Clinical Trials Register

Summary
EudraCT Number:	2010-023900-29
Sponsor's Protocol Code Number:	MAF-AGN-OPH-RET-004
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:	2012-02-09
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2010-023900-29

A.3

Full title of the trial

A 12-Month, Multicentre, Randomised, Parallel Group Study to Compare
the Efficacy and Safety of Ozurdex Versus Lucentis in Patients with
Branch Retinal Vein Occlusion

Studio multicentrico, randomizzato, a gruppi paralleli, della durata di 12 mesi, condotto per confrontare l'efficacia e la sicurezza di Ozurdex versus Lucentis in pazienti affetti da occlusione venosa retinica di branca

A.3.1

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

Comparison of Ozurdex versus Lucentis in the treatment of Branch
Retinal Vein Occlusion

Confrontare Ozurdex versus Lucentis nel trattamento da occlusione venosa retinica di branca

A.4.1

Sponsor's protocol code number

MAF-AGN-OPH-RET-004

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	ALLERGAN PHARMACEUTICALS IRELAND
B.1.3.4	Country	Ireland
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	Allergan Pharmaceuticals Ireland
B.4.2	Country	Israel
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Allergan Limited
B.5.2	Functional name of contact point	Allergan Limited EU Regulatory Dept
B.5.3	Address:
B.5.3.1	Street Address	1st Floor, Marlow International, The Parkway
B.5.3.2	Town/ city	Marlow, Bucks
B.5.3.3	Post code	SL7 1YL
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+44 1628 494444
B.5.5	Fax number	+44 1628 494449
B.5.6	E-mail	ml-eu_reg_affairs@allergan.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	Ozurdex
D.2.1.1.2	Name of the Marketing Authorisation holder	Allergan Pharmaceuticals Ireland
D.2.1.2	Country which granted the Marketing Authorisation	Ireland
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	Implant
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravitreal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	DEXAMETHASONE
D.3.9.1	CAS number	50-02-2
D.3.9.4	EV Substance Code	SUB07017MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	700
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	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	Comparator
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	Lucentis
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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	Solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravitreal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	RANIBIZUMAB
D.3.9.1	CAS number	347396-82-1
D.3.9.4	EV Substance Code	SUB22314
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	10
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	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	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

Macula oedema secondary to branch retinal vein occlusion

Edema maculare secondario ad occlusione venosa retinica di branca

E.1.1.1

Medical condition in easily understood language

Blockage of veins in the eye that leads to build up of fluid causing swelling in the the macula.This may lead to damage to the macula which affects your central vision

Blocco delle vene nell'occhio che porta alla formazione di liquidi che causano gonfiore nella macula. Questo causa danni alla macula che colpisce la visione centrale

E.1.1.2

Therapeutic area

Diseases [C] - Eye Diseases [C11]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10025415
E.1.2	Term	Macular oedema
E.1.2	System Organ Class	10015919 - Eye 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 compare the efficacy and safety of Ozurdex vs. Lucentis in subjects with BRVO

Confrontare l’efficacia e la sicurezza di Ozurdex vs. Lucentis in soggetti affetti da BRVO

E.2.2

Secondary objectives of the trial

None

Nessuno

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female, ≥ 18 years of age 2. Written informed consent has been obtained 3. Written Data Protection Consent (European sites only) has been obtained 4. Study eye must have clear ocular media and adequate pupil dilation to permit good quality photographic imaging 5. ME secondary to BRVO in the study eye with all of the following characteristics: a) involving the centre of the macula (fovea) b) central retina subfield thickness ≥ 320 μm as assessed with Spectralis optical coherence tomography (OCT) or ≥ 300 μm as assessed with Cirrus OCT c) less than 90 days from onset of BRVO symptoms to screening visit d) visual acuity (VA) decrease attributable to retinal oedema Note: Characteristics a and b will be confirmed by a CRC 6. Absence of severe macular ischemia (defined as an area of nonperfusion > 4 disc areas [DA] which involve the foveal avascular zone), as confirmed by a CRC 7. BCVA score of ≥ 20 to ≤ 70 letters (20/40 to 20/400 Snellen equivalent) using the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity protocol at both the screening visit and day 1 visit. 8. Female subjects of childbearing potential must have a negative urine pregnancy test at the screening (day -14) visit

