Clinical Trials Register

Summary
EudraCT Number:	2018-000338-36
Sponsor's Protocol Code Number:	IEDAT-03-2018
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:	2021-06-04
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2018-000338-36

A.3

Full title of the trial

Open-label, Long-term, Extension Treatment using Intra-Erythrocyte Dexamethasone Sodium Phosphate in Patients with Ataxia Telangiectasia Who Participated in the IEDAT-02-2015 Study.

Trattamento di estensione a lungo termine in aperto con l'utilizzo di desametasone sodio fosfato intra-eritrocitario in pazienti affetti da atassia telangiectasia che hanno partecipato allo studio IEDAT-02-2015

A.3.1

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

Open-label, Long-term, Extension Treatment using Intra-Erythrocyte Dexamethasone Sodium Phosphate in Patients with Ataxia Telangiectasia Who Participated in the IEDAT-02-2015 Study.

A.3.2

Name or abbreviated title of the trial where available

OLE-IEDAT

A.4.1

Sponsor's protocol code number

IEDAT-03-2018

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	Irene Maccabruni - EryDel S.p.A.
B.5.2	Functional name of contact point	Clinical Study Manager
B.5.3	Address:
B.5.3.1	Street Address	Via Meucci 3
B.5.3.2	Town/ city	Bresso (MI)
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	irene.maccabruni@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 (soluzione 25mg/ml)
D.3.2	Product code	[Dexamethasone sodium phosphate]
D.3.4	Pharmaceutical form	Solution for infusion
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.3.9.1	CAS number	2392-39-4
D.3.9.2	Current sponsor code	DSP
D.3.9.4	EV Substance Code	SUB174329
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
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	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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Neurological symptoms of Ataxia Telangiectasia

Sintomi neurologici di atassia teleangectasia

E.1.1.1

Medical condition in easily understood language

Patients with Ataxia Telangiectasia

Paziente affetti da atassia teleangectasia

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	21.0
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

E.2 Objective of the trial

E.2.1

Main objective of the trial

-To monitor and evaluate the long-term safety and tolerability of EDS-EP in AT patients.
-To evaluate the long term effect of EDS-EP in treating CNS symptoms as measured by the "Modified" International Cooperative Ataxia Rating Scale (mICARS), and Clinical Global Impression of severity and change (CGI-S/C)

-Monitorare e valutare la sicurezza e la tollerabilità a lungo termine di EDS-EP nei pazienti con AT.
-Valutare l'effetto a lungo termine di EDS-EP nel trattamento dei sintomi del SNC in base alla misurazione sulla scala di valutazione dell'atassia "modificata" dell'International Cooperative (International Cooperative Ataxia Rating Scale, mICARS) e all'impressione clinica globale di gravità e cambiamento (Clinical Global Impression of severity/change, CGI- S/C).

E.2.2

Secondary objectives of the trial

To evaluate the long-term effect of EDS-EP on health related Quality of Life (QoL; EQ-5D-5L scale).

-Valutare l'effetto a lungo termine di EDS-EP sulla qualità della vita correlata alla salute (Quality of Life, QoL; scala EQ-5D-5L).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1.Patient completed the double-blind period in the IEDAT-02-2015 trial
and must have completed the final (Visit 15/Month 12) efficacy
assessments of IEDAT-02-2015.
2.Patient tolerated the study medication, without any evidence of steroid
adverse events, or treatment-related severe/ serious adverse events.
3.Body weight > 15 kg.
4.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.
5.Patient does not present safety contraindications for continuation of treatment, as determined by the Principal Investigator (PI) according to
the procedures described below.
Procedure for selecting patients for further treatment:
The Principal Investigator will ask all patients who meet the aboverequirements, and determine their interest in continuing to receive treatment with the study medication in a new protocol. The Principal Investigator will then determine the eligibility of the patients on the basis of his/her clinical judgement of patients' status and their safety.

1. Il paziente ha completato il periodo in doppio cieco nella sperimentazione IEDAT-02-2015 e deve aver completato le valutazioni di efficacia finali (Visita 15/Mese 12) di IEDAT-02-2015.
2. Il paziente ha tollerato il farmaco in studio, senza alcuna evidenza di eventi avversi da steroidi o eventi avversi gravi/gravi correlati al trattamento.
3. Peso corporeo > 15 kg.
4. Il paziente e il suo genitore/caregiver (se inferiore all'età del consenso), o un rappresentante legale, hanno fornito il consenso informato scritto alla partecipazione. Se il consenso viene fornito esclusivamente dal caregiver in conformità con le normative locali, il paziente deve fornire il proprio assenso a partecipare allo studio.
5. Il paziente non presenta controindicazioni di sicurezza per la continuazione del trattamento, come determinato dallo sperimentatore principale (Principal Investigator, PI) secondo le procedure descritte di seguito.
Procedura per la selezione dei pazienti per l'ulteriore trattamento in IEDAT-03-2018
• Lo sperimentatore principale chiederà a tutti i pazienti che soddisfano i requisiti di cui sopra e determinerà il loro interesse a continuare a ricevere il trattamento con il farmaco in studio in un nuovo protocollo. Lo sperimentatore principale determinerà quindi l'idoneità dei pazienti sulla base del proprio giudizio clinico sullo stato dei pazienti e sulla loro sicurezza.

