Belimumab in Autoimmune Hepatitis (BELief)

April 21, 2026 updated by: University Health Network, Toronto

Belimumab in the Management of Autoimmune Hepatitis: A Multi-centre, Open-label Trial of add-on Belimumab Therapy to Standard of Care

Background: Autoimmune hepatitis (AIH) is a rare chronic and lifelong liver disease. Untreated, disease progresses to end-stage cirrhosis and the focus of therapy is with immunosuppression. Current therapies are limited, not targeted, and associated with side effects that patients report reduce quality of life. AIH is believed to arise as a consequence of genetic & environmental risks. Disease is characterised by impaired immunoregulation, that favours a chronic and relapsing hepatitis. As well as recognising an important role for cytotoxic T cells and regulatory T cells, it has become apparent that in AIH, as well as other related autoimmune conditions, that B-cells are important. AIH is characterised by a plasma cell rich interface hepatitis and elevated IgG concentrations. Furthermore B-cell lineages interact with regulatory T-cells. Off-label use of Rituximab, an anti-CD20 agent, has been described for patients with AIH. A number of other ways of effectively targeting B-cells in the treatment of related autoimmune diseases have also been developed, but there have been limited studies in people living with autoimmune hepatitis. Belimumab is a human monoclonal antibody that inhibits B-cell activating factor (BAFF), also known as B-lymphocyte stimulator. It is approved in the Canada to treat systemic lupus erythematosus and lupus nephritis. It has not been studied before in AIH, but off-label reports are published. In an open-label clinical trial of people living with autoimmune hepatitis, the investigator will now formally study the effect of adding Belimumab to existing standard of care, with the goal being to evaluate treatment efficacy, the ability to reduce the burden of existing therapies whilst still controlling AIH disease, and to describe the tolerability & safety of Belimumab in people with AIH. Study Design: Open label, multi-centre, Canadian clinical trial. Patient population: Patients with autoimmune hepatitis, excluding patients with decompensated liver disease, who either have active disease despite standard of care (Group A), or who are maintained with disease remission using standard of care therapy (Group B). 48 patients will be recruited. Intervention: Weekly sub-cutaneous Belimumab. Duration: 72 weeks with interim analysis after 24 patients have been treated for 24 weeks; target recruitment 48 patients. Evaluation: Safety, Serum liver tests, quality of life, exploratory immunologic biomarkers, optional liver biopsy or fine needle liver aspirate. Primary end-point: Group A: 50% or more of subjects have an ALT<2x ULN & corticosteroids at a dose of </= 5mg of Prednisone (or equivalent); Group B: 50% or more of subjects able to maintain remission (normal ALT, normal IgG) on monotherapy with Belimumab. Conclusion: Using a combination of makers of treatment efficacy and safety the investigator will test the hypothesis that Belimumab should be further formally evaluated for people living with AIH.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
48

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Gideon Hirschfield
  • Phone Number: 2654 416 340 4800
  • Email: BELief@uhn.ca

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada
    • British Columbia
      • Vancouver, British Columbia, Canada
        • Recruiting
        • G.I Research Institute
        • Contact:
    • Ontario
      • Hamilton, Ontario, Canada
        • Recruiting
        • McMaster University
        • Contact:
      • London, Ontario, Canada
        • Recruiting
        • London Health Sciences Centre
        • Contact:
      • Toronto, Ontario, Canada, M5G 2C4
        • Recruiting
        • Toronto General Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Ability to provide written informed consent
  • Established clinical diagnosis of autoimmune hepatitis for at least 6 months
  • Participant and clinician consent to follow AIH study therapy guidance for the duration of the open label clinical trial.

Group A:

  • ALT > 1.5 x ULN in the absence of clinical evidence or concern for alternative etiology, and assessed by the investigator as related to active AIH using standard of care evaluation.
  • Ongoing therapy with corticosteroids, and/or non-biologic immunosuppressants (AZA, MMF, MP) at a stable dosage for 4 weeks prior to screening

Group B:

  • Patients with normal ALT and normal IgG concentration
  • Ongoing therapy with single agent immunosuppression or immunosuppression with low dose Prednisone (10mg or less or budesonide 6mg or less)) alongside a second line agent (azathioprine, MMF, MP)
  • Fibroscan showing liver stiffness of < 16kPa.

