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

NCT ID: NCT03563053

Last Updated: 2024-10-08

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 104 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-12
• Study Completion Date: 2022-09-02

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).

Detailed Description

This was 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 ATTeST-IEDAT-02-2015 trial, completed the study assessments, do not present safety contraindication to continuation of treatment, and provided informed consent.

The study aimed to collect information on the long-term safety and efficacy of the trial treatment.

Patients meeting all selection criteria received monthly infusions of EDS-EP (dose range of ~14-22 mg DSP/infusion). If this dose of EDS-EP was not tolerated, the patient was discontinued from the study.

During the study, long-term efficacy assessments were performed every 6 months, while safety parameters were assessed at each monthly visit. The Schedule of Visits and assessments for the first 12 months were replicated for the second year onwards for patients who continued EryDex treatment beyond 12 months.

The analysis of the EryDex long-term safety and tolerability was based on the occurrence of Treatment-Emergent Adverse Events (TEAEs), including Serious AEs and discontinuations due to AEs. The long-term effect was measured by the "Modified" International Cooperative Ataxia Rating Scale, (mICARS), Rescored mICARS, Clinical Global Impression of severity and change (CGI-S/C) and health-related Quality of Life (QoL; EQ-5D-5L scale).

The ICARS, EQ-5D-5L and the CGI-C / S were administered by a properly qualified rater identified at each site who performed the ratings on the efficacy measures. The ICARS rater remained blinded to other assessments and did not have access to the safety data. The CGI rater did not have access to the ICARS ratings or safety data but was able to refer to other scales in scoring the CGI.

All patients enrolled in this study have participated in Study ATTeST-IEDAT-02-2015, and there was no de novo enrollment of new patients.

EryDel S.p.A (now Quince Therapeutics) decided to discontinue the IEDAT-03-2018 study in India due to the COVID-19 pandemic. On 13 Apr 2022, after the last patient completed one year of EryDex treatment, EryDel S.p.A. communicated the end of the open label extension study IEDAT-03-2018 and the stop of the EryDex treatment for patients in the context of this study.

Conditions

Ataxia Telangiectasia; Genetic Syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

active drug

\~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.

Group Type: EXPERIMENTAL

EryDex System

Intervention Type: 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.

Interventions

EryDex System

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.

Intervention Type: COMBINATION_PRODUCT

Eligibility Criteria

Inclusion Criteria

1. 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.

2. Patient tolerated the study medication, without any evidence of steroid adverse events, or treatment-related severe events / serious adverse events.

3. Body weight > 15 kg.

4. 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.

5. 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.

Exclusion Criteria

Patients who met one or more of the following criteria were not considered to be eligible to participate in the study:

General

1. Females that were:

1. Pregnant, or were breast-feeding (for EU countries only)

2. 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.

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

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

Medical History and Current Status

4. 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).

5. Current neoplastic disease.

6. Severe impairment of the immunological system.

7. Severe or unstable pulmonary disease.

8. Uncontrolled diabetes. Patients with diabetes that had been stabilized (i.e., no hypoglycemic or hyperglycemic episodes in the past 3 months) were 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 life-threatening morbidity, need for hospitalization, or mortality.

10. Eligibility of patients with abnormal laboratory test values were determined by the Investigator.

11. Confirmed haemoglobinopathies, e.g., haemoglobin C disease, sickle cell anaemia, 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 EryDex treatment administered in the ATTeST 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 were permitted.

15. Requires any other concomitant medication prohibited by the protocol.

16. Use of any drug that is a strong inducer / inhibitor of Cytochrome P450 3A4 (CYP3A4).

• Minimum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Quince Therapeutics S.p.A.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Guenter R Janhofer, MD, PhD

Role: STUDY_DIRECTOR

EryDel S.p.A.

Locations

Ataxia Center and HD Center of Excellence - UCLA

Los Angeles, California, United States

Division of Pediatric Allergy and Immunology - Johns Hopkins Hospital

Baltimore, Maryland, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

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

Houston, Texas, United States

Department of Neurology Royal Children's Hospital

Parkville, Victoria, Australia

Laboratory of Pediatric Immunology UZ Leuven

Leuven, , Belgium

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

Frankfurt, , Germany

Vijaya Health Centre, Department of Neurology

Chennai, Tamil Nadu, India

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

Bangalore, , India

Nizam's Institute of Medical Sciences Department of Neurology

Hyderabad, , India

Jaslok Hospital and Research Center Department of Pediatric Neurology

Mumbai, , India

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

Roma, , Italy

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

Oslo, , Norway

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

Warsaw, , Poland

Servicio de Neurolgia Pediatrica, Hospital Materno-Infantil La Paz

Madrid, , Spain

Razi Hospital, Clinical Investigation Center-Neuroscience

Tunis, , Tunisia

Nottingham University Hospitals NHS Trust - Queen's Medical Centre

Nottingham, Nottinghamshire, United Kingdom

Countries

United States; Australia; Belgium; Germany; India; Italy; Norway; Poland; Spain; Tunisia; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 39917433 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-000338-36

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

IEDAT-03-2018

Identifier Type: -

Identifier Source: org_study_id