Safety and Efficacy of GS-4774 for the Treatment of Chronic Hepatitis B

Study Overview
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Brief Summary
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The primary objectives of this study are to evaluate the safety and efficacy of GS-4774 in adults with chronic hepatitis B (CHB) viral infection who have been virally suppressed with an oral antiviral (OAV) medication.

Official Title
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A Phase 2, Randomized, Open-Label Study to Evaluate the Safety and Efficacy of GS-4774 for the Treatment of Virally-Suppressed Subjects With Chronic Hepatitis B

Conditions
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Chronic HBV Infection

Intervention / Treatment
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* Biological: GS-4774
* Drug: OAV Regimen


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study procedures Currently taking an approved HBV oral antiviral medication Documented evidence of chronic HBV infection (eg, HBsAg positive for more than 6 months) Virally-suppressed (HBV DNA below the lower limit of quantification (LLOQ) for ≥ 1 year) Key Exclusion Criteria: Cirrhosis Inadequate liver function Co-infection with hepatitic C virus (HCV), HIV or hepatitic D virus (HDV) Evidence of hepatocellular carcinoma Significant cardiovascular, pulmonary, or neurological disease Females who are pregnant or may wish to become pregnant during the study Received solid organ or bone marrow transplant Use of another investigational agents within 3 months of screening Current alcohol or substance abuse judged by the investigator to potentially interfere with compliance History of demyelinating disease (Guillain-Barre), Bell's Palsy, Crohn's disease ulcerative colitis, autoimmune disease Known hypersensitivity to study drug, 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). Participants under evaluation for possible malignancy are not eligible. 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OAV Alone<br>Participants will continue their prebaseline OAV regimen alone from baseline to Week 48. | Drug: OAV Regimen<br>* Administered prior to study enrollment (tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination)<br>|
| Experimental: OAV + GS-4774 2 YU<br>Participants will continue their prebaseline OAV regimen from baseline to Week 48, and will receive GS-4774 2 yeast units (YU) from baseline to Week 20. | Biological: GS-4774<br>* Administered as a subcutaneous injection every 4 weeks for a total of 6 doses<br>Drug: OAV Regimen<br>* Administered prior to study enrollment (tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination)<br>|
| Experimental: OAV + GS-4774 10 YU<br>Participants will continue their prebaseline OAV regimen from baseline to Week 48, and will receive GS-4774 10 YU from baseline to Week 20. | Biological: GS-4774<br>* Administered as a subcutaneous injection every 4 weeks for a total of 6 doses<br>Drug: OAV Regimen<br>* Administered prior to study enrollment (tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination)<br>|
| Experimental: OAV + GS-4774 40 YU<br>Participants will continue their prebaseline OAV regimen from baseline to Week 48, and will receive GS-4774 40 YU from baseline to Week 20. | Biological: GS-4774<br>* Administered as a subcutaneous injection every 4 weeks for a total of 6 doses<br>Drug: OAV Regimen<br>* Administered prior to study enrollment (tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, or telbivudine either as single agents or in combination)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HBsAg at Week 24 | The change from baseline to Week 24 in HBsAg was analyzed using a mixed effect model for repeated measures (MMRM). The model included included treatment, HBsAg baseline level (≤ 1000 IU/mL or > 1000 IU/mL), HBeAg baseline status (positive or negative), visit, and treatment-by-visit interaction as fixed effects and visit as a repeated measure. | Baseline; Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in HBsAg at Week 12 | The change from baseline to Week 12 in HBsAg was analyzed using a MMRM. The model included included treatment, HBsAg baseline level (≤ 1000 IU/mL or > 1000 IU/mL), HBeAg baseline status (positive or negative), visit, and treatment-by-visit interaction as fixed effects and visit as a repeated measure. | Baseline; Week 12 | 
| Change From Baseline in HBsAg at Week 48 | The change from baseline to Week 48 in HBsAg was analyzed using a MMRM. The model included included treatment, HBsAg baseline level (≤ 1000 IU/mL or > 1000 IU/mL), HBeAg baseline status (positive or negative), visit, and treatment-by-visit interaction as fixed effects and visit as a repeated measure. | Baseline; Week 48 | 
| Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 24 | HBsAg loss was defined as HBsAg level decreasing from >0.066 IU/mL at baseline to ≤ 0.066 IU/mL at any postbaseline visit. HBsAb seroconversion was defined as HBsAb level increasing from < 12 mIU/mL at baseline to ≥ 12 mIU/mL at any postbaseline visit. | Week 24 | 
| Percentage of Participants With HBsAg Loss and HBsAg Seroconversion at Week 48 | HBsAg loss was defined as HBsAg level decreasing from >0.066 IU/mL at baseline to ≤ 0.066 IU/mL at any postbaseline visit. HBsAb seroconversion was defined as HBsAb level increasing from < 12 mIU/mL at baseline to ≥ 12 mIU/mL at any postbaseline visit. | Week 48 | 
| Percentage of Participants With HBeAg Loss and HBeAg Seroconversion by Week 24 | HBeAg loss was defined as a qualitative HBeAg result changing from positive at baseline to negative at any postbaseline visit. HBeAb seroconversion was defined as a qualitative HBeAb result changing from negative at baseline to positive at any postbaseline visit. | Week 24 | 
| Percentage of Participants With HBeAg Loss and HBeAg Seroconversion by Week 48 | HBeAg loss was defined as a qualitative HBeAg result changing from positive at baseline to negative at any postbaseline visit. HBeAb seroconversion was defined as a qualitative HBeAb result changing from negative at baseline to positive at any postbaseline visit. | Week 48 | 
| Percentage of Participants With a 1-log Decline in HBsAg by Weeks 12, 24, and 48 | HBsAg 1-log decline was defined as ≥ 1 decline from baseline in log10 IU/mL serum HBsAg at any postbaseline visit within the targeted time window. | Baseline; Weeks 12, 24, and 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis B (HBV), Oral antiviral (OAV), GS-4774