A Study of SIPLIZUMAB in AILD and LT Patients (SET-SAIL)

A 12-Month, Open-Label Study Evaluating Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Siplizumab as Induction Therapy in Patients With Autoimmune Liver Diseases Undergoing Liver Transplantation (SET-SAIL)

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.

Study Overview

• Status: Recruiting
• Conditions: Autoimmune Liver Disease; Primary Sclerosing Cholangitis; Autoimmune Hepatitis; Cirrhosis, Liver; Liver Transplant Disorder; End Stage Liver DIsease
• Intervention / Treatment: Drug: Siplizumab

Detailed Description

The purpose of this study is to evaluate the safety of siplizumab when used as induction immunosuppression in patients with primary sclerosing cholangitis (PSC) or autoimmune hepatitis (AIH) undergoing liver transplantation. Induction immunosuppression drugs are very potent anti-rejection drugs that are given immediately after transplantation to prevent rejection. Siplizumab is investigational, meaning it has not yet been approved for market use for this disease condition by the United States Food and Drug Administration (FDA).

Adult patients (18 years of age and older) listed for LT with the specific AILD diagnoses of PSC or AIH

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

Participation in this study will last approximately 15 months (~ 3 months on the LT waitlist, up to 12 months participation post-LT)

• Study Type: Interventional
• Enrollment (Estimated): 8
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Amanda Alonso, MHA; Phone Number: 212-342-0261; Email: aa2974@cumc.columbia.edu
• Study Contact Backup: Name: Theresa Lukose, PharmD; Phone Number: 212-305-3839; Email: tt2103@cumc.columbia.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Irving Medical Center/NewYork-Presbyterian Hospital
      • Principal Investigator: Elizabeth Verna, MD
      • Contact: Theresa Lukose, PharmD; Phone Number: 212-305-3839; Email: tt2103@cumc.columbia.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Able to provide informed consent
2. Age ≥ 18 years old
3. Clinical diagnosis of AIH and/or PSC
4. Listed for liver transplantation
5. Epstein-Barr virus (EBV) seropositive within 12 months of screening

Exclusion Criteria:

1. Presence or history of significant liver disease other than AIH or PSC, including viral hepatitis, alcohol-related liver disease and biopsy-proven non-alcoholic steatohepatitis
2. Prior transplant
3. Listed for multiorgan transplant
4. Acute liver failure
5. Known malignancy, including cholangiocarcinoma and hepatocellular carcinoma
6. Other investigational products in the last 30 days or 5 half lives
7. Pregnant/lactating or unwilling to use contraception
8. Leukopenia (WBC less than 2,000/mm3
9. Absolute lymphocyte count < 200/mm3
10. Sero-positive for HIV-1
11. Hepatitis C Virus (HCV) antibody or RNA positive (within 6 months of screening)
12. HBsAg, hepatitis B virus (HBV) DNA or HBcAb positive (within 6 months of screening)
13. Alcohol use exceeding 30g/day for men or 20g/day for women, and/or known phosphatidylethanol (PETH) level >80 in the 3 months prior to LT
14. Untreated latent TB infection as detected by QuantiFERON Gold Plus Interferon Gamma Release Assay (IGRA) (or current standard interferon gamma release assay for TB)
15. Receipt of any live-attenuated vaccine within 2 months of transplant.

ADDITIONAL exclusion criteria to be reviewed at the time of transplant

1. Renal failure with dialysis or with estimated glomerular filtration rate (eGFR) < 30 at the time of LT
2. Model for end-stage liver disease (MELD)-Na score >30
3. Donor features of Donation after Cardiac Death (DCD), HCV Ab or nucleic acid testing (NAT+), HBcAb or HBsAg+, or blood types A, B, and O incompatible organ

