Evaluation of PTC:VS-TC for Refractory Viral Infections Post-Allogeneic Hematopoietic Stem Cell Transplantation in Pediatric and Young Adult Patients

The primary objective of this study is to evaluate the **safety** of virus-specific T lymphocytes selected in vitro from a family donor for the treatment of refractory viral infections, such as Adenovirus (ADV), Epstein-Barr virus (EBV), Cytomegalovirus (CMV), and BK virus, in young patients aged 0 to 30 years who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). This is clinically relevant as these infections are resistant to pharmacological therapies and pose significant health risks to immunocompromised patients.

Secondary objectives include:

• Evaluating the effectiveness of the PTC infusion in controlling the clinical and biological manifestations secondary to the viral infection being treated.

The clinical trial involves a study population of young patients aged between 0 and 30 years who have undergone an **allogeneic hematopoietic stem cell transplant** and subsequently developed post-transplant viral reactivation resistant to pharmacological therapies. The trial includes both male and female participants, and the population is considered vulnerable due to their medical condition. The sponsor has not provided the total number of participants. Participants were selected based on specific criteria, including the presence of viral infections such as Cytomegalovirus (CMV), Epstein-Barr virus (EBV), Adenovirus (ADV), and BK virus, as well as the absence of severe uncontrolled infections, acute or chronic uncontrolled Graft versus Host Disease (GvHD), and significant organ damage not related to viral infection. The study does not specify any particular lifestyle considerations such as diet or physical activity for the participants.

The clinical trial is designed to evaluate the **safety** of virus-specific T lymphocytes selected in vitro from a family donor for the treatment of refractory viral infections such as Adenovirus (ADV), Epstein-Barr virus (EBV), Cytomegalovirus (CMV), and BK virus in young patients aged 0 to 30 years who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). This is a Phase 3, randomized, double-blind, controlled trial with an estimated duration from September 28, 2022, to July 24, 2025. The trial involves the administration of a **somatic cell therapy medicinal product** in the form of a solution for infusion, delivered via intravenous use.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to assess eligibility based on criteria such as age, viral infection/reactivation status, and absence of severe uncontrolled infections or organ damage. The inclusion criteria also require informed consent from the patient or their legal guardian. Follow-up visits will be scheduled to monitor the participants' health status, collect data on adverse events, and assess primary and secondary endpoints, including organ damage, overall survival, specific cell viral immunity, and variation of viremia. The end-of-study visit will conclude the trial, summarizing the findings and evaluating the overall safety and efficacy of the treatment.

Participant involvement is expected to last until the end of the trial, unless early termination is warranted due to conditions such as the development of severe adverse events, withdrawal of consent, or non-compliance with the study protocol. The primary endpoint focuses on the collection of adverse events, defined as significant alterations in vital signs or organ function, assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5. Secondary endpoints include the evaluation of organ damage, overall survival, specific cell viral immunity, and changes in viremia levels. The trial aims to provide valuable insights into the therapeutic potential of virus-specific T lymphocytes in managing resistant viral infections post-transplantation.

The clinical trial involves the administration of an **experimental medication** known as PTC: VS-TC, which is a **Somatic Cell Therapy Medicinal Product**. This investigational product is formulated as a **solution for infusion** and is administered via the **intravenous route**. The active substance, PTC:VS-TC, is a structurally diverse substance categorized under cell therapy, specifically involving T cells that secrete **interferon-gamma (IFN-γ)**. The product is not a pediatric formulation and is not classified as an orphan drug. The administration schedule, including dosage and frequency, is determined based on the study protocol, although specific dosing details are not provided in the available data.

In addition to the experimental treatment, the study may involve the use of standard-of-care therapies as deemed necessary by the clinical investigators. These therapies are not specified in the provided data but are typically used to manage the underlying condition or any adverse effects that may arise during the trial. The trial does not include a placebo or comparator treatment, focusing solely on the evaluation of the experimental therapy's safety and efficacy.

Participant compliance with the treatment regimen is monitored throughout the study to ensure adherence to the dosing schedule and to assess the treatment's impact on the targeted viral infections. The primary objective of the trial is to evaluate the safety of the virus-specific T lymphocytes selected in vitro from a family donor for the treatment of refractory viral infections such as **Adenovirus (ADV)**, **Epstein-Barr virus (EBV)**, **Cytomegalovirus (CMV)**, and **BK virus** in young patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Efficacy in this clinical trial will be assessed through several secondary endpoints, including organ damage, overall survival, specific cell viral immunity, and variation of **viremia**. These parameters will be measured and collected at predetermined intervals throughout the study duration. The trial will utilize validated clinical, hematochemical, and radiological findings to evaluate these endpoints. The specific methods and tools for measuring these parameters are aligned with the standards set by the Common Terminology Criteria for Adverse Events (CTCAE) version 5. The trial is designed to assess the efficacy of virus-specific T lymphocytes in treating refractory viral infections such as Adenovirus (ADV), Epstein-Barr virus (EBV), Cytomegalovirus (CMV), and BK virus in patients who have undergone allogeneic hematopoietic stem cell transplantation (HSCT). The study will continue until the estimated end date of July 24, 2025, with recruitment having started on September 28, 2022.