Clinical Trials Register

Summary
EudraCT Number:	2017-003317-25
Sponsor's Protocol Code Number:	LTS14424
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2018-06-13
Trial 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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2017-003317-25

A.3

Full title of the trial

One year study to evaluate the long-term safety and tolerability of dupilumab in pediatric patients with asthma who participated in a previous dupilumab asthma clinical study

Egy éves vizsgálat a dupilumab hosszú távú biztonságosságának és tolerálhatóságának értékelésére olyan kiskorú asztmás betegek körében, akik részt vettek egy korábbi dupilumab asztma vizsgálatban

A.3.1

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

Assessment of the Safety and Efficacy of Dupilumab in Children with Asthma (Liberty Asthma Excursion)

A dupilumab biztonságosságának és hatásosságának értékelése asztmás gyermekekben (Liberty Asthma Excursion)

A.4.1

Sponsor's protocol code number

LTS14424

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1200-1757

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-aventis 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 Zrt
B.5.2	Functional name of contact point	NA
B.5.3	Address:
B.5.3.1	Street Address	Tó u. 1-5.
B.5.3.2	Town/ city	Budapest
B.5.3.3	Post code	1045
B.5.3.4	Country	Hungary
B.5.6	E-mail	kapcsolat@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.IMP: 3
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.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

Asthma

Asztma

E.1.1.1

Medical condition in easily understood language

Asthma

Asztma

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

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 long-term safety and tolerability of dupilumab in pediatric patients with asthma who participated in a previous dupilumab asthma clinical study.

A dupilumab biztonságosságának és hatásosságának értékelése asztmás gyermekekben (Liberty Asthma Excursion)

E.2.2

Secondary objectives of the trial

-To evaluate the long-term efficacy of dupilumab in pediatric patients with asthma who participated in a previous dupilumab asthma clinical study.
-To evaluate dupilumab in pediatric patients with asthma who participated in a previous dupilumab
asthma clinical study with regard to:
-Systemic exposure.
-Anti-drug antibodies (ADAs).
-Biomarkers.

• A dupilumab hosszú távú hatásosságának értékelése olyan kiskorú asztmás betegek körében, akik részt vettek egy korábbi dupilumab asztma vizsgálatban
• A dupilumab értékelése az alábbiak tekintetében olyan kiskorú asztmás betegek körében, akik részt vettek egy korábbi dupilumab asztma vizsgálatban:
– Szisztémás expozíció
– Hatóanyag elleni antitestek (ADA)
– Biomarkerek

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

-Pediatric patients with asthma who completed the treatment in a dupilumab asthma trial (EFC14153).
-Signed written informed consent/assent.

- A dupilumabbal végzett asztma vizsgálatot (EFC14153) teljesítő asztmás gyermekek
- Aláírt írásos beleegyező/hozzájáruló nyilatkozat

E.4

Principal exclusion criteria

-Any chronic lung disease other than asthma (eg, cystic fibrosis, bronchopulmonary dysplasia) which may impair lung function.
-Inability to follow the procedures of the study/noncompliance (eg, due to language problems or psychological disorders).
-Patients receiving concomitant treatment or required a new concomitant treatment prohibited in the study.
-Patients or his/her parent(s)/caregiver(s)/legal guardian(s) is related to the Investigator or any Sub-Investigator, research assistant, pharmacist, study coordinator, other staff thereof directly involved in the conduct of the study.
-Patients who experienced any hypersensitivity reactions to dupilumab in a previous dupilumab study, which, in the opinion of the Investigator, could indicate that continued treatment with dupilumab may present an unreasonable risk for the patient.
-Any abnormalities or adverse events at screening (last treatment visit in the study EFC14153 will be the screening visit) that per Investigator judgment would adversely affect patient’s participation in this study or would require permanent IMP discontinuation.
-For female patients who have commenced menstruating at any time during the study and are either:
-Found to have a positive urine pregnancy test, or
-Sexually active, not using an established acceptable contraceptive method.
-Planned live, attenuated vaccinations during the study.
-Patients with active autoimmune disease or patients using immunosuppressive therapy for autoimmune disease (eg, juvenile idiopathic arthritis, inflammatory bowel disease, systemic lupus erythematosus) at enrollment.