1.Uomini o donne di eta' ≥ 18 anni 2.Consenso informato scritto 3.Consenso scritto alla protezione dei dati personali 4.Occhio con la media oculare chiara e adeguata dilatazione della pupilla per permettere una buona qualita' delle immagini fotografiche 5.EM secondaria a BRVO nell`occhio in studio con tutte le seguenti caratteristiche: a) coinvolgimento del centro della macula (fovea) b) Spessore medio retinico centrale ≥ 320 μm rilevato con Spectralis OCT (Heidelberg) o ≥ 300 μm rilevato con Cirrus OCT (Carl Zeiss).c) meno di 90 giorni dalla comparsa dei sintomi BRVO alla visita di screening d) la diminuzione dell’acuita' visiva (VA) attribuibile ad edema retinico Nota: le caratteristiche a e b saranno confermata da un CRC 6.Assenza di grave ischemia maculare (definita come una zona di non perfusione > 4 aree del disco che coinvolgono la zona foveale avascolare), come confermato da un CRC 7.Punteggio BCVA da ≥ 20 a ≤ 70 lettere (20/40 a 20/400 equivalente Snellen) utilizzando lo studio Trattamento precoce per la retinopatia diabetica (ETDRS) protocollo sulla acuita' visiva sia alla visita di screening che alla visita giorno 1. 8.Soggetti di sesso femminile in eta' fertile devono avere un test di gravidanza sulle urine alla visita di screening (giorno -14)

E.4

Principal exclusion criteria

1.History of a medical condition that, in the opinion of the investigator, would preclude scheduled study visits, completion of the study, or a safe administration of study medication. 2.Ocular hypertension unless controlled with monotherapy. 3.Pregnant or nursing (lactating) women, 4.Pre-menopausal women of child-bearing potential not using adequate Contraception. 5.Participation in an investigational drug or device study within 30 days of the screening visit. 6.Any current or history of ocular disease in the study eye other than RVO that, in the opinion the investigator, may confound assessment of the macula or affect central vision, such as exudative age-related macular degeneration, geographic atrophy, diabetic retinopathy, uveitis, streaks, histoplasmosis, pathological myopia, retinal detachment, epiretinal membrane, macular hole, or significant cataract 7.History of cataract surgery in either eye within the past 3 months prior to the screening visit 8.History or evidence of serious ocular trauma or intraocular surgery (such as laser-assisted in situ keratomileusis, keratoplasty, vitrectomy) in the study eye within the past 6 months prior to the screening visit 9.History of severe or serious hypersensitivity to any components of the test article or fluorescein dye. 10.> 10-Letter improvement in BCVA between the screening visit and day 1 11.Brisk afferent pupillary defect (ie, obvious and unequivocal) 12.Aphakia in the study eye or violation of the posterior capsule in the study eye, unless it occurred as a result of a yttrium-aluminum-garnet laser posterior capsulotomy in association with prior, posterior intraocular lens implantation 13.Any active ocular infection (ie, bacterial, viral, parasitic, or fungal) in adnexa of either eye 14.History of radial optic neurotomy or sheathotomy 15.Laser photocoagulation for ME in the study eye within 3 months prior to the screening visit 16.Anticipated need for ocular surgery or ophthalmic laser treatment in the study eye during the 12-month study period 17.Prior anti-VEGF treatment in study or fellow eye within 3 months of screening or systemic anti-VEGF treatment within 6 months of the screening visit 18.Use of intraocular, intravitreal, or peri-ocular steroids in the study eye within 3 months of the screening visit 19.Use of systemic steroids (eg, oral, intravenous, intra-articular, epidural, intrabursal) within 1 month of screening or anticipated use at any time during the study. Inhaled and intranasal steroids are allowed. 20.IOP > 22 mm Hg at screening or day 1 visit in either eye.

