Clinical Trials Register

Summary
EudraCT Number:	2016-001607-23
Sponsor's Protocol Code Number:	EFC14153
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2017-05-24
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2016-001607-23

A.3

Full title of the trial

A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Dupilumab in Children 6 to <12 Years of Age with Uncontrolled Persistent Asthma

A.3.1

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

Evaluation of Dupilumab in Children with Uncontrolled Asthma (Liberty Asthma Voyage)

A.4.1

Sponsor's protocol code number

EFC14153

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02948959

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1179-4851

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/021/2017

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Sanofi-Aventis Recherche & 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 Recherche & 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 Sp. z o.o.
B.5.2	Functional name of contact point
B.5.3	Address:
B.5.3.1	Street Address	ul. Bonifraterska 17
B.5.3.2	Town/ city	Warszawa
B.5.3.3	Post code	00-203
B.5.3.4	Country	Poland
B.5.4	Telephone number	+482228 00 000
B.5.6	E-mail	informacja.medyczna@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 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	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)	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	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 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	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	175
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	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 in pre-filled syringe
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

E.1.1.1

Medical condition in easily understood language

Asthma

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	20.0
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 dupilumab in children 6 to <12 years of age with uncontrolled persistent asthma.

E.2.2

Secondary objectives of the trial

-To evaluate in children 6 to <12 years of age with uncontrolled persistent asthma:
-The safety and tolerability of dupilumab.
-The effect of dupilumab in improving patient-reported outcomes (PROs) including health related quality of life (HRQoL).
-The dupilumab systemic exposure and incidence of anti-drug antibodies.
-To evaluate the association between dupilumab treatment and pediatric immune responses to vaccines: any vaccination for tetanus, diphtheria, pertussis and/or seasonal trivalent/quadrivalent influenza vaccine.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-Children 6 to <12 years of age, with a physician diagnosis of persistent asthma for ≥12 months prior to Screening, based on clinical history and examination, pulmonary function parameters according to Global initiative for asthma (GINA) 2015 Guidelines and the following criteria:
-Existing background therapy of medium-dose inhaled corticosteroids (ICS) with second controller medication (ie, long-acting β2 agonist [LABA], leukotriene receptor antagonist [LTRA], long acting muscarinic antagonist [LAMA], or methylxanthines) or high-dose ICS alone or high dose ICS with second controller, for at least 3 months with a stable dose ≥1 month prior to Screening Visit 1.
-Pre-bronchodilator forced expiratory volume in 1 second (FEV1) ≤95% of predicted normal or pre bronchodilator FEV1/forced vital capacity (FVC) ratio <0.85 at Screening and Baseline Visits.
-Reversibility of at least 10% in FEV1 after the administration of 200 to 400 mcg (2 to 4 puff inhalations with metered-dose inhaler [MDI]) of albuterol/salbutamol or 45 to 90 mcg (2 to 4 puffswith MDI) of levalbuterol/levosalbutamol reliever medication before randomization (up to 3 opportunities during the same visit are allowed with a maximum of 12 puffs of reliever medication iftolerated by the patient).
-Must have experienced within 1 year prior to Screening Visit 1, any of the following events:
-Treatment with a systemic corticosteroid (SCS, oral or parenteral), as prescribed by a healthcare professional for worsening asthma at leastonce or,
-Hospitalization or emergency room visit for worsening asthma.
- Evidence of uncontrolled asthma, with at least one of the following criteria during the 4 (±1) weeks Screening Period:
-Asthma Control Questionnaire–Interviewer Administered (ACQ-IA) ACQ-5 score ≥1.5 on at least one day of the Screening Period.
-Use of reliever medication (ie, albuterol/salbutamol or levalbuterol/levosalbutamol), other than as a preventive for exercise induced bronchospasm, on 3 or more days per week, in at least one week during the Screening Period.
-Sleep awakening due to asthma symptoms requiring use of reliever medication at least once during the Screening Period.
-Asthma symptoms 3 or more days per week in at least one weekduring the Screening Period.

E.4

Principal exclusion criteria

-Patients <6 or ≥12 years of age.
-Patients with <16 kg bodyweight.
-Any other chronic lung disease (cystic fibrosis, bronchopulmonary dysplasia, etc) which may impair lung function.
-A subject with any history of life threatening asthma (ie, extreme exacerbation that requires intubation).
-Co-morbid disease that might interfere with the evaluation of investigational medicinal product (IMP).

E.5 End points

E.5.1

Primary end point(s)

Annualized rate of severe exacerbation events during treatment period

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline, Week 52

E.5.2

Secondary end point(s)

1) Change from baseline in pre-bronchodilator % predicted forced
expiratory volume in 1 second (FEV1)
2) Change from baseline in pre-bronchodilator % predicted
FEV1
3) Time to first severe exacerbation event
4) Time to first loss of asthma control event
5) Change from baseline in other lung function measurements: absolute and relative FEV1
6) Change from baseline in other lung function measurements: AM/PM peak expiratory flow (PEF)
7) Change from baseline in other lung function measurements: Forced Vital Capacity
8) Change from baseline in other lung function measurements: Forced expiratory flow (FEF) 25-75%
9) Change from baseline in other lung function measurements: Post bronchodilator % predicted FEV1
10) The effect of dupilumab on healthcare resource utilization
11) Change from baseline in morning asthma symptom score
12) Change from baseline in evening asthma symptom score
13) Number of nocturnal awakenings due to asthma symptoms requiring the use of reliever medication
14) Number of rescue medication inhalations
15) Assessment of Patient Reported Outcomes: Asthma Control Questionnaire
16) Assessment of Patient Reported Outcomes: Pediatric Asthma quality of life questionnaire
17) Assessment of IgG responses to vaccination during dupilumab treatment (may be analyzed as exploratory endpoint if insufficient power)
18) Adverse Events
19) Anti-Drug Antibodies
20) Serum Dupilumab Concentrations

E.5.2.1

Timepoint(s) of evaluation of this end point

1) Baseline, Week 12
2) Baseline, Weeks 2, 4, 8, 24, 36, 52
3) to 4): Up to 52 weeks
5) to 9) and 11) to 15): Baseline, Weeks 2, 4, 8, 12, 24, 36, 52
10) Baseline, Week 52
16) Baseline, Weeks 12, 24, 36, 52
17) 2 blood draws per vaccine scheduled: 1 prevaccination and 1 post-vaccination
18) Up to Week 64
19) Baseline, Weeks 12, 24, 52, 64
20) Baseline, Weeks 6, 12, 24, 52, 64

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

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

Australia

Brazil

Canada

Chile

Colombia

Hungary

Italy

Lithuania

Mexico

Poland

Romania

Russian Federation

South Africa

Spain

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

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

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:

785

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:

785

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

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

Pediatric Patients, aged 6 - <12 years will provide assent to enter the study and their parents/legal guardians will provide consent.

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

172

F.4.2.2

In the whole clinical trial

785

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 treatment, can be considered for eligibility into the a long term extension study.

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

2017-08-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-06-13

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-08-26

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