Trial Outcomes & Findings for Intra-Erythrocyte Dexamethasone Sodium Phosphate in Ataxia Teleangiectasia Patients (NCT NCT01255358)

NCT ID: NCT01255358

Last Updated: 2024-10-10

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 22 participants
• Primary outcome timeframe: At visits 2 (day 30), 4 (day 90) and 7 (final visit, day 180)
• Results posted on: 2024-10-10

Participant Flow

Study was carried out in 2 Italian Hospitals. Recruitment started on February 2011 and LPLV was performed on August 2011.

Patients had 30 days of wash-out from steroid assumption before starting the treatment. 26 patients were screened, 4 of them resulted screening failure, due to lymphocytes value below the limit (3) and concomitant disease (1).

Participant milestones

Measure	EryDex Patients treated with monthly treatment of EryDex (dexamethasone sodium phosphate encapsulated in autologous erythrocytes).
Overall Study STARTED	22
Overall Study COMPLETED	18
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Measure	EryDex Patients treated with monthly treatment of EryDex (dexamethasone sodium phosphate encapsulated in autologous erythrocytes).
Overall Study Adverse Event	2
Overall Study Protocol Violation	2

Baseline Characteristics

Intra-Erythrocyte Dexamethasone Sodium Phosphate in Ataxia Teleangiectasia Patients

Baseline characteristics by cohort

Measure	ERY-DEX n=22 Participants Patients treated with monthly treatment of ERY-DEX (dexamethasone sodium phosphate encapsulated in autologous erythrocytes)
Age, Categorical <=18 years	21 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	11.2 years STANDARD_DEVIATION 3.5 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	11 Participants n=5 Participants
Region of Enrollment Italy	22 participants n=5 Participants

PRIMARY outcome

Timeframe: At visits 2 (day 30), 4 (day 90) and 7 (final visit, day 180)

Population: Intent to treat population (ITT) patients receiving at least one treatment

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.

Outcome measures

Measure	ERY-DEX n=22 Participants Patients treated with monthly treatment of ERY-DEX (dexamethasone sodium phosphate encapsulated in autologous erythrocytes) 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)
Mean Change From Baseline in Neurological Symptoms Assessed by Using International Cooperative Ataxia Rating Scale (ICARS) Score - ITT Population V2	-2.2 units on a scale Standard Deviation 5.6
Mean Change From Baseline in Neurological Symptoms Assessed by Using International Cooperative Ataxia Rating Scale (ICARS) Score - ITT Population V4	-3.4 units on a scale Standard Deviation 7.3
Mean Change From Baseline in Neurological Symptoms Assessed by Using International Cooperative Ataxia Rating Scale (ICARS) Score - ITT Population V7	-4.0 units on a scale Standard Deviation 7.5

PRIMARY outcome

Timeframe: At visits 2 (day 30), 4 (day 90) and 7 (final visit, day 180)

Population: The PP Population includes 18 patients who have been treated according to protocol and fulfill the following criteria: * compliance with all entry criteria * absence of major protocol violations * adequate compliance with trial medication (at most one missed or out-of-window infusion of the study preparation).

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.

Outcome measures

Measure	ERY-DEX n=18 Participants Patients treated with monthly treatment of ERY-DEX (dexamethasone sodium phosphate encapsulated in autologous erythrocytes) 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)
Mean Change From Baseline in Neurological Symptoms Assessed by Using International Cooperative Ataxia Rating Scale (ICARS) Score - PP Population V2	-2.4 units on a scale Standard Deviation 4.9
Mean Change From Baseline in Neurological Symptoms Assessed by Using International Cooperative Ataxia Rating Scale (ICARS) Score - PP Population V4	-3.9 units on a scale Standard Deviation 7.1
Mean Change From Baseline in Neurological Symptoms Assessed by Using International Cooperative Ataxia Rating Scale (ICARS) Score - PP Population V7	-5.2 units on a scale Standard Deviation 7.0

SECONDARY outcome

Timeframe: At visit 7 (final visit, day 180)

Population: The ITT Population includes all 22 patients enrolled into the study.

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.

Outcome measures

Measure

ERY-DEX n=22 Participants Patients treated with monthly treatment of ERY-DEX (dexamethasone sodium phosphate encapsulated in autologous erythrocytes) 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)

Change From V4 to V7 in Investigator Global Assessment (IGA) - ITT Population

0.2 units on a scale Standard Deviation 0.6

SECONDARY outcome

Timeframe: At visit 7 (final visit, day 180)

Population: The PP Population includes 18 patients who have been treated according to protocol and fulfill the following criteria: * compliance with all entry criteria * absence of major protocol violations * adequate compliance with trial medication (at most one missed or out-of-window infusion of the study preparation).

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.

Outcome measures

Measure

ERY-DEX n=18 Participants Patients treated with monthly treatment of ERY-DEX (dexamethasone sodium phosphate encapsulated in autologous erythrocytes) 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)

Change From V4 to V7 in Investigator Global Assessment (IGA) - PP Population

0.2 units on a scale Standard Deviation 0.6

SECONDARY outcome

Timeframe: At visit 7 (final visit, day 180)

Population: The ITT Population includes all 22 patients enrolled into the study.

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).

Outcome measures

Measure

ERY-DEX n=22 Participants Patients treated with monthly treatment of ERY-DEX (dexamethasone sodium phosphate encapsulated in autologous erythrocytes) 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)

Mean Change From V4 to V7 in Ocular Motility - ITT Population

-0.3 units on a scale Standard Deviation 0.5

SECONDARY outcome

Timeframe: At visit 7 (final visit, day 180)

Population: The PP Population includes 18 patients who have been treated according to protocol and fulfill the following criteria: * compliance with all entry criteria * absence of major protocol violations * adequate compliance with trial medication (at most one missed or out-of-window infusion of the study preparation).

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).

Outcome measures

Measure

ERY-DEX n=18 Participants Patients treated with monthly treatment of ERY-DEX (dexamethasone sodium phosphate encapsulated in autologous erythrocytes) 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)

Mean Change From V4 to V7 in Ocular Motility - PP Population

-0.3 units on a scale Standard Deviation 0.5

SECONDARY outcome

Timeframe: At visits 4 (90 days) and 7 (180 days, final visit)

Population: The ITT Population includes all 22 patients enrolled into the study.

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)

Outcome measures

Measure	ERY-DEX n=22 Participants Patients treated with monthly treatment of ERY-DEX (dexamethasone sodium phosphate encapsulated in autologous erythrocytes) 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)
Change From Baseline for Vineland Adaptive Behaviour Scale (VABS) Total Score - ITT Population V4	1.0 units on a scale Standard Deviation 0.9
Change From Baseline for Vineland Adaptive Behaviour Scale (VABS) Total Score - ITT Population V7	1.3 units on a scale Standard Deviation 1.3

SECONDARY outcome

Timeframe: At visits 4 (90 days) and 7 (180 days, final visit)

Population: The PP Population includes 18 patients who have been treated according to protocol and fulfill the following criteria: * compliance with all entry criteria * absence of major protocol violations * adequate compliance with trial medication (at most one missed or out-of-window infusion of the study preparation).

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)

Outcome measures

Measure	ERY-DEX n=18 Participants Patients treated with monthly treatment of ERY-DEX (dexamethasone sodium phosphate encapsulated in autologous erythrocytes) 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)
Change From Baseline for Vineland Adaptive Behaviour Scale (VABS) Total Score - PP Population V4	1.1 units on a scale Standard Deviation 0.9
Change From Baseline for Vineland Adaptive Behaviour Scale (VABS) Total Score - PP Population V7	1.5 units on a scale Standard Deviation 1.1

SECONDARY outcome

Timeframe: Throughout the study, until the end of 6 months of treatment (day 180)

Population: The SP includes the 22 patients who have received at least one dose of planned trial treatment.

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

Outcome measures

Measure	ERY-DEX n=22 Participants Patients treated with monthly treatment of ERY-DEX (dexamethasone sodium phosphate encapsulated in autologous erythrocytes) 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)
Count of Participants on ERY-DEX Showing Treatment Emergent Adverse Events (TEAEs) Including Serious Adverse Events (SAEs) Participants with at least 1 TEAE	15 Participants
Count of Participants on ERY-DEX Showing Treatment Emergent Adverse Events (TEAEs) Including Serious Adverse Events (SAEs) Participants with at least 1 serious AE	2 Participants

Adverse Events

Ery-Dex

Serious events: 2 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Measure	Ery-Dex n=22 participants at risk Patients treated with monthly treatment of Ery-Dex (dexamethasone sodium phosphate encapsulated in autologous erythrocytes)
Infections and infestations Bronchopneumonia	4.5% 1/22 • Number of events 1 • The adverse events were monitored and collected during the 6 month study period Please note that non serious Adverse Events were monitored/assessed without regard to the specific Adverse Event Term but only by SOC.
Respiratory, thoracic and mediastinal disorders Bronchiectasis	4.5% 1/22 • Number of events 1 • The adverse events were monitored and collected during the 6 month study period Please note that non serious Adverse Events were monitored/assessed without regard to the specific Adverse Event Term but only by SOC.

Other adverse events

Measure	Ery-Dex n=22 participants at risk Patients treated with monthly treatment of Ery-Dex (dexamethasone sodium phosphate encapsulated in autologous erythrocytes)
General disorders General disorders	13.6% 3/22 • Number of events 3 • The adverse events were monitored and collected during the 6 month study period Please note that non serious Adverse Events were monitored/assessed without regard to the specific Adverse Event Term but only by SOC.
Immune system disorders immune disorders	9.1% 2/22 • Number of events 2 • The adverse events were monitored and collected during the 6 month study period Please note that non serious Adverse Events were monitored/assessed without regard to the specific Adverse Event Term but only by SOC.
Infections and infestations infections and infestations	68.2% 15/22 • Number of events 17 • The adverse events were monitored and collected during the 6 month study period Please note that non serious Adverse Events were monitored/assessed without regard to the specific Adverse Event Term but only by SOC.
Respiratory, thoracic and mediastinal disorders respiratory disorders	18.2% 4/22 • Number of events 4 • The adverse events were monitored and collected during the 6 month study period Please note that non serious Adverse Events were monitored/assessed without regard to the specific Adverse Event Term but only by SOC.

Additional Information

Clinical Study Coordinator

EryDel spa

Phone: +39 02 36504470

Email: guenter.janhofer@erydel.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60