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

• ClinicalTrials.gov Identifier: NCT02071082
• Recruitment Status: Completed
• First Posted: February 25, 2014
• Results First Posted: April 4, 2016
• Last Update Posted: November 16, 2018
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Study Description

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

Condition or disease	Intervention/treatment	Phase
HIV; HBV	Drug: E/C/F/TAF	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 79 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (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
• Actual Study Start Date: February 25, 2014
• Actual Primary Completion Date: January 23, 2015
• Actual Study Completion Date: October 26, 2016

Arms and Interventions

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 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®

Outcome Measures

Primary Outcome Measures :

1. 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.
2. 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 Outcome Measures :

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Arizona

Spectrum Medical Group

Phoenix, Arizona, United States, 85012

United States, California

AHF Research Center

Beverly Hills, California, United States, 90211

Peter J. Ruane MD, Inc.

Los Angeles, California, United States, 90036

Anthony Mills MD, Inc

Los Angeles, California, United States, 90069

United States, District of Columbia

Whitman Walker Health

Washington, District of Columbia, United States, 20009

United States, Florida

Barry M. Rodwick MD

Clearwater, Florida, United States, 33765

Gary J Richmond M.D.,P.A.

Fort Lauderdale, Florida, United States, 33316

Midway Immunology and Research Center

Fort Pierce, Florida, United States, 34982

AIDS Health Foundation/WPA

Miami Beach, Florida, United States, 33139

AIDS Research and Treatment Center of the Treasure Coast

Vero Beach, Florida, United States, 32960

Triple O Research Institute PA

West Palm Beach, Florida, United States, 33401

United States, Michigan

Be Well Medical Center PC

Berkley, Michigan, United States, 48072

United States, Missouri

KC Care Clinic

Kansas City, Missouri, United States, 64111

Southampton Healthcare, Inc.

Saint Louis, Missouri, United States, 63139

United States, New Mexico

Southwest CARE Center

Santa Fe, New Mexico, United States, 87505

United States, Texas

Central Texas Clinical Research

Austin, Texas, United States, 78705

St. Hope Foundation

Bellaire, Texas, United States

North Texas Infectious Diseases Consultants

Dallas, Texas, United States, 75246

Therapeutic Concepts

Houston, Texas, United States, 77004

Gordon E. Crofoot MD PA

Houston, Texas, United States, 77098

United States, Washington

Peter Shalit MD

Seattle, Washington, United States, 98104

Canada, Ontario

University Health Network/Toronto General Hospital

Toronto, Ontario, Canada, M5G 2N2

Maple Leaf Research/Maple Leaf Medical Clinic

Toronto, Ontario, Canada, M5G1K2

Japan

Center Hospital of the National Center for Global Health and Medicine

Shinjuku-ku, Tokyo, Japan, 1628655

Sponsors and Collaborators

Gilead Sciences

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

More Information

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT02071082 History of Changes
• Other Study ID Numbers: GS-US-292-1249
• First Posted: February 25, 2014
• Results First Posted: April 4, 2016
• Last Update Posted: November 16, 2018
• Last Verified: October 2017

Individual Participant Data (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; 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

Keywords provided by Gilead Sciences:

HIV; HBV; Coinfection

Additional relevant MeSH terms:

Hepatitis B; Hepatitis; Liver Diseases; Digestive System Diseases; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Genvoya; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents