Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03932513
Recruitment Status : Terminated (Study was halted due to suspected liver injury in another study with Inarigavir)
First Posted : April 30, 2019
Last Update Posted : April 29, 2020
Sponsor:
Collaborator:
CSI Medical Research Pte Ltd
Information provided by (Responsible Party):
Spring Bank Pharmaceuticals, Inc.

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
HBV Hepatitis B Hepatitis B, Chronic Drug: inarigivir soproxil 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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2, Open-label Study Evaluating the Intra-hepatic Effect of Inarigivir 400 mg Per Day and 400 mg Three Times Per Week on Immune Response and Viral Markers in Virally Suppressed Patients With Chronic Hepatitis B Infection
Actual Study Start Date : April 11, 2019
Actual Primary Completion Date : December 21, 2019
Actual Study Completion Date : December 21, 2019

Resource links provided by the National Library of Medicine


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 Name: SB 9200

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 Name: SB 9200




Primary Outcome Measures :
  1. Change in intra-hepatic immune response [ Time Frame: 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

  2. Change in intra-hepatic anti-viral response [ Time Frame: 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 :
  1. Proportion of patients with an adverse event (AE), or a clinically significant clinical laboratory abnormality [ Time Frame: 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

  2. Correlation of change of intra-hepatic immune markers, serum cytokines and PBMC activation [ Time Frame: 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

  3. Correlation of change of intra-hepatic antiviral response and serum anti-viral response [ Time Frame: 6 weeks ]
    Correlation of change from Baseline to Week 6 of intra-hepatic antiviral response and serum anti-viral response

  4. Comparison of change of intra-hepatic biomarkers of immune activation [ Time Frame: 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

  5. Comparison of change of peripheral biomarkers of immune activation [ Time Frame: 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

  6. Comparison of change of anti-viral response [ Time Frame: 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

  7. Characterization of hepatic immune cells [ Time Frame: 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.

  8. Characterization of exhaustion markers [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   21 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male or female, aged ≥ 21 to ≤ 70 years
  2. Chronic hepatitis B infection defined as HBsAg positive and on NUC therapy for at least one year.

    1. 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
    2. HBV DNA ≤ 20 IU/mL at Screening tested by the Central Laboratory
    3. 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.
  3. Ultrasound, computed tomography (CT) scan, or magnetic resonance imaging (MRI) within 3 months of randomization date with no evidence of hepatocellular carcinoma
  4. Must be willing and able to comply with all study requirements including two liver biopsies
  5. 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.
  6. 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:

  1. Any liver biopsy evidence of metavir F3 or F4 disease on any prior biopsy
  2. Any history of decompensation of liver disease including history of ascites, encephalopathy, or varices
  3. Evidence of advanced fibrosis at screening as defined by Fibroscan at the Screening Visit of ≥ 8 kilopascals
  4. 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.
  5. Creatinine > 1.2 mg/dL (SI unit > 106.08 μmol/L), creatinine clearance < 50 mL/min (SI unit < 0.83 L/s/m2)
  6. Co-infection with hepatitis C virus, human immunodeficiency virus, or hepatitis D virus
  7. Evidence or history of hepatocellular carcinoma
  8. 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.
  9. Significant cardiovascular, pulmonary, or neurological disease
  10. Received solid organ or bone marrow transplant
  11. Received within 3 months of Screening or expected to receive prolonged therapy with immunomodulators (e.g., corticosteroids) or biologics (e.g., monoclonal antibody, Interferon)
  12. 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
  13. Use of any herbal medications or supplements during the study period
  14. Use of another investigational agent within 3 months of Screening
  15. Current alcohol or substance abuse judged by the Investigator to potentially interfere with compliance
  16. Females who are pregnant or may wish to become pregnant during the study
  17. If the Investigator believes the prospective patient will not be able to comply with the requirements of the protocol and complete the study
  18. Any medical condition, in the opinion of the Investigator, that could interfere with evaluation of the study objectives or safety of the patients

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03932513


Locations
Layout table for location information
Singapore
National University Hospital
Singapore, Singapore
Sponsors and Collaborators
Spring Bank Pharmaceuticals, Inc.
CSI Medical Research Pte Ltd
Investigators
Layout table for investigator information
Principal Investigator: Prof. Lim Seng Gee National University Hospital, Singapore
Layout table for additonal information
Responsible Party: Spring Bank Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03932513    
Other Study ID Numbers: SBP-9200-HBV-203
First Posted: April 30, 2019    Key Record Dates
Last Update Posted: April 29, 2020
Last Verified: April 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Hepatitis, Chronic