RecruitingPhase 1NCT06455280

A Study of SIPLIZUMAB in AILD and LT Patients

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)

Sponsor

Elizabeth C. Verna

Enrollment

8 participants

Start Date

Sep 11, 2024

Study Type

INTERVENTIONAL

Conditions

Autoimmune Hepatitis Primary Sclerosing Cholangitis Liver Transplant Disorder Autoimmune Liver Disease

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.

Eligibility

Min Age: 18 Years

Inclusion Criteria5

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

Exclusion Criteria18

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.
Renal failure with dialysis or with estimated glomerular filtration rate (eGFR) \< 30 at the time of LT
Model for end-stage liver disease (MELD)-Na score \>30
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

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Interventions

DRUGSiplizumab

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.