Efficacy and Safety of E/C/F/TAF (Genvoya®) in HIV-1/Hepatitis B Co-infected Adults

A Phase 3b Open-label Study of the Efficacy and Safety of Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Single-Tablet Regimen in HIV-1/Hepatitis B Co-infected Adults

This study will assess the efficacy, safety, and tolerability of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) fixed-dose combination (FDC) in human immunodeficiency virus (HIV)/hepatitis B virus (HBV) coinfected adults.

Participants will be enrolled into two cohorts:

• Cohort 1: HIV/HBV coinfected adults who are HIV treatment-naive and HBV treatment-naive
• Cohort 2: HIV/HBV coinfected adults who are HIV-suppressed

Study Overview

• Status: Completed
• Conditions: HIV; HBV
• Intervention / Treatment: Drug: E/C/F/TAF

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2N2
      • University Health Network/Toronto General Hospital
    • Toronto, Ontario, Canada, M5G1K2
      • Maple Leaf Research/Maple Leaf Medical Clinic
• Japan
  • Tokyo
    • Shinjuku-ku, Tokyo, Japan, 1628655
      • Center Hospital of the National Center for Global Health and Medicine
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85012
      • Spectrum Medical Group
  • California
    • Beverly Hills, California, United States, 90211
      • AHF Research Center
    • Los Angeles, California, United States, 90036
      • Peter J. Ruane MD, Inc.
    • Los Angeles, California, United States, 90069
      • Anthony Mills MD, Inc
  • District of Columbia
    • Washington, District of Columbia, United States, 20009
      • Whitman Walker Health
  • Florida
    • Clearwater, Florida, United States, 33765
      • Barry M. Rodwick MD
    • Fort Lauderdale, Florida, United States, 33316
      • Gary J Richmond M.D.,P.A.
    • Fort Pierce, Florida, United States, 34982
      • Midway Immunology and Research Center
    • Miami Beach, Florida, United States, 33139
      • AIDS Health Foundation/WPA
    • Vero Beach, Florida, United States, 32960
      • AIDS Research and Treatment Center of the Treasure Coast
    • West Palm Beach, Florida, United States, 33401
      • Triple O Research Institute PA
  • Michigan
    • Berkley, Michigan, United States, 48072
      • Be Well Medical Center PC
  • Missouri
    • Kansas City, Missouri, United States, 64111
      • KC Care Clinic
    • Saint Louis, Missouri, United States, 63139
      • Southampton Healthcare, Inc.
  • New Mexico
    • Santa Fe, New Mexico, United States, 87505
      • Southwest CARE Center
  • Texas
    • Austin, Texas, United States, 78705
      • Central Texas Clinical Research
    • Bellaire, Texas, United States
      • St. Hope Foundation
    • Dallas, Texas, United States, 75246
      • North Texas Infectious Diseases Consultants
    • Houston, Texas, United States, 77004
      • Therapeutic Concepts
    • Houston, Texas, United States, 77098
      • Gordon E. Crofoot MD PA
  • Washington
    • Seattle, Washington, United States, 98104
      • Peter Shalit MD

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:

• Both Cohorts 1 and 2:

  • The ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures
  • HIV/HBV co-infected adult males and non-pregnant and non-lactating females

  • No evidence of hepatocellular carcinoma (HCC) or clinical or imaging evidence of cirrhosis (ascites, variceal bleeding, encephalopathy).

    --- Subjects should have documentation of an abdominal ultrasound in the 12 months prior to screening, or an abdominal ultrasound at screening, demonstrating the absence of cirrhosis and HCC.

  • Acute Hepatitis A virus (HAV) immunoglobulin M (IgM) negative
  • Hepatitis C virus (HCV) Ab negative, or HCV Ab positive with negative HCV RNA
  • Hepatitis D virus (HDV) Ab negative, or HDV Ab positive with negative HDV RNA
  • Estimated glomerular filtration rate (eGFR) ≥ 50 mL/min according to the Cockcroft-Gault formula
  • CD4+ count of > 200 cells/μL

  • Chronic HBV infection as defined by

    • HBsAg positive for ≥ 6 months Or
    • HBsAg positive at screening and either hepatitis B e antigen (HBeAg) or HBV DNA positive ≥ 6 months Or

    • At screening: positive total hepatitis B core antibody (HBcAb) and negative immunoglobulin M antibody to hepatitis B core antigen (HBcIgM) antibody, and

      • HBsAg positive, or
      • HBeAg positive, or
      • HBV DNA positive

• Cohort 1 (HIV and HBV treatment naive) only:

  • No current or prior anti-HIV treatment, including antiretroviral medications received for prevention (PrEP), or post exposure prophylaxis (PEP)
  • No current or prior anti-HBV treatment
  • Plasma HIV-1 RNA level ≥ 500 copies/mL at screening
  • Screening HBV DNA ≥ 3 log10 IU/mL and < 9 log10 IU/mL

• Cohort 2 (HIV suppressed) only:

