Extension Treatment Using EryDex System in Patients With AT Who Participated in the ATTeST-IEDAT-02-2015 Study

NCT03563053 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: IEDAT-03-20182018-000338-36
• Study Type: interventional
• Target: 104
• Locations: 11 countries
• Sites: 17

Brief Summary

Primary Objective To monitor and evaluate the long-term safety and tolerability of EDS-EP in AT patients. Secondary Objective To evaluate the long-term effect of EDS-EP on health-related Quality of Life (QoL; EQ-5D-5L scale). Exploratory Objective: To evaluate the long-term effect of EDS-EP in treating central nervous system (CNS) symptoms, as measured by the "Modified" International Cooperative Ataxia Rating Scale (mICARS), and Clinical Global Impression of severity and change (CGI-S/C).

Conditions

Ataxia Telangiectasia; Genetic Syndrome

Keywords

Ataxia Telangiectasia; AT; EryDex system; Dexamethasone; Dexamethasone sodium phosphate

Outcome Measures

Primary Outcomes (1)

• Number of Treatment-Emergent Adverse Event (TEAE), Treatment-emergent Serious Adverse Events (TESAE), and Adverse Events of Special Interest (AESI) Throughout the Study

  Assessment of TEAEs, treatment-emergent serious adverse events (TESAE), and adverse events of special interest (AESI) were performed throughout the study, from the time of signing of the ICF at Baseline Visit through to the Final Study Visit (Month 12 or early discontinuation). All patients were to be followed up through 30 days after the Final Visit (Month 12 or early discontinuation) or at least 60 days after the final infusion, whichever was longer.

  From Baseline (Visit 1 - Day 0) to Follow-up (~60 days after last infusion, i.e. up to 50.5 months)

Secondary Outcomes (4)

• Change From Baseline in Quality of Life Using EQ-5D-5L Scale to Month 36

  From Baseline (Visit 1- Day 0) to Month 36

• Number of Patients With Improving, Stable or Worsening Score Using a Clinical Global Impression of Change (CGI-C) From Baseline (Visit 1- Day 0) to Month 36

  From Baseline (Visit 1- Day 0) to Month 36

• Number of Patients With None to Severe (0 to 4) Scores in Clinical Global Impression of Severity (CGI-S)-Structured of Neurological Symptoms of AT From Baseline (Visit 1 - Day 0) to Month 36

  From Baseline (Visit 1- Day 0) to Month 36

• Change From Baseline of the Modified International Cooperative Ataxia Rating Scale (mICARS) Until Month 36

  From Baseline (Visit 1- Day 0) to Month 36

Study Arms (1)

active drug

EXPERIMENTAL

\~14-22 mg dexamethasone sodium phosphate (DSP) for 12 months. The duration of EryDex treatment could be extended further and continue until patients eventually withdrew consent, or the Investigator decided to discontinue treatment based on a risk / benefit assessment.

Combination Product: EryDex System

Interventions

EryDex System COMBINATION_PRODUCT

EryDex System was a combination product that was used to load dexamethasone sodium phosphate (DSP) into autologous erythrocytes (EDS) creating the EDS-end product which was infused into the patients. EryDex treatment consisted of a dose range correspondent to the ATTeST High Dose (obtained by loading 125 mg of DSP to the EryDex process and that, in the ATTeST, resulted in a mean of 17.4 ± 5.4 mg (mean ± standard deviation) of DSP infused to patients) administered via ex vivo encapsulation into EDS that were infused into the patient with A-T. The dose of EryDex treatment was selected to allow collection of long-term safety data on the dose of erythrocyte encapsulated DSP that was considered more effective among the two different doses that were employed in the ATTeST study, based on the analysis of the ATTeST blinded, Phase 3 study data.

active drug

Eligibility Criteria

• Age: 6 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient completed the double-blind period in the ATTeST study and completed the final (Visit 15 / Month 12) Efficacy Assessments of ATTeST or discontinued the study during the COVID-19 pandemic.
• Patient tolerated the study medication, without any evidence of steroid adverse events, or treatment-related severe events / serious adverse events.
• Body weight \> 15 kg.
• The patient and his / her parent / caregiver (if below the age of consent), or a legal representative, provided written informed consent to participate. If consent was provided solely by the caregiver in accordance with local regulations, the patient also was asked to provide their assent to participate in the study.
• Patient did not present safety contraindication for continuation of treatment, as determined by the Principal Investigator (PI) according to the procedures described below.
• Moreover, patients who were discontinued from the ATTeST study during the COVID-19 pandemic were eligible to receive the EryDex treatment in the IEDAT-03-2018 study, in the absence of safety contraindications to continuation of the treatment, and after signing the informed consent.
• There were no de novo enrolled patients.