- Az asztmán kívül bármilyen más krónikus tüdőbetegség (például cisztás fibrózis, bronchopulmonális diszplázia), amely csökkentheti a légzésfunkciót.
- A beteg nem tudja betartani a vizsgálati eljárásokat, vagy nem együttműködő (például nyelvi problémák vagy pszichés zavarok miatt).
- A beválasztási vizit idején a beteg olyan egyidejű kezelésben részesül vagy olyan új egyidejű kezelést rendelnek neki, amely a vizsgálatban nem engedélyezett.
- A beteg szülője/gyámja rokoni kapcsolatban áll a vizsgálatvezetővel, vizsgálóval, vizsgálati asszisztenssel, gyógyszerésszel, vizsgálati koordinátorral vagy bármely személlyel, aki érintett a vizsgálat lefolytatásában.
- A betegnél a dupilumab egy korábbi vizsgálatában a vizsgálati készítményre adott bármilyen túlérzékenységi reakció, ami a vizsgáló véleménye szerint azt jelezheti, hogy a dupilumabbal végzett további kezelés indokolatlan kockázatnak tenné ki a beteget.
- Bármilyen olyan rendellenesség vagy nemkívánatos esemény beválasztáskor (az EFC14153 vizsgálat utolsó kezelési vizitje lesz a beválasztási vizit), amely a vizsgálóorvos megítélése szerint kedvezőtlenül befolyásolhatja a beteg részvételét ebben a vizsgálatban, vagy amely a vizsgálati készítmény adagolásának tartós abbahagyását teheti szükségessé.
- Olyan lánybeteg, aki a vizsgálat során elkezd menstruálni és
o pozitív terhességi vizelettesztet ad, vagy
o aktív szexuális életet él és nem alkalmaz elfogadható fogamzásgátló módszert vagy
- A vizsgálat alatt élő, attenuált kórokozóval való oltás alkalmazását tervezik vagy
- A beválasztás során aktív autoimmun megbetegedésben szenvedő betegek vagy immunszuppresszív terápiát alkalmazó betegek

E.5 End points

E.5.1

Primary end point(s)

Treatment-emergent-adverse-event (TEAEs): The number (n) and percentage (%) of patients experiencing any TEAEs.

Bármilyen sürgősségi kezelést igénylő nemkívánatos eseményt (TEAE) észlelő betegek száma (n) és számaránya (%).

E.5.1.1

Timepoint(s) of evaluation of this end point

From Day 1 up to Week 64

Első naptól 64. hétig

E.5.2

Secondary end point(s)

1) Severe asthma exacerbation events: Annualized rate of severe asthma exacerbation events, during the treatment period
2) Change in % predicted FEV1: Change in percentage (%) predicted forced expiratory volume in 1 second (FEV1) - Clinically significant changes from baseline
3) Change in absolute FEV1: Change in absolute FEV1 - Clinically significant changes from baseline
4) Change in FVC: Change in forced vital capacity (FVC)
5) Change in FEF: Change in forced expiratory flow [FEF] 25-75%)
6) Assessment of dupilumab concentration: Serum dupilumab concentrations - Changes from first dupilumab injection
7) Assessment of immunogenicity: Titers of Anti-dupilumab antibodies
8) Assessment of blood Eosinophil count: Blood: Eosinophil count
9) Assessment of total anti-immunglobulin E (IgE): Serum: total IgE

1) súlyos asztmás exacerbációs események egy évre vetített aránya a kezelési időszakban.
2) %-ban kifejezett változás a FEV1 értékben – klinikailag jelentős eltérés az alapértéktől
3) Változás az abszolút FEV1 értékben
4) Változás az erőltetett vitálkapacitásban (FVC)
5) Változás a 25–75% közti erőltetett kilégzési áramlásban [FEF]
6) Szérum dupilumab koncentráció – eltérés az első injekció utáni értéktől
7) Immonigenicitási értékelés: dupilumab ellenes ellenanyag szintje
8) Vér eozinofil sejtek száma
9) Szérum totál anti-immunglobulin E (IgE) szintje

E.5.2.1

Timepoint(s) of evaluation of this end point

1) From Day 1 up to Week 52
2) to 9) From Day 1 up to Week 64

1) első naptól 52. hétig
2)-es ponttól 9)-es pontig: első naptól 64. hétig

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

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

E.8.1.1

Randomised

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

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

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

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

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

Utolsó beteg utolsó vizite

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 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:

236

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:

314

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

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 population

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

F.4.2.2

In the whole clinical trial

354

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

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

2018-08-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-08-06

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

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