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

Study Overview
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Brief Summary
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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).

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multi-center Study to Evaluate the Safety and Efficacy of GS-9620 for the Treatment of Virally-Suppressed Subjects With Chronic Hepatitis B

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: Vesatolimod
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo 4 Weeks (Cohort A)<br>Placebo tablet once a week for 4 weeks | Drug: Placebo<br>* Placebo to match vesatolimod tablet administered orally<br>|
| Experimental: Vesatolimod 1 mg 4 Weeks (Cohort A)<br>Vesatolimod 1 mg tablet once a week for 4 weeks | Drug: Vesatolimod<br>* Vesatolimod tablet administered orally<br>* Other names: GS-9620;|
| Experimental: Vesatolimod 2 mg 4 Weeks (Cohort A)<br>Vesatolimod 2 mg tablet once a week for 4 weeks | Drug: Vesatolimod<br>* Vesatolimod tablet administered orally<br>* Other names: GS-9620;|
| Experimental: Vesatolimod 4 mg 4 Weeks (Cohort A)<br>Vesatolimod 4 mg tablet once a week for 4 weeks | Drug: Vesatolimod<br>* Vesatolimod tablet administered orally<br>* Other names: GS-9620;|
| Placebo Comparator: Placebo 8 Weeks (Cohort B)<br>Placebo tablet once a week for 8 weeks | Drug: Placebo<br>* Placebo to match vesatolimod tablet administered orally<br>|
| Experimental: Vesatolimod 1 mg 8 Weeks (Cohort B)<br>Vesatolimod 1 mg tablet once a week for 8 weeks | Drug: Vesatolimod<br>* Vesatolimod tablet administered orally<br>* Other names: GS-9620;|
| Experimental: Vesatolimod 2 mg 8 Weeks (Cohort B)<br>Vesatolimod 2 mg tablet once a week for 8 weeks | Drug: Vesatolimod<br>* Vesatolimod tablet administered orally<br>* Other names: GS-9620;|
| Experimental: Vesatolimod 4 mg 8 Weeks (Cohort B)<br>Vesatolimod 4 mg tablet once a week for 8 weeks | Drug: Vesatolimod<br>* Vesatolimod tablet administered orally<br>* Other names: GS-9620;|
| Placebo Comparator: Placebo 12 Weeks (Cohort C)<br>Placebo tablet once a week for 12 weeks | Drug: Placebo<br>* Placebo to match vesatolimod tablet administered orally<br>|
| Experimental: Vesatolimod 1 mg 12 Weeks (Cohort C)<br>Vesatolimod 1 mg tablet once a week for 12 weeks | Drug: Vesatolimod<br>* Vesatolimod tablet administered orally<br>* Other names: GS-9620;|
| Experimental: Vesatolimod 2 mg 12 Weeks (Cohort C)<br>Vesatolimod 2 mg tablet once a week for 12 weeks | Drug: Vesatolimod<br>* Vesatolimod tablet administered orally<br>* Other names: GS-9620;|
| Experimental: Vesatolimod 4 mg 12 Weeks (Cohort C)<br>Vesatolimod 4 mg tablet once a week for 12 weeks | Drug: Vesatolimod<br>* Vesatolimod tablet administered orally<br>* Other names: GS-9620;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Serum Hepatitis B Surface Antigen (HBsAg) Level at 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. | Baseline to Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at 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. | Week 24 | 
| Composite Endpoint Measuring the Percentage of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss and Seroconversion at 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. | Week 48 | 
| Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at 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. | Week 24 | 
| Composite Endpoint Measuring the Percentage of Participants With HBsAg Loss and Seroconversion at 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. | Week 48 | 
| Change From Baseline in Serum HBsAg Level at Week 4 |  | Baseline; Week 4 | 
| Change From Baseline in Serum HBsAg Level at Week 8 |  | Baseline; Week 8 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HBV, Hepatitis B, GS-9620, TLR-7 Agonist