Study to Evaluate the Safety and Efficacy of Selgantolimod (SLGN)-Containing Combination Therapies for the Treatment of Chronic Hepatitis B (CHB)
- Conditions
- Chronic Hepatitis B
- Interventions
- 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
- Willing and able to provide informed consent
- Chronic HBV infection for at least 6 months
- Willing to follow protocol-specified contraception requirement
Key
- 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 VIR-2218 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. Cohort 2 Group A: VIR-2218 + SLGN + Nivolumab VIR-2218 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. Cohort 2 Group B: SLGN + Nivolumab Selgantolimod 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. 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 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. 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 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. Cohort 2 Group A: VIR-2218 + SLGN + Nivolumab Tenofovir Alafenamide 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. 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 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. Cohort 2 Group A: VIR-2218 + SLGN + Nivolumab Nivolumab 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. Cohort 2 Group B: SLGN + Nivolumab Tenofovir Alafenamide 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. Cohort 2 Group B: SLGN + Nivolumab Nivolumab 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. Cohort 2 Group A: VIR-2218 + SLGN + Nivolumab Selgantolimod 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.
- Primary Outcome Measures
Name Time Method Proportion of Participants Who Achieve Functional Cure Up to Week 60 Functional cure is defined as hepatitis B surface antigen (HBsAg) loss and hepatitis B virus (HBV) DNA \< lower limit of quantitation (LLOQ)
- Secondary Outcome Measures
Name Time Method Proportion of Participants With Hepatitis B Surface Antigen (HBsAg) Loss With and Without Anti-HBsAg Seroconversion 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 Up to 36 Weeks 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.
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
Trial Locations
- Locations (26)
Aalborg University Hospital
🇩🇰Aalborg, Denmark
Liverpool Hospital
🇦🇺Liverpool, New South Wales, Australia
Odense University Hospital
🇩🇰Odense, Denmark
Prince of Wales Hospital
🇭🇰Shatin, Hong Kong
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Seoul Saint Mary Hospital
🇰🇷Seoul, Korea, Republic of
Changi General Hospital
🇸🇬Singapore, Singapore
Singapore General Hospital
🇸🇬Singapore, Singapore
Thai Red Cross AIDS Research Centre (HIV-NAT)
🇹🇭Bangkok, Thailand
Auckland City Hospital
🇳🇿Grafton, New Zealand
Hvidovre Hospital
🇩🇰Hvidovre, Denmark
Aarhus University Hospital
🇩🇰Aarhus N, Denmark
Yonsei University Severance Hospital
🇰🇷Seoul, Korea, Republic of
Korea University Guro Hospital
🇰🇷Seoul, Korea, Republic of
National University Hospital
🇸🇬Singapore, Singapore
Siriraj Hospital
🇹🇭Bangkok, Thailand
Chiang Mai University, Maharaj Nakorn Chiang Mai Hospital
🇹🇭Muang, Thailand
Ramathibodi Hospital
🇹🇭Bangkok, Thailand
King's College Hospital NHS Foundation Trust
🇬🇧London, United Kingdom
Chung-Ang University Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
Princess Margaret Hospital (Hong Kong)
🇭🇰Hong Kong, Hong Kong
Queen Mary Hospital
🇭🇰Hong Kong, Hong Kong
Alice Ho Miu Ling Nethersole Hospital
🇭🇰Tai Po, Hong Kong