Recruiting NCT06455280

A Study of SIPLIZUMAB in AILD and LT Patients

Phase I Interventional Autoimmune Liver Disease Liver Transplant Disorder Autoimmune Hepatitis Primary Sclerosing Cholangitis

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied: The protocol lists: Siplizumab.
Who it may be relevant to: Registry conditions: Autoimmune Liver Disease, Liver Transplant Disorder, Autoimmune Hepatitis, Primary Sclerosing Cholangitis. Basic parameters: from 18 years · All.
What needs checking: Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place: United States
Next step: Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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)

Overview

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.

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)

Interventions

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.

Primary outcome measures

Serious infection in the first month post-transplant, [Time frame: 1 Month post-transplant]

Secondary outcome measures (7)

Incidence of immune-mediated liver injury [Time frame: 12 month Post-transplant]
Incidence of graft loss or death [Time frame: 12 month Post-transplant]
Incidence of BPAR [Time frame: 12 month Post-transplant]
Incidence of treated BPAR [Time frame: 12 month Post-transplant]
Incidence of refractory BPAR [Time frame: 12 month Post-transplant]
Incidence of development of donor specific antibodies (DSA) [Time frame: 12 month Post-transplant]
Incidence of recurrent AILD [Time frame: 12 month Post-transplant]

Eligibility criteria

Inclusion criteria

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 criteria

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.

ADDITIONAL exclusion criteria to be reviewed at the time 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation: N/A
Model: Single group
Masking: Open label
Primary purpose: Treatment

Study locations

United States · 1 center

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

Identifiers

NCT: NCT06455280 · AAAU7303

Primary sources (government registries)

ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