Belimumab for Autoimmune Hepatitis
(BELief Trial)
Trial Summary
Will I have to stop taking my current medications?
The trial does not specify that you need to stop your current medications. In fact, it mentions that participants will continue their existing standard of care therapies while adding Belimumab. However, certain biologics must not be used within a washout period (time without taking certain medications) before the trial.
What data supports the effectiveness of the drug Belimumab for treating autoimmune hepatitis?
Is Belimumab safe for use in humans?
How is the drug Belimumab different from other treatments for autoimmune hepatitis?
What is the purpose of this trial?
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.
Research Team
Gideon Hirschfield, MB BChir, PhD
Principal Investigator
University Health Network, Toronto
Eligibility Criteria
This trial is for patients with autoimmune hepatitis diagnosed at least 6 months ago, who are on stable immunosuppressant therapy but still have active disease or are in remission. They must consent to follow the study's treatment guidance and not show clinical evidence of advanced liver damage.Inclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive weekly subcutaneous Belimumab injections
Interim Analysis
Interim analysis conducted after 24 patients have been treated for 24 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
Treatment Details
Interventions
- Belimumab
Find a Clinic Near You
Who Is Running the Clinical Trial?
University Health Network, Toronto
Lead Sponsor
GlaxoSmithKline
Industry Sponsor
Dame Emma Walmsley
GlaxoSmithKline
Chief Executive Officer since 2017
MA in Classics and Modern Languages from Oxford University
Dr. Hal Barron
GlaxoSmithKline
Chief Medical Officer since 2018
MD from Harvard Medical School