HBVPhase 2NCT03932513
Evaluating the Effects of Inarigivir on Immune Response and Viral Markers in Chronic Hepatitis B Patients
A Phase 2 study testing inarigivir soproxil in people with HBV and Hepatitis B, run by F-star Therapeutics, Inc. at 1 site in Singapore.
Trial 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 Read more about this study
- Who is it for?
- Ages 21 to 70 years
- Conditions the study is for
- HBV, Hepatitis B, Hepatitis B, Chronic
- What is being tested?
- inarigivir soproxil
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteSingapore
- Study dates
- 11 Apr 2019to 21 Dec 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
- Females who are pregnant or may wish to become pregnant during the study
- If the Investigator believes the prospective patient will not be able to comply with the requirements of the protocol and complete the study
- Any medical condition, in the opinion of the Investigator, that could interfere with evaluation of the study objectives or safety of the patients
Trial locations and contacts
1 site in 1 country.
About this study
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
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
Read the 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
- Conditions
- HBV, Hepatitis B, Hepatitis B, Chronic
- Being tested
- inarigivir soproxil
- Medical subject headings
- Hepatitis B, Hepatitis B, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
inarigivir soproxilDrug
Also called SB 9200
Inarigivir 200mg and 400mg oral tablets, once daily
| Study group | Role | What they receive |
|---|---|---|
| Treatment A: inarigivir soproxil | Experimental | Inarigivir 400 mg once per day for 6 weeks (2800mg/week). Receives: Drug: inarigivir soproxil |
| Treatment B: inarigivir soproxil | Experimental | Inarigivir 400 mg three times per week for 6 weeks (1200mg/week). Receives: Drug: inarigivir soproxil |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 6 Weeks
Secondary outcomes (8)
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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2019
- Study start11 Apr 2019
- Primary completion21 Dec 2019
- Study completion21 Dec 2019
Why it stopped: Study was halted due to suspected liver injury in another study with Inarigavir
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HBVStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- F-star Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- CSI Medical Research Pte Ltd
- Responsible party
- Sponsor
- Investigators
- Prof. Lim Seng Gee, Principal investigator, National University Hospital, Singapore
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03932513
- Sponsor's protocol ID
- SBP-9200-HBV-203
- Status last verified
- Apr 2020
- First submitted
- 22 Mar 2019
- Last updated
- 29 Apr 2020
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03932513
- Acronym / sponsor ID
- SBP-9200-HBV-203
- Conditions
- HBV, Hepatitis B, Hepatitis B, Chronic
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study was halted due to suspected liver injury in another study with Inarigavir
- Enrolment
- 8 participants (actual)
- Lead sponsor
- F-star Therapeutics, Inc.Industry (pharma, biotech, devices)
- Collaborators
- CSI Medical Research Pte Ltd
- Study start
- 11 Apr 2019 (actual)
- Primary completion
- 21 Dec 2019 (actual)
- Study completion
- 21 Dec 2019 (actual)
- First posted
- 30 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment A: inarigivir soproxil | Experimental | Drug: inarigivir soproxilInarigivir 400 mg once per day for 6 weeks (2800mg/week). |
| Treatment B: inarigivir soproxil | Experimental | Drug: inarigivir soproxilInarigivir 400 mg three times per week for 6 weeks (1200mg/week). |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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.
- 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.
Key exclusion criteria (18 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| inarigivir soproxilAlso: SB 9200Inarigivir 200mg and 400mg oral tablets, once daily | Drug | Treatment A: inarigivir soproxil, Treatment B: inarigivir soproxil |
Primary outcome
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
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.
8 secondary outcomes
Proportion of patients 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
Time frame: 6 weeks
Correlation of change of intra-hepatic antiviral response and serum anti-viral response
Time frame: 6 weeks
Comparison of change of intra-hepatic biomarkers of immune activation
Time frame: 6 weeks
Comparison of change of peripheral biomarkers of immune activation
Time frame: 6 weeks
Comparison of change of anti-viral response
Time frame: 6 weeks
Characterization of hepatic immune cells
Time frame: 6 weeks
Characterization of exhaustion markers
Time frame: 6 weeks
Results and safety
The study was stopped early (reason given: Study was halted due to suspected liver injury in another study with Inarigavir). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Prof. Lim Seng Gee principal investigator
National University Hospital, Singapore
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing inarigivir soproxil in people with HBV and Hepatitis B, run by F-star Therapeutics, Inc. at 1 site in Singapore.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 29 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Singapore. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Study was halted due to suspected liver injury in another study with Inarigavir). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in intra-hepatic immune response (time frame: 6 Weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2020.