Intra-Erythrocyte Dexamethasone Sodium Phosphate in Ataxia Teleangiectasia Patients (IEDAT-01)

Evaluations of Effects of Intra-Erythrocyte Dexamethasone Sodium Phosphate on Neurological Symptoms in Ataxia Teleangiectasia Patients

The study has the aim to evaluate the improvement in CNS symptoms measured by International Co-operative Ataxia Rating Scale (ICARS) in patients with ataxia teleangectasia (AT), during a period of treatment with ERY-DEX (dexamethasone sodium phosphate ex vivo encapsulated into human autologous erythrocytes).

Study Overview

• Status: Completed
• Conditions: Genetic Syndrome; Nervous System Disorder
• Intervention / Treatment: Drug: Dexamethasone

Detailed Description

This is a multi-centre, single arm, open label, 6 months, phase II study to evaluate the effect of ERY-DEX in improving Central Nervous System (CNS) symptoms in patients with Ataxia Teleangectasia (AT). The study consists of a screening period (max duration of 30 days) and a treatment period (duration 6 months).

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Brescia, Italy, 25123
    • Spedali Civili
  • Rome, Italy, 00185
    • University La Sapienza

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• neurological signs of AT
• patients in autonomous gait or helped by a support
• proven molecular diagnosis of AT
• Males and females aged > 3 years
• Body weight >15 kg
• Plasma levels of Lymphocytes CD4+/mm3 > 500 (for patients aged 3-6 years) or > 200 (older than 6 years)
• written IC to participate.

Exclusion Criteria:

• Current or previous neoplastic disease
• History of severe impairment of the immunological system
• Chronic conditions representing a contraindication to the use of steroid drugs
• Non compliance with the study request
• Any previous steroid assumption within 30 days before starting ERY-DEX
• Have any other significant disease that in the Investigator's opinion would exclude the patient from the trial
• Females of childbearing potential who were pregnant, breast-feeding or were not using adequate contraceptive methods

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: ERY-DEX; Patients treated with monthly treatment of ERY-DEX (dexamethasone sodium phosphate encapsulated in autologous erythrocytes)

Drug: Dexamethasone; Dexamethasone sodium phosphate (2 vials, 250 mg/10 ml each) to be administered via encapsulation into autologous erythrocytes (ERY-DEX system). Final amount administered to the patient: about 10-15 mg of dexamethasone sodium phosphate, encapsulated into autologous blood (2 vials of 250 mg each of dexamethasone sodium phosphate will be used in the ex vivo process together with 50 ml of blood previously taken from the same patient). The treatment has to be repeated at intervals of 30 days (±10 days); Other Names: Dexamethasone sodium phosphate; Dex 21P

