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

Phase 2

Completed

Conditions: Chronic Hepatitis B

Interventions: Drug: Tenofovir Alafenamide
Drug: VIR-2218
Drug: Nivolumab
Drug: Selgantolimod

Registration Number: NCT04891770

Lead Sponsor: Gilead Sciences

Brief Summary: 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).

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 103

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1: TAF + VIR-2218 + SLGN + Nivolumab	Tenofovir Alafenamide	Nucleos(t)ide(s) (NUC)-suppressed participants with chronic hepatitis B (CHB) will receive tenofovir alafenamide (TAF) 25 mg orally once daily (QD) for 36 weeks and VIR-2218 200 mg subcutaneously (SC) once every 4 weeks (Q4W) for 24 weeks. From Week 12 onwards, participants will receive selgantolimod (SLGN) 3 mg orally once a week (QW) for 24 weeks and nivolumab 0.3 mg/kg intravenously (IV) Q4W for up to 24 weeks (only up to protocol amendment 2, nivolumab was no longer administered post implementation of protocol amendment 2). Participants who are on TAF treatment will continue TAF treatment over the duration of study follow-up. Participants will be followed up for 48 weeks post treatment.
Cohort 1: TAF + VIR-2218 + SLGN + Nivolumab	VIR-2218	Nucleos(t)ide(s) (NUC)-suppressed participants with chronic hepatitis B (CHB) will receive tenofovir alafenamide (TAF) 25 mg orally once daily (QD) for 36 weeks and VIR-2218 200 mg subcutaneously (SC) once every 4 weeks (Q4W) for 24 weeks. From Week 12 onwards, participants will receive selgantolimod (SLGN) 3 mg orally once a week (QW) for 24 weeks and nivolumab 0.3 mg/kg intravenously (IV) Q4W for up to 24 weeks (only up to protocol amendment 2, nivolumab was no longer administered post implementation of protocol amendment 2). Participants who are on TAF treatment will continue TAF treatment over the duration of study follow-up. Participants will be followed up for 48 weeks post treatment.
Cohort 1: TAF + VIR-2218 + SLGN + Nivolumab	Nivolumab	Nucleos(t)ide(s) (NUC)-suppressed participants with chronic hepatitis B (CHB) will receive tenofovir alafenamide (TAF) 25 mg orally once daily (QD) for 36 weeks and VIR-2218 200 mg subcutaneously (SC) once every 4 weeks (Q4W) for 24 weeks. From Week 12 onwards, participants will receive selgantolimod (SLGN) 3 mg orally once a week (QW) for 24 weeks and nivolumab 0.3 mg/kg intravenously (IV) Q4W for up to 24 weeks (only up to protocol amendment 2, nivolumab was no longer administered post implementation of protocol amendment 2). Participants who are on TAF treatment will continue TAF treatment over the duration of study follow-up. Participants will be followed up for 48 weeks post treatment.
Cohort 1: TAF + VIR-2218 + SLGN + Nivolumab	Selgantolimod	Nucleos(t)ide(s) (NUC)-suppressed participants with chronic hepatitis B (CHB) will receive tenofovir alafenamide (TAF) 25 mg orally once daily (QD) for 36 weeks and VIR-2218 200 mg subcutaneously (SC) once every 4 weeks (Q4W) for 24 weeks. From Week 12 onwards, participants will receive selgantolimod (SLGN) 3 mg orally once a week (QW) for 24 weeks and nivolumab 0.3 mg/kg intravenously (IV) Q4W for up to 24 weeks (only up to protocol amendment 2, nivolumab was no longer administered post implementation of protocol amendment 2). Participants who are on TAF treatment will continue TAF treatment over the duration of study follow-up. Participants will be followed up for 48 weeks post treatment.
Cohort 2 Group A: VIR-2218 + SLGN + Nivolumab	Tenofovir Alafenamide	Viremic participants with CHB will receive VIR-2218, 200 mg SC Q4W for 24 weeks. From Week 12 onwards, participants will receive SLGN 3 mg orally QW for 24 weeks and nivolumab 0.3 mg/kg IV Q4W for up to 24 weeks (only up to protocol amendment 2, nivolumab was no longer administered post implementation of protocol amendment 2). Participants who meet the criteria to initiate NUC treatment will receive TAF 25, mg orally, QD during the study. Participants will be followed up for 48 weeks post treatment.
Cohort 2 Group A: VIR-2218 + SLGN + Nivolumab	VIR-2218	Viremic participants with CHB will receive VIR-2218, 200 mg SC Q4W for 24 weeks. From Week 12 onwards, participants will receive SLGN 3 mg orally QW for 24 weeks and nivolumab 0.3 mg/kg IV Q4W for up to 24 weeks (only up to protocol amendment 2, nivolumab was no longer administered post implementation of protocol amendment 2). Participants who meet the criteria to initiate NUC treatment will receive TAF 25, mg orally, QD during the study. Participants will be followed up for 48 weeks post treatment.
Cohort 2 Group A: VIR-2218 + SLGN + Nivolumab	Nivolumab	Viremic participants with CHB will receive VIR-2218, 200 mg SC Q4W for 24 weeks. From Week 12 onwards, participants will receive SLGN 3 mg orally QW for 24 weeks and nivolumab 0.3 mg/kg IV Q4W for up to 24 weeks (only up to protocol amendment 2, nivolumab was no longer administered post implementation of protocol amendment 2). Participants who meet the criteria to initiate NUC treatment will receive TAF 25, mg orally, QD during the study. Participants will be followed up for 48 weeks post treatment.
Cohort 2 Group A: VIR-2218 + SLGN + Nivolumab	Selgantolimod	Viremic participants with CHB will receive VIR-2218, 200 mg SC Q4W for 24 weeks. From Week 12 onwards, participants will receive SLGN 3 mg orally QW for 24 weeks and nivolumab 0.3 mg/kg IV Q4W for up to 24 weeks (only up to protocol amendment 2, nivolumab was no longer administered post implementation of protocol amendment 2). Participants who meet the criteria to initiate NUC treatment will receive TAF 25, mg orally, QD during the study. Participants will be followed up for 48 weeks post treatment.
Cohort 2 Group B: SLGN + Nivolumab	Tenofovir Alafenamide	Viremic participants with CHB will receive SLGN 3 mg orally QW for 24 weeks and nivolumab 0.3 mg/kg IV Q4W for up to 24 weeks. . Viremic participants who meet the criteria to initiate NUC treatment will receive TAF 25 mg orally QD during the study. Participants will be followed up for 48 weeks post treatment. All treatments were administered up to protocol amendment 2 and after the implementation of protocol amendment 2, the treatments were discontinued for Cohort 2 Group B based on Sponsor decision.
Cohort 2 Group B: SLGN + Nivolumab	Nivolumab	Viremic participants with CHB will receive SLGN 3 mg orally QW for 24 weeks and nivolumab 0.3 mg/kg IV Q4W for up to 24 weeks. . Viremic participants who meet the criteria to initiate NUC treatment will receive TAF 25 mg orally QD during the study. Participants will be followed up for 48 weeks post treatment. All treatments were administered up to protocol amendment 2 and after the implementation of protocol amendment 2, the treatments were discontinued for Cohort 2 Group B based on Sponsor decision.
Cohort 2 Group B: SLGN + Nivolumab	Selgantolimod	Viremic participants with CHB will receive SLGN 3 mg orally QW for 24 weeks and nivolumab 0.3 mg/kg IV Q4W for up to 24 weeks. . Viremic participants who meet the criteria to initiate NUC treatment will receive TAF 25 mg orally QD during the study. Participants will be followed up for 48 weeks post treatment. All treatments were administered up to protocol amendment 2 and after the implementation of protocol amendment 2, the treatments were discontinued for Cohort 2 Group B based on Sponsor decision.

