Siplizumab for Autoimmune Liver Disease

(SET-SAIL Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Elizabeth Verna, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Elizabeth C. Verna

Disqualifiers: Viral hepatitis, Malignancy, HIV, others

No Placebo Group

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}

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)

Trial 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 (Monoclonal Antibodies)

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.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Columbia University Irving Medical Center/NewYork-Presbyterian Hospital New York, NY

Who Is Running the Clinical Trial?

Elizabeth C. Verna Lead Sponsor

ITB-Med LLC Industry Sponsor

References

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

Chronic Cholestatic Liver Injury Attributable to Vedolizumab. [2020] Drug-induced liver injury is a rare but clinically important diagnosis. Vedolizumab is an α4β7 integrin inhibitor recently approved for use in patients with moderate-to-severe inflammatory bowel disease. Cases of hepatoxicity due to vedolizumab in the pre-marketing stage were rare, and all cases resolved upon drug withdrawal. We present here the first reported case of hepatotoxicity attributable to vedolizumab, which despite drug cessation persisted with chronic cholestatic liver injury.

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

Treatment of autoimmune liver disease: current and future therapeutic options. [2022] Autoimmune liver disease spans three predominant processes, from the interface hepatitis of autoimmune hepatitis to the lymphocytic cholangitis of primary biliary cirrhosis, and finally the obstructive fibrosing sclerotic cholangiopathy of primary sclerosing cholangitis. Although all autoimmune in origin, they differ in their epidemiology, presentation and response to immunosuppressive therapy and bile acid based treatments. With an ongoing better appreciation of disease aetiology and pathogenesis, treatment is set ultimately to become more rational. We provide an overview of current and future therapies for patients with autoimmune liver disease, with an emphasis placed on some of the evidence that drives current practice.

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

Autoimmune liver disease. [2023] Autoimmune liver disorders are inflammatory liver diseases characterised histologically by a dense mononuclear cell infiltrate in the portal tract and serologically by the presence of non-organ and liver specific autoantibodies and increased levels of immunoglobulin G (IgG), in the absence of a known etiology. They usually respond to immunosuppressive treatment, which should be instituted as soon as diagnosis is made. The onset is variable and often mimics acute hepatitis. The previously accepted requirement of six month duration of symptoms before a diagnosis of autoimmune disease could be made has been abandoned.

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] Reports of moderate to severe liver injury associated with tocilizumab, an interleukin-6 (IL-6) receptor antagonist, have been reported in the post-marketing setting. This case series aims to characterize cases of tocilizumab-associated clinically significant hepatic injury.

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

[Research advances in autoimmune liver diseases in 2016]. [2018] Autoimmune liver diseases are a group of abnormal autoimmune-mediated inflammatory hepatobiliary injuries, mainly including autoimmune hepatitis(AIH), primary biliary cholangitis(PBC), and primary sclerosing cholangitis (PSC). The diagnosis and treatment of autoimmune liver diseases, an important type of non-viral liver disease, have become a prominent issue in hepatology. In 2016, many new advances have been achieved in the clinical and basic research on autoimmune liver diseases, including the phase 3 clinical trial of obeticholic acid, the proposal of UK-PBC risk score, and the research on gut microbiota associated with PSC. This article reviews the research advances in the diagnosis and treatment of autoimmune liver diseases in 2016.