Belimumab in Autoimmune Hepatitis
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Belimumab Auto-Injector [Benlysta].
- Who it may be relevant to
- Registry conditions: Autoimmune Hepatitis. Basic parameters: 18 years — 80 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Canada
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Official title
Belimumab in the Management of Autoimmune Hepatitis: A Multi-centre, Open-label Trial of add-on Belimumab Therapy to Standard of Care
Overview
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.
Interventions
- Drug Belimumab Auto-Injector [Benlysta]
Belimumab 200 MG/ML \[Benlysta\] will be given once a week as single-dose autoinjector
Primary outcome measures
- To investigate the effect of treatment with Belimumab on AIH disease activity and corticosteroid use in the management of AIH [Time frame: Week 48]
Secondary outcome measures (12)
- To investigate the effects of treatment with Belimumab on AIH disease activity and treatment burden [Time frame: 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]
- To see the effects of treatment with Belimumab on AIH disease activity and treatment burden [Time frame: Week 48, Week 72]
- To measure the effects of Belimumab on markers of AIH disease activity [Time frame: 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]
- To outline the effects of Belimumab on Patient Reported Outcomes (PRO) [Time frame: 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]
- To measure the effects of Belimumab on Patient Reported Outcomes (PRO) [Time frame: 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]
- To assess the safety of Belimumab in patients with autoimmune hepatitis [Time frame: Week 24, Week 48, Week 72]
- Safety and Tolerability [Time frame: 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]
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 > 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:
- 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
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
Canada · 5 centers
- University of Calgary — Calgary
- G.I Research Institute — Vancouver
- McMaster University — Hamilton
- London Health Sciences Centre — London
- Toronto General Hospital — Toronto
Identifiers
NCT: NCT06381453 · 23-5037 · 213168