Pharmacokinetics of anti-lymphocyte serum in the prevention of GvHD in children and adults receiving allogeneic hematopoietic stem cell transplantation - PHASAL-GA Study

The primary objective of the PHASAL-GA Study is to **characterize the pharmacokinetics (PK)** of anti-lymphocyte serum (SAL), specifically Thymoglobulin®, in pediatric and adult patients undergoing allogeneic hematopoietic stem cell (HSC) transplantation. Understanding the PK profile of SAL is clinically relevant as it aids in optimizing dosing regimens, minimizing adverse effects, and improving the efficacy of graft-versus-host disease (GvHD) prevention in this patient population.

Secondary objectives include:

• Evaluating the impact of covariates on the PK variability of SAL, which is crucial for identifying factors that may influence drug metabolism and distribution.
• Assessing the inter-individual PK variability of SAL, which is important for understanding differences in drug response among patients and tailoring individualized treatment plans.

The clinical trial involves **pediatric and adult patients** undergoing hematopoietic stem cell (HSC) allograft procedures with Thymoglobulin® packaging. The sponsor has not provided information regarding the total number of participants. The study population includes both male and female subjects, with an age range starting from 2 years and above. Participants are required to have a Lansky or Karnofsky score of at least 50%, indicating a certain level of general health status. The trial population was selected based on their receipt of Thymoglobulin therapy as part of a first HSC allograft. Participants must be enrolled in a social security plan, and those of childbearing potential are required to use an effective method of contraception throughout the study. The trial includes a vulnerable population, and informed consent is obtained from adult participants or the guardians of minor participants. Lifestyle considerations such as diet and physical activity are not specified in the provided data.

The clinical trial is designed to evaluate the **pharmacokinetics** of anti-lymphocyte serum, specifically Thymoglobulin®, in pediatric and adult patients undergoing hematopoietic stem cell (HSC) transplantation. This study is a Phase IV, low-intervention trial, characterized by its randomized, double-blind, and controlled design. The trial is expected to commence on April 1, 2023, and conclude by November 8, 2024, with the total duration of participant involvement being approximately five days, corresponding to the maximum treatment period with Thymoglobulin®. The primary endpoint is the measurement of plasma serum exposure, calculated using population pharmacokinetic methodology, while secondary endpoints include the objective function value and the coefficient of variation of the area under the curve (AUC).

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age (≥2 years), Lansky or Karnofsky score (≥50%), and informed consent. A pregnancy test will be conducted for participants of childbearing potential. Follow-up visits will be scheduled to monitor the administration of Thymoglobulin® and collect pharmacokinetic data. The end-of-study visit will occur after the completion of the treatment period to evaluate the primary and secondary endpoints. Conditions that may lead to early termination from the study include withdrawal of consent, adverse events, or non-compliance with the study protocol. The investigational medicinal product, Thymoglobulin®, is administered via infusion, with a maximum daily dose of 5 mg/kg and a total dose not exceeding 20 mg/kg over the treatment period.

The clinical trial involves the administration of **THYMOGLOBULINE 5 mg/ml**, a **poudre pour solution pour perfusion** intended for use as a **solution for infusion**. The active substance in this experimental medication is **rabbit anti-human thymocyte immunoglobulin**, classified under the ATC code **L04AA04** as an **antithymocyte immunoglobulin (rabbit)**. This product is manufactured by Genzyme Europe B.V. and is not a pediatric formulation. The medication is administered via infusion, with a maximum daily dose of 5 mg/kg and a total maximum dose of 20 mg/kg over a treatment period of up to 5 days. The substance is derived from a structurally diverse, blood-derived origin.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is on characterizing the pharmacokinetics of the anti-lymphocyte serum, specifically Thymoglobulin®, in patients undergoing allogeneic hematopoietic stem cell transplantation. Participant compliance with the dosing schedule will be monitored to ensure adherence to the prescribed infusion regimen.

Efficacy in this clinical trial will be assessed primarily through the measurement of plasma exposure to **anti-lymphocyte serum (SAL)**, specifically Thymoglobulin®. The primary endpoint involves calculating the mean area under the curve (AUC) and its standard deviation within the study population, utilizing population pharmacokinetics (PK) methodology. Secondary endpoints include the objective function value (OFV) and the coefficient of variation of the AUC. These parameters will provide insights into the pharmacokinetic profile of the investigational product in patients undergoing hematopoietic stem cell transplantation. The trial is designed to ensure that the investigational medicinal products are used in accordance with their marketing authorization, with additional diagnostic or monitoring procedures posing minimal additional risk or burden to participants compared to standard clinical practice.