Clinical Trials Register

Summary
EudraCT Number:	2016-003482-25
Sponsor's Protocol Code Number:	CICL670F2429
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:	2021-02-16
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

2016-003482-25

A.3

Full title of the trial

A single-arm interventional Phase IV, post-authorisation study evaluating the safety of pediatric patients with transfusional hemosiderosis treated with deferasirox crushed film coated tablets

Studio a braccio singolo, interventistico, di Fase IV, postautorizzazione di valutazione della sicurezza d¿impiego in pazienti pediatrici con emosiderosi trasfusionale trattati con deferasirox compresse rivestite con film frantumate

A.3.1

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

Phase IV safety study of crushed deferasirox film coated tablets in pediatric patients with transfusional hemosiderosis

Studio di fase IV per valutare la sicurezza d¿impiego di deferasirox compresse rivestite con film frantumate in pazienti pediatrici con emosiderosi trasfusionale

A.3.2

Name or abbreviated title of the trial where available

A.4.1

Sponsor's protocol code number

CICL670F2429

A.5.4

Other Identifiers

Name:

Number:

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	NOVARTIS PHARMA AG
B.1.3.4	Country	Switzerland
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	Novartis Pharma AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	NOVARTIS FARMA S.p.A
B.5.2	Functional name of contact point	Drug Regulatory Affairs
B.5.3	Address:
B.5.3.1	Street Address	Largo Umberto Boccioni, 1
B.5.3.2	Town/ city	ORIGGIO
B.5.3.3	Post code	21040
B.5.3.4	Country	Italy
B.5.4	Telephone number	0296541
B.5.5	Fax number	029659066
B.5.6	E-mail	info.studiclinici@novartis.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	Yes
D.2.1.1.1	Trade name	Exjade
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DEFERASIROX
D.3.9.1	CAS number	201530-41-8
D.3.9.2	Current sponsor code	ICL670
D.3.9.4	EV Substance Code	SUB21981
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	90
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	No
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	No
D.IMP: 2
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	Yes
D.2.1.1.1	Trade name	Exjade
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DEFERASIROX
D.3.9.1	CAS number	201530-41-8
D.3.9.2	Current sponsor code	ICL670
D.3.9.4	EV Substance Code	SUB21981
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	180
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	No
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	No
D.IMP: 3
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	Yes
D.2.1.1.1	Trade name	Exjade
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
D.2.1.2	Country which granted the Marketing Authorisation	European Union
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DEFERASIROX
D.3.9.1	CAS number	201530-41-8
D.3.9.2	Current sponsor code	ICL670
D.3.9.4	EV Substance Code	SUB21981
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	360
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	No
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	No

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

Transfusional Hemosiderosis

Emosiderosi trasfusionale

E.1.1.1

Medical condition in easily understood language

Transfusional Hemosiderosis

Emosiderosi trasfusionale

E.1.1.2

Therapeutic area

Diseases [C] - Blood and lymphatic diseases [C15]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.1
E.1.2	Level	LLT
E.1.2	Classification code	10019613
E.1.2	Term	Hemosiderosis
E.1.2	System Organ Class	100000004861

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 assess the safety of crushed deferasirox FCT with respect to selected gastrointestinal(GI) disorders in pediatric patients aged =2 to < 6 years
with transfusional iron overload up to 24 weeks including 30 days safety follow-up

Valutare la sicurezza d¿impiego di deferasirox compresse rivestite con film (FCT) frantumate in pazienti pediatrici di et¿ = 2 anni e < 6 anni con sovraccarico di ferro trasfusionale riguardo a disturbi gastrointestinali (GI) selezionati fino a 24 settimane, compresi 30 giorni di follow-up per la valutazione della sicurezza d¿impiego.

