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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04059198
Recruitment Status : Active, not recruiting
First Posted : August 16, 2019
Last Update Posted : January 27, 2020
Sponsor:
Collaborator:
PRA Health Sciences
Information provided by (Responsible Party):
Spring Bank Pharmaceuticals, Inc.

Tracking Information
First Submitted Date  ICMJE August 14, 2019
First Posted Date  ICMJE August 16, 2019
Last Update Posted Date January 27, 2020
Actual Study Start Date  ICMJE October 10, 2019
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 14, 2019)
  • Proportion of subjects reporting an adverse event, clinically significant adverse event, or laboratory abnormality [ Time Frame: 24 to 52 weeks ]
    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
  • 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 [ Time Frame: Baseline to Week 12 ]
    Percentage of subjects with a ≥1 log10 reduction in HBV DNA, a ≥1 log10 reduction in HBV RNA, and a ≥0.3 log10 reduction in quantitative hepatitis B surface antigen (HBsAg) from 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 [ Time Frame: Baseline to Week 24 ]
    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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 14, 2019)
  • Change from Baseline in serum levels of IFN-α, IFN-γ, TNF, IL-6, IL-10, and IP‑10 [ Time Frame: Week 4 ]
    Fold change from Baseline in serum levels of IFN-α, IFN-γ, TNF, IL-6, IL-10, and IP‑10 at Week 4
  • Change from Baseline in serum levels of IFN-α, IFN-γ, TNF, IL-6, IL-10, and IP‑10 [ Time Frame: Week 12 ]
    Fold change from Baseline in serum levels of IFN-α, IFN-γ, TNF, IL-6, IL-10, and IP‑10 at Week 12
  • Change from Baseline in serum levels of IFN-α, IFN-γ, TNF, IL-6, IL-10, and IP‑10 [ Time Frame: Week 24 ]
    Fold change from Baseline in serum levels of IFN-α, IFN-γ, TNF, IL-6, IL-10, and IP‑10 at Weeks 24
  • Change from Baseline in serum levels of IFN-α, IFN-γ, TNF, IL-6, IL-10, and IP‑10 [ Time Frame: Week 48 ]
    Fold change from Baseline in serum levels of IFN-α, IFN-γ, TNF, IL-6, IL-10, and IP‑10 at Weeks 48
  • Percentage of subjects who have a ≥0.5 log10 reduction in HBsAg [ Time Frame: Week 12 ]
    Percentage of subjects who have a ≥0.5 log10 reduction in hepatitis B surface antigen (HBsAg) at Week 12
  • Percentage of subjects who have a ≥0.5 log10 reduction in HBsAg [ Time Frame: Weeks 24 ]
    Percentage of subjects who have a ≥0.5 log10 reduction in hepatitis B surface antigen (HBsAg) at Week 24
  • Percentage of subjects with undetectable HBV DNA and HBV RNA [ Time Frame: Week 24 ]
    Percentage of subjects with undetectable hepatitis B virus (HBV) DNA and HBV RNA at Week 24
  • Percentage of subjects with ≥1 log10 reduction in HBsAg [ Time Frame: Week 24 ]
    Percentage of subjects with ≥1 log10 reduction in hepatitis B surface antigen (HBsAg) at Week 24
  • Percentage of subjects with undetectable HBV DNA and HBV RNA [ Time Frame: Week 48 ]
    Percentage of subjects with undetectable hepatitis B virus (HBV) DNA and HBV RNA at Week 48
  • Percentage of subjects with normal ALT [ Time Frame: Week 48 ]
    Percentage of subjects with normal alanine aminotransferase (ALT) at Week 48
  • Percentage of Subjects who were HBeAg-positive at Baseline with loss of HBeAg [ Time Frame: Week 24 ]
    Percentage of Subjects who were hepatitis B e-antigen (HBeAg)-positive at Baseline with loss of HBeAg at Week 24
  • Percentage of Subjects who were HBeAg-positive at Baseline with loss of HBeAg [ Time Frame: Week 48 ]
    Percentage of Subjects who were hepatitis B e-antigen (HBeAg)-positive at Baseline with loss of HBeAg at Week 48
  • Percentage of Subjects who were HBeAg-positive at Baseline with > 0.5 log10 reduction in HBeAg [ Time Frame: Week 12 ]
    Percentage of Subjects who were hepatitis B e-antigen (HBeAg)-positive at Baseline with > 0.5 log10 reduction in HBeAg at Week 12
  • Percentage of Subjects who were HBeAg-positive at Baseline with > 0.5 log10 reduction in HBeAg [ Time Frame: Week 24 ]
    Percentage of Subjects who were hepatitis B e-antigen (HBeAg)-positive at Baseline with > 0.5 log10 reduction in HBeAg at Week 24
  • Percentage of Subjects who were HBeAg-positive at Baseline with > 0.5 log10 reduction in HBeAg [ Time Frame: Week 48 ]
    Percentage of Subjects who were hepatitis B e-antigen (HBeAg)-positive at Baseline with > 0.5 log10 reduction in HBeAg at Week 48
  • Percentage of Subjects who were HBeAg-positive at Baseline with > 1 log10 reduction in HBeAg [ Time Frame: Week 12 ]
    Percentage of Subjects who were hepatitis B e-antigen (HBeAg)-positive at Baseline with > 1 log10 reduction in HBeAg at Week 12
  • Percentage of Subjects who were HBeAg-positive at Baseline with > 1 log10 reduction in HBeAg [ Time Frame: Week 24 ]
    Percentage of Subjects who were hepatitis B e-antigen (HBeAg)-positive at Baseline with > 1 log10 reduction in HBeAg at Week 24
  • Percentage of Subjects who were HBeAg-positive at Baseline with > 1 log10 reduction in HBeAg [ Time Frame: Week 48 ]
    Percentage of Subjects who were hepatitis B e-antigen (HBeAg)-positive at Baseline with > 1 log10 reduction in HBeAg at Week 48
  • Percentage of Subjects who enter the Long-term Follow-up Period with undetectable HBV DNA and HBV RNA [ Time Frame: Week 72 ]
    Percentage of Subjects who enter the Long-term Follow-up Period with undetectable heaptitis B virus (HBV) DNA and HBV RNA at Week 72
  • Percentage of Subjects who enter the Long-term Follow-up Period who remain HBV DNA <2000 IU [ Time Frame: Week 72 ]
    Percentage of Subjects who enter the Long-term Follow-up Period who remain hepatitis B virus (HBV) DNA <2000 IU at Week 72
  • Percentage of Subjects who enter the Long-term Follow-up Period with HBsAg loss [ Time Frame: Week 72 ]
    Percentage of Subjects who enter the Long-term Follow-up Period with hepatitis B surface antigen (HBsAg) loss at Week 72
  • Percentage of Subjects who enter the Long-term Follow-up Period with normal ALT [ Time Frame: Week 72 ]
    Percentage of Subjects who enter the Long-term Follow-up Period with normal alanine aminotransferase (ALT) at Week 72
  • Percentage of Subjects who enter the Long-term Follow-up Period who were HBeAg-positive at Baseline with loss of HBeAg [ Time Frame: Week 72 ]
    Percentage of Subjects who enter the Long-term Follow-up Period who were hepatitis B e-antigen (HBeAg)-positive at Baseline with loss of HBeAg at Week 72
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluating the Safety and Efficacy of Inarigivir in Non-cirrhotic Treatment Naive Subjects Infected With Hepatitis B Virus
Official Title  ICMJE A Phase 2, Exploratory Study Evaluating the Safety and Antiviral Efficacy of Inarigivir Soproxil in Non-cirrhotic Treatment-Naive Subjects Infected With Chronic Hepatitis B Virus
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hepatitis B
  • HBV
  • Hepatitis B, Chronic
Intervention  ICMJE
  • Drug: Inarigivir soproxil
    Inarigivir soproxil 400 mg tablets
  • Drug: Tenofovir alafenamide fumarate (TAF)
    Tenofovir alafenamide fumarate 25 mg tablet
    Other Name: VEMLIDY
Study Arms  ICMJE
  • Experimental: Arm 1 - Inarigivir Soproxil Daily
    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
    Interventions:
    • Drug: Inarigivir soproxil
    • Drug: Tenofovir alafenamide fumarate (TAF)
  • Experimental: Arm 2 - Inarigivir Soproxil 3 Times Weekly
    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
    Interventions:
    • Drug: Inarigivir soproxil
    • Drug: Tenofovir alafenamide fumarate (TAF)
  • Experimental: Arm 3 - Inarigivir Soproxil and TAF Daily
    400 mg Inarigivir daily in combination with TAF 25 mg daily for 24 weeks
    Interventions:
    • Drug: Inarigivir soproxil
    • Drug: Tenofovir alafenamide fumarate (TAF)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: August 14, 2019)
60
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE August 2022
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 date with no evidence of cirrhosis or hepatocellular carcinoma (HCC)
  3. Must be willing and able to comply with all study requirements
  4. Chronic HBV as defined by documented HBsAg or HBV DNA positive for 6 months or more
  5. 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.
  6. HBV DNA >2000 IU/mL for HBeAg-negative subjects and >20,000 IU/mL for HBeAg-positive subjects at Screening
  7. ALT <5× ULN and ≤200 U/L
  8. 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
  9. 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.
  10. Must have the ability to understand and sign a written informed consent form (ICF); consent must be obtained prior to initiation of study procedures

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:

    1. White blood cells <4000 cells/μL (<4.0×109/L)
    2. Hemoglobin <11 g/dL (<110 g/L) for females, <13 g/dL (<130 g/L) for males
    3. Platelets <130,000 per μL (<150×109/L)
    4. Albumin <3.5 g/dL (<35 g/L)
    5. International normalized ratio (INR) >1.5
    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
    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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Hong Kong
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04059198
Other Study ID Numbers  ICMJE SBP-9200-HBV-207
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Spring Bank Pharmaceuticals, Inc.
Study Sponsor  ICMJE Spring Bank Pharmaceuticals, Inc.
Collaborators  ICMJE PRA Health Sciences
Investigators  ICMJE
Study Director: Don Mitchell Spring Bank Pharmaceuticals
PRS Account Spring Bank Pharmaceuticals, Inc.
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP