Evaluating the Effects of Inarigivir on Immune Response and Viral Markers in Chronic Hepatitis B Patients
Study Details
Study Description
Brief Summary
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
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 Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Treatment A: inarigivir soproxil Inarigivir 400 mg once per day for 6 weeks (2800mg/week). |
Drug: inarigivir soproxil
Inarigivir 200mg and 400mg oral tablets, once daily
Other Names:
|
| Experimental: Treatment B: inarigivir soproxil Inarigivir 400 mg three times per week for 6 weeks (1200mg/week). |
Drug: inarigivir soproxil
Inarigivir 200mg and 400mg oral tablets, once daily
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Change in intra-hepatic immune response [6 Weeks]
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
- Change in intra-hepatic anti-viral response [6 Weeks]
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.
Secondary Outcome Measures
- Proportion of patients with an adverse event (AE), or a clinically significant clinical laboratory abnormality [6 weeks]
Proportion of patients during the Baseline to Week 6 inarigivir treatment period with an adverse event (AE), or a clinically significant clinical laboratory abnormality
- Correlation of change of intra-hepatic immune markers, serum cytokines and PBMC activation [6 weeks]
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
- Correlation of change of intra-hepatic antiviral response and serum anti-viral response [6 weeks]
Correlation of change from Baseline to Week 6 of intra-hepatic antiviral response and serum anti-viral response
- Comparison of change of intra-hepatic biomarkers of immune activation [6 weeks]
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
- Comparison of change of peripheral biomarkers of immune activation [6 weeks]
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
- Comparison of change of anti-viral response [6 weeks]
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
- Characterization of hepatic immune cells [6 weeks]
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.
- Characterization of exhaustion markers [6 weeks]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Male or female, aged ≥ 21 to ≤ 70 years
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Chronic hepatitis B infection defined as HBsAg positive and on NUC therapy for at least one year.
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Have at least one prior documented result of HBV DNA ≤ 20 IU/mL LLOQ from a local laboratory, 6 or more months prior to Screening
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HBV DNA ≤ 20 IU/mL at Screening tested by the Central Laboratory
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Have been on a commercially available HBV oral antiviral (OAV) treatment(s) (tenofovir alafenamide, tenofovir disoproxil fumarate, entecavir, adefovir, lamivudine, telbivudine, either as single agents or in combination) with no change in regimen for 3 months prior to screening.
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Ultrasound, computed tomography (CT) scan, or magnetic resonance imaging (MRI) within 3 months of randomization date with no evidence of hepatocellular carcinoma
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Must be willing and able to comply with all study requirements including two liver biopsies
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Negative urine or serum pregnancy test (for women of childbearing potential documented within the 24-hour period prior to the first dose of test drug. If the urine pregnancy test is positive, a follow-up serum test is required for confirmation. Additionally, all fertile males with partners of childbearing age and females must be using reliable contraception during the study and for 3 months after treatment completion. All fertile males must also refrain from sperm donation while on Active drug and for 3 months after completion of Active drug.
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Must have the ability to understand and sign a written informed consent form; consent must be obtained prior to initiation of study procedures
Exclusion Criteria:
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Any liver biopsy evidence of metavir F3 or F4 disease on any prior biopsy
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Any history of decompensation of liver disease including history of ascites, encephalopathy, or varices
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Evidence of advanced fibrosis at screening as defined by Fibroscan at the Screening Visit of ≥ 8 kilopascals
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Laboratory parameters not within defined thresholds: ALT or AST ≥ 40 IU, white blood cells < 4500 cells/μL (SI unit < 4.5 × 109/L), hemoglobin (HgB) < 12 g/dL (SI unit < 120 g/L) for females, < 13 g/dL (SI unit < 130 g/L) for males, platelets < 150,000 per μL (SI unit < 150 × 109/L), albumin < 3.5 g/dL (SI unit < 35 g/L), international normalized ratio (INR) > 1.5, total bilirubin > 1.2 mg/dL (SI unit > 20.52 μmol/L), or alpha-fetoprotein (AFP) > 50 ng/mL (SI unit > 180.25 nmol/L). Patients with an elevated indirect bilirubin and known Gilbert's disease can be included if direct bilirubin is within normal limits. Patients with an AFP > 50 ng/mL but ˂ 500 ng/mL can be included if computed tomography (CT) scan or magnetic resonance imaging (MRI) performed within 3 months shows no evidence of hepatocellular carcinoma.
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Creatinine > 1.2 mg/dL (SI unit > 106.08 μmol/L), creatinine clearance < 50 mL/min (SI unit < 0.83 L/s/m2)
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Co-infection with hepatitis C virus, human immunodeficiency virus, or hepatitis D virus
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Evidence or history of hepatocellular carcinoma
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Malignancy within 5 years prior to Screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc.). Patients under evaluation for possible malignancy are not eligible.
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Significant cardiovascular, pulmonary, or neurological disease
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Received solid organ or bone marrow transplant
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Received within 3 months of Screening or expected to receive prolonged therapy with immunomodulators (e.g., corticosteroids) or biologics (e.g., monoclonal antibody, Interferon)
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Patients currently taking medication(s) that are transported through organic anion transporting polypeptide 1 including, but not limited to, atazanavir, rifampin, cyclosporine, eltrombopag, gemfibrozil, lopinavir/ritonavir, and saquinavir
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Use of any herbal medications or supplements during the study period
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Use of another investigational agent within 3 months of Screening
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Current alcohol or substance abuse judged by the Investigator to potentially interfere with compliance
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Females who are pregnant or may wish to become pregnant during the study
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If the Investigator believes the prospective patient will not be able to comply with the requirements of the protocol and complete the study
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Any medical condition, in the opinion of the Investigator, that could interfere with evaluation of the study objectives or safety of the patients
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | National University Hospital | Singapore | Singapore |
Sponsors and Collaborators
- F-star Therapeutics, Inc.
- CSI Medical Research Pte Ltd
Investigators
- Principal Investigator: Prof. Lim Seng Gee, National University Hospital, Singapore
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SBP-9200-HBV-203