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)

AAAU7303

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-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.

2024-06-01

2025-12-31

2026-03-31

Not yet recruiting

Early phase I

8

Inclusion Criteria: 1. Able to provide informed consent 2. Age ≥ 18 years old 3. Clinical diagnosis of AIH and/or PSC 4. Listed for liver transplantation 5. EBV seropositive within 12 months of screening Exclusion Criteria: 1. 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 2. Prior transplant 3. Listed for multiorgan transplant 4. Acute liver failure 5. Known malignancy, including cholangiocarcinoma and hepatocellular carcinoma 6. Other investigational products in the last 30 days or 5 half lives 7. Pregnant/lactating or unwilling to use contraception 8. Leukopenia (WBC less than 2,000/mm3 9. Absolute lymphocyte count \< 200/mm3 10. Sero-positive for HIV-1 11. HCV antibody or RNA positive (within 6 months of screening) 12. HBsAg, HBV DNA or HBcAb positive (within 6 months of screening) 13. Alcohol use exceeding 30g/day for men or 20g/day for women, and/or known PETH level \>80 in the 3 months prior to LT 14. Untreated latent TB infection as detected by QuantiFERON Gold Plus IGRA (or current standard interferon gamma release assay for TB) 15. Receipt of any live-attenuated vaccine within 2 months of transplant. ADDITIONAL exclusion criteria to be reviewed at the TIME OF TRANSPLANT 1. Renal failure with dialysis or with eGFR \< 30 at the time of LT 2. MELD-Na score \>30 3. Donor features of Donation after Cardiac Death (DCD), HCV Ab or NAT+, HBcAb or HBsAg+, or ABO incompatible organ

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SINGLE_GROUP', 'interventionModelDescription': 'Open-Label Study', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 8, 'type': 'ESTIMATED'}}

2024-06-12