  • Receiving current antiretroviral regimen for at least 4 consecutive months
  • No current or prior regimen containing 3 active anti-HBV agents (i.e. cannot be on tenofovir alafenamide (TDF)/emtricitabine (FTC)/Entecavir or TDF/lamivudine(3TC)/Entecavir)
  • Maintained plasma HIV-1 RNA < 50 copies/mL for 6 consecutive months prior to and at the time of the screening visit. Unconfirmed virologic evaluation of ≥ 50 copies/mL after previously reaching viral suppression (transient detectable viremia, or "blip") and prior to screening is acceptable
  • Documented positive HIV antibody test
  • Screening HBV DNA < 9 log10 IU/mL

Key Exclusion Criteria:

• Females who are breastfeeding
• Positive serum pregnancy test (female of childbearing potential)
• Have an implanted defibrillator or pacemaker
• Current alcohol or substance use
• A history of malignancy within the past 5 years (prior to screening) or ongoing malignancy other than cutaneous Kaposi's sarcoma (KS), basal cell carcinoma, or resected, non-invasive carcinoma.
• Received solid organ or bone marrow transplant
• Any history of, or current evidence of, clinical hepatic decompensation (e.g., ascites, encephalopathy or variceal hemorrhage).
• Significant bone disease (e.g., osteomalacia, chronic osteomyelitis, osteogenesis imperfecta, osteochondroses), or multiple bone fractures
• Active, serious infections (other than HIV-1 infection) requiring parenteral antibiotic or antifungal therapy within 30 days prior to Day 1
• Subjects on hemodialysis, other forms of renal replacement therapy, or on treatment for underlying kidney diseases (including prednisolone, and dexamethasone)
• Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with the dosing requirements
• Investigational agents (unless approved by Gilead Sciences). Participation in any other clinical trial without prior approval from the sponsor is prohibited while participating in this trial

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HIV treatment-naive and HBV treatment-naive; HIV/HBV coinfected participants who are HIV treatment-naive and HBV treatment-naive will receive E/C/F/TAF for 48 weeks.	Drug: E/C/F/TAF; E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food; Other Names: Genvoya®
Experimental: HIV-suppressed; HIV/HBV coinfected participants who are HIV-suppressed will receive E/C/F/TAF for 48 weeks.	Drug: E/C/F/TAF; E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food; Other Names: Genvoya®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Plasma HIV-1 RNA Level < 50 Copies/mL	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
Percentage of Participants With Plasma HBV DNA Levels < 29 IU/mL	The percentage of participants with HBV DNA < 29 IU/mL at Week 24 was calculated using the missing = failure method.	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Plasma HIV-1 RNA Level < 50 Copies/mL	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
Percentage of Participants With Plasma HBV DNA Levels < 29 IU/mL	The percentage of participants with HBV DNA < 29 IU/mL at Week 48 was calculated using the missing = failure method.	Week 48
Percentage of Participants With Normalized Alanine Aminotransferase (ALT) at Week 24	ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit.	Baseline; Week 24
Percentage of Participants With Normalized ALT at Week 48	ALT normalization was defined as an ALT value that changed from above the normal range at baseline to within the normal range at the given postbaseline visit.	Baseline; Week 48
Percentage of Participants With Seroconversion to Hepatitis B Surface Antibody (Anti-HBs) at Week 24	Seroconversion to antibody is defined as (1) antigen loss and (2) positive postbaseline antibody value. Missing = excluded method.	Baseline; Week 24
Percentage of Participants With Seroconversion to Anti-HBs at Week 48	Seroconversion to antibody is defined as (1) antigen loss and (2) positive postbaseline antibody value. Missing = excluded method.	Baseline; Week 48
Percentage of Participants With Seroconversion to Hepatitis B e Antibody (Anti-HBe) at Week 24	Seroconversion to antibody is defined as (1) antigen loss and (2) positive postbaseline antibody value. Missing = excluded method.	Baseline; Week 24
Percentage of Participants With Seroconversion to Anti-HBe at Week 48	Seroconversion to antibody is defined as (1) antigen loss and (2) positive postbaseline antibody value. Missing = excluded method.	Baseline; Week 48
Change From Baseline in FibroTest® Score at Week 24	The FibroTest® score is used to assess liver fibrosis. Scores range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis.	Baseline; Week 24
Change From Baseline in FibroTest® Score at Week 48	The FibroTest® score is used to assess liver fibrosis. Scores range from 0.00 to 1.00, with higher scores indicating a greater degree of fibrosis.	Baseline; Week 48

Collaborators and Investigators

• Sponsor: Gilead Sciences

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2014
• Primary Completion (Actual): January 23, 2015
• Study Completion (Actual): October 26, 2016

Study Registration Dates

• First Submitted: February 21, 2014
• First Submitted That Met QC Criteria: February 21, 2014
• First Posted (Estimate): February 25, 2014

Study Record Updates

• Last Update Posted (Actual): November 16, 2018
• Last Update Submitted That Met QC Criteria: October 19, 2018
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: HIV; HBV; Coinfection
• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis; Hepatitis B; 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-292-1249

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; Statistical Analysis Plan (SAP)