Safety and Efficacy of GS-4774 in Combination With Tenofovir Disoproxil Fumarate (TDF) for the Treatment of Participants With Chronic Hepatitis B (CHB) and Who Are Currently Not on Treatment
Condition: Chronic Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic
Intervention: Tenofovir disoproxil fumarate; GS-4774
Intervention description: TDF 300 mg tablet administered orally once daily; GS-4774 subcutaneous injection administered every 4 weeks for a total of 6 doses
Intervention MeSH terms: Tenofovir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 195.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The primary objectives of this study are to evaluate the safety, tolerability, and efficacy
      of GS-4774 in adults with CHB and who are currently not on treatment. Participants will be
      randomized to receive TDF alone or GS-4774 plus TDF for 20 weeks. After Week 20, GS-4774 will
      be discontinued. All participants will continue on TDF and will be followed for an additional
      28 weeks. Following completion of the 48 week study period, all participants will be eligible
      for a treatment extension for 96 weeks.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Must have the ability to understand and sign a written informed consent form, which
             must be obtained prior to initiation of study

          -  Documented evidence of chronic hepatitis B virus (HBV) infection, for example,
             hepatitis B surface antigen (HBsAg) positive for more than 6 months

          -  Screening HBV DNA ≥ 2000 IU/mL

          -  A negative serum pregnancy test is required for females (unless surgically sterile or
             > 2 years post-menopausal)

        Key Exclusion Criteria:

          -  Cirrhosis

          -  Inadequate liver function

          -  Co-infection with hepatitis C virus (HCV), HIV or hepatitis D virus (HDV)

          -  Received antiviral treatment for HBV within 3 months of screening

          -  Evidence of hepatocellular carcinoma (eg, as evidenced by recent imaging)

          -  Significant cardiovascular, pulmonary, or neurological disease

          -  Women who are pregnant or may wish to become pregnant during the course of the study

          -  Received solid organ or bone marrow transplant

          -  Received prolonged therapy with immunomodulators (eg, corticosteroids) or biologics
             (eg, monoclonal antibody, interferon) within 3 months of screening

          -  Use of investigational agents within 3 months of screening

          -  Current alcohol or substance abuse judged by the investigator to potentially interfere
             with individual's compliance

          -  Receipt of immunoglobulin or other blood products within 3 months prior to enrollment

          -  History of demyelinating disease (Guillain-Barre), Bell's Palsy, Crohn's disease,
             Ulcerative colitis, or autoimmune disease

          -  Documented history of yeast allergy

          -  Known hypersensitivity to study drugs, metabolites or formulation excipients

          -  Malignancy within 5 years prior to screening, with the exception of specific cancers
             that are cured by surgical resection (basal cell skin cancer, etc). Individuals under
             evaluation for possible malignancy are not eligible

        Note: Other protocol defined Inclusion/Exclusion criteria may apply.