Clinical trial NCT02071082: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV
HBV
Keywords: HIV
HBV
Coinfection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2014-02-25
Enrollment: 79
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


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.

Primary outcomes:
measure: Percentage of Participants With Plasma HIV-1 RNA Level < 50 Copies/mL
timeFrame: Week 24
measure: Percentage of Participants With Plasma HBV DNA Levels < 29 IU/mL
timeFrame: Week 24
Secondary outcomes:
measure: Percentage of Participants With Plasma HIV-1 RNA Level < 50 Copies/mL
timeFrame: Week 48
measure: Percentage of Participants With Plasma HBV DNA Levels < 29 IU/mL
timeFrame: Week 48
measure: Percentage of Participants With Normalized Alanine Aminotransferase (ALT) at Week 24
timeFrame: Baseline; Week 24
measure: Percentage of Participants With Normalized ALT at Week 48
timeFrame: Baseline; Week 48
measure: Percentage of Participants With Seroconversion to Hepatitis B Surface Antibody (Anti-HBs) at Week 24
timeFrame: Baseline; Week 24
measure: Percentage of Participants With Seroconversion to Anti-HBs at Week 48
timeFrame: Baseline; Week 48
measure: Percentage of Participants With Seroconversion to Hepatitis B e Antibody (Anti-HBe) at Week 24
timeFrame: Baseline; Week 24
measure: Percentage of Participants With Seroconversion to Anti-HBe at Week 48
timeFrame: Baseline; Week 48
measure: Change From Baseline in FibroTest® Score at Week 24
timeFrame: Baseline; Week 24
measure: Change From Baseline in FibroTest® Score at Week 48
timeFrame: Baseline; Week 48
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Spectrum Medical Group
state: Arizona
city: Beverly Hills
country: United States
facility: AHF Research Center
state: California
city: Los Angeles
country: United States
facility: Peter J. Ruane MD, Inc.
state: California
city: Los Angeles
country: United States
facility: Anthony Mills MD, Inc
state: California
city: Washington
country: United States
facility: Whitman Walker Health
state: District of Columbia
city: Clearwater
country: United States
facility: Barry M. Rodwick MD
state: Florida
city: Fort Lauderdale
country: United States
facility: Gary J Richmond M.D.,P.A.
state: Florida
city: Fort Pierce
country: United States
facility: Midway Immunology and Research Center
state: Florida
city: Miami Beach
country: United States
facility: AIDS Health Foundation/WPA
state: Florida
city: Vero Beach
country: United States
facility: AIDS Research and Treatment Center of the Treasure Coast
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute PA
state: Florida
city: Berkley
country: United States
facility: Be Well Medical Center PC
state: Michigan
city: Kansas City
country: United States
facility: KC Care Clinic
state: Missouri
city: Saint Louis
country: United States
facility: Southampton Healthcare, Inc.
state: Missouri
city: Santa Fe
country: United States
facility: Southwest CARE Center
state: New Mexico
city: Austin
country: United States
facility: Central Texas Clinical Research
state: Texas
city: Bellaire
country: United States
facility: St. Hope Foundation
state: Texas
city: Dallas
country: United States
facility: North Texas Infectious Diseases Consultants
state: Texas
city: Houston
country: United States
facility: Therapeutic Concepts
state: Texas
city: Houston
country: United States
facility: Gordon E. Crofoot MD PA
state: Texas
city: Seattle
country: United States
facility: Peter Shalit MD
state: Washington
city: Toronto
country: Canada
facility: University Health Network/Toronto General Hospital
state: Ontario
city: Toronto
country: Canada
facility: Maple Leaf Research/Maple Leaf Medical Clinic
state: Ontario
city: Shinjuku-ku
country: Japan
facility: Center Hospital of the National Center for Global Health and Medicine
state: Tokyo
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: