nctId: NCT06381453 id: 23-5037 briefTitle: Belimumab in Autoimmune Hepatitis acronym: BELief overallStatus: NOT_YET_RECRUITING date: 2024-04-30 date: 2028-04-30 date: 2029-04-30 date: 2024-04-24 date: 2024-04-24 name: University Health Network, Toronto class: OTHER name: GlaxoSmithKline briefSummary: 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 studyType: INTERVENTIONAL phases: PHASE2 allocation: NA interventionModel: SINGLE_GROUP primaryPurpose: TREATMENT masking: NONE count: 48 type: ESTIMATED name: Belimumab Auto-Injector [Benlysta] measure: To investigate the effect of treatment with Belimumab on AIH disease activity and corticosteroid use in the management of AIH measure: To investigate the effects of treatment with Belimumab on AIH disease activity and treatment burden measure: To measure the effects of treatment with Belimumab on AIH disease activity and treatment burden measure: To see the effects of treatment with Belimumab on AIH disease activity and treatment burden measure: To measure the effects of Belimumab on markers of AIH disease activity measure: To evaluate the effects of Belimumab on markers of AIH disease activity measure: To outline the effects of Belimumab on Patient Reported Outcomes (PRO) measure: To assess the effects of Belimumab on Patient Reported Outcomes (PRO) measure: To measure the effects of Belimumab on Patient Reported Outcomes (PRO) measure: To evaluate the safety of Belimumab in patients with autoimmune hepatitis measure: To assess the safety of Belimumab in patients with autoimmune hepatitis measure: Safety and Tolerability measure: To report the safety of Belimumab in patients with autoimmune hepatitis sex: ALL minimumAge: 18 Years maximumAge: 80 Years stdAges: ADULT stdAges: OLDER_ADULT hasResults: False