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Open Label; subjects will receive 0.6 mg/kg/dose intravenously on the day of transplant (Day 0) intraoperatively and on post-transplant Day 4.	Drug: Siplizumab; Siplizumab is an anti-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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serious infection in the first month post-transplant,	viral, bacterial or fungal infection that leads to readmission, prolonged hospitalization, reoperation, intensive care unit admission, graft loss or death.	1 Month post-transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of graft loss or death	Loss of liver allograft or incidence of mortality	12 month Post-transplant
Incidence of BPAR	biopsy proven acute rejection within 12 Month post-transplant	12 month Post-transplant
Incidence of treated BPAR	biopsy proven acute rejection that requires treatment within 12 Month post-transplant	12 month Post-transplant
Incidence of refractory BPAR	biopsy proven acute rejection within 12 Month post-transplant that is not responsive to treatment	12 month Post-transplant
Incidence of development of donor specific antibodies (DSA)	Donor specific antibodies within 12 Month Post-transplant	12 month Post-transplant
Incidence of recurrent AILD	based upon histology for autoimmune hepatitis [AIH] and histology and/or imaging for primary sclerosing cholangitis [PSC]	12 month Post-transplant
Incidence of immune-mediated liver injury	biopsy proven acute rejection (BPAR), or recurrent AILD	12 month Post-transplant

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak plasma concentration (Cmax) after single dose of siplizumab	Cmax after single dose	12 hours Post-treatment
The area under the curve (AUC) from time zero to the last measurable plasma concentration sampling time.	AUC based on plasma concentrations over 84 days post-treatment	84 Days Post-transplant
Descriptive summary statistics by dosing level and visit/sampling time point	the frequency of siplizumab concentrations below the lower-limit of quantification (LLOQ)	12 month Post-transplant
CD2 receptor occupancy by dose level and subject	Measurement of CD2 receptor occupancy	12 month Post-transplant
Dynamics of T-cell subset recovery in the blood and allograft liver	Measurement of T-cell subset in the blood and allograft liver	12 month Post-transplant
Summary statistics of pharmacokinetic (PK) of Siplizumab	mean, standard deviation (SD), coefficient of variation (CV), median, minimum and maximum of siplizumab concentrations.	12 month Post-transplant
Change in Concentration T-Cells	Change in Concentration of T- cells (cells/uL)	12 month Post treatment
Change in Concentration of B- cells	Change in Concentration of B- cells (cells/uL)	12 month Post treatment
Change in Concentration of NK- cells	Change in Concentration of NK- cells (cells/uL)	12 month Post treatment

Collaborators and Investigators

• Sponsor: Elizabeth C. Verna
• Collaborators: ITB-Med LLC
• Investigators: Principal Investigator: Elizabeth Verna, MD, Columbia University Irving Medical Center/ New York Presbyterian hospital

Publications and helpful links

Helpful Links

• kwong, A., et al., OPTN/SRTR 2018 Annual Data Report: Liver. Am J Transplant, 2020. 20 Suppl s1: p. 193- 299.
• Qian, J., et al., Studies on the induction of tolerance to alloantigens. I. The abrogation of potentials for delayed-type-hypersensitivity response to alloantigens by portal venous inoculation with allogeneic cells. J Immunol, 1985. 134(6): p. 3656-61.
• gugenheim, J., et al., Delayed rejection of heart allografts in hypersensitized rats by extracorporeal donorspecific liver hemoperfusion. Transplantation, 1986. 41(3): p. 398-400.

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): March 31, 2028

Study Registration Dates

• First Submitted: June 7, 2024
• First Submitted That Met QC Criteria: June 7, 2024
• First Posted (Actual): June 12, 2024

Study Record Updates

• Last Update Posted (Actual): November 24, 2025
• Last Update Submitted That Met QC Criteria: November 19, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Liver Transplant Disorder; Primary Sclerosing Cholangitis; Cirrhosis, Liver; Autoimmune Hepatitis; End Stage Liver DIsease; Autoimmune Liver Disease
• Additional Relevant MeSH Terms: Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Digestive System Diseases; Biliary Tract Diseases; Liver Diseases; Bile Duct Diseases; Liver Failure; Hepatic Insufficiency; Fibrosis; Hepatitis, Chronic; Hepatitis; Pathological Conditions, Signs and Symptoms; Cholangitis; Cholangitis, Sclerosing; Liver Cirrhosis; End Stage Liver Disease; Hepatitis, Autoimmune; siplizumab
• Other Study ID Numbers: AAAU7303

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No