Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT02071082
First received: February 21, 2014
Last updated: July 11, 2016
Last verified: July 2016
  Purpose

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

Condition Intervention Phase
HIV
HBV
Drug: E/C/F/TAF
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Percentage of Participants With Plasma HIV-1 RNA Level < 50 Copies/mL [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Plasma HBV DNA Levels < 29 IU/mL [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The percentage of participants with HBV DNA < 29 IU/mL at Week 24 was calculated using the missing = failure method.


Secondary Outcome Measures:
  • Percentage of Participants With Plasma HIV-1 RNA Level < 50 Copies/mL [ 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.

  • Percentage of Participants With Plasma HBV DNA Levels < 29 IU/mL [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    The percentage of participants with HBV DNA < 29 IU/mL at Week 48 was calculated using the missing = failure method.

  • Percentage of Participants With Normalized Alanine Aminotransferase (ALT) at Week 24 [ Time Frame: Baseline; Week 24 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Normalized ALT at Week 48 [ Time Frame: Baseline; Week 48 ] [ Designated as safety issue: No ]
    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.

  • Percentage of Participants With Seroconversion to Hepatitis B Surface Antibody (Anti-HBs) at Week 24 [ Time Frame: Baseline; Week 24 ] [ Designated as safety issue: No ]
    Seroconversion to antibody is defined as (1) antigen loss and (2) positive postbaseline antibody value. Missing = excluded method.

  • Percentage of Participants With Seroconversion to Anti-HBs at Week 48 [ Time Frame: Baseline; Week 48 ] [ Designated as safety issue: No ]
    Seroconversion to antibody is defined as (1) antigen loss and (2) positive postbaseline antibody value. Missing = excluded method.

  • Percentage of Participants With Seroconversion to Hepatitis B e Antibody (Anti-HBe) at Week 24 [ Time Frame: Baseline; Week 24 ] [ Designated as safety issue: No ]
    Seroconversion to antibody is defined as (1) antigen loss and (2) positive postbaseline antibody value. Missing = excluded method.

  • Percentage of Participants With Seroconversion to Anti-HBe at Week 48 [ Time Frame: Baseline; Week 48 ] [ Designated as safety issue: No ]
    Seroconversion to antibody is defined as (1) antigen loss and (2) positive postbaseline antibody value. Missing = excluded method.

  • Change From Baseline in FibroTest® Score at Week 24 [ Time Frame: Baseline; Week 24 ] [ Designated as safety issue: No ]
    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.

  • Change From Baseline in FibroTest® Score at Week 48 [ Time Frame: Baseline; Week 48 ] [ Designated as safety issue: No ]
    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.


Enrollment: 79
Study Start Date: March 2014
Estimated Study Completion Date: September 2016
Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: Genvoya®

  Eligibility

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

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

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
  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: NCT02071082

  Show 42 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Moupali Das, MD, MPH Gilead Sciences
  More Information

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02071082     History of Changes
Other Study ID Numbers: GS-US-292-1249 
Study First Received: February 21, 2014
Results First Received: January 21, 2016
Last Updated: July 11, 2016
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Japan: Pharmaceuticals and Medical Devices Agency

Keywords provided by Gilead Sciences:
HIV
HBV
Coinfection

Additional relevant MeSH terms:
Hepatitis B
Hepadnaviridae Infections
DNA Virus Infections
Virus Diseases
Hepatitis, Viral, Human
Hepatitis
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on December 07, 2016