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieved Functional Cure	At Follow-up Week 24 (Cohort 1 and Cohort 2A: At Week 60; Cohort 2B: At Week 48)	Functional cure was defined as hepatitis B surface antigen (HBsAg) loss and hepatitis B virus (HBV) deoxyribonucleic acid (DNA) less than the lower limit of quantitation (LLOQ) at follow-up Week 24. LLOQ for HBV DNA CAP/CTM 2.0 is 20 IU/mL. LLOQ for HBV DNA Cobas 6800 is 10 IU/mL. The HBsAg loss was defined as HBsAg changing from positive at baseline to negative at any postbaseline visit. Percentages were rounded off.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With HBsAg Loss With and Without Anti-HBsAg Seroconversion	Up to Follow-up Week 48 (Cohort 1 and Cohort 2A: At Week 84; Cohort 2B: At Week 72)	HBsAg loss was defined as HBsAg changing from positive at baseline to negative at any postbaseline visit. HBsAg seroconversion was defined as HBsAg loss and HBsAb changes from negative/missing at baseline to positive at a postbaseline visit. Percentages were rounded-off.
Percentage 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 Follow-up Week 48 (Cohort 1 and Cohort 2A: At Week 84; Cohort 2B: At Week 72)	HBeAg loss is defined as HBeAg changing from positive at baseline to negative at any postbaseline visit. HBeAg seroconversion was defined as HBeAb test changing from negative or missing at baseline to positive at a postbaseline visit. Percentages were rounded-off.
Percentage of Participants Who Remain Off NUC Treatment During Follow-Up	Cohort 1 and Cohort 2A: From Week 36 up to Week 84 and for Cohort 2B: From Week 24 up to Week 72	NUC treatments included for analysis: adefovir dipivoxil, entecavir, telbivudine, tenofovir, tenofovir alafenamide, tenofovir alafenamide fumarate, tenofovir disoproxil fumarate, and lamivudine. Percentages were rounded-off.
Percentage of Participants Experiencing Hepatitis B Virus (HBV) Virologic Breakthrough During Study Treatments	Up to 36 Weeks	Virologic breakthrough was 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 during study treatments. LLOQ for HBV DNA CAP/CTM 2.0 is 20 IU/mL. LLOQ for HBV DNA Cobas 6800 is 10 IU/mL. Percentages were rounded-off.

Trial Locations

Locations (26): Liverpool Hospital
🇦🇺
Liverpool, New South Wales, Australia
Royal Melbourne Hospital
🇦🇺
Parkville, Victoria, Australia
Aalborg University Hospital
🇩🇰
Aalborg, Denmark
Aarhus University Hospital
🇩🇰
Aarhus N, Denmark
Hvidovre Hospital
🇩🇰
Hvidovre, Denmark
Odense University Hospital
🇩🇰
Odense, Denmark
Princess Margaret Hospital (Hong Kong)
🇭🇰
Hong Kong, Hong Kong
Queen Mary Hospital
🇭🇰
Hong Kong, Hong Kong
Prince of Wales Hospital
🇭🇰
Shatin, Hong Kong
Alice Ho Miu Ling Nethersole Hospital
🇭🇰
Tai Po, Hong Kong
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Liverpool Hospital
🇦🇺Liverpool, New South Wales, Australia