Evaluating the Effects of Inarigivir on Immune Response and Viral Markers in Chronic Hepatitis B Patients

NCT03932513 | Terminated Phase 2

• 1 other identifier: SBP-9200-HBV-203
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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

Conditions

HBV; Hepatitis B; Hepatitis B, Chronic

Outcome Measures

Primary Outcomes (2)

• 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

  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.

  6 Weeks

Secondary Outcomes (8)

• Proportion of patients with an adverse event (AE), or a clinically significant clinical laboratory abnormality

  6 weeks

• Correlation of change of intra-hepatic immune markers, serum cytokines and PBMC activation

  6 weeks

• Correlation of change of intra-hepatic antiviral response and serum anti-viral response

  6 weeks

• Comparison of change of intra-hepatic biomarkers of immune activation

  6 weeks

• Comparison of change of peripheral biomarkers of immune activation

  6 weeks

Study Arms (2)

Treatment A: inarigivir soproxil

EXPERIMENTAL

Inarigivir 400 mg once per day for 6 weeks (2800mg/week).

Drug: inarigivir soproxil

Treatment B: inarigivir soproxil

EXPERIMENTAL

Inarigivir 400 mg three times per week for 6 weeks (1200mg/week).

Drug: inarigivir soproxil

Interventions

inarigivir soproxil DRUG

Inarigivir 200mg and 400mg oral tablets, once daily

Also known as: SB 9200

Treatment A: inarigivir soproxil; Treatment B: inarigivir soproxil

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, aged ≥ 21 to ≤ 70 years
• Chronic hepatitis B infection defined as HBsAg positive and on NUC therapy for at least one year.
• 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
• HBV DNA ≤ 20 IU/mL at Screening tested by the Central Laboratory
• 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.
• Ultrasound, computed tomography (CT) scan, or magnetic resonance imaging (MRI) within 3 months of randomization date with no evidence of hepatocellular carcinoma
• Must be willing and able to comply with all study requirements including two liver biopsies
• 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.
• Must have the ability to understand and sign a written informed consent form; consent must be obtained prior to initiation of study procedures

You may not qualify if:

• Any liver biopsy evidence of metavir F3 or F4 disease on any prior biopsy
• Any history of decompensation of liver disease including history of ascites, encephalopathy, or varices
• Evidence of advanced fibrosis at screening as defined by Fibroscan at the Screening Visit of ≥ 8 kilopascals
• 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.
• Creatinine \> 1.2 mg/dL (SI unit \> 106.08 μmol/L), creatinine clearance \< 50 mL/min (SI unit \< 0.83 L/s/m2)
• Co-infection with hepatitis C virus, human immunodeficiency virus, or hepatitis D virus
• Evidence or history of hepatocellular carcinoma
• 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.
• Significant cardiovascular, pulmonary, or neurological disease
• Received solid organ or bone marrow transplant
• Received within 3 months of Screening or expected to receive prolonged therapy with immunomodulators (e.g., corticosteroids) or biologics (e.g., monoclonal antibody, Interferon)
• 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
• Use of any herbal medications or supplements during the study period
• Use of another investigational agent within 3 months of Screening
• Current alcohol or substance abuse judged by the Investigator to potentially interfere with compliance

Sponsors & Collaborators

• F-star Therapeutics, Inc.: lead
• CSI Medical Research Pte Ltd: collaborator

Study Sites (1)

National University Hospital

Singapore, Singapore

Location

MeSH Terms

Conditions

Hepatitis B; Hepatitis B, Chronic

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases; Hepatitis, Chronic; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Prof. Lim Seng Gee

  National University Hospital, Singapore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 22, 2019
• First Posted: April 30, 2019
• Study Start: April 11, 2019
• Primary Completion: December 21, 2019
• Study Completion: December 21, 2019
• Last Updated: April 29, 2020

Record last verified: 2020-04

Locations

SG (1)