A single center, open-label, study to evaluate the intra-hepatic effect of inarigivir dose per day and three times per week on immune response and viral markers in virally suppressed patients with chronic hepatitis B infection
This is a single center, open-label, study to evaluate the intra-hepatic effect of inarigivir dose per day and three times per week on immune response and viral markers in virally suppressed patients with chronic hepatitis B infection
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
8
Inarigivir 200mg and 400mg oral tablets, once daily
National University Hospital
Singapore, Singapore
Change in intra-hepatic immune response
Relative change from Baseline to Week 6 of intra-hepatic immune response (quantitative measurement of 500-600 genes using Nanostring technology) in hepatocytes and liver immune cells derived from the central immunology core biopsy
Time frame: 6 Weeks
Change in intra-hepatic anti-viral response
Relative change from Baseline to Week 6 of intra-hepatic anti-viral response (HBV DNA, HBV RNA, HBV core levels, cccDNA and HBsAg levels) using PCR assays in hepatocytes and liver immune cells derived from the intra-hepatic virology biopsy.
Time frame: 6 Weeks
Proportion of patients with an adverse event (AE), or a clinically significant clinical laboratory abnormality
Proportion of patients during the Baseline to Week 6 inarigivir treatment period with an adverse event (AE), or a clinically significant clinical laboratory abnormality
Time frame: 6 weeks
Correlation of change of intra-hepatic immune markers, serum cytokines and PBMC activation
Correlation of change from Baseline to Week 6 of intra-hepatic immune markers, serum cytokines and PBMC activation measured by interferon-stimulated gene (ISG) production
Time frame: 6 weeks
Correlation of change of intra-hepatic antiviral response and serum anti-viral response
Correlation of change from Baseline to Week 6 of intra-hepatic antiviral response and serum anti-viral response
Time frame: 6 weeks
Comparison of change of intra-hepatic biomarkers of immune activation
Comparison of change in mRNA expression using Nanostring Technology, from Baseline to Week 6 of intra-hepatic biomarkers of immune activation between inarigivir 400 mg per day and 400 mg three times per week
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Time frame: 6 weeks
Comparison of change of peripheral biomarkers of immune activation
Comparison of change in mRNA expression using Nanostring Technology, from Baseline to Week 6 of intra-hepatic and peripheral biomarkers of immune activation and anti-viral response between inarigivir 400 mg per day and 400 mg three times per week
Time frame: 6 weeks
Comparison of change of anti-viral response
Comparison of change in mRNA expression using Nanostring Technology, from Baseline to Week 6 of anti-viral response between inarigivir 400 mg per day and 400 mg three times per week
Time frame: 6 weeks
Characterization of hepatic immune cells
Characterization by immuno-phenotyping of hepatic immune cells at Baseline and Week 6. Hepatic immune cells are analyzed and sorted by phenotype using markers of cell activation status through flow cytometry.
Time frame: 6 weeks
Characterization of exhaustion markers
Characterization by immuno-phenotyping of exhaustion markers at Baseline and Week 6. Hepatic immune cells are analyzed and sorted by phenotype using markers T cell exhaustion through flow cytometry.
Time frame: 6 weeks