Clinical Trials Register

Summary
EudraCT Number:	2012-000180-25
Sponsor's Protocol Code Number:	WB28183
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-09-20
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

Spain - AEMPS

A.2

EudraCT number

2012-000180-25

A.3

Full title of the trial

A Phase III, randomized, double-blind, placebo-controlled study to assess the efficacy, safety and tolerability of lebrikizumab in adolescent patients with uncontrolled asthma who are on inhaled corticosteroids and second controller medication.

ENSAYO CLÍNICO DE FASE III, ALEATORIZADO, DOBLE CIEGO
Y CONTROLADO CON PLACEBO PARA DETERMINAR
LA EFICACIA, LA SEGURIDAD Y LA TOLERABILIDAD
DE LEBRIKIZUMAB EN PACIENTES ADOLESCENTES
CON ASMA NO CONTROLADA TRATADOS CON
CORTICOSTEROIDES INHALADOS Y UN SEGUNDO
MEDICAMENTO DE CONTROL

A.3.1

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

A Study of Lebrikizumab in Adolescent Patients With Uncontrolled Asthma Who Are on Inhaled Corticosteroids and a Second Controller Medication.

ENSAYO CLÍNICO DE LEBRIKIZUMAB EN PACIENTES ADOLESCENTES
CON ASMA NO CONTROLADA TRATADOS CON
CORTICOSTEROIDES INHALADOS Y UN SEGUNDO
MEDICAMENTO DE CONTROL

A.3.2

Name or abbreviated title of the trial where available

ACOUSTICS

A.4.1

Sponsor's protocol code number

WB28183

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01875003

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/279/2012

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	F. Hoffmann-La Roche Ltd
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	F. Hoffmann-La Roche Ltd
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	F. Hoffmann-La Roche Ltd
B.5.2	Functional name of contact point	Trial Information Support Line-TISL
B.5.3	Address:
B.5.3.1	Street Address	Grenzacherstrasse 124
B.5.3.2	Town/ city	Basel
B.5.3.3	Post code	4070
B.5.3.4	Country	Switzerland
B.5.6	E-mail	global.rochegenentechtrials@roche.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	lebrikizumab
D.3.2	Product code	RO5490255/F01-01
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	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LEBRIKIZUMAB
D.3.9.2	Current sponsor code	RO5490255
D.3.9.3	Other descriptive name	TNX-650, rhuMAb anti-IL13, aIL-13, MILR1444A
D.3.9.4	EV Substance Code	SUB31913
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	125
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	Yes
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	Lebrikizumab is a humanized monoclonal IgG4 antibody with an Fc region modification for increased stability that binds specifically to soluble interleukin-13 (IL-13).
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	lebrikizumab
D.3.2	Product code	RO5490255/F01-02
D.3.4	Pharmaceutical form	Solution for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	LEBRIKIZUMAB
D.3.9.2	Current sponsor code	RO5490255
D.3.9.3	Other descriptive name	TNX-650, rhuMAb anti-IL13, aIL-13, MILR1444A
D.3.9.4	EV Substance Code	SUB31913
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	125
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	Yes
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	Lebrikizumab is a humanized monoclonal IgG4 antibody with an Fc region modification for increased stability that binds specifically to soluble interleukin-13 (IL-13).

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	Subcutaneous use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection in pre-filled syringe
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Asthma

Asma

E.1.1.1

Medical condition in easily understood language

Asthma

Asma

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.1
E.1.2	Level	PT
E.1.2	Classification code	10003553
E.1.2	Term	Asthma
E.1.2	System Organ Class	10038738 - Respiratory, thoracic and mediastinal 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 evaluate the efficacy of lebrikizumab compared with placebo as measured by the rate of
asthma exacerbations
? To evaluate the safety of lebrikizumab compared with placebo as measured by the rate and
severity of adverse events and incidence of anti-therapeutic antibodies (ATAs)
? To evaluate the efficacy and safety of different dose levels of lebrikizumab compared with
placebo

Evaluar la eficacia de lebrikizumab en comparación con placebo, determinada mediante la tasa de exacerbaciones asmáticas.
? Evaluar la seguridad de lebrikizumab en comparación con placebo, determinada mediante la frecuencia e intensidad de los acontecimientos adversos y la incidencia de anticuerpos
antiterapéuticos (AAT).
? Evaluar la eficacia y la seguridad de distintas dosis de lebrikizumab en comparación con placebo.

