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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called siplizumab for individuals with autoimmune liver diseases, such as autoimmune hepatitis or primary sclerosing cholangitis, who are undergoing a liver transplant. The goal is to determine if siplizumab can safely prevent the immune system from attacking the new liver. Participants receive two doses of siplizumab during and shortly after the transplant. Suitable candidates have been diagnosed with autoimmune liver disease and are scheduled for a liver transplant. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

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

Research has shown that siplizumab is generally safe. Tested in over 779 people, most tolerated it well, meaning the treatment did not cause serious problems. Studies also indicate that siplizumab remains in the body for a few days after the last dose, aiding researchers in understanding its mechanism.

Although this trial is in its early stages, the extensive testing of siplizumab is a positive indicator of its safety. However, like any treatment, there is always a chance of side effects. Participants should be aware of this and discuss any concerns with their doctors. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Siplizumab is unique because it targets the CD2 receptor, which plays a role in the immune system's activity. Most treatments for autoimmune liver disease focus on general immune suppression, like corticosteroids or azathioprine. However, Siplizumab offers a more targeted approach, potentially reducing the risk of broad immunosuppression and its associated side effects. Researchers are excited about this treatment because it could offer a more precise and possibly safer way to manage autoimmune liver disease, especially around the time of liver transplants.

What evidence suggests that siplizumab might be an effective treatment for autoimmune liver disease?

Research shows that siplizumab, the investigational treatment in this trial, targets memory T cells, which play a crucial role in the body's immune response. These cells can cause issues like organ rejection and autoimmune liver diseases, including autoimmune hepatitis and primary sclerosing cholangitis. Studies have found siplizumab to be safe for over 779 people. This suggests it might help control immune activity that can lead to complications after a liver transplant. While most current data focus on its safety, targeting memory T cells offers a promising approach to reducing damage to transplanted organs and improving outcomes for people with autoimmune liver conditions. ^{1 2 3 6 7}

Who Is on the Research Team?

Elizabeth Verna, MD

Principal Investigator

Columbia University Irving Medical Center/ New York Presbyterian Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06455280

NCT06455280 | A Study of SIPLIZUMAB in AILD and LT ... The purpose of this study is to evaluate the safety of siplizumab when used as induction immunosuppression in patients with primary sclerosing cholangitis (PSC) ...

2. clinicaltrials.eu clinicaltrials.eu/inn/siplizumab/

Siplizumab – Application in Therapy and Current Clinical ... Medical Conditions Treated with Siplizumab · Autoimmune Liver Diseases: Including autoimmune hepatitis and primary sclerosing cholangitis in patients undergoing ...

3. clinicaltrial.be clinicaltrial.be/en/details/439305?per_page=20&only_recruiting=0&only_eligible=0&only_active=0

A Study of SIPLIZUMAB in AILD and LT Patients Secondary outcomes 7 · Incidence of immune-mediated liver injury · Incidence of graft loss or death · Incidence of BPAR · Incidence of treated BPAR.

4. withpower.com withpower.com/trial/phase-1-hepatitis-5-2024-2a685

Siplizumab for Autoimmune Liver Disease (SET-SAIL Trial) Tocilizumab, an IL-6 receptor antagonist, has been linked to severe liver injury in 12 reported cases, with significant outcomes including two liver transplants ...

5. recruit.cumc.columbia.edu recruit.cumc.columbia.edu/studyinfopage/2406

Study of Siplizumab-Based Treatment in Patients ... - RecruitMe The purpose of this research study is to see if the anti-rejection medications that patients normally take after transplant can be reduced or stopped completely ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/19917362/

Safety profile, pharmacokinetics, and pharmacodynamics ... Siplizumab exhibited an acceptable safety profile in this study. Detectable siplizumab concentrations were maintained for 3 days after the second dose.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05669001

NCT05669001 | A Study of TCD601 in de Novo Renal ... The purpose of this study is to evaluate the safety and efficacy of TCD601 (siplizumab), an anti-CD2 monoclonal antibody, in combination with a CNI-free regimen ...