Storia di una condizione clinioca che, a giudizio dello sperimentatore, precluderebbe in le visite dellostudio, il completamento dello studio, o la somministrazione sicura del farmaco in studio. Ipertensione oculare controllata meno con monoterapia. 3.Donne in gravidanza o in allattamento 4.Donne in eta' fertile in pre-menopausa che non usano contraccettivi adeguati. 5.Participatione a un farmaco sperimentale o dispositivo medico 30 giorni prima la visita di screening. 6. Qualsiasi storia clinica in corso o passata di malattia oculare negli occhio RVO diverso da quello che, a giudizio del ricercatore, poptrebbe confondere la valutazione della macula o influire la visione centrale, come essudativa legata all`eta' della degenerazione maculare, atrofia geografica, retinopatia diabetica, uveite, striature, istoplasmosi, miopia patologica, distacco di retina, membrana epiretiniche, foro maculare, o significativa cataratta 7.Intervento chirurgico di cataratta in entrambi gli occhi negli ultimi 3 mesi prima della visita di screening 8.Storia clinica o evidenza di traumi oculari gravi o interventi chirurgici intraoculare (come il laser-assistita in situ cheratoplastica, vitrectomia) nell`occhio in studio negli ultimi 6 mesi precedenti la visita di screening 9.Storia di ipersensibilita' grave o seria ai principi del farmaco in studio o al colorante fluoresceina. 10.> 10-Lettera miglioramento BCVA tra la visita di screening e giorno 1 11. Difetto alla pupillare (ad esempio, evidente e inequivocabile) 12. Afachia nell`occhio in studio o violazione della capsula posteriore nell`occhio in studio, a meno che non sia verificato come risultato di capsulotomia posteriore in associazione con la prima, impianto di lente intraoculare posteriore 13. Qualsiasi infezione oculari attive (batteriche, virali,parassitarie o fungine) 14. Storia di neurotomia ottica radiale o di guainotomia. 15.Fotocoagulazione per ME nell`occhio in studio entro 3 mesi prima della visita di screening 16.Anticipata la necessita' di un intervento oculare chirurgico o trattamento laser oftalmico nell`occhio in studio durante il periodo di 12 mesi dello studio 17.Anti-VEGF trattamento entro 3 mesi dallo screening o o trattamento sistemico anti VEGF trattamento entro 6 mesi dalla visita di screening 18.Uso di intraoculare, intravitreali, o peri-oculare steroidi nell`occhio in studio entro 3 mesi dalla visita di screening 19. Uso di steroidi per via sistemica (ad esempio, orale, endovenosa, intra-articolare, epidurale) entro 1 mese dallo screening o in qualsiasi momento durante lo studio. Sono ammessi steroidi per via inalatoria e intranasale. 20.IOP> 22 mm Hg allo screening o al giorno 1 in ciascun occhio

E.5 End points

E.5.1

Primary end point(s)

The primary efficacy variable is mean change in BCVA at month 12.

Variabile primaria di efficacia e' la variazione media in BCVA al 12 mese

E.5.1.1

Timepoint(s) of evaluation of this end point

BCVA assessment at screening, baseline, day 7 and at each monthly visit

Valutazione BCVA allo screening, al basale, al giorno 7 e ad ogni visita mensile

E.5.2

Secondary end point(s)

1.Mean change in the central retina subfield thickness between baseline and month 6, and between baseline and month 12 2. Proportion of subjects with ≥ 15-letter improvement in BCVA between baseline and month 12 3. Proportion of subjects with ≥ 15-letter decrease in BCVA between baseline and month 12 4. Change from baseline in vision-dependent subfields of the VFQ-25 questionnaire including near vision, far vision, and vision-dependent activity at month 3, month 6, and month 12. 5. Proportion of subjects in each treatment arm not completing the month 12 visit due to treatment failure. Treatment failure is defined as a subject withdrawn by the investigator prior to the final visit because of a lack of efficacy.

Variazione media nello spessore medio retinico centrale tra il basale e il mese 6, e tra il basale e il mese 12 Percentuale di soggetti con miglioramento ≥ di 15-lettera in BCVA tra il basale e il mese 12 Percentuale di soggetti con ≥ diminuzione di 15 lettere di BCVA tra il basale e il mese 12 Cambiamento dal basale nei sottocampi visione dipendente del questionario VFQ 25 compresa la visione da vicino, visione lontana, la visione e l`attivita'-dipendente al mese 3, al mese 6 e al mese 12 Percentuale di soggetti che hanno interrotto il trattamento per scarsa efficacia in entrambi i bracci prima del 12 mese. Per fallimento del trattamento si intende un soggetto ritirato dallo sperimentatore prima della visita finale a causa di una mancanza di efficacia.

E.5.2.1

Timepoint(s) of evaluation of this end point

1. OCT assessments that will be used in evaluation of timepoint will be done at baseline, month 6 and month 12. 2. and 3. BCVA assessments that will be used in evaluation of timepoints will be done at baseline and month 12. 4. VFQ-25 questionnaire completed at baseline, month 3, month 6, and month 12.

1. Valutazioni OCT che saranno utiliizzati per la valutazione dei timepoint che saranno eseguiti alla visita basale, mese 6 e mese 12 2. e 3. Valutazioni BCVA che veranno utilizzate per la valutazione dei tempi che saranno eseguiti alla visita basale e mese 12. 4. VFQ-25 questionario compilato al basale, mese 3, mese 6 e mese 12

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

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

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

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)

Yes

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

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

Israel

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

LVLS

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

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)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

100

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

200

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

360

F.4.2.2

In the whole clinical trial

400

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)

Subjects will return to their standard of care treatment as determined by their physician after completion of the trial.

Soggetti ritorneranno al cure standard come stabilito dal proprio medico dopo la conclusione dello studio clinico.

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	National Institute for Health Research comprehensive clinical research Network

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2011-10-21

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-07-14

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-11-04

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IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
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