Clinical Trials Register

Summary
EudraCT Number:	2012-002339-27
Sponsor's Protocol Code Number:	I4V-MC-JADX
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:	2012-12-21
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

2012-002339-27

A.3

Full title of the trial

A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Baricitinib (LY3009104) in Patients with Inadequate Response to Conventional Disease-Modifying Antirheumatic Drugs with Moderately to Severely Active Rheumatoid Arthritis

Studio randomizzato, in doppio cieco, Placebo-controllato, di fase 3 per valutare l'efficiacia e la sicurezza di Baricitinib (LY3009104) in pazienti con una risposta inadeguata ai farmaci antireumatici convenzionali (DMARDs) affetti da Artrite Reumatoide moderata o severa

A.3.1

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

A Phase 3 Study in Moderate to Severe Rheumatoid Arthritis

Studio di Fase 3 in pazienti affetti da Artrite Reumatoide moderata o severa

A.3.2

Name or abbreviated title of the trial where available

RA - BUILD

A.4.1

Sponsor's protocol code number

I4V-MC-JADX

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	ELI LILLY AND COMPANY
B.1.3.4	Country	United States
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	Eli Lilly and Company
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Eli Lilly and Company
B.5.2	Functional name of contact point	Clinical Trial Information
B.5.3	Address:
B.5.3.1	Street Address	Lilly Corporate Center
B.5.3.2	Town/ city	Indianapolis
B.5.3.3	Post code	IN46285
B.5.3.4	Country	United States
B.5.4	Telephone number	0044 1276 483015
B.5.5	Fax number	0044 1276 483378
B.5.6	E-mail	EU_Lilly_Clinical_Trials@lilly.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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	BARICITINIB
D.3.2	Product code	LY3009104
D.3.4	Pharmaceutical form	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.3.9.2	Current sponsor code	LY3009104
D.3.9.3	Other descriptive name	Baricitinib
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	4
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	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	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	BARICITINIB
D.3.2	Product code	LY3009104
D.3.4	Pharmaceutical form	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.3.9.2	Current sponsor code	LY3009104
D.3.9.3	Other descriptive name	Baricitinib
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	2
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.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	Tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Moderately to severely active rheumatoid arthritis

Artrite reumatoide attiva da moderata a grave

E.1.1.1

Medical condition in easily understood language

Rheumatoid arthritis

Artrite reumatoide

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	SOC
E.1.2	Classification code	10028395
E.1.2	Term	Musculoskeletal and connective tissue disorders
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue disorders

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	10039073
E.1.2	Term	Rheumatoid arthritis
E.1.2	System Organ Class	10028395 - Musculoskeletal and connective tissue 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

Determine whether Baricitinib 4 mg QD is superior to placebo in the treatment of patients with moderately to severely active RA who have had inadequate response to or are intolerant to at least 1 cDMARD (cDMARD-IR [inadequate response] patients) and who have not received a biologic DMARD, as assessed by the portion of patients achieving ACR20 at Week 12 ECG Addendum - Approved: 22-Aug-2012 Primary objective is to compare the change from baseline in QTcF interval at approximately 90 minutes following first dose of investigational product (Week 0) and at week 1, Week 4, and week 12 between Baricitinib 4 mg QD and placebo.

Determinare se il trattamento con Baricitinib 4 mg è superiore al trattamento con placebo in pazienti affetti da artrire reumatoide da moderata a severa che abbiano avuto uan risposta inadeguatq o che siano intolleranti ad almeno 1 cDMARD (pazienti cDMARD-IR[risposta inadeguata]) e che non abbiano ricevuto un DMARD biologico, valutato dal numero di pazienti che raggiungono l'ACR20 alla dodicesima settimana ECG Addendum - Approvato: 22-Agosto-2012 Obiettivo primario è comparare la variazione rispetto al basale nell'intervallo QTcF approssimativamente a 90 minuti dalla somministrazione della prima dose del prodotto sperimentale (Settimana 0) ed alla Settimana 1, 4 e 12 tra baricitinib 4 mg e placebo

E.2.2

Secondary objectives of the trial

- change from baseline to Week 12 in Health Assessment Questionnaire-Disability Index (HAQ-DI) score - change from baseline to week 12 in DAS28-high-sensitivity C-reactive protein (hsCRP) - proportion of patients achieving ACR20 at Week 12 (Baricitinib 2 mg compared to placebo)

- cambiamento del punteggio Health Assessment Questionnaire Disability Index (HAQ-DI) alla dodicesima settimana rispetto al basale - variazione del valore della DAS28-high-sensitivity C reactive protein (hsCRP) alla dodicesima settimana rispetto al basale - pazienti che alla dodicesima settimana raggiungono l'ACR20

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

PHARMACOGENETIC:
Vers:1
Date:2012/08/21
Title:A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Study to Evaluate the Efficacy and Safety of Baricitinib
(LY3009104) in Patients with Inadequate Response to Conventional Disease-Modifying Antirheumatic Drugs with
Moderately to Severely Active Rheumatoid Arthritis
Objectives:Samples will be stored, and analysis may be performed on genetic variants thought to play a role in active RA and
the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) signaling pathways.