E.2.2

Secondary objectives of the trial

To evaluate change in pre-bronchodilator FEV1, time to first asthma exacerbation, change in FeNO, change in patient-reported asthma-specific health related quality of life, change in asthma rescue medication use, and rate of urgent asthma-related health care utilization during the placebo-controlled period

To evaluate the acceptability (perceived pain) of injections of lebrikizumab

Evaluar la variación del volumen espiratorio forzado en el primer segundo (FEV1) antes de administrar un broncodilatador, el tiempo hasta la primera exacerbación asmática, la
variación de la fracción espirada de óxido nítrico (FeNO), la variación de la calidad de vida relacionada con la salud y específica del asma comunicada por el paciente, la variación del
uso de medicación antiasmática de rescate y la tasa de utilización de asistencia sanitaria urgente relacionada con el asma durante el período controlado con placebo.
? Evaluar la aceptabilidad (dolor percibido) de las inyecciones de lebrikizumab.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

? Adolescent patients, 12 - 17 years of age at the time of screening and randomization
? Asthma diagnosis for >/= 12 months at Visit 1
? Bronchodilator response during screening
? Pre-bronchodilator FEV1 of 40% - 90% predicted at both Visits 2 and 3
? On high dose inhaled corticosteroid (ICS) therapy for >/= 6 months prior to Visit 1
? On an eligible second controller medication for 6 months prior to Visit 1
? Uncontrolled asthma as defined by the protocol both during screening and at the time of randomization
? Demonstrated adherence with controller medication during the screening period.

- Edad de 12-17 años en las visitas 1 y 3.
- Diagnóstico de asma durante ? 12 meses antes de la visita 1.
- Respuesta broncodilatadora en la visita 1, 2 o 3 (véase en el manual de pruebas de función respiratoria la prueba de respuesta broncodilatadora).
- FEV1 antes de un broncodilatador del 40 %-90 % del valor teórico en las visitas 2 y 3.
- En tratamiento con CI en una dosis diaria total de 500-2000 ?g de propionato de fluticasona en IPS o equivalente durante ? 6 meses antes de la visita 1, sin modificaciones en las
4 semanas previas a la visita 1 y sin modificaciones previstas durante todo el estudio.
- En tratamiento con un segundo medicamento de control elegible (ABAP, ARLT, AMAP o teofilina) durante 6 meses antes de la visita 1
- Asma no controlada en la visita 1 o 2 y en la visita 3.
- Cumplimiento demostrado de la medicación de control durante el período de selección.

E.4

Principal exclusion criteria

? History of severe allergic reaction or anaphylactic reaction to a biologic agent or known hypersensitivity to any component of the lebrikizumab injection
? Maintenance oral corticosteroid therapy within 3 months of Visit 1
? Treatment with systemic (oral, intravenous, or intramuscular) corticosteroids within 4 weeks prior to Visit 1 or during the screening period
? Treatment with intra-articular corticosteroids within 4 weeks prior to Visit 1 or during the screening period or anticipated need for intra-articular corticosteroids during the course of the study
? Infection that meets the following criteria:
- Any infection requiring hospital admission or requiring treatment with IV or IM antibiotics within 4 weeks prior to Visit 1 or during screening:
- Any active infection that required treatment with oral antibiotics within 2 weeks prior to Visit 1 or during screening;
- Upper or lower respiratory tract infection within 4 weeks prior to Visit 1 or during screening;
- Active parasitic infection or Listeria monocytogenes infection within 6 months prior to Visit 1 or during screening;
? History of active tuberculosis requiring treatment
? Known immunodeficiency, including, but not limited to, HIV infection
? Evidence of acute or chronic hepatitis or known liver cirrhosis
? History of cystic fibrosis, bronchiectasis, and/or other clinically significant lung disease other than asthma
? Diagnosis or history of malignancy or current evaluation for potential malignancy
? Current smoker or former smoker with a history of > 10 pack-years
? History of alcohol or drug abuse
? Past and/or current use of any anti-IL-13 or anti-IL-4/IL-13 therapy, including lebrikizumab; use of other monoclonal antibody therapy, including omalizumab, within 6 months prior to Visit 1
? Initiation of or change in allergen immunotherapy within 3 months prior to Visit 1 or during screening.

