Clinical Trials Register

Summary
EudraCT Number:	2015-005241-31
Sponsor's Protocol Code Number:	IEDAT-02-2015
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-06-09
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Spain - AEMPS

A.2

EudraCT number

2015-005241-31

A.3

Full title of the trial

A Multi-center, Randomized, Double-blind, Placebo-controlled Trial to Evaluate the Effects of Intra-Erythrocyte Dexamethasone Sodium Phosphate on Neurological Symptoms in Patients with Ataxia Telangiectasia

Ensayo multicéntrico, aleatorizado, doble ciego, controlado con placebo para evaluar los efectos del fosfato sódico de dexametasona intra-eritrocito en los síntomas neurológicos de pacientes con Ataxia Telangiectasia

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

n/a

A.3.2

Name or abbreviated title of the trial where available

EDS in Ataxia Telangiectasia Patients - IEDAT-02

EDS en pacientes con pacientes con Ataxia Telangiectasia - IEDAT-02

A.4.1

Sponsor's protocol code number

IEDAT-02-2015

A.5.4

Other Identifiers

Name:

US IND

Number:

115929

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	EryDel S.p.A.
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	EryDel S.p.A.
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Antonio Ferrari at EryDel S.p.A.
B.5.2	Functional name of contact point	Global Medical Director
B.5.3	Address:
B.5.3.1	Street Address	Via L. Ariosto 23,25
B.5.3.2	Town/ city	Bresso (IM)
B.5.3.3	Post code	20091
B.5.3.4	Country	Italy
B.5.4	Telephone number	+390236504470
B.5.5	Fax number	+390236504474
B.5.6	E-mail	antonio.ferrari@erydel.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EMA/COMP/306983/2013
D.3 Description of the IMP
D.3.1	Product name	Dexamethasone sodium phosphate
D.3.4	Pharmaceutical form	Solution for blood fraction modification
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Dexamethasone sodium phosphate
D.3.9.2	Current sponsor code	DSP
D.3.9.3	Other descriptive name	DEXAMETHASONE SODIUM PHOSPHATE PH. EUR.
D.3.9.4	EV Substance Code	SUB174329
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Yes
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	Yes
D.3.11.13.1	Other medicinal product type	The IMP refers to dexamethasone sodium phosphate (DSP) for encapsulation into human autologous erythrocytes. DSP is formulated at 25 mg/mL in WFI to produce the drug product, DSP Solution.

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Patient with neurological symptoms of Ataxia Telangiectasia

Pacientes con síntomas neurológicos de la Ataxia Telangiectasia

E.1.1.1

Medical condition in easily understood language

Patients with neurological symptoms of Ataxia Telangiectasia

Pacientes con síntomas neurológicos de la Ataxia Telangiectasia

E.1.1.2

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.0
E.1.2	Level	PT
E.1.2	Classification code	10003594
E.1.2	Term	Ataxia telangiectasia
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

Initial Treatment Period (6 months)
To evaluate the effect of two dose ranges (~5-10 and ~14-22 mg DSP/infusion) of EryDex System end product [EDS-EP; the EDS is a combination product that is used to load dexamethasone sodium phosphate (DSP) into autologous erythrocytes, creating the EDS end product, which is infused into the patient], compared to placebo, on central nervous system (CNS) symptoms measured by the "Modified" International Cooperative Ataxia Rating Scale (mICARS) in patients with AT.

Extension Treatment Period (6 months)
To evaluate the efficacy of two dose ranges (~5-10 and ~14-22 mg DSP/infusion) of EDS-EP compared to placebo in treating CNS symptoms in AT patients during long-term treatment (up to 12 months), as measured by the "Modified" ICARS

Período de tratamiento inicial (6 meses)
Evaluar el efecto de dos intervalos de dosis (~5 a 10 y ~14 a 22 mg de DSP/infusión) del producto final del sistema EryDex (EDS-EP; el EDS es un producto de combinación que se usa para cargar fosfato sódico de dexametasona [[DSP] en eritrocitos autólogos, lo que crea el producto final del EDS, que se infunde en el paciente) en comparación con un placebo en los síntomas del sistema nervioso central (SNC) medidos mediante la escala cooperativa internacional para la cuantificación de la ataxia "modificada" (ICARSm) en pacientes con ataxia telangiectasia (AT).

