Clinical Trials Register

Summary
EudraCT Number:	2015-005241-31
Sponsor's Protocol Code Number:	IEDAT-02-2015
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-02-28
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

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

Sperimentazione multicentrica, randomizzata, in doppio cieco, controllata verso placebo volta a valutare gli effetti del Desametasone Sodio Fosfato Intra-Eritrocitario sui sintomi neurologici in pazienti con Atassia Teleangectasia

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

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	00390236504470
B.5.5	Fax number	00390236504474
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	Dexametasone Fosfato Sodico
D.3.4	Pharmaceutical form	Solution for haemofiltration
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	Dexametasone Fosfato Sodico
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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	DSP for encapsulation into autologus erythrocytes

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

Pazienti con sintomi neurologici da Atassia Telengectasia

E.1.1.1

Medical condition in easily understood language

Patients with neurological symptoms of Ataxia Telangiectasia

Pazienti con sintomi neurologici da Atassia Telengectasia

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	20.1
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

Periodo di trattamento iniziale (6 mesi)
Valutare l’effetto di due range di dosaggio (~5-10 e ~14-22 mg DSP/infusione) del prodotto finale EryDex System [EDS-EP EryDex System End Product; l’EDS è un prodotto combinato usato per introdurre il desametasone sodio fosfato (DSP) negli eritrociti autologhi, creando il prodotto finale EDS, che viene infuso nel paziente], rispetto al placebo, sui sintomi del sistema nervoso centrale (SNC) misurati con la Scala Cooperativa Internazionale “Modificata” di Valutazione dell’Atassia (‘Modified’ International Cooperative Ataxia Rating Scale, mICARS) in pazienti con atassia-teleangectasia (AT).

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).

Periodo di trattamento iniziale (6 mesi)
Valutare l’effetto di EDS-EP, rispetto al placebo, in questa popolazione sull’impressione clinica globale di cambiamento dal basale (Clinical Global Impression of Change from baseline, CGI-C):
- Scala di impressione clinica globale (Clinical Global Impression of Severity, CGI-S) sulla gravità dei sintomi neurologici della AT;
- Comportamento adattivo misurato con la Scala Vineland per il comportamento adattivo (Vineland Adaptive Behavior Scales, VABS);

Periodo di estensione del trattamento (6 mesi)
Valutare la sicurezza e la tollerabilità di EDS-EP a lungo termine (fino a 12 mesi) in pazienti affetti da AT;
 Confrontare gli effetti dei due range di dosaggio di EDS-EP sulla base dell’impressione generale del medico (CGI-C e CGI-S), del comportamento adattivo (VABS) e della qualità di vita (QoL) (scala 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. Il paziente soddisfa i criteri clinici per la diagnosi di AT. I segni neurologici della AT (mancanza di coordinazione della testa e degli occhi nella deviazione laterale dello sguardo, atassia nella deambulazione associata a una base di appoggio inappropriatamente stretta) devono essere documentati.
2. Il paziente deambula autonomamente o è aiutato dall’uso periodico di un supporto.
3. Il paziente ha una diagnosi genetica accertata di AT (documentazione pre-esistente o referto dell’esame del laboratorio centrale).
4. Il paziente ha almeno 6 anni di età, di qualunque sesso
5. Peso corporeo >15 kg.
6. Il paziente e il genitore/o la persona che lo assiste (caregiver) (se minorenne), o un rappresentante legale, fornisce il modulo di consenso informato per partecipare allo studio. Se il consenso viene fornito esclusivamente dal caregiver in conformità alle normative locali, il paziente deve fornire l’assenso alla partecipazione allo studio.

E.4

Principal exclusion criteria

General
General
1. Females that are of childbearing potential, 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.

Generali
1. I soggetti di sesso femminile, in stato di gravidanza o in fase di allattamento. Saranno eleggibili i soggetti di sesso femminile in età fertile che usano metodi di contraccezione adeguati, come stabilito dal loro operatore sanitario. 2. Una invalidità che potrebbe impedire al paziente di rispettare tutte le istruzioni dello studio.
3. Attuale partecipazione a un altro studio clinico.
Anamnesi medica e stato attuale
4. CD4+ conta dei linfociti <400/mm3 (per pazienti di 6 anni di età) o <200/mm3 (per pazienti >6 anni).
5. Perdita/Prelievo di 250 ml o più di sangue nelle 4 settimane che precedono lo screening.
6. Malattia neoplastica attuale o malattia neoplastica precedente non in remissione per almeno 2 anni.
7. Anamnesi di deterioramento severo del sistema immunitario.
8. Malattia polmonare grave o instabile.
9. Diabete non controllato. Saranno eleggibili i pazienti con diabete stabilizzato (ovvero nessun episodio di ipoglicemia o iperglicemia negli ultimi 3 mesi).
10. Qualsiasi altra malattia grave, instabile o seria, o condizione, che secondo l’opinione dello Sperimentatore metterebbe il paziente a rischio di vita imminente, necessità di ospedalizzazione o mortalità.
11. Qualsiasi anomalia clinicamente significativa sugli esami di laboratorio standard (ematologia, biochimica, analisi delle urine) allo screening che rimane anormale alla ripetizione dell’esame. L’eleggibilità di pazienti con valori anomali degli esami di laboratorio sarà valutata dallo sperimentatore dopo consultazione con il monitor medico.
12. Emoglobinopatie confermate, es. malattia da emoglobina C, anemia falcemica, o talassemia.
13. Insufficienza renale e/o epatica di grado moderato o severo.
Farmaci precedenti/concomitanti
14. Assunzione di steroidi, in forma orale o parenterale, nelle 4 settimane prima del basale. Sarà consentito il trattamento con steroidi tramite inalazione o intranasali per asma o allergie, così come l’uso di steroidi topici.
15. Condizione cronica o reazione allergica precedente che rappresentino una controindicazione all’uso del desametasone o di altri farmaci steroidei.
16. Ha preso parte a qualsiasi altra sperimentazione per un farmaco sperimentale e ha ricevuto una dose entro 30 giorni oppure 10 emivite (a seconda di quale è maggiore) dall’inizio del periodo di screening di 30 giorni.
17. Ha partecipato a una sperimentazione in precedenza con EDS.
18. Ha bisogno di un qualunque farmaco compreso tra quelli vietati nel protocollo.
19. Ha assunto un farmaco o un trattamento noti per causare tossicità ad organi importanti durante l’ultimo anno.
20. Utilizzo di qualsiasi farmaco che è un forte induttore/inibitore di CYP3A4 nelle 4 settimane prima del basale.

E.5 End points

E.5.1

Primary end point(s)

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

E.5.2.1

Timepoint(s) of evaluation of this end point

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

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

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in 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

Information not present in EudraCT

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.

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.

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

E.8.9.2

In all countries concerned by the trial days

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:

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

Yes

F.3.3.2

Women of child-bearing potential using contraception

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

Terapia Standard

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

2016-06-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-11-02

P. End of Trial
P.	End of Trial Status	Completed

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials