Intra-Erythrocyte Dexamethasone Sodium Phosphate in Ataxia Teleangiectasia Patients

Phase 2

Completed

Conditions: Nervous System Disorder
Genetic Syndrome

Interventions: Drug: Dexamethasone

Registration Number: NCT01255358

Lead Sponsor: Quince Therapeutics S.p.A.

Brief Summary: 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).

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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 22

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 & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ERY-DEX	Dexamethasone	Patients treated with monthly treatment of ERY-DEX (dexamethasone sodium phosphate encapsulated in autologous erythrocytes)

Primary Outcome Measures

Name	Time	Method
Mean Change From Baseline in Neurological Symptoms Assessed by Using International Cooperative Ataxia Rating Scale (ICARS) Score - ITT Population	At visits 2 (day 30), 4 (day 90) and 7 (final visit, day 180)	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.
Mean Change From Baseline in Neurological Symptoms Assessed by Using International Cooperative Ataxia Rating Scale (ICARS) Score - PP Population	At visits 2 (day 30), 4 (day 90) and 7 (final visit, day 180)	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.

Secondary Outcome Measures

Name	Time	Method
Change From V4 to V7 in Investigator Global Assessment (IGA) - ITT Population	At visit 7 (final visit, day 180)	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.
Change From V4 to V7 in Investigator Global Assessment (IGA) - PP Population	At visit 7 (final visit, day 180)	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.
Mean Change From V4 to V7 in Ocular Motility - ITT Population	At visit 7 (final visit, day 180)	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).
Mean Change From V4 to V7 in Ocular Motility - PP Population	At visit 7 (final visit, day 180)	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).
Change From Baseline for Vineland Adaptive Behaviour Scale (VABS) Total Score - ITT Population	At visits 4 (90 days) and 7 (180 days, final visit)	VABS aggregate scale is used. VABS is divided into 4 adaptive domains and 11 subdomains: 1. Communication: Receptive, Expressive, Written; 2. Daily Living Skills: Personal, Domestic, Community; 3. Socialisation: Interpersonal Relationships, Play \& Leisure Time, Coping Skills; 4. 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)
Change From Baseline for Vineland Adaptive Behaviour Scale (VABS) Total Score - PP Population	At visits 4 (90 days) and 7 (180 days, final visit)	VABS aggregate scale is used. VABS is divided into 4 adaptive domains and 11 subdomains: 1. Communication: Receptive, Expressive, Written; 2. Daily Living Skills: Personal, Domestic, Community; 3. Socialisation: Interpersonal Relationships, Play \& Leisure Time, Coping Skills; 4. 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)
Count of Participants on ERY-DEX Showing Treatment Emergent Adverse Events (TEAEs) Including Serious Adverse Events (SAEs)	Throughout the study, until the end of 6 months of treatment (day 180)	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