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

Gilead Sciences

Status and phase: Completed; Phase 2

Conditions: Chronic Hepatitis B

Treatments: Drug: Tenofovir Alafenamide; Drug: VIR-2218; Drug: Nivolumab; Drug: Selgantolimod

Study type: Interventional

Funder types: Industry

Identifiers

NCT04891770

GS-US-465-4439

2021-000672-11 (EudraCT Number)

Details and patient eligibility

About

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).

Enrollment: 103 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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103 participants in 3 patient groups

Cohort 1: TAF + VIR-2218 + SLGN + Nivolumab

Experimental group

Description:

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.

Treatment:

Drug: Selgantolimod

Drug: Nivolumab

Drug: VIR-2218

Drug: Tenofovir Alafenamide

Cohort 2 Group A: VIR-2218 + SLGN + Nivolumab

Experimental group

Description:

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.

Treatment:

Drug: Selgantolimod

Drug: Nivolumab

Drug: VIR-2218

Drug: Tenofovir Alafenamide

Cohort 2 Group B: SLGN + Nivolumab

Experimental group

Description:

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.

Treatment:

Drug: Selgantolimod

Drug: Nivolumab

Drug: Tenofovir Alafenamide