E.2.2

Secondary objectives of the trial

to evaluate adverse events (AEs) suspected to be related to the crushed
deferasirox FCT during the study

Valutare gli eventi avversi (AE) sospettati di essere correlati a deferasirox compresse rivestite con film (FCT) frantumate di durante lo studio
- Valutare la sicurezza d¿impiego complessiva di deferasirox compresse rivestite con film (FCT) frantumate
- Valutare l¿efficacia del trattamento con deferasirox FCT
- Valutare la soddisfazione del paziente del trattamento, la palatabilit¿ e i sintomi gastrointestinali (GI) mediante ¿Observer Reported Outcomes (ObsROs)¿

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

o Patients =2 to <6 years old diagnosed with transfusional
hemosiderosis
o Documented history of red blood cell transfusions
o Written informed consent/assent before any study-specific
procedures.
o For patients on prior DFX: Serum ferritin (SF) >500 ng/mL, measured
at screening visit 1 and requiring a DFX daily dose equivalent to FCT =
7mg/kg/day.
o For patients on a prior chelator other than DFX (e.g. deferiprone or
deferaxamine) or chelation naive: Serum ferritin (SF) >1000 ng/mL
measured at screening visits 1 and 2

1. Pazienti di età > 2 anni e < 6 anni con diagnosi di emosiderosi trasfusionale.
2. Anamnesi documentata di trasfusioni di globuli rossi.
3. Consenso/assenso informato scritto ottenuto prima di qualsiasi procedura specifica per lo studio. Il consenso sarà ottenuto dai genitori o dal tutore del paziente. Gli sperimentatori otterranno anche l’assenso del paziente in base alle normative locali, regionali o nazionali.
4. Nei pazienti con precedente terapia con deferasirox: ferritina sierica (SF) > 500 ng/mL, misurata alla Visita 1 di screening e che richiedono una dose giornaliera di deferasirox equivalente a FCT = 7 mg/kg/die.
5. Nei pazienti con precedente terapia chelante diversa da deferasirox (per esempio, deferiprone o deferoxamina) o naïve alla terapia chelante: ferritina sierica (SF) > 1000 ng/mL, misurata alla Visita 1 e alla Visita 2 di screening.

E.4

Principal exclusion criteria

o History of hypersensitivity to any of the study drug or excipients.
o Serum creatinine > age adjusted ULN measured at any screening visit
o Creatinine clearance below 90 mL/minute measured at any screening visit.
o ALT and/or AST > 2.5 x ULN measured at screening visit 1.
o Total bilirubin (TBIL) >1.5 x ULN measured at screening visit 1.
o Patients with significant impaired GI function or GI disease that may significantly alter the absorption of oral deferasirox FCT (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
o Patients unwilling or unable to comply with the protocol

1. Pazienti che ricevono più di un chelante del ferro allo stesso tempo come terapia ferro-chelante in corso. (I pazienti che hanno ricevuto una terapia d’associazione nella loro storia medica ma che sono al momento trattati con un singolo farmaco ferro-chelante sono eleggibili).
2. Pazienti che continuano il trattamento con deferoxamina o deferiprone in aggiunta al trattamento in studio. (I pazienti che passano al trattamento con deferasirox o che continuano il trattamento con deferasirox sono eleggibili).
3. Eventi avversi non guariti se il paziente era stato precedentemente trattato con deferiprone o deferoxamina o deferasirox.
4. Proteinuria significativa, come indicato da un rapporto urinario proteina/creatinina > 0,5 mg/mg in un campione di urine (seconde urine del mattino), valutato alla Visita 1 di screening.
5. Creatininemia > ULN aggiustato per l’età in qualsiasi visita di screening.
6. Clearance della creatinina inferiore a 90 mL/minuto a qualsiasi visita di screening. La clearance della creatinina sarà calcolata utilizzando la formula di Schwartz utilizzando la creatininemia misurata in occasione di ogni visita rispettiva.
7. ALT e/o AST > 2,5 x ULN misurata alla Visita 1 di screening.
8. Bilirubina totale (TBIL) > 1,5 x ULN misurata alla Visita 1 di screening.
9. Pazienti con compromissione cronica o acuta significativa della funzionalità gastrointestinale (GI) o gastropatie che possono alterare significativamente l’assorbimento di deferasirox FTC assunto per via orale (ad es. colite ulcerosa, nausea non controllata, vomito, diarrea, sindrome da malassorbimento o resezione dell’intestino tenue).
10. Anamnesi positiva e/o evidenza di laboratorio di epatite B o epatite C in fase attiva (HBsAg in assenza di HBsAb OPPURE HCV Ab positivo con HCV RNA positivo).
11. Epatopatia di gravità corrispondente a Classe di Child-Pugh B o C.
12. Anamnesi positiva per ipersensibilità al farmaco in studio o agli eccipienti.
13. Pazienti partecipanti ad un altro studio clinico o in trattamento con un farmaco sperimentale.
14. Pazienti con un’anamnesi positiva di sieropositività HIV.
15. Pazienti che non intendono o non possono aderire al protocollo.
16. Anamnesi positiva per patologie neoplastiche a carico di qualsiasi sistema od organo, trattate o non trattate, entro gli ultimi 5 anni, indipendentemente dall’evidenza di recidiva locale o metastasi, ad eccezione del carcinoma basocellulare cutaneo localizzato.
17. Condizioni mediche significative che potrebbero interferire con la capacità di partecipare a questo studio (ad es. ipertensione arteriosa non controllata, cardiopatia instabile non controllata dalla terapia medica standard, malattie sistemiche cardiovascolari, renali, epatiche, ecc.).
18. Pazienti di sesso femminile che raggiungono il menarca e che non acconsentano a sottoporsi al test di gravidanza (personalmente o i genitori/il tutore) o in caso il risultato del test di gravidanza fosse positivo.

