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Hepatitis BPhase 2NCT04023721

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

A Phase 2 study testing Inarigivir soproxil and Nucleoside/nucleotide (NUC) analogue inhibitors in people with Hepatitis B and HBV, run by F-star Therapeutics, Inc. at 7 sites in 2 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Hepatitis B, HBV, Hepatitis B, Chronic
What is being tested?
Inarigivir soproxil and Nucleoside/nucleotide (NUC) analogue inhibitors
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
64 participants
Where
7 sitesin 2 countries
Study dates
18 Jun 2019to 16 Jul 2020
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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 (Cohort 1) or randomization (Cohort 2) date with no evidence of cirrhosis or hepatocellular carcinoma (HCC)
  • Must be willing and able to comply with all study requirements
  • Have HBV DNA <LLOQ at Screening
  • 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
  • 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
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  • 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
  • In addition, subjects must meet the cohort-specific criteria listed below:
  • Cohort 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.
  • HBsAg <1000 IU at Screening
  • Planning to discontinue NUC therapy
  • Cohort 2:
  • 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.
  • Planning to continue NUC therapy

Who cannot join

  • 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:
  • 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)
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  • 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
  • Received solid organ or bone marrow transplant
  • Received within 3 months of Screening or expected to receive prolonged therapy with immunomodulators (eg, corticosteroids) or biologics (eg, monoclonal antibody, IFN)
  • 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
  • Use of another investigational agent within 3 months of Screening
  • Current alcohol or substance abuse judged by the Investigator to potentially interfere with compliance
  • Females who are pregnant or may wish to become pregnant during the study
  • If the Investigator believes the prospective subject will not be able to comply with the requirements of the protocol and complete the study
  • Any medical condition that, in the opinion of the Investigator, could interfere with evaluation of the study objectives or safety of the subjects

Trial locations and contacts

7 sites in 2 countries.

7 sites in 2 countries

Canada5 sites

  • University of Calgary

    Calgary, Alberta

  • Toronto General Hospital

    Toronto, Ontario

  • Toronto Liver Center

    Toronto, Ontario

  • GI Research Institute

    Vancouver, British Columbia

  • LAIR Centre

    Vancouver, British Columbia

Other trials in Canada

United Kingdom2 sites

  • Barts Health NHS Trust

    London, England

  • King's College Hospital NHS Foundation Trust

    London, England

Other trials in United Kingdom

About this study

Official title: A Phase 2, Exploratory Study Evaluating the Safety and Antiviral Efficacy of Inarigivir Soproxil in Non-cirrhotic, Hepatitis B e Antigen-negative Subjects Infected With Chronic Hepatitis B Virus and Receiving or Stopping Treatment With a Nucleoside/Nucleotide Inhibitor

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.

Being tested
Inarigivir soproxil, Nucleoside/nucleotide (NUC) analogue inhibitors
Medical subject headings
Hepatitis B, Hepatitis B, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Inarigivir soproxilDrug

    Inarigivir soproxil 200 mg tablets

  • Nucleoside/nucleotide (NUC) analogue inhibitorsDrug

    Continuation of prestudy NUC therapy

Study groups in NCT04023721
Study groupRoleWhat they receive
Cohort 1 - Inarigivir Soproxil AloneExperimentalCohort 1, 400 mg Inarigivir daily for 24 weeks and after treatment discontinuation will be followed for a further 18 months.
Receives: Drug: Inarigivir soproxil
Cohort 2 Arm A - Inarigivir Soproxil and NUCExperimentalCohort 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.
Receives: Drug: Inarigivir soproxil; Drug: Nucleoside/nucleotide (NUC) analogue inhibitors
Cohort 2 Arm B - Inarigivir Soproxil and NUCExperimentalCohort 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.
Receives: Drug: Inarigivir soproxil; Drug: Nucleoside/nucleotide (NUC) analogue inhibitors

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Proportion of subjects in Cohort 1 and 2 reporting an adverse event, clinically significant adverse event, or laboratory abnormality from start to end of treatment, and 30 days after stopping treatment

    Measured: 28 to 52 weeks

  2. Change in quantitative HBsAg (Cohort 1)

    Reduction in quantitative hepatitis B surface antigen (HBsAg) by >0.3 log10 from Baseline to Week 24 of subjects in Cohort 1

    Measured: Baseline to Week 24

  3. Change in the percentage of subjects with loss of HBsAg (Cohort 1)

    Percentage of subjects in Cohort 1 with loss of hepatitis B surface antigen (HBsAg) from Baseline to Weeks 24 and 48

    Measured: Baseline to Weeks 24 and Week 48

  4. Percentage of subjects with ALT flares (Cohort 1)

    Percentage of subjects in Cohort 1 with alanine transaminase (ALT) flares, defined as ALT >200 IU or hepatitis B virus (HBV) DNA >20,000 IU

    Measured: 96 Weeks

  5. Percentage of subjects with suppression of HBV DNA <2000 IU/L (Cohort 1)

    Percentage of subjects in Cohort 1 with suppression of hepatitis B virus (HBV) DNA <2000 IU/L at Weeks 24 and 48

    Measured: Weeks 24

  6. Percentage of subjects with suppression of HBV DNA <2000 IU/L (Cohort 1)

    Percentage of subjects in Cohort 1 with suppression of hepatitis B virus (HBV) DNA <2000 IU/L at Weeks 24 and 48

    Measured: Weeks 48

  7. Percentage of subjects with ALT <40 IU/L (Cohort 1)

    Percentage of subjects in Cohort 1 with alanine transaminase (ALT) <40 IU/L at Weeks 24, 48, 72, and 96

    Measured: Weeks 24

  8. Percentage of subjects with ALT <40 IU/L (Cohort 1)

    Percentage of subjects in Cohort 1 with alanine transaminase (ALT) <40 IU/L at Weeks 24, 48, 72, and 96

    Measured: Weeks 48

  9. Percentage of subjects with ALT <40 IU/L (Cohort 1)

    Percentage of subjects in Cohort 1 with alanine transaminase (ALT) <40 IU/L at Weeks 24, 48, 72, and 96

    Measured: Weeks 72

  10. Percentage of subjects with ALT <40 IU/L (Cohort 1)

    Percentage of subjects in Cohort 1 with alanine transaminase (ALT) <40 IU/L at Weeks 24, 48, 72, and 96

    Measured: Weeks 96

  11. Percentage of subjects who lose HBsAg (Cohort 1)

    Percentage of subjects in Cohort 1 who lose hepatitis B surface antigen (HBsAg) at Weeks 72 and 96

    Measured: Weeks 72

  12. Percentage of subjects who lose HBsAg (Cohort 1)

    Percentage of subjects in Cohort 1 who lose hepatitis B surface antigen (HBsAg) at Weeks 72 and 96

    Measured: Weeks 96

  13. Percentage of subjects with suppression of HBV DNA <2000 IU/L (Cohort 2)

    Percentage of subjects in Cohort 2 with suppression of hepatitis B virus (HBV) DNA <2000 IU/L at Weeks 72 and 96 (off inarigivir treatment)

    Measured: Weeks 72

  14. Percentage of subjects with suppression of HBV DNA <2000 IU/L (Cohort 2)

    Percentage of subjects in Cohort 2 with suppression of hepatitis B virus (HBV) DNA <2000 IU/L at Weeks 72 and 96 (off inarigivir treatment)

    Measured: Weeks 96

  15. Percentage of subjects with ALT <40 IU/L (Cohort 2 )

    Percentage of subjects in Cohort 2 with alanine transaminase (ALT) <40 IU/L at Weeks 72 and 96 (off inarigivir treatment)

