None listed
Conditions
Brief summary
This study is to evaluate the safety, tolerability, and efficacy of nivolumab treatment with or without GS-4774 in adults with HBeAg-negative chronic hepatitis B infection and currently on oral antivirals treatment. As per the treatment group, participants will be assigned to receive a single intravenous dose of nivolumab or a combination of dose of nivolumab and subcutaneous injections of GS-4774. All subjects will be followed for 24 weeks after receiving nivolumab
Interventions
Approximately twenty four adult subjects with HBeAg-negative, Chronic Hepatitis B (CHB) and who are currently receiving treatment with an Oral Antiviral (OAV) will be assigned to one of the 4 dosing groups below:
The first four subjects will be assigned to:
Sentinel A: 2 subjects treated with single intravenous dose of nivolumab at 0.1 mg/kg on Day 1 of treatment and followed for 24 weeks after receiving nivolumab
Sentinel B: 2 subjects treated with single intravenous dose of nivolumab at 0.3 m
Approximately twenty four adult subjects with HBeAg-negative, Chronic Hepatitis B (CHB) and who are currently receiving treatment with an Oral Antiviral (OAV) will be assigned to one of the 4 dosing groups below: The first four subjects will be assigned to: Sentinel A: 2 subjects treated with single intravenous dose of nivolumab at 0.1 mg/kg on Day 1 of treatment and followed for 24 weeks after receiving nivolumab Sentinel B: 2 subjects treated with single intravenous dose of nivolumab at 0.3 mg/kg on Day 1 of treatment and followed for 24 weeks after receiving nivolumab Once safety is demonstrated in Sentinels A and B, a group of 10 subjects will be assigned to Cohort A and following completion of enrollment in this cohort, another group of 10 subjects will be assigned to Cohort B. Cohort A: 10 subjects treated with single dose of intravenous nivolumab at up to 0.3 mg/kg on Day 1 of treatment and followed for 24 weeks after receiving nivolumab Cohort B: 10 subjects treated with subcutaneous injection of GS 4774 40 YU on Day 1 of treatment and subcutaneous injection of GS 4774 40 YU plus single intravenous dose of nivolumab at up to 0.3 mg/kg on Day 28 and followed for 24 weeks after receiving nivolumab
Sponsors
Gilead Sciences, Inc.
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Must have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study 2. Documented evidence of chronic HBV infection (e.g., HBsAg positive for more than 6 months) 3. Must be HBeAg negative at screening 4. Have been receiving approved HBV oral antiviral treatment for greater than/equal to 1 year prior to screening 5. A negative serum pregnancy test is required for female subjects (unless surgically sterile or greater than two years post-menopausal) 6. Male subjects and female subjects of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
Exclusion criteria
1. Cirrhosis 2. Inadequate liver function 3. Co-infection with hepatitis C virus (HCV), HIV or hepatitis D virus (HDV) 4. Evidence of hepatocellular carcinoma (e.g., as evidenced by recent imaging) 5. Presence of active infections 6. Women who are pregnant or may wish to become pregnant during the course of the study 7. Received solid organ or bone marrow transplant 8. Received prolonged therapy with immunomodulators (e.g., corticosteroids) or biologics (e.g., monoclonal Ab, interferon) within 3 months of screening 9. Use of investigational agents within 3 months of screening 10. Current alcohol or substance abuse judged by the investigator to potentially interfere with subject compliance 11. History of significant autoimmune disease 12. Documented history of yeast allergy 13. Known hypersensitivity to study drugs, metabolites or formulation excipients 14. Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc). Subjects under evaluation for possible malignancy are not eligible
Outcome results
None listed