Study To Evaluate Safety and Efficacy of Vesatolimod for the Treatment of Chronic Hepatitis B Virus in Virally-Suppressed Participants

Phase 2

Completed

Conditions: Chronic Hepatitis B

Interventions: Drug: Placebo
Drug: Vesatolimod

Registration Number: NCT02166047

Lead Sponsor: Gilead Sciences

Brief Summary: The primary objectives of this study are to evaluate the safety, tolerability, and efficacy of vesatolimod in participants with chronic hepatitis B (CHB) infection currently being treated with oral antivirals (OAV).

Participants will be randomized in 3 sequential cohorts (Cohorts A, B, and C). Within each cohort, participants will be randomized in a 1:3:3:3 ratio to placebo or one of the doses of vesatolimod (1, 2, or 4 mg).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 162

Inclusion Criteria

Must have the ability to understand and sign a written informed consent form; consent must be obtained prior to initiation of study procedures
Documented evidence of CHB infection (eg, hepatitis B surface antigen [HBsAg] positive for more than 6 months) with detectable HBsAg levels at screening
Have been on approved HBV OAV treatment for ≥ 1 year prior to screening, with HBV DNA below lower limit of quantitation (LLOQ), measured at least once, 6 or more months prior to screening, and HBV DNA < 20 IU/mL at screening
Currently taking an approved HBV OAV (tenofovir, entecavir, adefovir, lamivudine, or telbivudine, either as single agents or in combination) with no change in regimen for 3 months prior to screening
Willing to provide blood sample for toll-like receptor 7 (TLR-7) and interleukin 28 B (IL28B) single-nucleotide polymorphism (SNP) assessment
Must be willing and able to comply with all study requirements

Key

Exclusion Criteria

Extensive bridging fibrosis or cirrhosis
Laboratory parameters not within defined thresholds for neutropenia, anemia, thrombocytopenia, leukopenia, or other evidence of inadequate liver function
Coinfection with hepatitis C virus (HCV), HIV, or hepatitis D virus (HDV)
Evidence of hepatocellular carcinoma
Malignancy within 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc.). Participants under evaluation for possible malignancy are not eligible.
Significant cardiovascular, pulmonary, or neurological disease
Any of the following conditions that may worsen in response to interferon (IFN):
- Autoimmune disease (eg, lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, sarcoidosis, moderate or severe psoriasis)
- Poorly controlled diabetes mellitus
- Significant psychiatric disorders
- Thyroid disorder (unless controlled under treatment)
- Significant pulmonary diseases (eg, chronic obstructive pulmonary disease)
- Retinal disease
- Immunodeficiency disorders
Received solid organ or bone marrow transplant
Received prolonged therapy with immunomodulators (eg, corticosteroids) or biologics (eg, monoclonal Ab, interferon) within 3 months of screening
Use of another investigational agents within 3 months of screening
Current alcohol or substance abuse judged by the investigator to potentially interfere with compliance
Females who are pregnant or may wish to become pregnant during the study

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Placebo 12 Weeks (Cohort C)	Placebo	Placebo tablet once a week for 12 weeks
Placebo 8 Weeks (Cohort B)	Placebo	Placebo tablet once a week for 8 weeks
Placebo 4 Weeks (Cohort A)	Placebo	Placebo tablet once a week for 4 weeks
Vesatolimod 2 mg 4 Weeks (Cohort A)	Vesatolimod	Vesatolimod 2 mg tablet once a week for 4 weeks
Vesatolimod 1 mg 4 Weeks (Cohort A)	Vesatolimod	Vesatolimod 1 mg tablet once a week for 4 weeks
Vesatolimod 4 mg 12 Weeks (Cohort C)	Vesatolimod	Vesatolimod 4 mg tablet once a week for 12 weeks
Vesatolimod 1 mg 12 Weeks (Cohort C)	Vesatolimod	Vesatolimod 1 mg tablet once a week for 12 weeks
Vesatolimod 4 mg 4 Weeks (Cohort A)	Vesatolimod	Vesatolimod 4 mg tablet once a week for 4 weeks
Vesatolimod 1 mg 8 Weeks (Cohort B)	Vesatolimod	Vesatolimod 1 mg tablet once a week for 8 weeks
Vesatolimod 2 mg 8 Weeks (Cohort B)	Vesatolimod	Vesatolimod 2 mg tablet once a week for 8 weeks
Vesatolimod 4 mg 8 Weeks (Cohort B)	Vesatolimod	Vesatolimod 4 mg tablet once a week for 8 weeks
Vesatolimod 2 mg 12 Weeks (Cohort C)	Vesatolimod	Vesatolimod 2 mg tablet once a week for 12 weeks

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Level at Week 24	Baseline to Week 24	A mixed effect model for repeated measures (MMRM) was used to analyze HBsAg change from baseline, which included treatment, baseline HBsAg level (\> 5000 IU/mL or ≤ 5000 IU/mL), HBeAg baseline status (positive or negative), visit and treatment-by-visit interaction as fixed effect and visit as repeated measurement.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Serum HBsAg Level at Week 12	Baseline; Week 12
Change From Baseline in Serum HBsAg Level at Week 48	Baseline; Week 48
Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 24	Week 24	HBeAg loss was defined as qualitative HBeAg result changing from positive at baseline to negative at any postbaseline visit within the targeted time window. HBeAg seroconversion was defined as qualitative hepatitis B envelope antibody (HBeAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window. Participants who had missing information were assumed to have no HBeAg loss and no HBeAg seroconversion.
Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 24	Week 24	HBsAg loss was defined as qualitative HBsAg result changing from positive at baseline to negative at any postbaseline visit within the targeted time window. HBsAg seroconversion was defined as qualitative hepatitis B surface antibody (HBsAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window. Participants who had missing information were assumed to have no HBsAg loss and no HBsAg seroconversion.
Change From Baseline in Serum HBsAg Level at Week 4	Baseline; Week 4
Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at Week 48	Week 48	HBeAg loss was defined as qualitative HBeAg result changing from positive at baseline to negative at any postbaseline visit within the targeted time window. HBeAg seroconversion was defined as qualitative hepatitis B envelope antibody (HBeAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window. Participants who had missing information were assumed to have no HBeAg loss and no HBeAg seroconversion. Only participants who were HBeAg+ at baseline were included.
Change From Baseline in Serum HBsAg Level at Week 8	Baseline; Week 8
Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at Week 48	Week 48	HBsAg loss was defined as qualitative HBsAg result changing from positive at baseline to negative at any postbaseline visit within the targeted time window. HBsAg seroconversion was defined as qualitative hepatitis B surface antibody (HBsAb) result changing from negative at baseline to positive at any postbaseline visit within the targeted time window. Participants who had missing information were assumed to have no HBsAg loss and no HBsAg seroconversion.