Open-Label Extension Study of Dexamethasone Sodium Phosphate in Patients with Ataxia Telangiectasia Following IEDAT-04-2022 Participation

The primary objective of this study is to evaluate the **safety** and tolerability of EryDex in patients with **Ataxia Telangiectasia (A-T)**. This is clinically relevant as it aims to ensure that the treatment does not pose undue risk to patients, which is crucial for its potential use in managing this rare genetic disorder. Additionally, the study seeks to explore the effect of EryDex on neurological symptoms in patients with A-T, which could provide insights into its therapeutic benefits beyond safety.

The clinical trial involves a total of **57 participants** diagnosed with **Ataxia Telangiectasia (A-T)**. The study population includes both male and female subjects, with an age range encompassing children and adolescents. Participants were selected based on their completion of the IEDAT-04-2022 study, including final efficacy assessments, and must not present any safety contraindications for the continuation of treatment as determined by the investigator. Additionally, participants are required to have a body weight of at least 15 kg. The trial population includes a vulnerable group, reflecting the specific needs and considerations of individuals with A-T. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed as an open-label extension study to evaluate the **safety** and tolerability of EryDex in patients with **Ataxia Telangiectasia** (A-T) who have previously participated in the IEDAT-04-2022 study. The trial aims to assess the effect of EryDex on neurological symptoms in these patients. The study is a Phase III trial, which is not categorized as low intervention. The trial is expected to commence recruitment on November 4, 2024, and conclude by October 31, 2026. Participants will receive **dexamethasone sodium phosphate** encapsulated into autologous erythrocytes, administered as a solution for infusion.

Participants eligible for this study must have completed the IEDAT-04-2022 study, including final efficacy assessments, and must not present any safety contraindications for continued treatment. Additionally, participants must have a body weight of at least 15 kg. The primary endpoint of the study is the evaluation of safety and tolerability, which will be assessed through treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), discontinuations due to adverse events, and changes in vital signs, laboratory parameters, and physical and neurological examination findings. The Columbia Suicide Severity Rating Scale (C-SSRS) will also be utilized.

The trial involves a sequence of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on the criteria mentioned. Follow-up visits will be scheduled to monitor the safety and efficacy of the treatment, with assessments conducted at each visit. The end-of-study visit will mark the conclusion of the participant's involvement, where final evaluations will be performed. The expected length of participant involvement is up to 12 months, corresponding to the maximum treatment period. Conditions that may lead to early termination from the study include the occurrence of significant adverse events or any safety concerns as determined by the investigator.

The clinical trial involves the use of **Dexamethasone sodium phosphate** for encapsulation into autoerythrocytes. This experimental medication is provided in the form of a **solution for infusion**. The active substance, **dexamethasone sodium phosphate**, is administered intravenously. The maximum daily dose is 36.6 mg, with a total maximum dose of 273.6 mg over a treatment period of up to 12 months. The medication is encapsulated ex-vivo into human autologous erythrocytes, which are then reintroduced into the patient. This process is facilitated by the EryDex system, which includes several devices to ensure proper encapsulation and administration.

The EryDex system utilizes a series of devices, including the Red Cell Loader, which is a non-invasive active device equipped with a centrifuge unit, pumps, and a shaker/heater table. It automates the encapsulation process without direct contact with the subject's blood. The system also employs Hypotonic Solutions 1 and 2 to temporarily reduce the osmolarity of red blood cells, enabling the passive diffusion of the active substance. The PIGPA Hypertonic Solution is used to restore physiological osmolarity and maintain the encapsulation of the active substance within the red blood cells. Additionally, the Syringe Kit, a sterile single-use device, facilitates the collection and processing of patient blood.

No non-experimental treatments, such as standard-of-care therapy, placebo, or comparator treatments, are specified in this study. Participant compliance is monitored through the controlled administration of the encapsulated medication and the use of the EryDex system, ensuring adherence to the dosing schedule and treatment protocol. The trial aims to evaluate the safety and tolerability of the EryDex system in patients with Ataxia Telangiectasia, as well as its effects on neurological symptoms associated with the condition.

Efficacy in this clinical trial will be assessed through the evaluation of the effect of EryDex on neurological symptoms in patients with **Ataxia Telangiectasia**. The trial is designed as an open-label extension study following participation in a previous study, IEDAT-04-2022 (NEAT). The primary endpoint focuses on safety and tolerability, with efficacy being an exploratory objective. The assessment of efficacy will involve monitoring changes in neurological symptoms, although specific scales or measurement tools are not detailed in the provided data. The trial will utilize Dexamethasone sodium phosphate for ex-vivo encapsulation into human autologous erythrocytes, administered as a solution for infusion. The maximum treatment period is set at 12 months. The study will employ various devices, such as the Red Cell Loader and EryKit_01, to facilitate the encapsulation process, ensuring the precise administration of the investigational product. The trial is categorized as a Phase III clinical trial, with an estimated end date of October 31, 2026.