Open-label, Long-term, Extension Treatment Using Intra-Erythrocyte Dexamethasone Sodium Phosphate in Patients With Ataxia Telangiectasia Who Participated in the IEDAT-02-2015 Study

Study Overview
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Brief Summary
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This is an international (North America, Europe, Africa, Asia and Australia), multi-center, prospective, open-label treatment study, designed to continue to provide the study medication to all patients who completed 12 months of treatment (including those treated with placebo) in the IEDAT-02-2015 trial, completed the study assessments, do not present safety contraindication to continuation of treatment, and provided informed consent. The study aims to collect information on the long-term safety and efficacy of the trial treatment.

Detailed Description
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This is an international (North America, Europe, Africa, Asia and Australia), multi-center, prospective, open-label treatment study, designed to continue to provide the study medication to all patients who completed 12 months of treatment (including those treated with placebo) in the IEDAT-02-2015 trial, completed the study assessments, do not present safety contraindication to continuation of treatment, and provided informed consent. The study aims to collect information on the long-term safety and efficacy of the trial treatment. Patients meeting all selection criteria will receive monthly infusions of EDS-EP (dose range of  14-22 mg DSP/infusion). If this dose of EDS-EP is not tolerated, the patient should be discontinued from the study. During the study, long-term efficacy assessments will be performed every 6 months, while safety parameters will be assessed at each monthly visit. The ICARS, EQ-5D-5L and the CGI-C/S will be administered by a site rater. All patients enrolled in this study will have participated in Study IEDAT-02-2015, and there will be no de novo enrollment of new patients. The Principal Investigator will ask all patients who meet the above requirements, and determine their interest in continuing to receive treatment with the study medication in a new protocol. The Principal Investigator will then determine the eligibility of the patients on the basis of his/her clinical judgement of patients' status and their safety.

Official Title
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Open-label, Long-term, Extension Treatment Using Intra-Erythrocyte Dexamethasone Sodium Phosphate in Patients With Ataxia Telangiectasia Who Participated in the IEDAT-02-2015 Study

Conditions
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Ataxia Telangiectasia

Intervention / Treatment
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* Combination Product: EryDex System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient completed the double-blind period in the IEDAT-02-2015 trial and must have completed the final (Visit 15/Month 12) efficacy assessments of IEDAT-02-2015. Patient tolerated the study medication, without any evidence of steroid adverse events, or treatment-related severe/ serious adverse events Body weight > 15 kg. The patient and his/her parent/caregiver (if below the age of consent), or a legal representative, has provided written informed consent to participate. If consent is provided solely by the caregiver in accordance with local regulations, the patient must provide assent to participate in the study Patient does not present safety contraindication for continuation of treatment, as determined by the Principal Investigator (PI) according to the procedures described below. Procedure for selecting patients for further treatment in IEDAT-03-2018: The Principal Investigator will ask all patients who meet the above requirements, and determine their interest in continuing to receive treatment with the study medication in a new protocol. The Principal Investigator will then determine the eligibility of the patients on the basis of his/her clinical judgement of patients' status and their safety. Exclusion Criteria: General Females that are pregnant, or are breast-feeding (for EU countries only); of childbearing potential, pregnant, or are breast-feeding (for US and Rest of World countries). Females of childbearing potential using adequate birth control, as determined by their Health Care Provider, will be eligible. A disability that may prevent the patient from completing all study requirements. Current participation in a clinical study with another investigational drug. Medical History and Current Status CD4+ lymphocytes count <400/mm3 (for patients 6 years of age) or <200/mm3 (for patients >6 years). Current neoplastic disease. Severe impairment of the immunological system. Severe or unstable pulmonary disease. Uncontrolled diabetes. Patients with diabetes that has been stabilized (i.e. no hypoglycemic or hyperglycemic episodes in the past 3 months) will be eligible. Any other severe, unstable, or serious disease or condition that in the Investigator's opinion would put the patient at risk for imminent lifethreatening morbidity, need for hospitalization, or mortality. Eligibility of patients with abnormal laboratory test values will be determined by the Investigator. Confirmed hemoglobinopathies, e.g. hemoglobin C disease, sickle cell anemia, or thalassemia. Moderate or severe renal and/or hepatic impairment. Patients who experienced moderate/ severe steroid side effects, or moderate/ severe adverse events associated with the study medication administered in the IEDAT-02 study. Prior/Concomitant Medication Requires treatment with an oral or parenteral steroid. Treatment with inhaled or intranasal steroids for asthma or allergies, as well as use of topical steroids will be permitted. Requires any other concomitant medication prohibited by the protocol. Use of any drug that is a strong inducer/inhibitor of CYP3A4.

