Evaluation of Neurological Effects of Dexamethasone Sodium Phosphate Encapsulated in Autologous Erythrocytes in Pediatric Ataxia Telangiectasia: A Randomized, Double-Blind, Placebo-Controlled Trial

The primary objective of this multi-center, randomized, double-blind, placebo-controlled trial is to evaluate the effect of **EryDex** on central nervous system (CNS) symptoms in subjects with **Ataxia Telangiectasia** (A-T), specifically in the 6- to 9-year-old primary analysis population. This is measured by the change in the RmICARS score from baseline to Visit 9 (Day 168) compared to placebo. The clinical relevance of this objective lies in its potential to provide evidence for the efficacy of EryDex in alleviating neurological symptoms associated with A-T, a rare genetic disorder characterized by progressive neurological impairment.

Secondary objectives include:

• Evaluating the overall clinical effect of EryDex compared to placebo in the same population, based on the change in the Clinical Global Impression of Severity (CGI-S) from baseline to Visit 9 (Day 168).
• Assessing the Clinical Global Impression of Change (CGI-C) at Visit 9 (Day 168).

The clinical trial involves a total of **51 participants** diagnosed with **Ataxia Telangiectasia**. The study population includes both male and female subjects, aged between 6 to 9 years. Participants were selected based on specific clinical criteria, including documented neurological signs of Ataxia Telangiectasia and genetic confirmation of the condition. All subjects are required to have a body weight of at least 15 kg. The trial population is considered vulnerable, given the age range and the nature of the condition. Participants' general health status is characterized by their ability to walk autonomously or with periodic support, as indicated by an ICARS score for walking capacities between 0 and 4. Written informed consent was obtained from the subjects and their caregivers or legal representatives, with assent provided by the subjects where applicable. The trial does not specify any particular lifestyle considerations such as diet or physical activity.

The clinical trial is designed as a **randomized, double-blind, placebo-controlled** study to evaluate the neurological effects of EryDex on subjects with **Ataxia Telangiectasia**. The primary objective is to assess the effect of EryDex on central nervous system symptoms, measured by the change in the RmICARS score from baseline to Visit 9 (Day 168), compared to placebo in the primary analysis population of 6- to 9-year-old subjects. The trial is expected to commence recruitment on April 30, 2024, and conclude by July 31, 2025, with a maximum treatment period of 6 months.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as clinical diagnosis of Ataxia Telangiectasia, genetic confirmation, and a body weight of at least 15 kg. Following the screening, eligible participants will be randomized to receive either the investigational product, **Dexamethasone sodium phosphate** for encapsulation into autoerythrocytes, or a placebo. The investigational product is administered as a solution for infusion, with a maximum daily dose of 36.6 mg and a total dose of 136.8 mg over the treatment period.

Study visits will include baseline assessments, regular follow-up visits to monitor efficacy and safety, and an end-of-study visit. The primary efficacy endpoint will be evaluated at Visit 9 (Day 168), with secondary endpoints including the overall clinical effect based on CGI-S and CGI-C scores. Participants are expected to be involved in the study for the entire duration unless conditions arise that necessitate early termination, such as adverse events or withdrawal of consent.

The clinical trial involves the administration of **Dexamethasone sodium phosphate**, a **solution for infusion** specifically designed for encapsulation into autoerythrocytes. This experimental medication is administered **intravenously**. The maximum daily dose is 36.6 mg, with a total maximum dose of 136.8 mg over a treatment period of up to 6 months. The encapsulation process involves the use of the EryDex System, which includes several devices such as the Syringe Kit, EryKit_01, and Red Cell Loader. These devices facilitate the collection and processing of the patient's blood, allowing for the encapsulation of the active substance into the patient's erythrocytes. The process is supported by sterile, single-use solutions like Hypotonic Solution 1 and 2, and PIGPA Hypertonic Solution, which aid in the osmolarity adjustments necessary for the encapsulation process.

In addition to the experimental treatment, the study employs a **placebo** control, which is a **Sodium chloride 0.372% solution**. This solution serves as a comparator to evaluate the efficacy of the experimental treatment. The placebo is administered in a manner consistent with the experimental treatment to maintain the double-blind nature of the trial. The use of a placebo is critical in assessing the true effect of the experimental medication on the neurological symptoms of patients with Ataxia Telangiectasia.

The efficacy of the investigational product, EryDex, in subjects with **Ataxia Telangiectasia** will be assessed through a multi-center, randomized, double-blind, placebo-controlled trial. The primary efficacy endpoint is the evaluation of the effect of EryDex on central nervous system (CNS) symptoms, specifically measured by the change in the RmICARS (Revised International Cooperative Ataxia Rating Scale) score from baseline to Visit 9 (Day 168) compared to placebo. This assessment will focus on the primary analysis population, which includes subjects aged 6 to 9 years.

Secondary efficacy endpoints include the evaluation of the overall clinical effect of EryDex compared to placebo, based on the Clinical Global Impression-Severity (CGI-S) scale from baseline to Visit 9 (Day 168). Additionally, the Clinical Global Impression-Change (CGI-C) scale will be used to assess changes from baseline to the same visit. These efficacy parameters will be collected and analyzed at specified timepoints throughout the trial to determine the therapeutic impact of EryDex on the target population.