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

Overview

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

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: January 23, 2015

Interventions

  • Drug: E/C/F/TAF
    • E/C/F/TAF (150/150/200/10 mg) FDC tablet administered orally once daily with food

Arms, Groups and Cohorts

  • 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.
  • Experimental: HIV-suppressed
    • HIV/HBV coinfected participants who are HIV-suppressed will receive E/C/F/TAF for 48 weeks.

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

  • Percentage of Participants With Plasma HIV-1 RNA Level < 50 Copies/mL
    • 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.
  • Percentage of Participants With Plasma HBV DNA Levels < 29 IU/mL
    • Time Frame: Week 48
    • 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
    • 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
    • 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
    • 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
    • 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
    • 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
    • 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
    • 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
    • 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.

Participating in This Clinical Trial

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.

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Gilead Sciences
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Gilead Study Director, Study Director, Gilead Sciences

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