E.4

Principal exclusion criteria

Females that are
a. pregnant, or are breast-feeding (for EU countries only);
b. of childbearing potential, pregnant, or are breast-feeding (for US and Rest of World countries).
Females of childbearing potential using adequate birth control will be eligible. A woman is considered of childbearing potential (WOCBP), i.e.
fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include
hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an
alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal
state in women not using hormonal contraception or hormonal replacement therapy. However in the absence of 12 months of
amenorrhea, a single FSH measurement is insufficient. See Section 11.7
Concomitant Medications for adequate methods of birth control.
2.A disability that may prevent the patient from completing all study
requirements.
3.Current participation in a clinical study with another investigational
drug.
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.Current neoplastic disease.
6.Severe impairment of the immunological system.
7.Severe or unstable pulmonary disease.
8.Uncontrolled diabetes.
Patients with diabetes that has been stabilized (i.e. no hypoglycemic or hyperglycemic episodes in the past 3 months) will be eligible.
9.Any other severe, unstable, or serious disease or condition that in the
Investigator's opinion would put the patient at risk for imminent lifethreatening morbidity, need for hospitalization, or mortality.
10.Eligibility of patients with abnormal laboratory test values will be determined by the Investigator.
11.Confirmed hemoglobinopathies, e.g. hemoglobin C disease, sickle cell anemia, or thalassemia.
12.Moderate or severe renal and/or hepatic impairment.
13.Patients who experienced moderate/ severe steroid side effects, or moderate/ severe adverse events associated with the study medication
administered in the IEDAT-02 study.
Prior/Concomitant Medication
14.Requires treatment with an oral or parenteral steroid. Treatment with inhaled or intranasal steroids for asthma or allergies, as well as use of
topical steroids will be permitted.
15.Requires any other concomitant medication prohibited by the protocol.
16.Use of any drug that is a strong inducer/inhibitor of CYP3A4.

Principi generali
1. Donne
a. in stato di gravidanza o in allattamento (solo per i paesi dell'UE);
b. in età fertile, in gravidanza o in allattamento (per Stati Uniti e Paesi del resto del mondo).
Saranno ritenute idonee le donne in età fertile che utilizzano un metodo contraccettivo adeguato, come determinato dal loro operatore sanitario di riferimento.
2. Una disabilità che può impedire alla paziente di completare tutti i requisiti dello studio.
3. Partecipazione attuale a uno studio clinico con un altro farmaco sperimentale.
Anamnesi medica e stato attuale
4. Conta dei linfociti CD4 + < 400/mm3 (per i pazienti di età pari a 6 anni) o <150/mm3 (per i pazienti > 6 anni). In presenza di infezioni orali, come la candidosi orale, documentate allo screening o ricorrenti secondo la documentazione di anamnesi, il limite aumenta a < 200/mm3 (per i pazienti > 6 anni).
5. Malattia neoplastica in corso.
6. Grave compromissione del sistema immunitario.
7. Malattia polmonare grave o instabile.
8. Diabete non controllato.
I pazienti con diabete stabilizzato (cioè nessun episodio ipoglicemico o iperglicemico negli ultimi 3 mesi) saranno ammissibili.
9. Qualsiasi altra malattia o condizione grave, instabile o seria che, secondo l'opinione dello sperimentatore, metterebbe il paziente a rischio di imminente morbilità potenzialmente letale, necessità di ricovero o mortalità.
10. L'ammissibilità dei pazienti con valori anomali degli esami di laboratorio sarà determinata dallo sperimentatore.
11. Emoglobinopatie confermate, ad es. malattia da emoglobina C, anemia falciforme o talassemia.
12. Insufficienza renale e/o epatica moderata o grave.
13. Pazienti che hanno manifestato effetti collaterali da steroidi moderati/gravi o eventi avversi moderati/gravi associati al farmaco in studio somministrato nella sperimentazione IEDAT-02.
Farmaci precedenti/concomitanti
14. Necessità di trattamento con uno steroide orale o parenterale. Sarà consentito il trattamento con steroidi per via inalatoria o intranasale per asma o allergie, nonché l'uso di steroidi topici.
15. Necessità di qualsiasi altro farmaco concomitante proibito dal protocollo.
16. Uso di qualsiasi forte induttore/inibitore di CYP3A4.

E.5 End points

E.5.1

Primary end point(s)

To monitor and evaluate the long-term safety and tolerability of EDS-EP in AT patients

Monitorare e valutare la sicurezza e la tollerabilità a lungo termine di EDS-EP nei pazienti con AT.

E.5.1.1

Timepoint(s) of evaluation of this end point

During the study, long-term efficacy assessments will be performed every 6 months, while safety parameters will be assessed at each monthly visit.

Durante lo studio, verranno eseguite valutazioni di efficacia a lungo termine ogni 6 mesi, mentre i parametri di sicurezza saranno valutati a ciascuno
visita mensile.

E.5.2

Secondary end point(s)

To evaluate the long-term effect of EDS-EP on health related Quality of Life (QoL; EQ-5D-5L scale).

Valutare l'effetto a lungo termine di EDS-EP sulla qualità della vita correlata alla salute (Quality of Life, QoL; scala EQ-5D-5L).

E.5.2.1

Timepoint(s) of evaluation of this end point

Durante lo studio, verranno eseguite valutazioni di efficacia a lungo termine ogni 6 mesi, mentre i parametri di sicurezza saranno valutati a ciascuno
visita mensile.

During the study, long-term efficacy assessments will be performed every 6 months, while safety parameters will be assessed at each monthly visit.

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

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

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

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Studio in aperto

Open Label

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

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.8.4.1

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

India

Tunisia

United States

Belgium

Germany

Italy

Norway

Poland

Spain

United Kingdom

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

LPLV

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.1.1.1

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:

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Inclusion criterion 4:
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 re

Criterio di inclusione 4:
Il paziente e il suo genitore/caregiver (se inferiore all'età del consenso), o un rappresentante legale, hanno fornito il consenso informato scritto alla partecipazione. Se il consenso viene fornito esclusivamente dal caregi

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

155

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

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

2021-03-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-05-12

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2023-01-20

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IMP with orphan designation in the indication
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