Ages Eligible for Study
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Minimum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Open-label, Long-term, Extension Treatment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: active drug<br> 14-22 mg dexamethasone sodium phosphate (DSP) | Combination Product: EryDex System<br>* EryDex System is a combination product that is used to load dexamethasone sodium phosphate (DSP) into autologous erythrocytes (EDS) creating the EDS-end product which is infused into the patients<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long term safety/tolerability of EDS-EP: # of pts with treatment related Adverse Events (CTCAE4.0) | AEs will be listed and summarized by body system and preferred term. Incidence of AEs(%),intensity and relatedness to study drug will be reported. SAEs and events newly occurring or worsening after administration of study medication will be summarized. AEs that result in death/discontinuation of the study medication will be listed separately | 1 year | 
| Long term safety/tolerability of EDS-EP: lab parameters according to clinical practice such as hematology, biochemistry, urinalysis, HbA1c (haemoglobin A1c or glycated haemoglobin test), CD4+ lymphocytes count, CRP (C reactive protein) | Values will be listed and summarized as normal or abnormal, according to local normal ranges, depending on the lab assessment (not possible to provide unique range and unit of measure due to changes from lab to lab). Abnormal and clinically notable values will be identified and listed for each parameter | 1 year | 
| Long term safety/tolerability of EDS-EP: 12-lead ECG (Electrocardiography) | Results will be listed and summarized as normal or abnormal, according guidelines (PR interval: < 100 msec or > 210 msec; QRS interval: < 50 msec or > 120 msec; QTc interval: > 450 msec; Heart rate: < 50 bpm (sinus bradycardia) or > 120 bpm (sinus tachycardia); Morphology: presence of T-wave inversion, abnormal R-waves, pathological Q-waves, significant ST elevation or depression). Abnormal and clinically notable values will be identified and listed | 1 year | 
| Long term safety/tolerability of EDS-EP: physical and neurological exam | Results will be listed and summarized as normal or abnormal, according to local assessment. Examination includes general appearance,skin,neck(including thyroid),eyes/ears,nose,mouth,throat,lungs,heart, abdomen,back,lymphnodes,extremities,nervous system. Abnormal and clinically notable values will be identified and listed for each parameter | 1 year | 
| Long term safety/tolerability of EDS-EP: Columbia Suicide Severity Rating Scale (CSSRS) | Outcome will be listed and summarized on the basis of the answers: answer of yes to any of the 6 questions may indicate a need for referral to a trained mental health professional and an answer of yes to questions 4, 5 or 6 indicate high-risk | 1 year | 
| Long term safety/tolerability of EDS-EP: Bone Mineral Density | Z-scores will be listed and summarized as normal or abnormal, following guidelines provided in the 2013 International Society for Clinical Densitometry Official Pediatric Position. Abnormal and clinically notable values will be identified and listed for each parameter | 1 year | 
| Long term safety/tolerability of EDS-EP: Tanner staging | The results (stages from I to V, according to the age, from 0 to 18) will be listed and summarized. Abnormal and clinically notable values will be identified and listed for each parameter | 1 year | 
| Long term safety/tolerability of EDS-EP: sterility test | Outcome can be Positive or negative. Results will be listed and summarized | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate the long-term effect of EDS-EP on health related Quality of Life (EQ-5D-5L scale: EuroQol 5 dimension 5 level scale) | Descriptive analyses will be performed to evaluate the long-term effects of EDS-EP on health-related Quality of Life (QoL), assessed by EQ-5D-5L scale. EQ-5D-5L descriptive system scoring: from 5, min/worst, to 25, best/max); EQ-VAS (EQ Visual Analogue scale) scoring: from 0, min/worst, to 100, best/max | 1 year |