Chronic HBV-infected, HBeAg-negative subjects, who are non-cirrhotic and meet the cohort-specific criteria. Criteria for the planned cohorts are as follows: Cohort 1 Subjects who have been on NUC treatment for =3 years, have HBsAg <1000 IU at Baseline, and are planning to discontinue NUC therapy Cohort 2 Subjects who have been suppressed on a NUC for =1 year, and have HBV DNA below LLOQ, and are planning to continue NUC therapy
Conditions
Interventions
Product Name: Inarigivir Soproxil
Product Code: SB9200
Pharmaceutical Form: Tablet
Sponsors
Spring Bank Pharmaceuticals, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants in all cohorts must meet all the following inclusion criteria to be enrolled into the study: 1. HBV-infected male and female participants aged 18 to 70 years, inclusive 2. Ultrasound, computed tomography (CT) scan, or magnetic resonance imaging (MRI) within 6 months of enrollment (Cohort 1) or randomisation (Cohort 2) date with no evidence of cirrhosis or hepatocellular carcinoma (HCC) 3. Must be willing and able to comply with all study requirements 4. Have HBV DNA 280 on elastography 6. Negative urine or serum pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of IP. If the urine pregnancy test is positive, a follow-up serum test is required for confirmation 7. Women of childbearing potential must agree to use a highly effective method of contraception. Men with female partners who are of childbearing potential must agree that they or their partners will use a highly effective method of contraception. • Women of childbearing potential are sexually mature women who have not undergone bilateral tubal ligation, bilateral oophorectomy, or hysterectomy; or who have not been postmenopausal (ie, who have not menstruated at all) for at least 1 year. • Highly effective methods of contraception are hormonal contraceptives (oral, injectable, patch, intrauterine devices), male partner sterilisation, or total abstinence from heterosexual intercourse, when this is the preferred and usual lifestyle of the participant. Note: The double-barrier method (eg, synthetic condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel), periodic abstinence (such as calendar, symptothermal, post-ovulation), withdrawal (coitus interruptus), lactational amenorrhea method, and spermicide only are not acceptable as highly effective methods of contraception. 8. Must have the ability to understand and sign a written informed consent form (ICF); consent must be obtained prior to initiation of study procedures In addition, participants must meet the cohort-specific criteria listed below: Cohort 1: a. HBeAg-negative participants on documented NUCs for =3 years with undetectable HBV DNA by polymerase chain reaction (PCR) documented at least annually over the last 2 years. NUCs can include tenofovir, entecavir, telbivudine, lamivudine, adefovir, and tenofovir-5TC. b. HBsAg =65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: Participants in all cohorts who meet any of the following exclusion criteria are not eligible to be enrolled into the study: 1. Any prior liver biopsy evidence of metavir F3 or F4 disease 2. Any history of decompensation of liver disease including history of ascites, encephalopathy, or varices 3. Evidence of advanced fibrosis as defined by Fibroscan at the Screening Visit of =8 kPa. If Fibroscan is not available, participants with both a Fibrotest =0.65 and aspartate transaminase (AST):platelet ratio index (APRI) =1.0 are excluded (participants will not be excluded if only 1 of the Fibrotest or APRI results is higher than allowed) 4. Laboratory parameters not within defined thresholds: 4.1 White blood cells 1.5 4.6 Total bilirubin >1.2 mg/dL (>20.52 µmol/L) or alpha-fetoprotein (AFP) >50 ng/mL (>180.25 nmol/L). Participants with an elevated indirect bilirubin and limits. Participants with an AFP >50 ng/mL but 1.2 mg/dL (>106.08 µmol/L) and creatinine clearance <50 mL/min (<0.83 L/s/m2) 5. Co-infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or hepatitis D virus 6. Evidence or history of HCC 