Study to Evaluate the Safety and Efficacy of Selgantolimod (SLGN)-Containing Combination Therapies for the Treatment of Chronic Hepatitis B (CHB)

Study Overview
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Brief Summary
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The primary objectives of this study are to evaluate the safety and tolerability of study treatment(s) (selgantolimod-containing combination therapies) and to evaluate the efficacy of study treatment(s) as measured by the proportion of participants who achieve functional cure, defined as hepatitis B surface antigen (HBsAg) loss and hepatitis B virus (HBV)deoxyribonucleic acid (DNA) < lower limit of quantitation (LLOQ) at Follow-up (FU) Week 24 in participants with chronic hepatitis B (CHB).

Official Title
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A Phase 2a, Open-Label Study to Evaluate the Safety and Efficacy of Selgantolimod (SLGN)-Containing Combination Therapies for the Treatment of Chronic Hepatitis B (CHB)

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: Tenofovir Alafenamide
* Drug: VIR-2218
* Drug: Nivolumab
* Drug: Selgantolimod


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Willing and able to provide informed consent Chronic HBV infection for at least 6 months Willing to follow protocol-specified contraception requirement Key Exclusion Criteria: Have extensive fibrosis or cirrhosis in the liver Have or had liver cancer (hepatocellular carcinoma) Have an autoimmune disease Have chronic liver disease other than HBV Females who are breastfeeding, pregnant, or who 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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: TAF + VIR-2218 + SLGN + Nivolumab<br>Nucleos(t)ide(s) (NUC)-suppressed participants with chronic hepatitis B (CHB) will receive: Tenofovir alafenamide (TAF) 25 mg once daily for 36 weeks (up to 84 weeks). VIR-2218 200 mg once every 4 weeks for 24 weeks. At Week 12 the following will be added: Selgantolimod (SLGN) 3 mg once a week on the same day for 24 weeks. Nivolumab 0.3 mg/kg once every 4 weeks for up to 24 weeks (Up to protocol amendment 2). Participants who are on TAF treatment will continue TAF treatment over the duration of study follow-up. After the implementation of protocol amendment 2, nivolumab treatment was no longer administered. | Drug: Tenofovir Alafenamide<br>* Administered as film-coated oral tablets<br>* Other names: GS-7340;Drug: VIR-2218<br>* Administered as a sub-cutaneous (SC) injection<br>Drug: Nivolumab<br>* Administered intravenously<br>* Other names: Opdivo®;Drug: Selgantolimod<br>* Administered as film-coated oral tablets<br>* Other names: GS-9688;|
| Experimental: Cohort 2 Group A: VIR-2218 + SLGN + Nivolumab<br>Viremic participants with CHB will receive: VIR-2218 200 mg once every 4 weeks for 24 weeks. At Week 12, the following will be added: SLGN 3 mg once a week on the same day for 24 weeks Nivolumab 0.3 mg/kg once every 4 weeks for up to 24 weeks (Up to protocol amendment 2). Viremic participants who meet criteria to initiate NUC treatment will receive TAF 25 mg once daily for up to 36 weeks during the study. After the implementation of protocol amendment 2, nivolumab treatment was no longer administered. | Drug: Tenofovir Alafenamide<br>* Administered as film-coated oral tablets<br>* Other names: GS-7340;Drug: VIR-2218<br>* Administered as a sub-cutaneous (SC) injection<br>Drug: Nivolumab<br>* Administered intravenously<br>* Other names: Opdivo®;Drug: Selgantolimod<br>* Administered as film-coated oral tablets<br>* Other names: GS-9688;|
| Experimental: Cohort 2 Group B: SLGN + Nivolumab<br>Viremic participants with CHB will receive: SLGN 3 mg once a week on the same day for 24 weeks. Nivolumab 0.3 mg/kg once every 4 weeks for up to 24 weeks. Viremic participants who meet criteria to initiate NUC treatment will receive TAF 25 mg once daily for up to 36 weeks during the study. Cohort 2 Group B, all treatments were administered up to protocol amendment 2 and after the implementation of protocol amendment 2, the treatments were discontinued based on Sponsor decision due to low likelihood of efficacy. | Drug: Tenofovir Alafenamide<br>* Administered as film-coated oral tablets<br>* Other names: GS-7340;Drug: Nivolumab<br>* Administered intravenously<br>* Other names: Opdivo®;Drug: Selgantolimod<br>* Administered as film-coated oral tablets<br>* Other names: GS-9688;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants Who Achieve Functional Cure | Functional cure is defined as hepatitis B surface antigen (HBsAg) loss and hepatitis B virus (HBV) DNA < lower limit of quantitation (LLOQ) | Up to Week 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Participants With Hepatitis B Surface Antigen (HBsAg) Loss With and Without Anti-HBsAg Seroconversion |  | Up to 84 Weeks | 
| Proportion of Participants With Hepatitis B e Antigen (HBeAg) Loss With and Without Anti-HBeAg Seroconversion in Participants With CHB Who Are HBeAg-Positive at Baseline |  | Up to 84 Weeks | 
| Proportion of Participants Who Remain Off Nucleos(t)ide(s) (NUC) Treatment During Follow-Up |  | Week 36 up to Week 84 | 
| Proportion of Participants Experiencing Hepatitis B Virus (HBV) Virologic Breakthrough | Virologic breakthrough is defined as confirmed HBV DNA ≥ LLOQ after 2 consecutive HBV DNA < LLOQ in participants who are complying with NUC therapy or confirmed HBV DNA ≥ 1 log10 IU/mL increase from nadir. | Up to 36 Weeks |