Belimumab in Autoimmune Hepatitis

NCT ID: NCT06381453

Last Updated: 2025-02-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-12-11
• Study Completion Date: 2029-04-30

Brief Summary

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.

Conditions

Autoimmune Hepatitis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Belimumab

200mg subcutaneous injection once a week

Group Type: EXPERIMENTAL

Belimumab Auto-Injector [Benlysta]

Intervention Type: DRUG

Belimumab 200 MG/ML \[Benlysta\] will be given once a week as single-dose autoinjector

Interventions

Belimumab Auto-Injector [Benlysta]

Belimumab 200 MG/ML \[Benlysta\] will be given once a week as single-dose autoinjector

Intervention Type: DRUG

Other Intervention Names

Benlysta

Eligibility Criteria

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 > 2 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 >10 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gideon Hirschfield, MB BChir, PhD

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Locations

Toronto General Hospital

Toronto, Ontario, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Gideon Hirschfield

Role: CONTACT

BELief@uhn.ca

416 340 4800 ext. 2654

Facility Contacts

Gideon Hirschfield

Role: primary

gideon.hirschfield@uhn.ca

416-340-4548

Other Identifiers

213168

Identifier Type: OTHER

Identifier Source: secondary_id

23-5037

Identifier Type: -

Identifier Source: org_study_id