Exclusion Criteria:

  • Primary liver disease other than AIH
  • High probability of NAFLD as assessed by the investigator.
  • ALT >15 x ULN
  • Patients positive for HBsAg or HBcAb and/or Hepatitis C RNA
  • Prior use if corticosteroid >15mg daily
  • A positive pregnancy test and/or breast feeding

  • The presence of advanced liver disease as defined by any of:

    1. Total Bilirubin >3 x ULN.
    2. Platelet count <100 x109/L.
    3. INR >1.5
  • Live vaccines within 30 days prior to screening or at any time during the study
  • The use of other biologics including TNF inhibitors, abatacept, or tocilizumab within the washout period

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Belimumab
200mg subcutaneous injection once a week
Drug: Belimumab Auto-Injector [Benlysta]
Belimumab 200 MG/ML [Benlysta] will be given once a week as single-dose autoinjector
Other Names:
  • Benlysta

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
To investigate the effect of treatment with Belimumab on AIH disease activity and corticosteroid use in the management of AIH
Time Frame: Week 48

Group A:

Proportion of subjects achieving a response of ALT<1.5x ULN and corticosteroids </= 5mg of Prednisone (or equivalent)

Group B:

Proportion of subjects able to maintain remission (normal ALT, normal IgG) on monotherapy with Belimumab
Week 48

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
To see the effects of treatment with Belimumab on AIH disease activity and treatment burden
Time Frame: Week 48, Week 72
  • Changes in corticosteroid dose compared to baseline >/= 50% reduction
  • Changes in corticosteroid dose compared to baseline (expressed as % of initial dosage)
Week 48, Week 72
To measure the effects of Belimumab on markers of AIH disease activity
Time Frame: Week 24, Week 48, Week 72
- Changes in serial biochemistry and IgG compared to baseline
Week 24, Week 48, Week 72
To evaluate the effects of Belimumab on markers of AIH disease activity
Time Frame: Week 24, Week 48, Week 72
- Changes in liver stiffness as measured by elastography compared to baseline
Week 24, Week 48, Week 72
To outline the effects of Belimumab on Patient Reported Outcomes (PRO)
Time Frame: Week 24, Week 48, Week 72
- Change in CLDQ domain scores from Baseline to end of treatment
Week 24, Week 48, Week 72
To assess the effects of Belimumab on Patient Reported Outcomes (PRO)
Time Frame: Week 24, Week 48, Week 72
- Change in Fatigue Scale domain scores from Baseline to end of treatment
Week 24, Week 48, Week 72
To measure the effects of Belimumab on Patient Reported Outcomes (PRO)
Time Frame: Week 24, Week 48, Week 72
- Change in SF-36 domain scores from Baseline to end of treatment
Week 24, Week 48, Week 72
To evaluate the safety of Belimumab in patients with autoimmune hepatitis
Time Frame: Week 24, Week 48, Week 72
- Incidence and frequency of Adverse Events (AEs) and Serious Adverse Events (SAEs) from baseline to end of study.
Week 24, Week 48, Week 72
To assess the safety of Belimumab in patients with autoimmune hepatitis
Time Frame: Week 24, Week 48, Week 72
- Proportion of patients experiencing AE from baseline to end of study.
Week 24, Week 48, Week 72
To report the safety of Belimumab in patients with autoimmune hepatitis
Time Frame: Week 24, Week 48, Week 72
- Change in suicidality score from baseline to end of study
Week 24, Week 48, Week 72
To investigate the effects of treatment with Belimumab on AIH disease activity and treatment burden
Time Frame: Week 48, Week 72
  • Proportion of subjects with ALT<1.5x ULN and able to stop corticosteroids
  • Proportion of patients with normal ALT, normal IgG and able to stop both corticosteroids and Azathioprine/Mycophenolate Mofetil/6-Mercaptopurine
  • Proportion of patients with normal ALT, normal IgG and able to stop corticosteroids
Week 48, Week 72
To measure the effects of treatment with Belimumab on AIH disease activity and treatment burden
Time Frame: Week 48, Week 72
- Time to biochemical disease relapse (ALT>1.5xULN having reached values <1.5x ULN)
Week 48, Week 72
Safety and Tolerability
Time Frame: Week 24, Week 48, Week 72
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Week 24, Week 48, Week 72

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University Health Network, Toronto

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
GlaxoSmithKline

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Gideon Hirschfield, MB BChir, PhD, University Health Network, Toronto

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 11, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 30, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 30, 2029

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
February 29, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 18, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 24, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 24, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 21, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 23-5037
  • 213168 (Other Identifier: Protocol Number)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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