Safety, Tolerability and Antiviral Activity of Selgantolimod in Virally-Suppressed Participants With 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, tolerability and antiviral activity of selgantolimod (formerly GS-9688) in virally suppressed chronic hepatitis B (CHB) adults on oral antiviral (OAV) agents.

Official Title
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A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Multi-center Study to Evaluate the Safety, Tolerability and Antiviral Activity of GS-9688 in Virally-Suppressed Adult Subjects With Chronic Hepatitis B

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: Selgantolimod
* Drug: Placebo
* Drug: Hepatitis B virus (HBV) OAV Therapy


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, which must be obtained prior to initiation of study procedures Adult males and non-pregnant, non-lactating females Documented evidence of chronic HBV infection with detectable hepatitis B surface antigen (HBsAg) levels On commercially available HBV OAV treatment(s) for at least 6 months with no change in regimen for 3 months prior to screening HBV Deoxyribonucleic acid (DNA) ≤ 20 IU/mL for 6 or more months prior to screening Screening Electrocardiogram (ECG) without clinically significant abnormalities Key Exclusion Criteria: Extensive bridging fibrosis or cirrhosis Adults meeting any of the protocol defined exclusionary laboratory parameters at screening: Alanine aminotransferase (ALT) > 3x Upper Limit of Normal (ULN) International normalized ratio (INR) > ULN unless the adult is stable on an anticoagulant regimen Albumin < 3.5 g/dL Direct bilirubin > 1.5x ULN Platelet Count < 100,000/uL Estimated creatinine clearance < 60 mL/min (using the Cockcroft-Gault method) Co-infection with human immunodeficiency virus, hepatitis C virus or hepatitis D virus Prior history of hepatocellular carcinoma (HCC) or screening alpha-fetoprotein ≥ 50 ng/mL without imaging Diagnosis of autoimmune disease, poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease, hemoglobinopathy, retinal disease, or are immunosuppressed. Chronic liver disease of a non-HBV etiology, except for non-alcoholic fatty liver disease Received solid organ or bone marrow transplant Received prolonged therapy with immunomodulators or biologics within 3 months of screening Use of another investigational agent within 90 days of screening, unless allowed by the Sponsor 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Selgantolimod 3 mg: HBeAg-positive CHB Participants<br>Participants with Hepatitis B e Antigen (HBeAg)-positive CHB will remain on their current OAV and receive selgantolimod 3 mg (2 x 1.5 mg tablet) orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/early discontinuation (ED). At Week 48, per Principal Investigator's (PI's) discretion, participants can continue in the Treatment Free Follow-Up (TFFU) phase for up to an additional 48 weeks. | Drug: Selgantolimod<br>* Tablet(s) administered orally once weekly<br>* Other names: GS-9688;Drug: Hepatitis B virus (HBV) OAV Therapy<br>* Commercially available HBV OAV therapy could include one of the following: Tenofovir disoproxil fumarate (TDF; Viread®) Entecavir (Baraclude®) Adefovir (Hepsera®) Lamivudine (Epivir® ) Telbivudine (Tyzeka®) Tenofovir alafenamide (TAF; Vemlidy®)<br>|
| Experimental: Selgantolimod 3 mg: HBeAg-negative CHB Participants<br>Participants with HBeAg-negative CHB will remain on their current OAV and receive selgantolimod 3 mg (2 x 1.5 mg tablet) orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks. | Drug: Selgantolimod<br>* Tablet(s) administered orally once weekly<br>* Other names: GS-9688;Drug: Hepatitis B virus (HBV) OAV Therapy<br>* Commercially available HBV OAV therapy could include one of the following: Tenofovir disoproxil fumarate (TDF; Viread®) Entecavir (Baraclude®) Adefovir (Hepsera®) Lamivudine (Epivir® ) Telbivudine (Tyzeka®) Tenofovir alafenamide (TAF; Vemlidy®)<br>|
| Experimental: Selgantolimod 1.5 mg: HBeAg-positive CHB Participants<br>Participants with HBeAg-positive CHB will remain on their current OAV and receive selgantolimod 1.5 mg (1 x 1.5 mg tablet) plus 1 tablet of placebo orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks. | Drug: Selgantolimod<br>* Tablet(s) administered orally once weekly<br>* Other names: GS-9688;Drug: Placebo<br>* Placebo to match (PTM) selgantolimod tablet(s) administered orally once weekly<br>Drug: Hepatitis B virus (HBV) OAV Therapy<br>* Commercially available HBV OAV therapy could include one of the following: Tenofovir disoproxil fumarate (TDF; Viread®) Entecavir (Baraclude®) Adefovir (Hepsera®) Lamivudine (Epivir® ) Telbivudine (Tyzeka®) Tenofovir alafenamide (TAF; Vemlidy®)<br>|
