Clinical Trials Register

Summary
EudraCT Number:	2013-000856-16
Sponsor's Protocol Code Number:	DRI12544
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:	2013-05-16
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

Spain - AEMPS

A.2

EudraCT number

2013-000856-16

A.3

Full title of the trial

A Randomized, Double-Blind, Placebo-Controlled, Dose-Ranging Study to Evaluate Dupilumab in Patients with Moderate to Severe Uncontrolled Asthma

Estudio de búsqueda de dosis, aleatorizado, doble ciego, controlado con placebo para evaluar Dupilumab en pacientes con asma no controlada de moderada a grave

A.3.1

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

An Evaluation of Dupilumab in Patients with Moderate to Severe Uncontrolled Asthma

Evaluación de Dupilumab en pacientes con asma no controlada de moderada a grave

A.4.1

Sponsor's protocol code number

DRI12544

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1138-3962

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	Sanofi-aventis recherche et développement
B.1.3.4	Country	France
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	Sanofi-aventis recherche et développement
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	sanofi-aventis, s.a.
B.5.2	Functional name of contact point	CSU Director, Bibiana Figueres
B.5.3	Address:
B.5.3.1	Street Address	c/ Josep Pla nº2, 5ª planta
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08019
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34 93 485 94 66
B.5.5	Fax number	+34 93 489 54 66
B.5.6	E-mail	bibiana.figueres@sanofi.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	Dupilumab
D.3.2	Product code	SAR231893
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	Dupilumab
D.3.9.2	Current sponsor code	SAR231893
D.3.9.3	Other descriptive name	REGN668
D.3.9.4	EV Substance Code	SUB88511
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	150
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)	Yes
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	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	Dupilumab
D.3.2	Product code	SAR231893
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	Dupilumab
D.3.9.2	Current sponsor code	SAR231893
D.3.9.3	Other descriptive name	REGN668
D.3.9.4	EV Substance Code	SUB88511
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	100
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)	Yes
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	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	Solution for injection
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	16.0
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 different doses and regimens of dupilumab in patients with moderate to severe, uncontrolled asthma

Evaluar la eficacia de diferentes dosis y regímenes de dupilumab en pacientes con asma no controlada de moderada a grave

E.2.2

Secondary objectives of the trial

To evaluate different doses and regimens of dupilumab in patients with moderate to severe uncontrolled asthma, with regard to:
- Safety and tolerability
- Dupilumab systemic exposure and anti-drug antibodies

Evaluar diferentes dosis y regímenes de dupilumab en pacientes con asma no controlada de moderada a grave, con respecto a:
? Seguridad y tolerabilidad
? Exposición sistémica a dupilumab y anticuerpos anti-fármaco

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- Patients with a physician diagnosis of moderate to severe, uncontrolled asthma for ?12 months, based on the Global Initiative for Asthma (GINA) 2009 Guidelines and:
- Existing treatment with moderate- or high-dose inhaled corticosteroid / long-acting beta-2 agonist
- Forced expiratory volume (FEV1) 40 to 80% of predicted normal
- Juniper Asthma Control Questionnaire, 5-question version (ACQ-5) score ?1.5
- Reversibility of at least 12% and 200 mL in forced expiratory volume (FEV1)
- Has experienced, within prior year: hospitalization, emergency or urgent care visit or systemic corticosteroid treatment for worsening asthma

Pacientes con un diagnóstico médico de asma no controlada de moderada a grave durante más o igual a 12 meses, según las directrices de la Iniciativa global para el asma (Global Initiative for Asthma, GINA) de 2009 y los siguientes criterios:
- Tratamiento existente con dosis de moderadas a altas de ICS/LABA [sup o igual 250 microg de propionato de fluticasona (o un ICS equivalente) dos veces al día] con una dosis estable de ICS/LABA durante mas o igual a 1 mes antes de la visita 1.
- Volumen espiratorio forzado (Forced expiratory volume, FEV1) entre el 40 y el 80% del valor normal previsto en la visita 1 y en la visita 2 antes de la aleatorización
- Puntuación en el cuestionario de control del asma de Juniper, versión de 5 preguntas (Asthma Control Questionnaire, ACQ-5) sup o igual 1,5 en las visitas 1 y 2
- Reversibilidad de al menos un 12% y 200 ml en el FEV1 después de 200 mL
- Hospitalización o visita médica de emergencia/urgencia por empeoramiento del asma
Pacientes que han firmado su consentimiento informado

E.4

Principal exclusion criteria

- Patients <18 years
- Chronic obstructive pulmonary disease (COPD) or other lung diseases (eg, emphysema, idiopathic pulmonary fibrosis, Churg Strauss syndrome, allergic bronchopulmonary aspergillosis) which impair pulmonary function tests
- Chest X-ray within 12 months of screening visit or at screening visit with clinically significant findings of lung disease(s) other than asthma
- Current smoker or cessation of smoking within 6 months prior to Visit 1
- Previous smoker with a smoking history >10 pack-years

- Pacientes menores de 18 años
- Enfermedad pulmonar obstructiva crónica (EPOC) u otras enfermedades pulmonares (por ejemplo, enfisema, fibrosis pulmonar idiopática, síndrome Churg-Strauss, aspergilosis broncopulmonar alérgica) que afectan las pruebas de función pulmonar
- Radiografía de tórax en los 12 meses previos a la visita de selección o en la visita de selección con resultados clínicos significativos de enfermedad(es) pulmonar(es) que no sean asma
- Fumador actual o el cese del hábito de fumar dentro de los 6 meses previos a la visita 1
- Fumador previo con una historia de tabaquismo > 10 paquetes-año

E.5 End points

E.5.1

Primary end point(s)

Change from baseline in forced expiratory volume (FEV1)

Cambio del FEV1 desde el basal a la semana 12

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 12

Semana 12

E.5.2

Secondary end point(s)

1) Relative change from baseline in FEV1
2) Annualized rate of loss of asthma control
3) Time to loss of asthma control
4) Change from baseline in asthma symptom scores

1) Cambio relativo (%) del FEV1 desde el basal
2) Tasa anualizada de acontecimientos de pérdida de control del asma
3) Tasa anualizada de acontecimientos de exacerbación grave
4) Tiempo hasta los acontecimientos de pérdida de control del asma durante el período de tratamiento

E.5.2.1

Timepoint(s) of evaluation of this end point

1/4) Week 12
2/3) Week 24

1/4) Semana 12
2/3) Semana 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

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

Yes

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

Yes

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

Australia

Chile

Japan

Korea, Republic of

Mexico

New Zealand

Russian Federation

South Africa

Turkey

Ukraine

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

Última visita del último 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

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:

1470

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

140

F.4.2.2

In the whole clinical trial

1500

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)

None

Ninguno

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

2013-06-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-06-17

P. End of Trial
P.	End of Trial Status	Completed

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