Safety and Feasibility of Autologous Cord Blood-Derived Mononuclear Cells in Neonatal Hypoxic-Ischemic Encephalopathy

The primary objective of this study is to evaluate the **safety** and feasibility of a curative treatment using autologous cord blood stem cells in patients with **neonatal hypoxic-ischaemic encephalopathy**. This objective is clinically relevant as it aims to establish a foundational understanding of the treatment's risk profile and practical application, which is crucial for advancing therapeutic options for this condition.

The secondary objectives are to assess the efficacy of this cell-based treatment in preventing neurologic sequelae and to determine the optimal timing for the administration of the cell preparation. These objectives are significant as they aim to enhance the therapeutic strategy by potentially reducing long-term neurological impairments and optimizing treatment protocols.

The clinical trial focuses on **neonatal hypoxic-ischaemic encephalopathy** and involves a study population comprising both male and female neonates. The trial includes a vulnerable population, specifically newborns, as indicated by the age range category code. The sponsor has not provided the total number of participants. Participants were selected based on specific criteria, including the presence of signs of encephalopathy within 6 hours of age, an abnormal electroencephalogram or aEEG within the same timeframe, and the requirement for therapeutic hypothermia. Additionally, maternal health considerations include the absence of infections such as VIH, HTLV 1 or 2, Hepatitis B or C, and a negative serology for syphilis. Written parental consent is also a prerequisite for participation. The trial 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** and feasibility of a curative treatment using **autologous cord blood-derived mononuclear cells** in neonates diagnosed with **neonatal hypoxic-ischaemic encephalopathy**. This study is structured as a Phase II, randomized, double-blind, controlled trial. The trial is expected to span from February 2020 to February 2028, with participant involvement lasting up to three years. The investigational product, a suspension for intravenous infusion, is administered with a maximum daily dose of 500 million colony-forming units per gram.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as signs of encephalopathy within six hours of birth, absence of maternal infections, and written parental consent. Follow-up visits will be scheduled to monitor the occurrence of clinical or paraclinical adverse events and assess the feasibility of the cell therapy procedure. The primary endpoints include the safety profile and the percentage of children for whom the procedure is completed according to quality criteria. Secondary endpoints focus on preliminary efficacy, measured by neurodevelopmental function until the age of two years.

The end-of-study visit will conclude the participant's involvement, evaluating long-term safety and efficacy outcomes. Conditions that may lead to early termination from the study include the occurrence of significant adverse events or failure to meet the quality criteria for the cell therapy procedure. The trial's design ensures rigorous monitoring and assessment to achieve its primary and secondary objectives, contributing valuable data to the field of neonatal care.

The clinical trial involves the administration of **autologous cord blood-derived mononuclear cells** as the experimental treatment. This investigational product is formulated as a **suspension for intravenous infusion**. The active substance, **autologous cord blood-derived mononuclear cells**, is a structurally diverse substance utilized in cell therapy. The product is administered intravenously, with a dosage of 50 million cells per kilogram of body weight. The maximum daily dose is set at 500 million cells, and the total dose should not exceed 100 million cells over the course of the treatment. The treatment period is limited to a maximum of three days. The product is not classified as a pediatric formulation, and it is not designated as an orphan drug.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are specified. The focus is solely on evaluating the safety and feasibility of the autologous cord blood-derived mononuclear cells in the context of treating neonatal hypoxic-ischemic encephalopathy. Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the protocol. The trial aims to provide insights into the potential therapeutic benefits of this cell-based treatment in a neonatal population.

Efficacy in this clinical trial will be assessed through the evaluation of **neurodevelopmental function** in children up to 2 years of age. This secondary endpoint aims to provide preliminary efficacy data on the use of autologous cord blood stem cells as a treatment for neonatal hypoxic-ischemic encephalopathy. The assessment of neurodevelopmental function will be conducted at specified intervals throughout the follow-up period, allowing for a comprehensive analysis of the treatment's impact on the developmental progress of the participants. The data collected will be analyzed to determine any significant improvements or changes in neurodevelopmental outcomes attributable to the intervention. The study will ensure that all assessments are conducted using standardized and validated methods to maintain the integrity and reliability of the efficacy data.