E.5 End points

E.5.1

Primary end point(s)

number and percentage of patients with selected gastrointestinal disorders (esophagitis, stomatitis, mouth ulceration, gastric ulcers, haemorrhage, abdominal pain, diarrhea, nausea and vomiting) up to 24 weeks including 30 days safety follow-up

Eventi avversi e in particolare eventi avversi gastrointestinali selezionati (esofagite, stomatite, ulcerazioni buccali, ulcere gastriche, emorragia, dolore addominale, diarrea, nausea e vomito).
Ematologia, biochimica (compresi i parametri di funzionalità renale ed epatica) ed esami urine
- Elettrocardiogramma (ECG)
- Segni vitali
- Esame audiometrico e valutazione oculistica

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 2, week 3, week 4, week 8, week 12, week 16, week 20 and week 24

Settimana 2, settimana 4, settimana 8, settimana 12, settimana 16, settimana 20 e settimana 24

E.5.2

Secondary end point(s)

o To assess the overall safety of crushed FCT of deferasirox
o To assess the efficacy of deferasirox FCT treatment
o To evaluate patient treatment satisfaction, palatability and
gastrointestinal (GI) symptoms with Observer Reported Outcomes
(ObsROs)

Trattamento con deferasirox FCT utilizzando ObsROs:
- Soddisfazione alla terapia chelante del ferro modificata (mSICT)
- Palatabilit¿
- Sintomi gastrointestinali

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 2, week 3, week 4, week 8, week 12, week 16, week 20 and week
24

Settimana 2, settimana 3, settimana 4, settimana 8, settimana 12, settimana 16, settimana 20 e settimana 24

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

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

Yes

E.6.13.1

Other scope of the trial description

treatment satisfaction, palatability, GI symptoms with Observer Reported Outcomes

soddisfazione del paziente al trattamento, palatabilit¿,sintomi gastrointestinali con ORS (Observer Reported Outcomes)

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)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

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

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

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

Chile

Egypt

Lebanon

Malaysia

Oman

Russian Federation

Saudi Arabia

Thailand

Turkey

United Arab Emirates

United States

France

Italy

United Kingdom

E.8.7

Trial has a data monitoring committee

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

Completion of this study as a whole will occur upon the availability of the last data point

Il completamento di questo studio nel suo complesso si verificher¿ sulla disponibilit¿dell'ultima registrazione dei datii

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)

F.1.2

Adults (18-64 years)

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

F.3.3.1

Women of childbearing potential not using contraception

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

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 of care

terapia satndard

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

2017-11-13

Ethics Committee Opinion of the trial application

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

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:
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