A Study of SIPLIZUMAB in AILD and LT Patients

Официальное название

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)

Обзор

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.

Подробное описание

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)

Вмешательства

• Препарат 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.

Первичные конечные точки

• Serious infection in the first month post-transplant, [Срок оценки: 1 Month post-transplant]

Вторичные конечные точки (7)

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

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

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

Идентификаторы

NCT: NCT06455280 · AAAU7303

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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