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

Phase 3

Completed

• Conditions: HIV; HBV
• Interventions: Drug: E/C/F/TAF

• Registration Number: NCT02071082
• Lead Sponsor: Gilead Sciences

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 available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2014-02-21
• Study First Submitted QC: 2014-02-21
• Study Start: 2014-02-25
• Study First Posted: 2014-02-25
• Primary Completion: 2015-01-23
• Results First Submitted: 2016-01-21
• Results First Submitted QC: 2016-03-07
• Results First Posted: 2016-04-04
• Study Completion: 2016-10-26
• Status Verified: 2017-10
• Last Update Submitted: 2018-10-19
• Last Update Posted: 2018-11-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 79

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
HIV treatment-naive and HBV treatment-naive	E/C/F/TAF	HIV/HBV coinfected participants who are HIV treatment-naive and HBV treatment-naive will receive E/C/F/TAF for 48 weeks.
HIV-suppressed	E/C/F/TAF	HIV/HBV coinfected participants who are HIV-suppressed will receive E/C/F/TAF for 48 weeks.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Plasma HIV-1 RNA Level < 50 Copies/mL	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 Normalized ALT at Week 48	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 e Antibody (Anti-HBe) at Week 24	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	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	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	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.
Percentage of Participants With Seroconversion to Anti-HBs at Week 48	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 Plasma HBV DNA Levels < 29 IU/mL	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	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 Seroconversion to Hepatitis B Surface Antibody (Anti-HBs) at Week 24	Baseline; Week 24	Seroconversion to antibody is defined as (1) antigen loss and (2) positive postbaseline antibody value. Missing = excluded method.

Trial Locations

Locations (24)

Be Well Medical Center PC; 🇺🇸 Berkley, Michigan, United States

AHF Research Center; 🇺🇸 Beverly Hills, California, United States

Barry M. Rodwick MD; 🇺🇸 Clearwater, Florida, United States

Anthony Mills MD, Inc; 🇺🇸 Los Angeles, California, United States

Peter J. Ruane MD, Inc.; 🇺🇸 Los Angeles, California, United States

Gary J Richmond M.D.,P.A.; 🇺🇸 Fort Lauderdale, Florida, United States

Midway Immunology and Research Center; 🇺🇸 Fort Pierce, Florida, United States

AIDS Health Foundation/WPA; 🇺🇸 Miami Beach, Florida, United States

Triple O Research Institute PA; 🇺🇸 West Palm Beach, Florida, United States

AIDS Research and Treatment Center of the Treasure Coast; 🇺🇸 Vero Beach, Florida, United States

KC Care Clinic; 🇺🇸 Kansas City, Missouri, United States

St. Hope Foundation; 🇺🇸 Bellaire, Texas, United States

Central Texas Clinical Research; 🇺🇸 Austin, Texas, United States

Southwest CARE Center; 🇺🇸 Santa Fe, New Mexico, United States

North Texas Infectious Diseases Consultants; 🇺🇸 Dallas, Texas, United States

Therapeutic Concepts; 🇺🇸 Houston, Texas, United States

University Health Network/Toronto General Hospital; 🇨🇦 Toronto, Ontario, Canada

Peter Shalit MD; 🇺🇸 Seattle, Washington, United States

Gordon E. Crofoot MD PA; 🇺🇸 Houston, Texas, United States

Maple Leaf Research/Maple Leaf Medical Clinic; 🇨🇦 Toronto, Ontario, Canada

Spectrum Medical Group; 🇺🇸 Phoenix, Arizona, United States

Southampton Healthcare, Inc.; 🇺🇸 Saint Louis, Missouri, United States

Center Hospital of the National Center for Global Health and Medicine; 🇯🇵 Shinjuku-ku, Tokyo, Japan

Whitman Walker Health; 🇺🇸 Washington, District of Columbia, United States