OTHER SUBSTUDIES:
Protocol Addendum I4V-MC-JADX(1) Approved: 22-Aug-201 ECG Addendum Approved: 22-Aug-2012

FARMACOGENETICA:
Vers:1
Data:2012/08/21
Titolo:Studio randomizzato, in doppio cieco,
Placebo-controllato, di fase 3 per valutare l'efficiacia e la sicurezza di Baricitinib (LY3009104) in pazienti con una risposta inadeguata ai farmaci antireumatici convenzionali (DMARDs) affetti da Artrite Reumatoide moderata o severa
Obiettivi:Saranno conservati campioni sui quali potrebbero essere effettuate analisi sulle varianti genetiche che si ritiene rivestano un qualche ruolo nella AR attiva e nelle vie di segnalazione di Janus chinasi (JAK)/fattori trascrizionali STAT (signal transducer and activator of transcription).

ALTRI SOTTOSTUDI:
Protocol Addendum I4V-MC-JADX(1) Approved: 22-Aug-201 ECG Addendum Approved: 22-Aug-2012

E.3

Principal inclusion criteria

-almeno 18 anni di età -diagnosi di Artrite Reumatoide iniziata in età adulta come definito dai criteri per la classificazione di AR ACR/EULAR 2010 - AR da moderata a severa definita come almeno 6/68 articolazioni lasse e 6/66 tumefazioni delle articolazioni - Valore della Proteina reattiva C > o uguale ad 1.2 ULN Risposta insufficiente o intolleranza ai cDMARDs o entrambe: uso regolare di un cDMARD per almeno 12 settimane prima di entrare in studio con un una dose continua e stabile per almeno le precedenti 8 settimane; Pe i pazienti che non in trattamento con cDMARD al momento dell'entrata in studio, l'investigatore dovrà documentare in cartella che il paziente ha fallito, non era in grado di tollerare o aveva qualche cntroindicazone per il trattamento con cDMARDs

- are at least 18 years of age - have a diagnosis of adult-onset RA as defined by the ACR/EULAR 2010 Criteria for the Classification of RA - have moderately to severely active RA defined as the presence of at least &768 tender joints and at least 6/66 swollen joints - have a c-reactive protein (or hsCRP) measurement > or equal 1.2 times the upper limit of normal (ULN) Have had an insufficient response or are intolerant to cDMARDs and either: have had regular use of a cDMARD for at least the 12 weeks prior to study entry; for patients not receiving a cDMARD at the time of entry, the investigator will document in the patient's history that the patient had failes, was unable to tolerate, or had a contraindication to treatment with cDMARD

E.4

Principal exclusion criteria

are currently receiving corticosteroids at doses >10mg per day of prednisone (or equivalent) or have been receiving an unstable dosing regimen of corticosteroids within 2 weeks of study entry or within 6 weeks of planned randomization •have started treatment with NSAIDs or have been receiving an unstable dosing regimen of NSAIDs within 2 weeks of study entry or within 6 weeks of planned randomization •are currently receiving concomitant treatment with MTX, hydroxychloroquine, and sulfasalazine • have ever received any biologic DMARD • have received interferon therapy within 4 weeks prior to study entry or are anticipated to require interferon therapy during the study •have had 3 or more joints injected with intraarticular corticosteroids within 2 weeks prior to study entry or within 6 weeks prior to planned randomization• have active fibromyalgia • have a diagnosis of any systemic inflammatory condition other than RA • have a diagnosis of Felty’s syndrome• have a history or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, hematological, neurological, or neuropsychiatric disorders or any other serious and/or unstable illness that, in the opinion of the investigator, could constitute a risk when taking investigational product or could interfere with the interpretation of data • have an eGFR based on the most recent available serum creatinine using the Modification of Diet in Renal Disease (MDRD) method of <40 mL/min/1.73 m2 • have a history of chronic liver disease with the most recent available aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5 times the ULN or the most recent available total bilirubin >1.5 times the ULN • have, or have a history of, lymphoproliferative disease; or have signs or symptoms suggestive of possible lymphoproliferative disease, including lymphadenopathy or splenomegaly; or have active primary or recurrent malignant disease; or have been in remission from clinically significant malignancy for <5 years • have been exposed to a live vaccine within 12 weeks prior to planned randomization or are expected to need/receive a live vaccine during the course of the study (with the exception of herpes zoster vaccination) • have a current or recent clinically serious viral, bacterial, fungal, or parasitic infection • have had symptomatic herpes zoster infection within 12 weeks prior to study entry •are immunocompromised and, in the opinion of the investigator, are at an unacceptable risk for participating in the study

