Clinical trial NCT03563053: Extension Treatment Using EryDex System in Patients With AT Who Participated in the ATTeST-IEDAT-02-2015 Study
Official title: Open-label, Long-term, Extension Treatment Using Intra-Erythrocyte Dexamethasone Sodium Phosphate (EryDex System) in Patients With Ataxia Telangiectasia Who Participated in the ATTeST-IEDAT-02-2015 Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Ataxia Telangiectasia
Genetic Syndrome
Keywords: Ataxia Telangiectasia
AT
EryDex system
Dexamethasone
Dexamethasone sodium phosphate
Lead sponsor: Quince Therapeutics S.p.A.
Sponsor class: INDUSTRY
First posted: 2018-06-20
Enrollment: 104
Sex: ALL
Minimum age (years): 6
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open-label, Long-term, Extension Treatment
Primary purpose: TREATMENT

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.

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).

Primary outcomes:
measure: Number of Treatment-Emergent Adverse Event (TEAE), Treatment-emergent Serious Adverse Events (TESAE), and Adverse Events of Special Interest (AESI) Throughout the Study
timeFrame: From Baseline (Visit 1 - Day 0) to Follow-up (~60 days after last infusion, i.e. up to 50.5 months)
Secondary outcomes:
measure: Change From Baseline in Quality of Life Using EQ-5D-5L Scale to Month 36
timeFrame: From Baseline (Visit 1- Day 0) to Month 36
measure: 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
timeFrame: From Baseline (Visit 1- Day 0) to Month 36
measure: 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
timeFrame: From Baseline (Visit 1- Day 0) to Month 36
measure: Change From Baseline of the Modified International Cooperative Ataxia Rating Scale (mICARS) Until Month 36
timeFrame: From Baseline (Visit 1- Day 0) to Month 36
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Ataxia Center and HD Center of Excellence - UCLA
state: California
city: Baltimore
country: United States
facility: Division of Pediatric Allergy and Immunology - Johns Hopkins Hospital
state: Maryland
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Houston
country: United States
facility: Department of Pediatrics Division of Child and Adolescent Neurology Mitochondrial Clinic - University of Texas Medical School
state: Texas
city: Parkville
country: Australia
facility: Department of Neurology Royal Children's Hospital
state: Victoria
city: Leuven
country: Belgium
facility: Laboratory of Pediatric Immunology UZ Leuven
city: Frankfurt
country: Germany
facility: Klinik für Kinder- und Jugendmedizin, Allergologie, pneumologie und Mukoviszidose, Universitätsklinikum Frankfurt
city: Chennai
country: India
facility: Vijaya Health Centre, Department of Neurology
state: Tamil Nadu
city: Bangalore
country: India
facility: National Institute of Mental Health and Neurosciences (NIMHANS) Department of Neurology
city: Hyderabad
country: India
facility: Nizam's Institute of Medical Sciences Department of Neurology
city: Mumbai
country: India
facility: Jaslok Hospital and Research Center Department of Pediatric Neurology
city: Roma
country: Italy
facility: Dipartimento Neuroscienze umane e salute mentale, Policlinico Umberto I Università La Sapienza
city: Oslo
country: Norway
facility: Norwegian National Unit for Newborn Screening, Division of Pediatric and Adolescent Medicine, Oslo University Hospital
city: Warsaw
country: Poland
facility: Department of Clinical Immunology - The Children's Memorial Health Institute
city: Madrid
country: Spain
facility: Servicio de Neurolgia Pediatrica, Hospital Materno-Infantil La Paz
city: Tunis
country: Tunisia
facility: Razi Hospital, Clinical Investigation Center-Neuroscience
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust - Queen's Medical Centre
state: Nottinghamshire
Study officials:
affiliation: EryDel S.p.A.
name: Guenter R Janhofer, MD, PhD
role: STUDY_DIRECTOR
References: