Intra-Erythrocyte Dexamethasone Sodium Phosphate in Ataxia Telangiectasia Patients

NCT02770807 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: IEDAT-02-20152015-005241-31
• Study Type: interventional
• Target: 176
• Locations: 12 countries
• Sites: 22

Brief Summary

Objectives: The objective of study was to evaluate the safety and the efficacy of EryDex (Dexamethasone sodium phosphate encapsulated in autologous erythrocytes, using the EryDex System - EDS) at two dose levels (low dose and high dose DSP/infusion), compared to placebo, on Neurological Symptoms in Patients With Ataxia Telangiectasia. Initial Double-Blind Treatment Period (0 to 6 Months) Primary Efficacy Objective:

• Evaluate the effect of EryDex at two dose levels (low dose and high dose DSP/infusion), compared to placebo, on central nervous system (CNS) symptoms measured by the change in the Modified International Cooperative Ataxia Rating Scale (mICARS) from baseline to Month 6 (Visit 9) in patients with ataxia telangiectasia (A-T). Secondary Efficacy Objectives:
• Evaluate the effect of EryDex, compared to placebo, on the Clinical Global Impression of Change (CGI-C) in patients with A-T from baseline to Month 6 (Visit 9).
• Evaluate the effect of EryDex, compared to placebo, on measures of Clinical Global Impression of Severity (CGI-S; structured) in patients with A-T from baseline to Month 6 (Visit 9)
• Evaluate the effect of EryDex, compared to placebo, on measures of Adaptive behavior measures in patients with A-T by the Vineland Adaptive Behavior Scales (VABS) from baseline to Month 6 (Visit 9). Safety Objectives:
• Evaluate the safety and tolerability of two non-overlapping doses of EryDex, compared to placebo, in patients with A-T over the 12-month double-blind study duration. Extension Treatment Period (6-12 Months): Primary Objective:
• Evaluate the efficacy of EryDex at two dose levels (low dose and high dose DSP/infusion) compared to placebo, in treating CNS symptoms in A-T patients during longer-term treatment (up to 12 months), as measured by the mICARS. Secondary Objectives:
• Evaluate the longer-term (up to 12 months) safety and tolerability of EryDex in A-T patients.
• Compare the effects of EryDex on the CGI-C and CGI-S (structured), VABS, and QoL using the EQ-5D-5L scale.

Conditions

Nervous System Disease; Genetic Syndrome

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Modified International Cooperative Ataxia Rating Scale (mICARS)

  The International Cooperative Ataxia Rating Scale (ICARS) was an assessment of the degree of impairment in patients with cerebellar ataxia and was administered in its entirety; however, the primary efficacy assessment was based on the modified (m)ICARS, which excluded the Oculomotor domain (items 17 to 19) and items 8 to 12 of the Kinetic Functions domain of the ICARS. The mICARS was a 54 points maximum score (min 0) questionnaire divided into 3 sections: * Posture and Gait Disturbance section-7 items (min score 0, max score 34) * Kinetic Function-2 items (min score 0, max score 12) * Speech Disorder- 2 items (min score 0, max score 8). The assessment was designed to be completed within 30 minutes, and higher scores - both for total and subscores - indicate a higher level of disease impairment. The subscores are added to give the total score.

  to Month 6 (Visit 9)

Secondary Outcomes (5)

• Number of Patients With Improving, Stable or Worsening Score Using a Clinical Global Impression of Change (CGI-C)

  to Month 6 (Visit 9)

• 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

  to Visit 9 (Month 6)

• Change From Baseline of Vineland Adaptive Behavior Scale (VABS-II) Scores - Last Observation Carried Forward (LOCF)

  to Visit 9 (Month 6)

• Number of Patients With at Least One Treatment-Emergent Adverse Event (TEAE) at Month 6

  to Visit 9 (Month 6)

• Number of Patients With at Least One Treatment-Emergent Adverse Event (TEAE) at Month 12

  to Visit 15 (Month 12)

Study Arms (3)

EryDex Low Dose DSP

EXPERIMENTAL

EDS-EP dose range of \~5-10 mg DSP/infusion. This study treatment was to be administered by IV infusion once per month for 12 consecutive months (6 months Initial Treatment Period + 6 months Extension Treatment Period). Each patient underwent a 30-day Screening Period, during which any previous treatments with other corticosteroid compounds were withdrawn (washout from previous treatment). Other Names: EryDex System end product Low dose DSP

Drug: EryDex Low dose DSP

EryDex High Dose DSP

EXPERIMENTAL

EDS-EP dose range of \~14-22 mg DSP/infusion. This study treatment was to be administered by IV infusion once per month for 12 consecutive months (6 months Initial Treatment Period + 6 months Extension Treatment Period). Each patient underwent a 30-day Screening Period, during which any previous treatments with other corticosteroid compounds were withdrawn (washout from previous treatment). Other Names: EryDex System end product High dose DSP

Drug: EryDex High dose DSP

Placebo

PLACEBO COMPARATOR

Patients were treated with autologous erythrocytes prepared with the EDS process using a placebo solution. Placebo was to be administered by IV infusion once per month for 12 consecutive months (6 months Initial Treatment Period + 6 months Extension Treatment Period). Each patient underwent a 30-day Screening Period, during which any previous treatments with other corticosteroid compounds were withdrawn (washout from previous treatment).

Drug: Pooled Placebo

Interventions

EryDex Low dose DSP DRUG

EDS-EP dose range of \~5-10 mg DSP/infusion

Also known as: EryDex System end product

EryDex Low Dose DSP

EryDex High dose DSP DRUG

EDS-EP dose range of \~14-22 mg DSP/infusion

Also known as: EryDex System end product

EryDex High Dose DSP

Pooled Placebo DRUG

EDS processed autologous erythrocytes using a sodium chloride \[NaCl\] solution.

