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

• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: February 21, 2014
• First Posted Date: February 25, 2014
• Results First Submitted Date: January 21, 2016
• Results First Posted Date: April 4, 2016
• Last Update Posted Date: November 16, 2018
• Actual Study Start Date: February 25, 2014
• Actual Primary Completion Date: January 23, 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 7, 2016)

• 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.

Original Primary Outcome Measures (submitted: February 21, 2014)

• Percentage of participants with plasma HBV DNA levels < 29 copies/mL [ Time Frame: Week 24 ]
• Percentage of participants with plasma HIV-1 RNA level < 50 copies/mL per the FDA snapshot definition [ Time Frame: Week 24 ]

• Change History: Complete list of historical versions of study NCT02071082 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: March 7, 2016)

• 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.

Original Secondary Outcome Measures (submitted: February 21, 2014)

• Percentage of participants with plasma HBV DNA levels < 29 copies/mL [ Time Frame: Week 48 ]
• Percentage of participants with plasma HIV-1 RNA level < 50 copies/mL per FDA snapshot definition [ Time Frame: Week 48 ]
• Percentage of participants with normalized alanine aminotransferase (ALT) [ Time Frame: Weeks 24 and 48 ]
• Percentage of participants with seroconversion [ Time Frame: Weeks 24 and 48 ]
• Change in FibroTest® score [ Time Frame: Baseline to Weeks 24 and 48 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

Brief Summary

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

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• HIV
• HBV

Intervention

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®

Study Arms

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 7, 2016): 79
• Original Estimated Enrollment (submitted: February 21, 2014): 100
• Actual Study Completion Date: October 26, 2016
• Actual Primary Completion Date: January 23, 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, Japan, United States

Administrative Information

• NCT Number: NCT02071082
• Other Study ID Numbers: GS-US-292-1249
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.
• URL: http://www.gilead.com/research/disclosure-and-transparency

• Responsible Party: Gilead Sciences
• Study Sponsor: Gilead Sciences
• Collaborators: Not Provided

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: October 2017