| Experimental: Selgantolimod 1.5 mg: HBeAg-negative CHB Participants<br>Participants with HBeAg-negative CHB will remain on their current OAV and receive selgantolimod 1.5 mg (1 x 1.5 mg tablet) plus 1 tablet of placebo orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks. | Drug: Selgantolimod<br>* Tablet(s) administered orally once weekly<br>* Other names: GS-9688;Drug: Placebo<br>* Placebo to match (PTM) selgantolimod tablet(s) administered orally once weekly<br>Drug: Hepatitis B virus (HBV) OAV Therapy<br>* Commercially available HBV OAV therapy could include one of the following: Tenofovir disoproxil fumarate (TDF; Viread®) Entecavir (Baraclude®) Adefovir (Hepsera®) Lamivudine (Epivir® ) Telbivudine (Tyzeka®) Tenofovir alafenamide (TAF; Vemlidy®)<br>|
| Experimental: Placebo: HBeAg-positive CHB Participants<br>Participants with HBeAg-positive CHB will remain on their current OAV and receive 2 tablets of placebo orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks. | Drug: Placebo<br>* Placebo to match (PTM) selgantolimod tablet(s) administered orally once weekly<br>Drug: Hepatitis B virus (HBV) OAV Therapy<br>* Commercially available HBV OAV therapy could include one of the following: Tenofovir disoproxil fumarate (TDF; Viread®) Entecavir (Baraclude®) Adefovir (Hepsera®) Lamivudine (Epivir® ) Telbivudine (Tyzeka®) Tenofovir alafenamide (TAF; Vemlidy®)<br>|
| Experimental: Placebo: HBeAg-negative CHB Participants<br>Participants with HBeAg-negative CHB will remain on their current OAV and receive 2 tablets of placebo orally on the same day once a week (every 7 days) for 24 doses. After the 24th dose, participants will continue their current OAV therapy until Week 48/ED. At Week 48, per PI's discretion, participants can continue in the TFFU phase for up to an additional 48 weeks. | Drug: Placebo<br>* Placebo to match (PTM) selgantolimod tablet(s) administered orally once weekly<br>Drug: Hepatitis B virus (HBV) OAV Therapy<br>* Commercially available HBV OAV therapy could include one of the following: Tenofovir disoproxil fumarate (TDF; Viread®) Entecavir (Baraclude®) Adefovir (Hepsera®) Lamivudine (Epivir® ) Telbivudine (Tyzeka®) Tenofovir alafenamide (TAF; Vemlidy®)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum Quantitative Hepatitis B Surface Antigen (qHBsAg) From Baseline at Week 24 |  | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 4 |  | Week 4 | 
| Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 8 |  | Week 8 | 
| Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 12 |  | Week 12 | 
| Percentage of Participants With ≥ 1 log10 IU/mL Decline in Serum qHBsAg From Baseline at Week 48 |  | Week 48 | 
| Change From Baseline in Serum qHBsAg at Week 4 |  | Baseline, Week 4 | 
| Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 8 |  | Baseline, Week 8 | 
| Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 12 |  | Baseline, Week 12 | 
| Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 24 |  | Baseline, Week 24 | 
| Change From Baseline in Serum qHBsAg (log10 IU/mL) at Week 48 |  | Baseline, Week 48 | 
| Percentage of Participants With Hepatitis B Surface Antigen (HBsAg) Loss at Week 12 | HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a postbaseline visit. | Week 12 | 
| Percentage of Participants With HBsAg Loss at Week 24 | HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a postbaseline visit. | Week 24 | 
| Percentage of Participants With HBsAg Loss at Week 48 | HBsAg loss was defined as qualitative HBsAg changing from positive at baseline to negative at a postbaseline visit. | Week 48 | 
| Percentage of Participants With HBeAg Loss and Seroconversion at Week 12 | HBeAg loss was defined as qualitative HBeAg changing from positive at baseline to negative at a postbaseline visit. HBeAg seroconversion was defined as HBeAb test changing from negative or missing at baseline to positive at a postbaseline visit. | Week 12 | 
| Percentage of Participants With HBeAg Loss and Seroconversion at Week 24 | HBeAg loss was defined as qualitative HBeAg changing from positive at baseline to negative at a postbaseline visit. HBeAg seroconversion was defined as HBeAb test changing from negative or missing at baseline to positive at a postbaseline visit. | Week 24 | 
| Percentage of Participants With HBeAg Loss and Seroconversion at Week 48 | HBeAg loss was defined as qualitative HBeAg changing from positive at baseline to negative at a postbaseline visit. HBeAg seroconversion was defined as hepatitis B e antibody (HBeAb) test changing from negative or missing at baseline to positive at a postbaseline visit. | Week 48 | 
| Percentage of Participants With Virologic Breakthrough | Virologic breakthrough was defined as having two consecutive visits of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) ≥ 69 IU/mL. | Baseline up to Week 48 | 
| Percentage of Participants With Drug Resistance Mutations | The criteria for a drug resistance mutation was having two consecutive visits of HBV DNA ≥ 69 IU/mL. | Baseline up to Week 48 |