United States, 32806
      • IDOCF/ValuhealthMD, LLC
    • Tampa, Florida, United States, 33614
      • St. Joseph's Comprehensive Research Institute
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Infectious Disease Specialists of Atlanta
    • Macon, Georgia, United States, 31201
      • Mercer University Mercer Medicine
  • Illinois
    • Chicago, Illinois, United States, 60613
      • Howard Brown Health Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Michigan
    • Berkley, Michigan, United States, 48072
      • Be Well Medical Center
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin County Medical Center
  • Missouri
    • Saint Louis, Missouri, United States, 63108
      • Central West Clinical Research Inc
  • New York
    • Manhasset, New York, United States, 11030
      • North Shore University Hospital / Division of Infectious Diseases
  • North Carolina
    • Charlotte, North Carolina, United States, 28209
      • ID Consultants, P.A.
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • South Carolina
    • Columbia, South Carolina, United States, 29203
      • University of South Carolina School of Medicine Division of Infectious Disease
  • Texas
    • Dallas, Texas, United States, 75219
      • Southwest Infectious Disease Clinical Research Inc
    • Fort Worth, Texas, United States, 76104
      • Tarrant County Infectious Disease Associates
    • Houston, Texas, United States, 77004
      • Therapeutic Concepts, PA
    • Houston, Texas, United States, 77098
      • Gordon E. Crofoot, MD., PA
    • Longview, Texas, United States, 75605
      • DCOL Center for Clinical Research
  • Washington
    • Seattle, Washington, United States, 98104
      • Peter Shalit, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Ability to understand and sign a written informed consent form
• Plasma HIV 1 RNA levels ≥ 5,000 copies/mL
• No prior use of any approved or experimental anti-HIV drug for any length of time
• Screening genotype report must show sensitivity to TDF and emtricitabine (FTC)
• Normal ECG
• Adequate renal function: Estimated glomerular filtration rate ≥ 70 mL/min according to the Cockcroft Gault formula
• Hepatic transaminases ≤ 2.5 x upper limit of the normal range (ULN)
• Total bilirubin ≤ 1.5 mg/dL, or normal direct bilirubin
• Adequate hematologic function
• CD4+ cell count > 50 cells/µL
• Serum amylase ≤ 5 x ULN
• Normal thyroid-stimulating hormone (TSH)
• Females of childbearing potential must have a negative serum pregnancy test
• Females of childbearing potential must agree to utilize highly effective contraception methods from screening throughout the duration of study treatment and for 30 days following the last dose of study drugs
• Female subjects 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
• Female subjects who are postmenopausal must have documentation of cessation of menses for ≥ 12 months and hormonal failure
• Female subjects 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 test at screening
• Male subjects must agree to utilize a highly effective method of contraception during heterosexual intercourse throughout the study period and for 90 days following discontinuation of investigational medicinal product
• Age ≥ 18 years
• Life expectancy ≥ 1 year

Key Exclusion Criteria:

• New AIDS-defining condition diagnosed within the 30 days prior to screening
• Hepatitis B surface Antigen positive
• Hepatitis C Antibody positive
• Proven acute hepatitis in the 30 days prior to study entry
• Subjects experiencing decompensated cirrhosis
• Females who are breastfeeding
• Positive serum pregnancy test (female of childbearing potential)
• Have an implanted defibrillator or pacemaker
• Receiving ongoing therapy with any of the disallowed medications, including drugs not to be used with elvitegravir and cobicistat
• Have been treated with immunosuppressant therapies or chemotherapeutic agents within 3 months of study screening, or expected to receive these agents or systemic steroids during the study
• Current alcohol or substance
• History of or ongoing malignancy (including untreated carcinoma in-situ) other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma or resected, non-invasive cutaneous squamous carcinoma
• Active, serious infections (other than HIV 1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Baseline
• Participation in any other clinical trial without prior approval is prohibited while participating in this trial
• Medications contraindicated for use with emtricitabine or tenofovir disoproxil fumarate
• Any known allergies to the excipients of E/C/F/TAF or E/C/F/TDF FDC tablets
• Any other clinical condition or prior therapy that would make the subject unsuitable for the study or unable to comply with the dosing requirements

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: E/C/F/TAF; E/C/F/TAF plus E/C/F/TDF placebo for at least 48 weeks	Drug: E/C/F/TAF; 150/150/200/10 mg FDC tablet administered orally once daily; Other Names: Genvoya®; Drug: 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 at least 48 weeks	Drug: E/C/F/TDF; 150/150/200/300 mg FDC tablet administered orally once daily; Other Names: Stribild®; Drug: E/C/F/TAF Placebo; Tablet administered orally once daily
EXPERIMENTAL: E/C/F/TAF Open-Label; Following study unblinding, participants from the E/C/F/TAF and E/C/F/TDF arms may have the option to receive E/C/F/TAF during an open-label extension phase. Also, participants who are actively participating in a Gilead-sponsored study of cobicistat-boosted darunavir plus nucleoside/nucleotide reverse transcriptase inhibitors (NRTI) who have reached the protocol-defined secondary endpoint (Week 48) and remain virologically suppressed are eligible to participate and receive E/C/F/TAF in this open-label extension phase.	Drug: E/C/F/TAF; 150/150/200/10 mg FDC tablet administered orally once daily; Other Names: Genvoya®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With HIV-1 RNA < 50 Copies/mL at Week 24	The percentage of participants achieving HIV-1 RNA < 50 copies/mL at Week 24 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 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in CD4+ Cell Count at Weeks 24 and 48		Baseline; Weeks 24 and 48
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
Change From Baseline in log10 HIV-1 RNA at Weeks 24 and 48		Baseline; Weeks 24 and 48

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Sax PE, Zolopa A, Brar I, Elion R, Ortiz R, Post F, Wang H, Callebaut C, Martin H, Fordyce MW, McCallister S. Tenofovir alafenamide vs. tenofovir disoproxil fumarate in single tablet regimens for initial HIV-1 therapy: a randomized phase 2 study. J Acquir Immune Defic Syndr. 2014 Sep 1;67(1):52-8. doi: 10.1097/QAI.0000000000000225.

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 28, 2011
• Primary Completion (ACTUAL): October 17, 2012
• Study Completion (ACTUAL): August 22, 2016

Study Registration Dates

• First Submitted: December 14, 2011
• First Submitted That Met QC Criteria: December 22, 2011
• First Posted (ESTIMATE): December 23, 2011

Study Record Updates

• Last Update Posted (ACTUAL): November 19, 2018
• Last Update Submitted That Met QC Criteria: October 19, 2018
• Last Verified: August 1, 2017

More Information

Terms related to this study

• Keywords: HIV; HIV-1; Treatment-Naive
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Elvitegravir, Cobicistat, Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination
• Other Study ID Numbers: GS-US-292-0102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.
• IPD Sharing Time Frame: 18 months after study completion
• IPD Sharing Access Criteria: A secured external environment with username, password, and RSA code.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No