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.
Able to provide informed consent
Age ≥ 18 years old
Clinical diagnosis of AIH and/or PSC
Listed for liver transplantation
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
Single group
Siplizumab
DrugSiplizumab 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.
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.
Incidence of immune-mediated liver injury
biopsy proven acute rejection (BPAR), or recurrent AILD
Incidence of graft loss or death
Loss of liver allograft or incidence of mortality
Incidence of BPAR
biopsy proven acute rejection within 12 Month post-transplant
Incidence of treated BPAR
biopsy proven acute rejection that requires treatment within 12 Month post-transplant
Peak plasma concentration (Cmax) after single dose of siplizumab
Cmax after single dose
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
Descriptive summary statistics by dosing level and visit/sampling time point
the frequency of siplizumab concentrations below the lower-limit of quantification (LLOQ)
Summary statistics of pharmacokinetic (PK) of Siplizumab
mean, standard deviation (SD), coefficient of variation (CV), median, minimum and maximum of siplizumab concentrations.
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