A Study of SIPLIZUMAB in AILD and LT Patients

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)

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