7. Malignancy within 5 years prior to Screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc). Participants under evaluation for possible malignancy are not eligible 8. Significant cardiovascular, pulmonary, or neurological disease 9. Received solid organ or bone marrow transplant 10. Received within 3 months of Screening or expected to receive prolonged therapy with immunomodulators (eg, corticosteroids) or biologics (eg, monoclonal antibody, IFN) 11. Participants currently taking medication(s) that are transported through organic anion transporting polypeptide 1 (OATP1) including, but not limited to, atazanavir, rifampin, cyclosporine, eltrombopag, gemfibrozil, lopinavir/ritonavir, and saquinavir 12. Use of another investigational agent within 3 months of Screening 13. Current alcohol or substance abuse judged by the Investigator to potentially interfere with compliance 14. Females who are pregnant or may wish to become pregnant during the study 15. If the Investigator believes the prospective participant will not be able to comply with the requirements of the protocol and complete the study 16. Any medical condition that, in the opinion of the Investigator, could interfere with evaluation of the study objectives or safety of the participants
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives are to identify safety and antiviral efficacy of inarigivir in participants receiving nucleoside/nucleotide (NUC) analogue inhibitors and in subjects who discontinue NUCs.;Secondary Objective: Secondary Objectives: Both cohorts: 1. To evaluate markers of innate immunity in serum including interferon (IFN)-a, IFN-?, tumor necrosis factor (TNF), interleukin-6 (IL-6), IL-10, and IFN-?-inducible protein-10 (IP-10) 2. To assess duration, predictive factors, and sustainability of antiviral effect. ;Primary end point(s): Primary Endpoints: 1. The primary endpoint for safety is the proportion of subjects reporting an adverse event or experiencing a clinically significant adverse event or laboratory abnormality from start of treatment to end of inarigivir treatment and 30 days after stopping inarigivir 2. Antiviral efficacy defined by the following: Cohort 1 (subjects who stop treatment with NUCs and start treatment with inarigivir): 1. Reduction in quantitative HBsAg by >0.3 log10 from Baseline to Week 24 2. Percentage of subjects with loss of HBsAg from Baseline to Weeks 24 and 48 3. Percentage of subjects with ALT flares 4. Percentage of subjects with suppression of HBV DNA <2000 IU/L at Weeks 24 and 48 5. Percentage of subjects with ALT <40 IU/L at Weeks 24, 48, 72, and 96 6. Percentage of subjects who lose HBsAg at Weeks 72 and 96 Cohort 2 (subjects who continue treatment with NUCs and start treatment with inarigivir): 1. Percentage of subjects with suppression of HBV DNA <2000 IU/L at Weeks 72 and 96 (off inarigivir treatment) 2. Percentage of subjects with ALT <40 IU/L at Weeks 72 and 96 (off inarigivir treatment) 3. Percentage of subjects with HBsAg <1000 IU at Weeks 72 and 96 (off inarigivir treatment) ;Timepoint(s) of evaluation of this end point: answered in question E.5.1 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Endpoints: Both cohorts: Fold change from Baseline in serum levels of IFN-a, IFN-?, TNF, IL-6, IL-10, and IP-10 at all assessment timepoints Cohort 2 only: To evaluate the following: • Percentage of subjects with HBsAg decline >0.3 log10 at Weeks 12, 24, 48, 72, and 96 • Percentage of subjects with HBsAg decline >0.5 log10 at Weeks 12, 24, 48, 72, and 96 • Percentage of subjects with HBsAg loss at Weeks 24, 48, 72, and 96 • Percentage of subjects with undetectable HBV DNA at Weeks 24, 48, 72, and 96 • Percentage of subjects who suppress HBsAg <100 IU at Weeks 24, 48, 72, and 96 • Change in serum HBV DNA, HBsAg, and HBV RNA in log10 IU/mL from Baseline to Weeks 12, 24, 48, 72, and 96 ;Timepoint(s) of evaluation of this end point: answered in question E.5.2 | — |
Countries
Canada, United Kingdom
Contacts
Public ContactDon Mitchell
Spring Bank Pharmaceuticals, Inc.
Outcome results
None listed