-riceve una dose di prednisone > 10 mg al giorno o ha ricevuto un dosaggio non stabile di corticosteroidi nelle 2 settimane precedenti l'ingresso in studio o le sei settimane di randomizzazione. -ha iniziato un trattamento con NSAIDs o ha ricevuto NSAIDs ad un dosaggio non stabile nelle 2 settimane dall'entrata in studio o nelle 6 di randomizzazione.-Sta ricevendo un trattameto con MTX, idroclorochine o sulfosalazine-ha ricevuto un DMARD biologico-ha ricevuto terapia con interferone nelle 4 settimane prima dell'ingresso in studio-ha ricevuto 3 o più iniezioni articolari di corticosteroidi nelle 2 settimane precedenti l'ingresso in studio o nelle 6 settimane di randomizzazione-ha una fibromialgia attiva-ha una diagnosi di un'altra infammazone sistemica oltre all'AR-anamnesi di disfunzioni cardiache, respiratorie, epatiche, gastrointestinali, endocrine, ematologiche, neurologiche, o neuropsiatriche o di qualsiasi altro tipo che l'investigatore potrebbe ritenere rischiosa per l'ingreso in studio-ha un eGFR valuatto tramite creatinina sierica utilizzando il metodo MDRD < 40 mL/min/1.73 m2-disfunzioni epatiche croniche con AST ed ALT < 1.5 ULN o Bilirubina > 1.5 ULN-disordini linfoproliferativi-sia stato esposto a vaccinazioni live entro le 12 settimane dalla randomizzazione pianificata-attuale o recente infezione virale, batterica, fungina o parassitaria-infezione da herpes zooster sintomatico nelle 12 settimane precedenti l'ingresso in studio- immunocompromesso.

E.5 End points

E.5.1

Primary end point(s)

Proportion of patients achieving ACR20 response (baricitinib 4mg compared to placebo)

Pazienti che raggiungono l'ACR20 (Baricitinib 4 mg vs placebo)

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 12

Settimana 12

E.5.2

Secondary end point(s)

DAS28-high-sensitivity C-reactive protein (hsCRP): - Proportion of patients achieving ACR20 response (baricitinib 2mg compared to placebo)

-DAS28-high-sensitivity C-reactive protein (hsCRP) -pazienti che raggiungono l'ACR 20 (Baricitinib 2 mg vs placebo)

E.5.2.1

Timepoint(s) of evaluation of this end point

DAS28-high-sensitivity C-reactive protein (hsCRP): Change from baseline to Weeks 12 and 24 - Proportion of patients achieving ACR20 response (baricitinib 2mg compared to placebo) : Week 12

-DAS28-high-sensitivity C-reactive protein (hsCRP): variazoni a 12 e 24 settimane rispetto al basale -pazienti che raggiungono l'ACR 20 (Baricitinib 2 mg vs placebo): 12 settimane

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

E.6.10

Pharmacogenetic

Yes

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

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

Argentina

Canada

Croatia

Japan

Korea, Democratic People's Republic of

Korea, Republic of

Mexico

Taiwan

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

LVSL

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:

600

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

183

F.4.2.2

In the whole clinical trial

660

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)

Patients who complete this study through week 24will be eligible to partecipate in a separate extension study (Study I4V-MC-JADY [JADY]) lasting for up to 2 years if enrollment criteria for Study JADY are met or to posttreatment fllow-up period of this study.

Pazienti che hanno completato questo studio per le 24 settimane saranno elegibili per la patecipazione ad uno studio di estenzione separato (I4V-MC-JADY[JADY]) per i successivi 2 anni se i criteri di arruolamento per lo studio JADY saranno adeguati o ad un posttrattamento di follow up.

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

2013-01-07

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-12-19

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-01-07

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