Evaluation of Donor Specific Immunomodulatory Cells (DSIMC) for Tolerance Induction in Deceased Donor Liver Transplantation Recipients

The primary objective of this study is the **safety evaluation** of a tolerance induction protocol using immunomodulatory cell therapy following deceased donor liver transplantation. This is clinically relevant as it aims to assess the potential of cell-based immunotherapy to minimize systemic immunosuppression, which is crucial for improving patient outcomes and reducing the long-term side effects associated with traditional immunosuppressive therapies.

Secondary objectives include determining the percentage of patients that can achieve immunosuppression freedom at 36 months after liver transplantation. This objective is significant as it evaluates the long-term efficacy of the treatment in reducing dependency on immunosuppressive drugs, thereby potentially improving the quality of life for patients with end-stage liver disease undergoing liver transplantation.

The clinical trial involves **patients with end-stage liver disease** who are undergoing liver transplantation with a deceased donor organ. The study population includes adult participants aged 18 years and above, encompassing both male and female subjects. The trial does not involve a vulnerable population. Participants are required to have a Model for End-Stage Liver Disease (MELD) score of less than 20 and a Bar score of less than 9, with a white blood cell count greater than 2.0 x 10^9 cells/L. All participants must be able to read and understand the patient information and provide written consent. The sponsor has not provided information regarding the total number of participants or specific lifestyle considerations such as diet or physical activity. The selection criteria focus on individuals with an indication for deceased donor liver transplantation, ensuring a targeted and relevant study cohort.

The clinical trial is designed to evaluate the **safety** and efficacy of a tolerance induction protocol using **immunomodulatory cell therapy** in patients with end-stage liver disease undergoing liver transplantation with a deceased donor organ. The trial employs a randomized, double-blind, controlled design to ensure the reliability and validity of the results. The estimated duration of the trial is from August 15, 2024, to September 30, 2030, with primary and secondary endpoints assessed at 12 and 36 months post-transplantation, respectively.

Participants will be required to attend several study visits throughout the trial. The initial visit, known as the inclusion or screening visit, will determine eligibility based on criteria such as age, gender, and specific health parameters, including a MELD score of less than 20 and a WBC count greater than 2.0 x10^9 Cells/L. Following successful screening, participants will undergo the transplantation procedure and receive the investigational product, **Donor specific immunomodulatory cells (DSIMC)**, administered via infusion.

Subsequent follow-up visits will be scheduled to monitor the safety and efficacy of the treatment, with assessments conducted at regular intervals. These visits will include evaluations of liver function and the level of immunosuppression required. The end-of-study visit will occur at the conclusion of the participant's involvement, which is expected to last up to 36 months, depending on individual response and study outcomes.

Participants may be withdrawn from the study early if they experience adverse effects that compromise their safety, fail to comply with study procedures, or if the study is terminated for any reason. The trial aims to provide valuable insights into the potential of cell-based immunotherapy to minimize systemic immunosuppression in liver transplantation patients.

The clinical trial involves the administration of **Donor specific immunomodulatory cells (DSIMC)**, which are utilized as the experimental medication. DSIMC is a **solution for injection** and is classified as a structurally diverse substance used in **cell therapy**. The pharmaceutical form of DSIMC is a solution intended for infusion, and it is not a pediatric formulation. The administration route is via **infusion**, and the frequency of administration is determined by the study protocol, although specific dosing schedules are not provided in the available data. The product is developed by Karolinska and is not classified as an orphan drug.

In this clinical trial, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are explicitly mentioned. The focus of the study is on the safety evaluation of a tolerance induction protocol using immunomodulatory cell therapy following deceased donor liver transplantation. Participant compliance with the treatment regimen will be monitored according to the study's compliance protocols, although specific methods of compliance monitoring are not detailed in the provided information.

Efficacy in this clinical trial will be assessed through the evaluation of specific endpoints related to the use of donor-specific immunomodulatory cells (DSIMC) in liver transplantation. The primary endpoint focuses on the safety evaluation of the protocol at 12 months following deceased donor liver transplantation. This will involve monitoring and documenting any adverse events or complications associated with the treatment.

The secondary endpoints will assess the percentage of patients who are completely weaned off immunosuppression at 36 months post-transplantation while maintaining optimal liver function. Additionally, the level of immunosuppression in patients who are not fully weaned will be evaluated at the same time point. These assessments will provide insights into the long-term efficacy of the immunomodulatory cell therapy in reducing the need for systemic immunosuppression.