Belimumab for Autoimmune Hepatitis

(BELief Trial)

Overseen By Gideon Hirschfield

Age: 18+

Sex: Any

Trial Phase: Phase 2

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 All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 72 weeks

48 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test Belimumab, a medication that may help manage autoimmune hepatitis (AIH), a chronic liver disease. The goal is to determine if Belimumab can enhance treatment effectiveness and reduce the side effects of current therapies. Participants with AIH who either have active disease despite current treatments or maintain remission with standard medication may be suitable candidates. The trial will monitor safety, liver health, and quality of life over 72 weeks. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that Belimumab is likely to be safe for humans?

Research shows that Belimumab is generally safe for people with autoimmune diseases. One study found promising results for using Belimumab to treat autoimmune hepatitis, with some patients experiencing positive outcomes. Although specific data for autoimmune hepatitis is limited, Belimumab is already approved in Canada for other autoimmune conditions like systemic lupus erythematosus and lupus nephritis. This approval suggests that Belimumab is considered safe for treating autoimmune disorders. However, while early results are encouraging, Belimumab hasn't been extensively studied for autoimmune hepatitis. Ongoing research will provide more insight into its safety for this condition. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for autoimmune hepatitis?

Belimumab is unique because it targets the specific underlying immune system activity driving autoimmune hepatitis. Unlike standard treatments that typically involve corticosteroids or immunosuppressants, which broadly suppress the immune system and can lead to significant side effects, belimumab specifically inhibits a protein called BLyS (B-lymphocyte stimulator). This protein plays a key role in the survival and activity of B cells, which are part of the immune system that can mistakenly attack the liver in autoimmune hepatitis. Researchers are excited about belimumab because it offers a more targeted approach, potentially reducing side effects and improving treatment outcomes for patients with autoimmune hepatitis.

What evidence suggests that Belimumab might be an effective treatment for autoimmune hepatitis?

Research has shown that Belimumab, the treatment under study in this trial, might be effective for autoimmune hepatitis (AIH). In some individuals with AIH, Belimumab led to a full recovery, significantly improving their symptoms. It works by blocking a protein called BAFF, which reduces the activity of certain immune cells that attack the liver. This mechanism has proven useful in treating other autoimmune diseases like lupus. Early findings suggest that Belimumab might also help reduce the need for other medications with more side effects. So far, it has shown promise without major side effects in the limited reports available. ^{1 2 6 7 8}

Who Is on the Research Team?

Gideon Hirschfield, MB BChir, PhD

Principal Investigator

University Health Network, Toronto

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Belimumab

Trial Overview 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.

How Is the Trial Designed?

Group I: Belimumab Experimental Treatment 1 Intervention

200mg subcutaneous injection once a week

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

GlaxoSmithKline

Industry Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

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

Published Research Related to This Trial

Budesonide was found to be an effective treatment for autoimmune hepatitis (AIH) and overlap syndrome, achieving complete response and remission in 61.1% of the 18 patients studied.

Patients with liver fibrosis had a higher rate of treatment failure and experienced more side effects, suggesting that budesonide may be more effective and safer for patients without advanced liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liver fibrosis may reduce the efficacy of budesonide in the treatment of autoimmune hepatitis and overlap syndrome. Efe, C., Ozaslan, E., Kav, T., et al.[2012]

In a retrospective study of six patients with autoimmune hepatitis (AIH) or primary biliary cholangitis (PBC), the anti-BAFF therapy belimumab improved disease control in all three AIH patients, helping to reduce reliance on corticosteroids and calcineurin inhibitors.

While belimumab did not show clear improvements in liver function tests for PBC patients, it did lead to significant improvements in sicca symptoms and fatigue for patients with concomitant Sjögren's disease, suggesting potential benefits in managing related symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Belimumab treatment in autoimmune hepatitis and primary biliary cholangitis - a case series. Kolev, M., Sarbu, AC., Möller, B., et al.[2023]

Recent advances in the management of autoimmune hepatitis include new guidelines that redefine remission criteria, requiring complete biochemical and histological normalization, which may lead to fewer patients achieving remission with standard treatments.

Combination therapy using budesonide and azathioprine has been proven safe and effective for non-cirrhotic patients, highlighting a promising treatment option in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnosis and treatment of autoimmune hepatitis. Vierling, JM.[2022]

The standard treatment for autoimmune hepatitis involves corticosteroids followed by steroid-sparing therapy, which is crucial for achieving clinical and biochemical remission and improving patient outcomes.

Less than 20% of patients can successfully withdraw from treatment after 2 years of sustained remission, indicating the chronic nature of the disease and the potential need for liver transplantation in cases of progressive liver disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Autoimmune Hepatitis. Goel, A., Kwo, P.[2023]

In a study of 84 patients with type 1 autoimmune hepatitis followed for an average of 70.5 months, 13% developed decompensated liver cirrhosis, highlighting the serious progression of the disease despite treatment.

Key factors influencing disease progression included starting corticosteroid doses of less than 20 mg/day, relapses shortly after initial treatment, and elevated alanine aminotransferase levels above 40 IU/L, indicating that maintaining lower enzyme levels is crucial for better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Persistent normalization of serum alanine aminotransferase levels improves the prognosis of type 1 autoimmune hepatitis. Miyake, Y., Iwasaki, Y., Terada, R., et al.[2013]

In a study of 146 patients with type 1 autoimmune hepatitis, those who responded to corticosteroid therapy within 6 months had a significantly lower risk of progressing to cirrhosis (18% vs. 54%) and required liver transplantation (2% vs. 15%).