1 Antecedentes de reacción alérgica grave o anafiláctica a un fármaco biológico o hipersensibilidad conocida a cualquiera de los componentes de la inyección de lebrikizumab.
2 Tratamiento de mantenimiento con corticosteroides por vía oral, en los 3 meses previos a la visita 1.
3. Tratamiento con corticosteroides sistémicos (por vía oral, intravenosa [IV] o intramuscular [IM]) en las 4 semanas previas a la visita 1 o durante el período de selección por cualquier
motivo, incluido un episodio de exacerbación aguda.
4 Tratamiento con corticosteroides intraarticulares en las 4 semanas previas a la visita 1 o durante el período de selección o necesidad prevista de corticosteroides intraarticulares
durante el estudio.
5 Infección que cumpla cualquiera de los criterios siguientes:
Infección que motive el ingreso hospitalario durante ? 24 horas en las 4 semanas previas a la visita 1 o durante la selección.
Infección que precise tratamiento con antibióticos IV o IM en las 4 semanas previas a la visita 1 o durante la selección.
Infección activa que precise tratamiento con antibióticos orales en las 2 semanas previas a la visita 1 o durante la selección.
Infección de las vías respiratorias superiores o inferiores en las 4 semanas previas a la visita 1 o durante la selección.
Infección parasitaria activa o infección por Listeria monocytogenes en los 6 meses previos a la visita 1 o durante la selección.
6 Antecedentes de tuberculosis activa con necesidad de tratamiento.
7 Inmunodeficiencia conocida, incluida, entre otras, la infección por el VIH.
8 Datos de hepatitis aguda o crónica o cirrosis hepática conocida.
9. Elevación de la AST, ALT o bilirrubina total ? 2,0 veces LSN durante la selección.
9. Elevación de la AST, ALT o bilirrubina total ? 2,0 veces LSN durante la selección.
10. Anomalía clínicamente importante en los ECG o las pruebas analíticas de selección que, podría suponer un riesgo adicional al administrar el fármaco del estudio al paciente.
11. Antecedentes de fibrosis quística, bronquiectasias u otra neumopatía con importancia clínica distinta del asma.
12. Diagnóstico o antecedentes de neoplasia maligna o de evaluación en curso por una posible neoplasia maligna.
14. Antecedentes de alcoholismo o toxicomanía
15. Fumador activo, ex fumador con antecedentes de tabaquismo de > 10 cajetillas-año
17. Uso Actual o en el pasado de un anticuerpo monoclonal aprobado o en investigación distinto de anti-IL-13 o
anti-IL-4/IL-13, entre otros, omalizumab, anti-IL-5 o anti-IL-17, en los 6 meses previos a la visita 1 o el equivalente a 5 semividas del fármaco (lo que sea más largo) o durante la
selección.

E.5 End points

E.5.1

Primary end point(s)

Rate of asthma exacerbations during the 52-week placebo-controlled period

Tasa de exacerbaciones asmáticas durante el período controlado con placebo de 52 semanas.

E.5.1.1

Timepoint(s) of evaluation of this end point

52 weeks

52 semanas

E.5.2

Secondary end point(s)

1. Relative change in pre-bronchodilator FEV1 (liters)
2. Time to first asthma exacerbation
3. Change in fractional exhaled nitric oxide (FeNO)
4. Change in asthma-specific, health-related quality of life: overall score of the Standardized Asthma Quality of Life Questionnaire for 12 years and older (AQLQ +12)
5. Change in asthma rescue medication use
6. Rate of urgent asthma-related health care utilization

Variación relativa del FEV1 (litros) antes del broncodilatador entre el momento basal y la semana 52.
Tiempo hasta la primera exacerbación asmática durante el período controlado con placebo de 52 semanas.
Variación de la FeNO entre el momento basal y la semana 52.
Variación de la calidad de vida relacionada con la salud y específica del asma, determinada mediante la puntuación global en el Cuestionario de calidad de vida en el asma normalizado para pacientes de 12 años o más (AQLQ +12), entre el momento basal y la semana 52.
Variación del uso de medicación antiasmática de rescate entre el momento basal y la semana 52.
Tasa de utilización de asistencia sanitaria urgente relacionada con el asma durante el período controlado con placebo de 52 semanas.

E.5.2.1

Timepoint(s) of evaluation of this end point

1. from baseline to week 52
2. week 52
3 to 5. from baseline to week 52
6. 52 weeks

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

Yes

E.6.13.1

Other scope of the trial description

TOLERABILITY

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

Serbia

Argentina

Brazil

Canada

Colombia

Czech Republic

France

Germany

Hungary

India

Italy

Korea, Republic of

Portugal

Spain

Israel

Mexico

Peru

Poland

Russian Federation

Slovakia

South Africa

Taiwan

Ukraine

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

LVLS

Ultima visita ultimo paciente

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:

375

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)

Yes

F.1.1.6.1

Number of subjects for this age range:

375

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

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

For patients considered to be minors according to national legislation, the written consent of the parent or legal guardian must be obtained, as well as the assent of the minor according to his or her capacity to understand the information provided.

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

115

F.4.2.2

In the whole clinical trial

375

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)

Roche will evaluate the appropriateness of continuing to provide lebrikizumab to study patients after the study is completed.

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

2013-11-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-11-05

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-12-28

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