Also known as: Placebo EDS infusion

Placebo

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 met clinical criteria for diagnosis of A-T. The neurological signs of A-T (incoordination of the head and eyes in lateral gaze deflection, gait ataxia associated with an inappropriately narrow base) must have been documented. Such signs of A-T illustrated the body systems in which changes were confirmed, but the listed changes were examples and other changes in those systems may have been observed and documented to confirm the diagnosis of A-T.
• Patient was in autonomous gait or was helped by periodic use of a support (i.e., score for Item 1 of the full ICARS - Walking Capacities between 0 and 4, included).
• Patient was investigated for the proven genetic diagnosis of A-T (prior documentation or by central laboratory test report).
• Patient was at least 6 years of age.
• Body weight was \>15 kg.
• The patient and 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 must have provided assent to participate in the study.

You may not qualify if:

• General
• Females that were:
• Pregnant or breast-feeding (for European Union \[EU\] countries only).
• Of childbearing potential, pregnant, or breast-feeding (for US and Rest of World countries) not using adequate birth control, as determined by their Healthcare Provider.
• A disability that may have prevented the patient from completing all study requirements.
• Current participation in another clinical study.
• 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 increased to \<200/mm3 (for patients \>6 years).
• Loss/removal of 250 mL or more of blood within the past 4 weeks prior to screening.
• Current neoplastic disease or previous neoplastic disease not in remission for at least 2 years.
• History of severe impairment of the immunological system.
• Severe or unstable pulmonary disease.
• Uncontrolled diabetes.
• Any other severe, unstable, or serious disease or condition that in the Investigator's opinion put the patient at risk for imminent life-threatening morbidity, need for hospitalization, or mortality.
• Any clinically significant abnormality on standard laboratory examinations (hematology, biochemistry, urinalysis) at screening that remains abnormal on repeat testing. Eligibility of patients with abnormal laboratory test values was determined by the Investigator in consultation with the Medical Monitor.

Sponsors & Collaborators

• Quince Therapeutics S.p.A.: lead

Study Sites (22)

UCLA-Ataxia Center and HD Center of Exellence

Los Angeles, California, 900951694, United States

Location

The Ataxia-Telangiectasia Clinical Center, The Johns Hopkins Hospital

Baltimore, Maryland, 21287-3923, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

UT Health

Houston, Texas, 77030, United States

Location

Royal Children's Hospital

Melbourne, Victoria, 3052, Australia

Location

Laboratoriumgeneeskunde

Leuven, 3000, Belgium

Location

Klinik für Kinder- und Jugendmedizin Pädiatrische Allergologie, Pneumologie und Mukoviszidose, Universitätsklinikum Frankfurt

Frankfurt am Main, Hesse, 60590, Germany

Location

National Institute of Mental Health and Neurosciences

Bangalore, Karnataka, 560 029, India

Location

Amrita Institute of Medical Sciences and Research Centre

Kochi, Kerala, 682041, India

Location

Jaslok Hospital and Research Centre

Mumbai, Maharashtra, 400026, India

Location

PD Hinduja National Hospital and Medical Research

Mahīm, Mumbai, 400016, India

Location

Vijaya Health Centre, Department of Neurology

Chennai, Tamil Nadu, 600026, India

Location

Nizam's Institute of Medical Sciences

Hyderabad, Telangana, 500082, India

Location

All India Institute of Medical Sciences

New Delhi, 110029, India

Location

Sheba Medical Center

Tel Litwinsky, 52621, Israel

Location

U.O. Neurologia e Psichiatria dell'Infanzia e dell' Adolescenza. ASST Spedali Civili, Piazzale Spedali Civili, 1

Brescia, 25123, Italy

Location

Dipartimento di Pediatria e Neuropsichiatria Infantile, Università Sapienza di Roma, Azienda Policlinico Universitario Umberto I

Rome, 00185, 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

Hospital Universitario La Paz.

Madrid, Spain

Location

El Razi Hospital

Manouba, 2010, Tunisia

Location

Nottingham University Hospitals NHS Trust - Queen's Medical Centre

Nottingham, Nottinghamshire, United Kingdom

Location

Related Publications (2)

• 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

• Zielen S, Crawford T, Benatti L, Magnani M, Kieslich M, Ryan M, Meyts I, Gulati S, Borgohain R, Yadav R, Pal P, Hegde A, Kumar S, Venkateswar A, Udani V, Vinayan KP, Nissenkorn A, Fazzi E, Leuzzi V, Stray-Pedersen A, Pietrucha B, Pascual SI, Gouider R, Koenig MK, Wu S, Perlman S, Thye D, Janhofer G, Horn B, Whitehouse W, Lederman H. Safety and efficacy of intra-erythrocyte dexamethasone sodium phosphate in children with ataxia telangiectasia (ATTeST): a multicentre, randomised, double-blind, placebo-controlled phase 3 trial. Lancet Neurol. 2024 Sep;23(9):871-882. doi: 10.1016/S1474-4422(24)00220-5.

  PMID: 39152028 DERIVED

MeSH Terms

Conditions

Nervous System Diseases; Genetic Diseases, Inborn

Condition Hierarchy (Ancestors)

Congenital, Hereditary, and Neonatal Diseases and Abnormalities

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: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The Sponsor, Investigator, site staff, and patients were not aware of the treatment assignments.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 2, 2016
• First Posted: May 12, 2016
• Study Start: March 2, 2017
• Primary Completion: May 13, 2021
• Study Completion: May 13, 2021
• Last Updated: May 10, 2024
• Results First Posted: May 9, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1); BE (1); IN (7); TU (1); DE (1); NO (1); US (4); GB (1); ES (1); PL (1); IT (2); IL (1)