Período de tratamiento de extensión (6 meses):
Evaluar la eficacia de dos intervalos de dosis (~5 a 10 y ~14 a 22 mg de DSP/infusión) del EDS-EP en comparación con el placebo en el tratamiento de los síntomas del SNC en pacientes con AT durante el tratamiento a largo plazo (hasta 12 meses), según lo medido mediante la ICARS "modificada".

E.2.2

Secondary objectives of the trial

Initial Treatment Period (6 months)
To evaluate the effect of EDS-EP, compared to placebo, in this population on the Clinical Global Impression of Change from baseline (CGI-C) and on the following efficacy measures:
- Clinical Global Impression of Severity (CGI-S) of neurological symptoms of AT;
- Adaptive behavior measured by the Vineland Adaptive Behavior Scales (VABS);

Extension Treatment Period (6 months)
To evaluate the long-term (up to 12 months) safety and tolerability of EDS-EP in AT patients;
To compare the effects of the two dose ranges of EDS-EP on the clinician's global impression (CGI-C and CGI-S), adaptive behavior (VABS), and QoL (EQ-5D-5L scale).

Período de tratamiento inicial (6 meses)
Evaluar el efecto del EDS-EP en comparación con el placebo en esta población en la Impresión global clínica del cambio (CGI-C) con respecto al inicio y respecto de las siguientes medidas de eficacia:
- Impresión global clínica de gravedad (CGI-S) de los síntomas neurológicos de la AT.
- Conducta adaptativa medida mediante las escalas de conducta adaptativa de Vineland (Vineland Adaptive Behavior Scales, VABS).

Período de tratamiento de extensión (6 meses):
Evaluar la seguridad y la tolerabilidad a largo plazo (hasta 12 meses) del EDS-EP en pacientes con AT;
Comparar los efectos de los dos intervalos de dosis del EDS-EP en la impresión global del médico clínico (CGI-C y CGI-S), la conducta adaptativa (VABS) y la QoL (escala EQ-5D-5L).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patient meets clinical criteria for diagnosis of AT. The neurological signs of AT (incoordination of the head and eyes in lateral gaze deflection, gait ataxia associated with an inappropriately narrow base) must be documented.
2. Patient is in autonomous gait or is helped by periodic use of a support.
3. Patient will be investigated for the proven genetic diagnosis of AT (prior documentation or by central laboratory test report).
4. Patient is at least 6 years of age, of either sex
5. Body weight > 15 kg.
6. The patient and his/her parent/caregiver (if below the age of consent), or a legal representative, has provided written informed consent to participate. If consent is provided solely by the caregiver in accordance with local regulations, the patient must provide assent to participate in the study.

1. El paciente cumple con los criterios clínicos para el diagnóstico de AT. Se deben documentar los signos neurológicos de AT (falta de coordinación de la cabeza y los ojos en el desvío lateral de la mirada, marcha atáxica asociada a una base inadecuadamente estrecha).
2. El paciente presenta capacidad de marcha autónoma o recibe asistencia mediante el uso periódico de apoyo.
3. Se investigará al paciente para determinar que presente el diagnóstico genético comprobado de AT (documentación previa o mediante un informe de análisis del laboratorio central).
4. El paciente tiene, al menos, 6 años de edad; puede ser de cualquier sexo.
5. Peso corporal >15 kg.
6. El paciente y su padre/madre/cuidador (si es menor de edad para otorgar el consentimiento), o un representante legal, han proporcionado el consentimiento informado por escrito para participar.
Si solamente el cuidador proporciona el consentimiento de conformidad con las regulaciones locales, el paciente debe proporcionar el asentimiento para participar en el estudio.

