Evaluating the Safety and Efficacy of Inarigivir in Non-cirrhotic Treatment Naive Subjects Infected With Hepatitis B Virus

NCT04059198 | Terminated Phase 2 DMC

• 1 other identifier: SBP-9200-HBV-207
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 2

Brief Summary

An open-label, Phase 2, exploratory study to examine the safety and efficacy of inarigivir in non-cirrhotic, hepatitis B treatment-naive subjects with chronic HBV infection.

Conditions

Hepatitis B; HBV; Hepatitis B, Chronic

Outcome Measures

Primary Outcomes (3)

• Proportion of subjects reporting an adverse event, clinically significant adverse event, or laboratory abnormality

  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

  24 to 52 weeks

• Percentage of subjects with a ≥1 log10 reduction in HBV DNA, a ≥1 log10 reduction in HBV RNA, and a ≥0.3 log10 reduction in quantitative HBsAg

  Percentage of subjects with a ≥1 log10 reduction in HBV DNA, a ≥1 log10 reduction in HBV RNA, and a ≥0.3 log10 reduction in quantitative hepatitis B surface antigen (HBsAg) from Baseline to Week 12.

  Baseline to Week 12

• Percentage of subjects with a ≥1 log10 reduction in HBV DNA, a ≥1 log10 reduction in HBV RNA, and a ≥0.5 log10 reduction in quantitative HBsAg

  Percentage of subjects with a ≥1 log10 reduction in HBV DNA, a ≥1 log10 reduction in HBV RNA, and a ≥0.5 log10 reduction in quantitative hepatitis B surface antigen (HBsAg) from Baseline to Week 24.

  Baseline to Week 24

Secondary Outcomes (23)

• Change from Baseline in serum levels of IFN-α, IFN-γ, TNF, IL-6, IL-10, and IP-10

  Week 4

• Change from Baseline in serum levels of IFN-α, IFN-γ, TNF, IL-6, IL-10, and IP-10

  Week 12

• Change from Baseline in serum levels of IFN-α, IFN-γ, TNF, IL-6, IL-10, and IP-10

  Week 24

• Change from Baseline in serum levels of IFN-α, IFN-γ, TNF, IL-6, IL-10, and IP-10

  Week 48

• Percentage of subjects who have a ≥0.5 log10 reduction in HBsAg

  Week 12

Study Arms (3)

Arm 1 - Inarigivir Soproxil Daily

EXPERIMENTAL

Inarigivir Soproxil Alone 400 mg Inarigivir daily for 12 weeks followed by 400 mg daily in combination with TAF 25 mg daily for 12 weeks

Drug: Inarigivir soproxil; Drug: Tenofovir alafenamide fumarate (TAF)

Arm 2 - Inarigivir Soproxil 3 Times Weekly

EXPERIMENTAL

400 mg Inarigivir 3 times weekly for 12 weeks followed by 400 mg 3 times weekly in combination with TAF 25 mg daily for 12 weeks

Drug: Inarigivir soproxil; Drug: Tenofovir alafenamide fumarate (TAF)

Arm 3 - Inarigivir Soproxil and TAF Daily

EXPERIMENTAL

400 mg Inarigivir daily in combination with TAF 25 mg daily for 24 weeks

Drug: Inarigivir soproxil; Drug: Tenofovir alafenamide fumarate (TAF)

Interventions

Inarigivir soproxil DRUG

Inarigivir soproxil 400 mg tablets

Arm 1 - Inarigivir Soproxil Daily; Arm 2 - Inarigivir Soproxil 3 Times Weekly; Arm 3 - Inarigivir Soproxil and TAF Daily

Tenofovir alafenamide fumarate (TAF) DRUG

Tenofovir alafenamide fumarate 25 mg tablet

Also known as: VEMLIDY

Arm 1 - Inarigivir Soproxil Daily; Arm 2 - Inarigivir Soproxil 3 Times Weekly; Arm 3 - Inarigivir Soproxil and TAF Daily

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HBV-infected male and female subjects aged 18 to 70 years, inclusive
• Ultrasound, computed tomography (CT) scan, or magnetic resonance imaging (MRI) within 6 months of enrollment date with no evidence of cirrhosis or hepatocellular carcinoma (HCC)
• Must be willing and able to comply with all study requirements
• Chronic HBV as defined by documented HBsAg or HBV DNA positive for 6 months or more
• Not on any antiviral medications for at least 6 months. If a subject is hepatitis B e antigen (HBeAg)-negative, they will be eligible if they have not received antiviral medications for at least 3 months. Antiviral medications include lamivudine, telbivudine, adefovir, tenofovir, entecavir, IFN therapies of any type, and all other medications with potential antiviral activity.
• HBV DNA \>2000 IU/mL for HBeAg-negative subjects and \>20,000 IU/mL for HBeAg-positive subjects at Screening
• ALT \<5× ULN and ≤200 U/L
• 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
• 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.
• Must have the ability to understand and sign a written informed consent form (ICF); consent must be obtained prior to initiation of study procedures

You may not qualify if:

• Any prior liver biopsy evidence of metavir F3 or F4 disease
• Any history of decompensation of liver disease including history of ascites, encephalopathy, or varices
• 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)
• Laboratory parameters not within defined thresholds:
• White blood cells \<4000 cells/μL (\<4.0×109/L)
• Hemoglobin \<11 g/dL (\<110 g/L) for females, \<13 g/dL (\<130 g/L) for males
• Platelets \<130,000 per μL (\<150×109/L)
• Albumin \<3.5 g/dL (\<35 g/L)
• International normalized ratio (INR) \>1.5
• 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
• Creatinine \>1.2 mg/dL (\>106.08 μmol/L) and creatinine clearance \<50 mL/min (\<0.83 L/s/m2)
• Co-infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or hepatitis D virus
• Evidence or history of HCC
• 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
• Significant cardiovascular, pulmonary, or neurological disease

Sponsors & Collaborators

• F-star Therapeutics, Inc.: lead
• PRA Health Sciences: collaborator

Study Sites (2)

Queen Mary Hospital

Hong Kong, Hong Kong Island, Hong Kong

Location

Prince of Wales Hospital

Shatin, New Territories, Hong Kong

Location

MeSH Terms

Conditions

Hepatitis B; Hepatitis B, Chronic

Interventions

tenofovir alafenamide

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis; Liver Diseases; Digestive System Diseases; Hepatitis, Chronic; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Don Mitchell

  Spring Bank Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2019
• First Posted: August 16, 2019
• Study Start: October 10, 2019
• Primary Completion: April 2, 2020
• Study Completion: April 2, 2020
• Last Updated: July 21, 2020

Record last verified: 2020-07

Locations

HK (2)