A Study of SIPLIZUMAB in AILD and LT Patients

NCT06455280 | Recruiting Phase 1 FDA Drug

• 1 other identifier: AAAU7303
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Autoimmune Liver Disease; Liver Transplant Disorder; Autoimmune Hepatitis; Primary Sclerosing Cholangitis; End Stage Liver DIsease; Cirrhosis, Liver

Keywords

Autoimmune Liver Disease; Liver Transplant Disorder; Autoimmune Hepatitis; Primary Sclerosing Cholangitis; End Stage Liver DIsease; Cirrhosis, Liver

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Incidence of immune-mediated liver injury

  12 month Post-transplant

• Incidence of graft loss or death

  12 month Post-transplant

• Incidence of BPAR

  12 month Post-transplant

• Incidence of treated BPAR

  12 month Post-transplant

• Incidence of refractory BPAR

  12 month Post-transplant

Other Outcomes (9)

• Peak plasma concentration (Cmax) after single dose of siplizumab

  12 hours Post-treatment

• The area under the curve (AUC) from time zero to the last measurable plasma concentration sampling time.

  84 Days Post-transplant

• Descriptive summary statistics by dosing level and visit/sampling time point

  12 month Post-transplant

Study Arms (1)

Open Label

EXPERIMENTAL

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

Interventions

Siplizumab DRUG

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.

Open Label

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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
• Prior transplant
• Listed for multiorgan transplant
• Acute liver failure
• Known malignancy, including cholangiocarcinoma and hepatocellular carcinoma
• Other investigational products in the last 30 days or 5 half lives
• Pregnant/lactating or unwilling to use contraception
• Leukopenia (WBC less than 2,000/mm3
• Absolute lymphocyte count \< 200/mm3
• Sero-positive for HIV-1
• Hepatitis C Virus (HCV) antibody or RNA positive (within 6 months of screening)
• HBsAg, hepatitis B virus (HBV) DNA or HBcAb positive (within 6 months of screening)
• 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
• Untreated latent TB infection as detected by QuantiFERON Gold Plus Interferon Gamma Release Assay (IGRA) (or current standard interferon gamma release assay for TB)
• Receipt of any live-attenuated vaccine within 2 months of transplant.

Sponsors & Collaborators

• Elizabeth C. Verna: lead
• ITB-Med LLC: collaborator

Study Sites (1)

Columbia University Irving Medical Center/NewYork-Presbyterian Hospital

New York, New York, 10032, United States

RECRUITING

Related 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.

MeSH Terms

Conditions

Hepatitis, Autoimmune; Cholangitis, Sclerosing; End Stage Liver Disease; Liver Cirrhosis

Interventions

siplizumab

Condition Hierarchy (Ancestors)

Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Autoimmune Diseases; Immune System Diseases; Cholangitis; Bile Duct Diseases; Biliary Tract Diseases; Liver Failure; Hepatic Insufficiency; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Elizabeth Verna, MD

  Columbia University Irving Medical Center/ New York Presbyterian Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Theresa Lukose, PharmD

CONTACT

212-305-3839; tt2103@cumc.columbia.edu

Amanda Alonso, MHA

CONTACT

212-342-0261; aa2974@cumc.columbia.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Frank Cardile Associate Professor of Medicine

Model Details: Open-Label Study

Study Record Dates

• First Submitted: June 7, 2024
• First Posted: June 12, 2024
• Study Start: September 11, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): March 31, 2028
• Last Updated: November 24, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)