Siplizumab for Autoimmune Liver Disease

(SET-SAIL Trial)

Overseen By Amanda Alonso, MHA

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Elizabeth C. Verna

Disqualifiers: Viral hepatitis, Malignancy, HIV, others

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

Compensation: Varies

Number of Visits: 2

Duration: 1 week

8 Participants Needed

Trial Summary

What is the purpose of this trial?

There is a significant unmet need for safe and effective therapeutic approaches to prevent immune-mediated graft injury and its complications in liver transplant (LT) recipients with autoimmune liver disease (AILD) including autoimmune hepatitis and primary sclerosing cholangitis. Siplizumab is an anti-cluster of differentiation 2 (CD2) monoclonal antibody that has demonstrated a favorable safety profile of siplizumab in over 779 human subjects and has been shown to target memory T cells-a key driver in the immune processes surrounding rejection and autoimmunity post LT in AILD. The purpose of this pilot, open-label phase 1 study is to determine the safety of siplizumab for induction in patients with AILD undergoing LT. Up to eight (8) subjects will receive siplizumab 0.6 mg/kg/dose on the day of transplant (Day 0) and Day 4 post-transplant, for a total of two doses. All subjects will be followed in the study for 12 months post-LT.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

How does the drug Siplizumab differ from other treatments for autoimmune liver disease?

Siplizumab is unique because it targets specific immune cells, potentially offering a more targeted approach compared to traditional immunosuppressive therapies, which broadly suppress the immune system. ^{1 2 3 4 5}

Research Team

Elizabeth Verna, MD

Principal Investigator

Columbia University Irving Medical Center/ New York Presbyterian Hospital

Eligibility Criteria

This trial is for liver transplant recipients with autoimmune liver diseases like autoimmune hepatitis and primary sclerosing cholangitis. Participants should not have other conditions that could interfere with the study or pose a risk.

Inclusion Criteria

I have been diagnosed with autoimmune hepatitis or primary sclerosing cholangitis.

I am on the waiting list for a liver transplant.

Able to provide informed consent

Exclusion Criteria

I am on the waiting list for a multiorgan transplant.

Pregnant/lactating or unwilling to use contraception

Leukopenia (WBC less than 2,000/mm3)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

3 months

Treatment

Participants receive siplizumab 0.6 mg/kg/dose intravenously on the day of transplant (Day 0) and on post-transplant Day 4

1 week

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including measurement of CD2 receptor occupancy and incidence of immune-mediated liver injury

12 months

Regular visits (in-person and virtual)

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Siplizumab

Trial Overview The trial tests Siplizumab, an anti-CD2 monoclonal antibody, to see if it's safe and can prevent immune-mediated graft injury post-transplant in patients with AILD. It involves two doses of the drug given around the time of transplant.

Participant Groups

Group I: Open Label Experimental Treatment 1 Intervention

subjects will receive 0.6 mg/kg/dose intravenously on the day of transplant (Day 0) intraoperatively and on post-transplant Day 4.

Who Is Running the Clinical Trial?

Elizabeth C. Verna

Lead Sponsor

Trials

1

Recruited

8+

ITB-Med LLC

Industry Sponsor

Trials

12

Recruited

390+

Findings from Research

Vedolizumab, an α4β7 integrin inhibitor used for treating inflammatory bowel disease, has been associated with rare cases of drug-induced liver injury, with previous cases resolving after stopping the medication.

This report highlights the first documented case of persistent hepatotoxicity from vedolizumab, leading to chronic cholestatic liver injury even after the drug was discontinued, indicating a need for careful monitoring of liver function in patients using this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic Cholestatic Liver Injury Attributable to Vedolizumab. Stine, JG., Wang, J., Behm, BW.[2020]

Autoimmune liver diseases, including autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis, have distinct characteristics and responses to treatments, highlighting the need for tailored therapeutic approaches.

As our understanding of the causes and mechanisms of these diseases improves, future treatments are expected to become more effective and rational, potentially enhancing patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of autoimmune liver disease: current and future therapeutic options. Trivedi, PJ., Hirschfield, GM.[2022]

Autoimmune liver disorders are characterized by inflammation and the presence of specific autoantibodies, and they typically respond well to immunosuppressive treatments when diagnosed early.

The traditional guideline requiring a six-month duration of symptoms for diagnosis has been changed, allowing for quicker identification and treatment of these conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autoimmune liver disease. Mieli-Vergani, G., Vergani, D.[2023]

Tocilizumab, an IL-6 receptor antagonist, has been linked to severe liver injury in 12 reported cases, with significant outcomes including two liver transplants and three deaths, indicating a serious safety concern.

The drug may exacerbate existing viral hepatitis conditions, with various types of viral infections reported, suggesting that tocilizumab disrupts immune protection and liver cell regeneration, worsening liver health in some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case series analysis of serious exacerbations of viral hepatitis and non-viral hepatic injuries in tocilizumab-treated patients. Biehl, A., Harinstein, L., Brinker, A., et al.[2021]

In 2016, significant advancements were made in the treatment of autoimmune liver diseases, including the phase 3 clinical trial of obeticholic acid, which shows promise for managing conditions like primary biliary cholangitis (PBC).

New diagnostic tools, such as the UK-PBC risk score, were proposed, and research into the gut microbiota's role in primary sclerosing cholangitis (PSC) has opened new avenues for understanding and potentially treating these diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Research advances in autoimmune liver diseases in 2016]. Li, B., Wang, QX., Ma, X.[2018]

References

1. United States pubmed.ncbi.nlm.nih.gov

Chronic Cholestatic Liver Injury Attributable to Vedolizumab. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Treatment of autoimmune liver disease: current and future therapeutic options. [2022]

3. India pubmed.ncbi.nlm.nih.gov

Autoimmune liver disease. [2023]

4. United States pubmed.ncbi.nlm.nih.gov

A case series analysis of serious exacerbations of viral hepatitis and non-viral hepatic injuries in tocilizumab-treated patients. [2021]

5. China pubmed.ncbi.nlm.nih.gov

[Research advances in autoimmune liver diseases in 2016]. [2018]