Belimumab for Autoimmune Hepatitis
(BELief Trial)
Recruiting in Palo Alto (17 mi)
Overseen byGideon Hirschfield, MB BChir, PhD
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University Health Network, Toronto
Must be taking: Corticosteroids, Non-biologic immunosuppressants
Must not be taking: Other biologics
Disqualifiers: Primary liver disease, NAFLD, Hepatitis, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
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.
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?
Belimumab, which targets B cell activation, has shown benefits in treating Sjögren's disease, a condition with similar immune system involvement as autoimmune hepatitis. This suggests it might help patients with autoimmune hepatitis who do not respond to standard treatments.
12345Is Belimumab safe for use in humans?
Belimumab has been used in patients with autoimmune conditions like Sjögren's disease and has shown benefits, suggesting it is generally safe for human use.
35678How is the drug Belimumab different from other treatments for autoimmune hepatitis?
Belimumab is unique because it targets the B cell activating factor (BAFF), which is involved in the activation of B cells that play a role in autoimmune diseases. This makes it a novel option for patients with autoimmune hepatitis who do not respond to conventional treatments.
3591011Eligibility 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
I can sign and understand the consent form.
I have been diagnosed with autoimmune hepatitis for over 6 months.
I agree to follow the study's treatment plan as advised.
+5 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive weekly subcutaneous Belimumab injections
72 weeks
Weekly visits for injections
Interim Analysis
Interim analysis conducted after 24 patients have been treated for 24 weeks
24 weeks
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The trial studies Belimumab, a monoclonal antibody that inhibits B-cell activating factor, as an addition to standard care for AIH. It aims to see if it can control the disease with fewer side effects than current treatments over a period of 72 weeks.
1Treatment groups
Experimental Treatment
Group I: BelimumabExperimental Treatment1 Intervention
200mg subcutaneous injection once a week
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Toronto General HospitalToronto, Canada
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Who Is Running the Clinical Trial?
University Health Network, TorontoLead Sponsor
GlaxoSmithKlineIndustry Sponsor
References
Treatment of Autoimmune Hepatitis. [2023]The goal of autoimmune hepatitis treatment is to achieve clinical and biochemical remission, which is associated with significantly improved outcomes. Induction treatment with corticosteroids and the subsequent addition of steroid-sparing therapy with gradual tapering of corticosteroids remains the standard of care. Several alternatives to azathioprine and second-line agents, such as mycophenolate mofetil, tacrolimus, cyclosporine, sirolimus, or rituximab, have been evaluated in those with intolerance or inadequate response to standard-of-care therapy. Treatment withdrawal is achievable in less than 20% of patients after 2 years of sustained remission. Liver transplantation should be considered in those with progressive liver disease or those with complications such as hepatocellular carcinoma.
Persistent normalization of serum alanine aminotransferase levels improves the prognosis of type 1 autoimmune hepatitis. [2013]Autoimmune hepatitis shows a good response to immunosuppressive treatment, and the prognosis may be determined by the clinical course. The present study was conducted in order to analyze the factors contributing to the outcomes of patients with type 1 autoimmune hepatitis.
Liver fibrosis may reduce the efficacy of budesonide in the treatment of autoimmune hepatitis and overlap syndrome. [2012]The aim of the present study was to assess the efficacy and tolerability of budesonide as an alternative first line treatment option for autoimmune hepatitis (AIH) and the overlap syndrome.
Rapidity of treatment response and outcome in type 1 autoimmune hepatitis. [2012]Corticosteroid therapy is effective in type 1 autoimmune hepatitis. This study determines if the rapidity of response affects outcome.
Belimumab treatment in autoimmune hepatitis and primary biliary cholangitis - a case series. [2023]Label="Background" NlmCategory="UNASSIGNED">The majority of patients with autoimmune hepatitis (AIH) achieve complete remission with established treatment regiments. In patients with intolerance or insufficient response to these drugs, the remaining options are limited and novel treatment approaches necessary. In primary biliary cholangitis (PBC), ursodeoxycholic acid (UDCA) and fibrates have improved prognosis dramatically, but there remains a proportion of patients with refractory disease.In patients with refractory AIH and/or PBC, we used a novel treatment strategy with the anti-B cell activating factor, belimumab. The first three patients had concomitant Sjögren's disease. The connecting element between all three diseases is B cell activation, including elevated levels of the B cell activating factor (BAFF). Furthermore, belimumab has been shown to be beneficial in Sjögren's disease.
Efficacy of rituximab in difficult-to-manage autoimmune hepatitis: Results from the International Autoimmune Hepatitis Group. [2022]Treatment options remain limited for patients with autoimmune hepatitis (AIH), while there are still concerns over the consequences of long-term corticosteroid use. A few studies have suggested a role for B cell-driven autoimmune liver injury in AIH. This multicentre, international retrospective cohort study from the International Autoimmune Hepatitis Group aims to evaluate the clinical efficacy and safety of rituximab in difficult-to-manage AIH.
Consequences of treatment withdrawal in type 1 autoimmune hepatitis. [2014]Drug-related side effects are considered the major consequences of relapse and re-treatment in patients with autoimmune hepatitis. Our goals were to determine whether relapse is associated with disease progression and whether treatment end points can be refined.
Avoidability of drug-induced liver injury (DILI) in an elderly hospital cohort with cases assessed for causality by the updated RUCAM score. [2020]Drug-induced liver injury (DILI) represents an increasing morbidity in the general population, but more so in the elderly cohort of patients. Despite this, the concept of its prevention through prospective analysis has largely remained unexamined. We evaluated the utility of recently validated adverse drug reactions (ADR) avoidability tool in a cohort of elderly patients with DILI.
[Autoimmune hepatitis]. [2013]Autoimmune hepatitis is chronic liver disease with two subtypes, type 1 with anti nuclear or smooth muscle antibodies and type 2 with LKM1 or LC1 antibodies, and both with hypergammaglobulinemia and typical histology. Prevalence of AIH is between 10 to 17 per 100000 in Europe. Up to 20-40 % of cases present with acute hepatitis. Budesonide can be used as a first line induction therapy in non-cirrhotic patients, and tiopurines, mercaptopurine or mycophenolic acid as maintenance therapies. Patients not responding to conventional therapy can be treated with ciclosporin, tacrolimus or rituximab or finally with liver transplantation.
Diagnosis and treatment of autoimmune hepatitis. [2022]Autoimmune hepatitis is a chronic liver disease characterized by elevated aminotransferase levels, autoantibodies, increased γ-globulin or IgG levels and biopsy evidence of interface hepatitis. Recent advances include new practice guidelines that redefine criteria for remission to require complete biochemical and histological normalization on therapy; comparisons between the revised original and simplified diagnostic scoring systems; refined characterization of autoantibodies and their diagnostic performance parameters; proof of the safety and efficacy of combination budesonide and azathioprine therapy for non-cirrhotic patients; scrutiny of overlap syndromes; further analyses of the outcomes of orthotopic liver transplantation and the diagnosis and treatment of recurrent and de novo autoimmune hepatitis after transplantation. Anticipated consequences of the application of the new definition of therapeutic remission include a reduction in the proportion of patients achieving remission with conventional immunosuppression regimens and a corresponding increase in the need for alternative therapies.
Efficacy and Safety of Immunosuppressive Therapy for PBC-AIH Overlap Syndrome Accompanied by Decompensated Cirrhosis: A Real-World Study. [2023]To explore the efficacy and safety of immunosuppressive therapy for the treatment of primary biliary cirrhosis-autoimmune hepatitis (PBC-AIH) overlap syndrome accompanied by decompensated cirrhosis.