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 (OLE-IEDAT)

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.

Study Overview

• Status: Recruiting
• Conditions: Ataxia Telangiectasia
• Intervention / Treatment: Combination product: EryDex System

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Irene Maccabruni, BS; Phone Number: +393458415028; Email: irene.maccabruni@erydel.com

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3052
      • Completed
      • Department of Neurology Royal Children's Hospital
• Belgium
  • Leuven, Belgium, 3000
    • Completed
    • Laboratory of Pediatric Immunology UZ Leuven
• Germany
  • Frankfurt, Germany, 60590
    • Completed
    • Klinik für Kinder- und Jugendmedizin, Allergologie, pneumologie und Mukoviszidose, Universitätsklinikum Frankfurt
• India
  • Bangalore, India, 560 029
    • Completed
    • National Institute of Mental Health and Neurosciences (NIMHANS) Department of Neurology
  • Chennai, India, 600 026
    • Completed
    • Vijaya Health Centre Department of Neurology
  • Hyderabad, India, 500 082
    • Completed
    • Nizam's Institute of Medical Sciences Department of Neurology
  • Mumbai, India, 400 026
    • Completed
    • Jaslok Hospital and Research Center Department of Pediatric Neurology
  • Mumbai, India, 400016
    • Completed
    • P.D. Hinduja National Hospital and Medical Research Centre Department of Pediatric Neurology
  • New Delhi, India, 110 029
    • Completed
    • All India Institute of Medical Sciences Child Neurology Division Department of Pediatrics
• Italy
  • Roma, Italy
    • Recruiting
    • Dipartimento Neuroscienze umane e salute mentale, Policlinico Umberto I Università La Sapienza
    • Contact: Vincenzo Leuzzi, MD; Email: vincenzo.leuzzi@uniroma1.it
• Poland
  • Warsaw, Poland, 04-730
    • Completed
    • Department of Clinical Immunology - The Children's Memorial Health Institute
• Spain
  • Madrid, Spain, 28046
    • Completed
    • Servicio de Neurolgia Pediatrica, Hospital Materno-Infantil La Paz
• Tunisia
  • Tunis, Tunisia
    • Recruiting
    • Razi Hospital, Clinical Investigation Center-Neuroscience
    • Contact: Riadh Gouider, MD; Email: riadh.gouider@gnet.tn
• United States
  • California
    • Los Angeles, California, United States, 90095
      • Completed
      • Ataxia Center and HD Center of Excellence - UCLA
  • Maryland
    • Baltimore, Maryland, United States, 21287-3923
      • Completed
      • Division of Pediatric Allergy and Immunology - Johns Hopkins Hospital
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Completed
      • Cincinnati Children's Hospital Medical Center
  • Texas
    • Houston, Texas, United States, 77030
      • Completed
      • Department of Pediatrics Division of Child and Adolescent Neurology Mitochondrial Clinic - University of Texas Medical School

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

1. Females that are

   1. pregnant, or are breast-feeding (for EU countries only);
   2. 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.

2. A disability that may prevent the patient from completing all study requirements.

3. Current participation in a clinical study with another investigational drug.

   Medical History and Current Status

4. CD4+ lymphocytes count <400/mm3 (for patients 6 years of age) or <200/mm3 (for patients >6 years).
5. Current neoplastic disease.
6. Severe impairment of the immunological system.
7. Severe or unstable pulmonary disease.
8. Uncontrolled diabetes. Patients with diabetes that has been stabilized (i.e. no hypoglycemic or hyperglycemic episodes in the past 3 months) will be eligible.
9. 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.
10. Eligibility of patients with abnormal laboratory test values will be determined by the Investigator.
11. Confirmed hemoglobinopathies, e.g. hemoglobin C disease, sickle cell anemia, or thalassemia.
12. Moderate or severe renal and/or hepatic impairment.

13. 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

14. 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.
15. Requires any other concomitant medication prohibited by the protocol.
16. Use of any drug that is a strong inducer/inhibitor of CYP3A4.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: active drug; ~14-22 mg dexamethasone sodium phosphate (DSP)	Combination product: EryDex System; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Erydel
• Investigators: Study Director: Guenter R Janhofer, MD, EryDel S.p.A.

Study record dates

Study Major Dates

• Study Start (Actual): June 12, 2018
• Primary Completion (Anticipated): December 1, 2021
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: May 23, 2018
• First Submitted That Met QC Criteria: June 8, 2018
• First Posted (Actual): June 20, 2018

Study Record Updates

• Last Update Posted (Actual): August 9, 2021
• Last Update Submitted That Met QC Criteria: August 6, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Neurologic Manifestations; Genetic Diseases, Inborn; Dyskinesias; DNA Repair-Deficiency Disorders; Neurocutaneous Syndromes; Cerebellar Diseases; Primary Immunodeficiency Diseases; Spinocerebellar Ataxias; Ataxia; Telangiectasis; Cerebellar Ataxia; Ataxia Telangiectasia
• Other Study ID Numbers: IEDAT-03-2018

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No