You may not qualify if:

• Patients who met one or more of the following criteria were not considered to be eligible to participate in the study:
• General
• Females that were:
• Pregnant, or were breast-feeding (for EU countries only)
• Of childbearing potential, pregnant, or were breast-feeding (for US and Rest of World countries).
• Females of childbearing potential using adequate birth control, as determined by their Health Care Provider, were eligible.
• A disability that may prevent the patient from completing all study requirements.
• Current participation in another clinical study with another investigational drug.
• Medical History and Current Status
• Cluster differential 4 positive (CD4+) lymphocytes count \< 400 / mm3 (for patients 6 years of age) or \< 150 / mm3 (for patients \> 6 years). In presence of oral infections, like oral candidiasis, documented at the screening or recurrent as per medical history documentation, the limit increases to \< 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 had been stabilized (i.e., no hypoglycemic or hyperglycemic episodes in the past 3 months) were eligible.
• Any other severe, unstable, or serious disease or condition that in the Investigator's opinion would put the patient at risk for imminent life-threatening morbidity, need for hospitalization, or mortality.

Sponsors & Collaborators

• Quince Therapeutics S.p.A.: lead

Study Sites (17)

Ataxia Center and HD Center of Excellence - UCLA

Los Angeles, California, 90095, United States

Location

Division of Pediatric Allergy and Immunology - Johns Hopkins Hospital

Baltimore, Maryland, 21287-3923, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Department of Pediatrics Division of Child and Adolescent Neurology Mitochondrial Clinic - University of Texas Medical School

Houston, Texas, 77030, United States

Location

Department of Neurology Royal Children's Hospital

Parkville, Victoria, 3052, Australia

Location

Laboratory of Pediatric Immunology UZ Leuven

Leuven, 3000, Belgium

Location

Klinik für Kinder- und Jugendmedizin, Allergologie, pneumologie und Mukoviszidose, Universitätsklinikum Frankfurt

Frankfurt, 60590, Germany

Location

Vijaya Health Centre, Department of Neurology

Chennai, Tamil Nadu, India

Location

National Institute of Mental Health and Neurosciences (NIMHANS) Department of Neurology

Bangalore, 560 029, India

Location

Nizam's Institute of Medical Sciences Department of Neurology

Hyderabad, 500 082, India

Location

Jaslok Hospital and Research Center Department of Pediatric Neurology

Mumbai, 400 026, India

Location

Dipartimento Neuroscienze umane e salute mentale, Policlinico Umberto I Università La Sapienza

Roma, Italy

Location

Norwegian National Unit for Newborn Screening, Division of Pediatric and Adolescent Medicine, Oslo University Hospital

Oslo, Norway

Location

Department of Clinical Immunology - The Children's Memorial Health Institute

Warsaw, 04-730, Poland

Location

Servicio de Neurolgia Pediatrica, Hospital Materno-Infantil La Paz

Madrid, 28046, Spain

Location

Razi Hospital, Clinical Investigation Center-Neuroscience

Tunis, Tunisia

Location

Nottingham University Hospitals NHS Trust - Queen's Medical Centre

Nottingham, Nottinghamshire, United Kingdom

Location

Related Publications (1)

• Koenig MK, Leuzzi V, Gouider R, Yiu EM, Pietrucha B, Stray-Pedersen A, Perlman SL, Wu S, Burgers T, Borgohain R, Kandadai RM, Meyts I, Bucciol G, Udwadia-Hegde A, Yadav R, Roberts D, Dane A, Roden M, Thye D, Horn B, Lederman HM, Whitehouse WP. Long-term safety of dexamethasone sodium phosphate encapsulated in autologous erythrocytes in pediatric patients with ataxia telangiectasia. Front Neurol. 2025 Jan 23;15:1526914. doi: 10.3389/fneur.2024.1526914. eCollection 2024.

  PMID: 39917433 DERIVED

MeSH Terms

Conditions

Ataxia Telangiectasia; Genetic Diseases, Inborn

Condition Hierarchy (Ancestors)

Spinocerebellar Ataxias; Cerebellar Ataxia; Cerebellar Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocutaneous Syndromes; Ataxia; Dyskinesias; Neurologic Manifestations; Telangiectasis; Vascular Diseases; Cardiovascular Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Primary Immunodeficiency Diseases; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Limitations and Caveats

India was particularly affected by COVID-19-dependent treatment and visit interruptions.This long interruption would have resulted in insufficient long-term safety data. For this reason, EryDel (now Quince Therapeutics) decided to discontinue the IEDAT-03-2018 study in India.

Results Point of Contact

• Title: Irene Maccabruni, M.Sc.
• Organization: Quince Therapeutics (former Erydel SpA)

imaccabruni@quincetx.com

+39 02 36504470

Study Officials

• Guenter R Janhofer, MD, PhD

  EryDel S.p.A.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Masking Details: It's a open label extension study, so no blinding was applicable.
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open-label, Long-term, Extension Treatment

Study Record Dates

• First Submitted: May 23, 2018
• First Posted: June 20, 2018
• Study Start: June 12, 2018
• Primary Completion: September 2, 2022
• Study Completion: September 2, 2022
• Last Updated: October 8, 2024
• Results First Posted: October 8, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); AU (1); ES (1); TU (1); IN (4); DE (1); IT (1); PL (1); BE (1); GB (1); NO (1)