Elderly patients (aged 60 and above) were more likely to respond quickly to treatment compared to younger adults, and this rapid response was associated with the presence of the HLA DRB1 *04 gene, suggesting a potential genetic factor influencing treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rapidity of treatment response and outcome in type 1 autoimmune hepatitis. Czaja, AJ.[2012]

In a study of 22 patients with difficult-to-manage autoimmune hepatitis (AIH), rituximab treatment led to significant and sustained improvements in liver function tests for up to 2 years, indicating its efficacy in managing this condition.

Rituximab also allowed for a reduction in corticosteroid doses in 62% of patients, highlighting its potential to minimize the side effects associated with long-term steroid use, with no serious adverse events reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of rituximab in difficult-to-manage autoimmune hepatitis: Results from the International Autoimmune Hepatitis Group. Than, NN., Hodson, J., Schmidt-Martin, D., et al.[2022]

Autoimmune hepatitis (AIH) is a chronic liver disease with two subtypes, affecting 10 to 17 per 100,000 people in Europe, and can present acutely in 20-40% of cases.

Budesonide is recommended as a first-line treatment for non-cirrhotic patients, while other medications like tiopurines and mycophenolic acid are used for maintenance; patients who do not respond to these treatments may require more advanced therapies, including liver transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Autoimmune hepatitis]. Färkkilä, M.[2013]

In a study of 28 patients with primary biliary cirrhosis-autoimmune hepatitis overlap syndrome, those treated with a combination of ursodeoxycholic acid (UDCA) and immunosuppressive therapy achieved significantly higher biochemical remission rates (60%) compared to those receiving UDCA alone (9%) after 12 months.

The combination therapy also resulted in fewer liver-related adverse events (2 out of 14 patients) compared to the UDCA-only group (9 out of 14 patients), suggesting that this approach may enhance safety and efficacy for patients with decompensated cirrhosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Immunosuppressive Therapy for PBC-AIH Overlap Syndrome Accompanied by Decompensated Cirrhosis: A Real-World Study. Fan, X., Zhu, Y., Men, R., et al.[2023]

In a study of 132 patients with type 1 autoimmune hepatitis, those who experienced multiple relapses after treatment withdrawal were significantly more likely to develop cirrhosis and face worse outcomes, such as liver transplantation or hepatic death, compared to those who maintained remission.

Patients who sustained remission had a higher rate of normal laboratory results at the time of drug withdrawal, suggesting that achieving and maintaining normal lab indices may be crucial in preventing relapses and improving long-term prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consequences of treatment withdrawal in type 1 autoimmune hepatitis. Montano-Loza, AJ., Carpenter, HA., Czaja, AJ.[2014]

In a study of 38 elderly patients with drug-induced liver injury (DILI), approximately 32.3% of DILI-drug pairs were deemed 'avoidable' using the Liverpool adverse drug reactions avoidability tool (LAAT), indicating potential for prevention strategies.

The findings suggest that a significant portion of DILI cases in this population could be prevented, highlighting the importance of using tools like LAAT for improving patient safety and reducing healthcare costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Avoidability of drug-induced liver injury (DILI) in an elderly hospital cohort with cases assessed for causality by the updated RUCAM score. Danjuma, MI., Almasri, H., Alshokri, S., et al.[2020]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9883290/

Belimumab treatment in autoimmune hepatitis and primary ... Our preliminary data supports belimumab to be an effective treatment option for patients with autoimmune hepatitis. This is in line with the experience of ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06381453

NCT06381453 | Belimumab in Autoimmune Hepatitis Duration: 72 weeks with interim analysis after 24 patients have been treated for 24 weeks; target recruitment 48 patients. Evaluation: Safety, Serum liver tests ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2589555920300574

Belimumab is a promising third-line treatment option for ... In 2 patients with autoimmune hepatitis, belimumab led to complete response and remission. •. No adverse events related to belimumab and/or disease ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11923927/

Evaluation of biological therapies in autoimmune hepatitis Belimumab and Rituximab show promise as effective alternatives for managing refractory AIH, demonstrating significant improvements in clinical outcomes and ...

5. cureus.com cureus.com/articles/317826-role-of-b-cell-inhibition-in-autoimmune-hepatitis-lessons-learnt-from-systemic-lupus-erythematosus

Role of B-Cell Inhibition in Autoimmune Hepatitis Belimumab shows promise in managing probable AIH as a steroid-sparing agent, particularly in patients with concurrent SLE or Sjogren.

6. jhep-reports.eu jhep-reports.eu/article/S2589-5559(20)30057-4/fulltext

Belimumab is a promising third-line treatment option for ... Belimumab is a B cell-activating factor inhibitor that has been proposed for the treatment of autoimmune hepatitis. · In 2 patients with ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37716078/

Hepatic safety and efficacy of immunomodulatory drugs ... There is little data on the hepatic efficacy and safety of immunomodulatory drugs used in patients with autoimmune hepatitis (AIH), despite their established ...

8. cdn-uat.mdedge.com cdn-uat.mdedge.com/files/s3fs-public/issues/articles/70466_main_42.pdf

SLE: Belimumab Safety, Efficacy Sustained Over 6 Years In most cases, autoimmune hepatitis can be con- trolled, although ongoing treatment might be required. About 65% of patients will remit within 18 months ...