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)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 103
- 试验地点
- 26
- 主要终点
- Percentage of Participants Who Achieved Functional Cure
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willing and able to provide informed consent
- •Chronic HBV infection for at least 6 months
- •Willing to follow protocol-specified contraception requirement
排除标准
- •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.
研究组 & 干预措施
Cohort 1: TAF + VIR-2218 + SLGN + 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.
干预措施: Tenofovir Alafenamide (Drug)
Cohort 1: TAF + VIR-2218 + SLGN + 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.
干预措施: VIR-2218 (Drug)
Cohort 1: TAF + VIR-2218 + SLGN + 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.
干预措施: Nivolumab (Drug)
Cohort 1: TAF + VIR-2218 + SLGN + 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.
干预措施: Selgantolimod (Drug)
Cohort 2 Group A: VIR-2218 + SLGN + 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.
干预措施: Tenofovir Alafenamide (Drug)
Cohort 2 Group A: VIR-2218 + SLGN + 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.
干预措施: VIR-2218 (Drug)
Cohort 2 Group A: VIR-2218 + SLGN + 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.
干预措施: Nivolumab (Drug)
Cohort 2 Group A: VIR-2218 + SLGN + 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.
干预措施: Selgantolimod (Drug)
Cohort 2 Group B: SLGN + 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.
干预措施: Tenofovir Alafenamide (Drug)
Cohort 2 Group B: SLGN + 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.
干预措施: Nivolumab (Drug)
Cohort 2 Group B: SLGN + 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.
干预措施: Selgantolimod (Drug)
结局指标
主要结局
Percentage of Participants Who Achieved Functional Cure
时间窗: 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.
次要结局
- 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))
- 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))
- 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)
- Percentage of Participants Experiencing Hepatitis B Virus (HBV) Virologic Breakthrough During Study Treatments(Up to 36 Weeks)