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in Neurological Symptoms Assessed by Using International Cooperative Ataxia Rating Scale (ICARS) Score - ITT Population	ICARS ia a 100-point semiquantitative scale, which goes from 0 to 100, offering a compartimentalised quantification of 4 subscores: Posture and Gait Disturbances (maximum score = 34), Kinetic Functions (maximum score = 52), Speech Disorders (maximum score = 8), and Oculomotor Disorders (maximum score = 6) for a possible total score of 100 points. The minimum score is 0 (normal), while the maximum score is 100 and corresponds to the worst status of the patient. This means that for each subscale, higher scores indicate higher levels of impairment.	At visits 2 (day 30), 4 (day 90) and 7 (final visit, day 180)
Mean Change From Baseline in Neurological Symptoms Assessed by Using International Cooperative Ataxia Rating Scale (ICARS) Score - PP Population	ICARS ia a 100-point semiquantitative scale, which goes from 0 to 100, offering a compartimentalised quantification of 4 subscores: Posture and Gait Disturbances (maximum score = 34), Kinetic Functions (maximum score = 52), Speech Disorders (maximum score = 8), and Oculomotor Disorders (maximum score = 6) for a possible total score of 100 points. The minimum score is 0 (normal), while the maximum score is 100 and corresponds to the worst status of the patient. This means that for each subscale, higher scores indicate higher levels of impairment.	At visits 2 (day 30), 4 (day 90) and 7 (final visit, day 180)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From V4 to V7 in Investigator Global Assessment (IGA) - ITT Population	An evaluation of the global health status of the patients by the IGA was performed. IGA consisted of an evaluation of neurological signs and symptoms as neuromotor disorders, posture and deambulation, disturbances of the oro-pharyngeal apparatus, presence of peripheral neuropathy, neurodevelopmental disturbances, intellectual level, and behavior disturbances based only on a subjective judgment of the Investigator on a single scale: a 5-point qualitative scale as: very much improved (1),; slightly improved (2),; no change (3),; slightly worsened (4),; very much worsened (5) was used to assess changes from V4 to V7. The higher the score, the worse the outcome.	At visit 7 (final visit, day 180)
Change From V4 to V7 in Investigator Global Assessment (IGA) - PP Population	An evaluation of the global health status of the patients by the IGA was performed. IGA consisted of an evaluation of neurological signs and symptoms as neuromotor disorders, posture and deambulation, disturbances of the oro-pharyngeal apparatus, presence of peripheral neuropathy, neurodevelopmental disturbances, intellectual level, and behavior disturbances based only on a subjective judgment of the Investigator on a single scale: a 5-point qualitative scale as: very much improved (1),; slightly improved (2),; no change (3),; slightly worsened (4),; very much worsened (5) was used to assess changes from V4 to V7. The higher the score, the worse the outcome.	At visit 7 (final visit, day 180)
Mean Change From V4 to V7 in Ocular Motility - ITT Population	An evaluation of ocular motility measured by an ad hoc form was performed at V4 and V7. At V4 and V7, ocular motility was assessed through a 5-point qualitative scale: very much improved (1), slightly improved (2), no change (3), slightly worsened (4), very much worsened (5).	At visit 7 (final visit, day 180)
Mean Change From V4 to V7 in Ocular Motility - PP Population	An evaluation of ocular motility measured by an ad hoc form was performed at V4 and V7. At V4 and V7, ocular motility was assessed through a 5-point qualitative scale: very much improved (1), slightly improved (2), no change (3), slightly worsened (4), very much worsened (5).	At visit 7 (final visit, day 180)
Change From Baseline for Vineland Adaptive Behaviour Scale (VABS) Total Score - ITT Population	VABS aggregate scale is used. VABS is divided into 4 adaptive domains and 11 subdomains: Communication: Receptive, Expressive, Written;; Daily Living Skills: Personal, Domestic, Community;; Socialisation: Interpersonal Relationships, Play & Leisure Time, Coping Skills;; Motor Skills: Gross, Fine. For each *question* in each of the 11 subdomains, score ranges from 0 to 4 (the higher the value the better the outcome): 0 = the subject never performs the behaviour without help or reminders;; 1 = rarely performs (as above);; 2 = sometimes performs (as above);; 3 = often performs (as above);; 4 = almost always performs (as above); The total subdomain score is the sum of each *question* scores and the total domain score is the sum of each subdomains' scores. Domains min-max interval scores: 0-74 Communication, 0-74 Daily Living Skills, 0-62 Socialization, 0-111 Motor Skills, Sum-of-domains score 0-321(the higher the score, the better the outcome)	At visits 4 (90 days) and 7 (180 days, final visit)
Change From Baseline for Vineland Adaptive Behaviour Scale (VABS) Total Score - PP Population	VABS aggregate scale is used. VABS is divided into 4 adaptive domains and 11 subdomains: Communication: Receptive, Expressive, Written;; Daily Living Skills: Personal, Domestic, Community;; Socialisation: Interpersonal Relationships, Play & Leisure Time, Coping Skills;; Motor Skills: Gross, Fine. For each *question* in each of the 11 subdomains, score ranges from 0 to 4 (the higher the value the better the outcome): 0 = the subject never performs the behaviour without help or reminders;; 1 = rarely performs (as above);; 2 = sometimes performs (as above);; 3 = often performs (as above);; 4 = almost always performs (as above); The total subdomain score is the sum of each *question* scores and the total domain score is the sum of each subdomains' scores. Domains min-max interval scores: 0-74 Communication, 0-74 Daily Living Skills, 0-62 Socialization, 0-111 Motor Skills, Sum-of-domains score 0-321(the higher the score, the better the outcome)	At visits 4 (90 days) and 7 (180 days, final visit)
Count of Participants on ERY-DEX Showing Treatment Emergent Adverse Events (TEAEs) Including Serious Adverse Events (SAEs)	The effect of ERY-DEX on treatment emergent adverse events was expressed as the number of patients showing at least one TEAE or 1 serious AE	Throughout the study, until the end of 6 months of treatment (day 180)

Collaborators and Investigators

• Sponsor: Quince Therapeutics S.p.A.
• Investigators: Principal Investigator: Luciana Chessa, MD, A.O. Sant'Andrea Rome Italy

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2011
• Primary Completion (Actual): September 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: December 3, 2010
• First Submitted That Met QC Criteria: December 6, 2010
• First Posted (Estimated): December 7, 2010

Study Record Updates

• Last Update Posted (Actual): October 10, 2024
• Last Update Submitted That Met QC Criteria: July 12, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Dexamethasone; Ataxia Teleangiectasia; AT; Dexamethasone sodium phosphate; ERY-DEX
• Additional Relevant MeSH Terms: Neurologic Manifestations; Dyskinesias; Nervous System Diseases; Ataxia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Protease Inhibitors; Dexamethasone; Dexamethasone acetate; BB 1101; Dexamethasone 21-phosphate
• Other Study ID Numbers: IEDAT-01; 2010-022315-19 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO