Belimumab in Autoimmune Hepatitis

NCT06381453 | Recruiting Phase 2 DMC

• 2 other identifiers: 23-5037213168
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 5

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

Outcome Measures

Primary Outcomes (1)

• To investigate the effect of treatment with Belimumab on AIH disease activity and corticosteroid use in the management of AIH

  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 Outcomes (12)

• To investigate the effects of treatment with Belimumab on AIH disease activity and treatment burden

  Week 48, Week 72

• To measure the effects of treatment with Belimumab on AIH disease activity and treatment burden

  Week 48, Week 72

• To see the effects of treatment with Belimumab on AIH disease activity and treatment burden

  Week 48, Week 72

• To measure the effects of Belimumab on markers of AIH disease activity

  Week 24, Week 48, Week 72

• To evaluate the effects of Belimumab on markers of AIH disease activity

  Week 24, Week 48, Week 72

Study Arms (1)

Belimumab

EXPERIMENTAL

200mg subcutaneous injection once a week

Drug: Belimumab Auto-Injector [Benlysta]

Interventions

Belimumab Auto-Injector [Benlysta] DRUG

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

Also known as: Benlysta

Belimumab

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• Total Bilirubin \>3 x ULN.
• Platelet count \<100 x109/L.
• 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

Sponsors & Collaborators

• University Health Network, Toronto: lead
• GlaxoSmithKline: collaborator

Study Sites (5)

University of Calgary

Calgary, Alberta, Canada

RECRUITING

G.I Research Institute

Vancouver, British Columbia, Canada

RECRUITING

McMaster University

Hamilton, Ontario, Canada

RECRUITING

London Health Sciences Centre

London, Ontario, Canada

RECRUITING

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

RECRUITING

MeSH Terms

Conditions

Hepatitis, Autoimmune

Interventions

belimumab

Condition Hierarchy (Ancestors)

Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Gideon Hirschfield, MB BChir, PhD

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gideon Hirschfield

CONTACT

416 340 4800; BELief@uhn.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 29, 2024
• First Posted: April 24, 2024
• Study Start: December 11, 2024
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): April 30, 2029
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

CA (5)