    Measured: Weeks 72

  16. Percentage of subjects with ALT <40 IU/L (Cohort 2 )

    Percentage of subjects in Cohort 2 with alanine transaminase (ALT) <40 IU/L at Weeks 72 and 96 (off inarigivir treatment)

    Measured: Weeks 96

  17. Percentage of subjects with HBsAg <1000 IU (Cohort 2)

    Percentage of subjects in Cohort 2 with alanine transaminase (ALT) <40 IU/L at Weeks 72 and 96 (off inarigivir treatment)

    Measured: Weeks 72

  18. Percentage of subjects with HBsAg <1000 IU (Cohort 2)

    Percentage of subjects in Cohort 2 with alanine transaminase (ALT) <40 IU/L at Weeks 72 and 96 (off inarigivir treatment)

    Measured: Weeks 96

Secondary outcomes (7)

  1. Change in serum levels of IFN-α, IFN-γ, TNF, IL-6, IL-10, and IP-10

    Fold change from Baseline in markers of innate immunity in serum of IFN-α, IFN-γ, TNF, IL-6, IL-10, and IP-10 in subjects in Cohort 1 and 2

    Measured: Baseline to Week 96 (100 weeks)

  2. Percentage of subjects with HBsAg decline >0.3 log10 (Cohort 2)

    Percentage of subjects in Cohort 2 with hepatitis B surface antigen (HBsAg) decline >0.3 log10 at Weeks 12, 24, 48, 72, and 96

    Measured: Weeks 12, 24, 48, 72, and 96

  3. Percentage of subjects with HBsAg decline >0.5 log10 (Cohort 2)

    Percentage of subjects in Cohort 2 with hepatitis B surface antigen (HBsAg) decline >0.5 log10 at Weeks 12, 24, 48, 72, and 96

    Measured: Weeks 12, 24, 48, 72, and 96

  4. Percentage of subjects with HBsAg loss (Cohort 2)

    Percentage of subjects in Cohort 2 with hepatitis B surface antigen (HBsAg) loss at Weeks 24, 48, 72, and 96

    Measured: Weeks 24, 48, 72, and 96

  5. Percentage of subjects with undetectable HBV DNA (Cohort 2)

    Percentage of subjects in Cohort 2 with undetectable hepatitis B virus (HBV) DNA at Weeks 24, 48, 72, and 96

    Measured: Weeks 24, 48, 72, and 96

  6. Percentage of subjects who suppress HBsAg <100 IU (Cohort 2)

    Percentage of subjects in Cohort 2 who suppress hepatitis B surface antigen (HBsAg) <100 IU at Weeks 24, 48, 72, and 96

    Measured: Weeks 24, 48, 72, and 96

  7. Change in serum HBV DNA, HBsAg, and HBV RNA in log10 IU/mL (Cohort 2)

    Change in serum hepatitis B virus (HBV) DNA, hepatitis B surface antigen (HBsAg), and HBV RNA in log10 IU/mL from Baseline to Weeks 12, 24, 48, 72, and 96 for subjects in Cohort 2

    Measured: Baseline to Week 96 (100 weeks)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jul 2019
  2. Study start18 Jun 2019
  3. Primary completion16 Jul 2020
  4. Study completion16 Jul 2020

Why it stopped: Safety

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
64 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04023721
Sponsor's protocol ID
SBP-9200-HBV-206
Status last verified
Jul 2020
First submitted
21 Jun 2019
Last updated
22 Jul 2020
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Inarigivir soproxil and Nucleoside/nucleotide (NUC) analogue inhibitors in people with Hepatitis B and HBV, run by F-star Therapeutics, Inc. at 7 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 18 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 22 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 7 sites in Canada, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was stopped early (reason given: Safety). Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of subjects reporting an adverse event, clinically significant adverse event, or laboratory abnormality (time frame: 28 to 52 weeks). The study lists 18 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04023721.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jul 2020.

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