E.4

Principal exclusion criteria

General
1. Females that are pregnant or are breast-feeding. Females of childbearing potential using adequate birth control, as determined by their Health Care Provider, will be eligible.
2. A disability that may prevent the patient from completing all study requirements.
3. Current participation in another clinical study.

Medical History and Current Status
4. CD4+ lymphocytes count <400/mm3 (for patients 6 years of age) or <200/mm3 (for patients >6 years).
5. Loss/removal of 250 mL or more of blood within the past 4 weeks prior to screening.
6. Current neoplastic disease or previous neoplastic disease not in remission for at least 2 years.
7. History of severe impairment of the immunological system.
8. Severe or unstable pulmonary disease.
9. Uncontrolled diabetes.
Patients with diabetes that has been stabilized (i.e. no hypoglycemic or hyperglycemic episodes in the past 3 months) will be eligible.
10. 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.
11. 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 will be determined by the Investigator in consultation with the Medical Monitor.
12. Confirmed hemoglobinopathies, e.g. hemoglobin C disease, sickle cell anemia, or thalassemia.
13. Moderate or severe renal and/or hepatic impairment.

Prior/Concomitant Medication
14. Any previous oral or parenteral steroid use within 4 weeks before Baseline. Treatment with inhaled or intranasal steroids for asthma or allergies, as well as use of topical steroids will be permitted.
15. Chronic condition or prior allergic reaction representing a contraindication to the use of dexamethasone or other steroid drugs.
16. Has participated in any other trial with an investigational drug and received a dose within 30 days or 10 half-lives (whichever is greater) from the start of the 30-day Screening Period.
17. Has participated in a previous trial with EDS.
18. Requires any concomitant medication prohibited by the protocol.
19. Has taken a drug or treatment known to cause major organ system toxicity during the past year.
20. Use of any drug that is a strong inducer/inhibitor of CYP3A4 within 4 weeks before baseline.

General
1. Mujeres embarazadas o en período de lactancia. Las mujeres en edad fértil que usen un método anticonceptivo adecuado, según lo determinado por su proveedor de atención médica, serán elegibles.
2. Una discapacidad que pueda impedir que el paciente complete todos los requisitos del estudio.
3. Participación actual en otro estudio clínico.

Antecedentes médicos y condición actual
4. Recuento de linfocitos CD4+ <400/mm3 (para pacientes de 6 años de edad) o <200/mm3 (para pacientes >6 años).
5. Pérdida/extracción de 250 ml de sangre o más en las 4 semanas anteriores a la selección.
6. Enfermedad neoplásica actual o enfermedad neoplásica previa que no haya presentado remisión durante, al menos, 2 años.
7. Antecedentes de afectación grave del sistema inmunitario.
8. Enfermedad pulmonar grave o inestable.
9. Diabetes no controlada.
Los pacientes con diabetes estabilizada (es decir, con ausencia de episodios hipoglucémicos o hiperglucémicos en los últimos 3 meses) serán elegibles.
10. Cualquier otra enfermedad o afección grave, inestable o seria que, a criterio del investigador, pueda poner al paciente en riesgo de presentar una morbilidad inminente que represente un riesgo para la vida, de necesitar hospitalización o de mortalidad.
11. Cualquier anomalía clínicamente significativa en los exámenes de laboratorio estándares (hematología, bioquímica, análisis de orina) en la selección que permanezca anormal cuando se repitan los análisis. La elegibilidad de los pacientes con valores anómalos en los análisis de laboratorio estará determinada por el investigador, quien lo consultará con el monitor médico.
12. Hemoglobinopatías confirmadas, p. ej., hemoglobinopatía C, anemia drepanocítica o talasemia.
13. Insuficiencia renal y/o hepática moderada o grave.

