Evaluating the Safety and Efficacy of Inarigivir in Non-cirrhotic, Hepatitis B e Antigen-negative Subjects Infected With HBV Virus and Receiving or Stopping Treatment With a NUC Inhibitor

NCT ID: NCT04023721

Last Updated: 2020-07-22

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 64 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-06-18
• Study Completion Date: 2020-07-16

Brief Summary

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 HBV infection.

Conditions

Hepatitis B; HBV; Hepatitis B, Chronic

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1 - Inarigivir Soproxil Alone

Cohort 1, 400 mg Inarigivir daily for 24 weeks and after treatment discontinuation will be followed for a further 18 months.

Group Type: EXPERIMENTAL

Inarigivir soproxil

Intervention Type: DRUG

Inarigivir soproxil 200 mg tablets

Cohort 2 Arm A - Inarigivir Soproxil and NUC

Cohort 2, Arm A, 400 Inarigivir daily in addition to their prestudy nucleoside/nucleotide (NUC) analogue inhibitors for 48 weeks. At Week 48 subjects will stop both inarigivir and the NUC and be followed for a further 48 weeks off treatment.

Group Type: EXPERIMENTAL

Inarigivir soproxil

Intervention Type: DRUG

Inarigivir soproxil 200 mg tablets

Nucleoside/nucleotide (NUC) analogue inhibitors

Intervention Type: DRUG

Continuation of prestudy NUC therapy

Cohort 2 Arm B - Inarigivir Soproxil and NUC

Cohort 2, Arm B, 400 mg Inarigivir daily plus prestudy nucleoside/nucleotide (NUC) analogue inhibitors for at least 24 weeks and up to 48 weeks. After treatment discontinuation of both inarigivir and the NUC, subjects will be followed off treatment up to Week 96.

Group Type: EXPERIMENTAL

Inarigivir soproxil

Intervention Type: DRUG

Inarigivir soproxil 200 mg tablets

Nucleoside/nucleotide (NUC) analogue inhibitors

Intervention Type: DRUG

Continuation of prestudy NUC therapy

Interventions

Inarigivir soproxil

Inarigivir soproxil 200 mg tablets

Intervention Type: DRUG

Nucleoside/nucleotide (NUC) analogue inhibitors

Continuation of prestudy NUC therapy

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. HBV-infected male and female subjects 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 randomization (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 <LLOQ at Screening

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 throughout the study and for 3 months after discontinuing study treatment. Men with female partners who are of childbearing potential must agree that they or their partners will use a highly effective method of contraception throughout the study and for 3 months after discontinuing study treatment. Male subjects must not donate sperm throughout the study and for 3 months after discontinuing study treatment.

• 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 sterilization, or total abstinence from heterosexual intercourse, when this is the preferred and usual lifestyle of the subject. 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, subjects must meet the cohort-specific criteria listed below:

Cohort 1:

1. HBeAg-negative subjects 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.

2. HBsAg <1000 IU at Screening

3. Planning to discontinue NUC therapy

Cohort 2:

1. HBeAg-negative subjects 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.

2. Planning to continue NUC therapy

Exclusion Criteria

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, subjects with both a Fibrotest ≥0.65 and aspartate transaminase (AST):platelet ratio index (APRI) ≥1.0 are excluded (subjects 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 Hemoglobin <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 normalized 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). Subjects with an elevated indirect bilirubin and known Gilbert's disease can be included if direct bilirubin is within normal limits. Subjects 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). Subjects 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. Subjects 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 subject 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 subjects

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

PRA Health Sciences

INDUSTRY

Sponsor Role: collaborator

F-star Therapeutics, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Don Mitchell

Role: STUDY_DIRECTOR

Spring Bank Pharmaceuticals

Locations

University of Calgary

Calgary, Alberta, Canada

GI Research Institute

Vancouver, British Columbia, Canada

LAIR Centre

Vancouver, British Columbia, Canada

Toronto General Hospital

Toronto, Ontario, Canada

Toronto Liver Center

Toronto, Ontario, Canada

Barts Health NHS Trust

London, England, United Kingdom

King's College Hospital NHS Foundation Trust

London, England, United Kingdom

Countries

Canada; United Kingdom

Other Identifiers

SBP-9200-HBV-206

Identifier Type: -

Identifier Source: org_study_id