This is an open-label, Phase 2, exploratory study to examine the safety and efficacy of inarigivir in non-cirrhotic, hepatitis B e antigen (HBeAg)-negative subjects with chronic hepatitis B virus (HBV) infection.
- Conditions
- 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 therapyCohort 2 Subjects who have been suppressed on a NUC for =1 year, and have HBV DNA below LLOQ, and are planning to continue NUC therapyTherapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- EUCTR2019-000896-17-GB
- Lead Sponsor
- Spring Bank Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 60
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 5. ALT normal or, if elevated, <2× ULN with a documented etiology for elevation such as non-alcoholic fatty liver disease (NAFLD) confirmed by either ultrasound or controlled attenuation parameter (CAP) score >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 <1000 IU at Screening
c. Planning to discontinue NUC therapy
Cohort 2:
a. HBeAg-negative participants on documented NUCs for =1 year with undetectable HBV DNA by PCR documented on at least 1 occasion in the last 6 months. NUCs can include tenofovir, entecavir, telbivudine, lamivudine, adefovir, and tenofovir-5TC.
b. Planning to continue NUC therapy
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 10
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 <4000 cells/µL (<4.0×109/L)
4.2 Haemoglobin <11 g/dL (<110 g/L) for females, <13 g/dL (<130 g/L) for males
4.3 Platelets <130,000 per µL (<130×109/L)
4.4 Albumin <3.5 g/dL (<35 g/L)
4.5 International normalised ratio (INR) >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 <500 ng/mL can be included if CT scan or MRI performed within 3 months shows no evidence of HCC
4.7 Creatinine >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
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method