Medicamentos previos/concomitantes
14. Cualquier uso de esteroides orales o parenterales previos en las 4 semanas anteriores al inicio. Se permitirán el tratamiento con esteroides inhalados o intranasales para el asma o alergias, así como también el uso de esteroides tópicos.
15. Afección crónica o reacción alérgica anterior que represente una contraindicación respecto del uso de la dexametasona u otros fármacos esteroideos.
16. Ha participado en algún otro ensayo con un fármaco en investigación y ha recibido una dosis en el plazo de los 30 días o las 10 semividas (el que sea mayor) del inicio del período de selección de 30 días.
17. Ha participado en un ensayo anterior con el EDS.
18. Requiere de algún medicamento concomitante prohibido por el protocolo.
19. Durante el año anterior, ha recibido un fármaco o tratamiento que, según se sabe, produce toxicidad de los sistemas de órganos principales.
20. Uso de cualquier fármaco que constituye un inductor/inhibidor potente del CYP3A4 en el plazo de las 4 semanas anteriores al inicio.

E.5 End points

E.5.1

Primary end point(s)

El criterio de valoración principal de la eficacia será el cambio desde el inicio hasta las evaluaciones de seguimiento los días 90 y 180 en la puntuación total en la Escala Cooperativa Internacional de Clasificación de la Ataxia (International Cooperative Ataxia Rating Scale, ICARS) “Modificada”.

E.5.1.1

Timepoint(s) of evaluation of this end point

The primary efficacy endpoint will be the change from baseline to the follow-up assessments at Days 90 and 180, in the total score on the "Modified" International Cooperative Ataxia Rating Scale (ICARS). The analysis will be done once all subjects have completed day 180 assessments (month 6)

E.5.2

Secondary end point(s)

Key Secondary Efficacy Endpoint
The key secondary efficacy end point is the CGI-C rating of change from baseline at the follow-up assessments at Days 90 and 180.

Other Secondary Efficacy Endpoints
The following secondary efficacy endpoints will be assessed in the study:
- The change of CGI-S score from baseline to follow-up based on repeated measures at Days 90 and 180
- The change of VABS score from baseline to follow-up based on repeated measures at Days 90 and 180

Criterio de valoración secundario de la eficacia clave
El criterio de valoración secundario de la eficacia clave es la clasificación en la CGI-C del cambio desde el inicio en las evaluaciones de seguimiento los días 90 y 180.

Otros criterios secundarios de valoración de la eficacia
En el estudio se evaluarán los siguientes criterios de valoración secundarios de la eficacia:
- El cambio en la puntuación CGI-S desde el inicio hasta el seguimiento en función de medidas repetidas los días 90 y 180
- El cambio en la puntuación VABS desde el inicio hasta el seguimiento en función de medidas repetidas los días 90 y 180

E.5.2.1

Timepoint(s) of evaluation of this end point

Days 90 and 180
For more details, please refer to study protocol.

Días 90 y 180
Si desea obtener más información, consulte el protocolo del estudio.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Belgium

Costa Rica

Germany

Israel

Italy

Norway

Poland

Spain

Tunisia

Turkey

United Kingdom

United States

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

A patient will be considered to have "completed" the Initial Treatment Period of the study when he/she returns for the final evaluations on Month 6. Patients who continue in the Extension Treatment Period will be considered to have "completed" this period of the study when he/she returns for the final evaluations on Month 12.

Se considerará que un paciente ha “completado” el periodo de tratamiento inicial del estudio cuando vuelva para las evaluaciones finales en el mes 6. Se considerará que los pacientes que continúen en el periodo de tratamiento de extensión han “completado” este periodo del estudio cuando vuelvan para las evaluaciones finales en el mes 12

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

180

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

117

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

F.4.2.2

In the whole clinical trial

180

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Standard care

Práctica clínica habitual

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2016-05-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-05-19

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-05-13

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