Clinical Trials Register

Summary
EudraCT Number:	2013-003254-24
Sponsor's Protocol Code Number:	R668-AD-1224
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2014-03-06
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

Czechia - SUKL

A.2

EudraCT number

2013-003254-24

A.3

Full title of the trial

A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY TO DEMONSTRATE THE EFFICACY AND LONG-TERM SAFETY OF DUPILUMAB IN ADULT PATIENTS WITH MODERATE-TO-SEVERE ATOPIC DERMATITIS

Randomizovaná, dvojitě zaslepená, placebem kontrolovaná studie k prokázání účinnosti a dlouhodobé bezpečnosti dupilumabu u dospělých pacientů se středně závažnou až závažnou atopickou dermatitidou.

A.3.1

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

EFFICACY AND LONG TERM SAFETY STUDY OF DUPILUMAB IN ADULT
PATIENTS WITH MODERATE0-TO-SEVERE ATOPIC DERMATITIS.

A.4.1

Sponsor's protocol code number

R668-AD-1224

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	Regeneron Pharmaceuticals, Inc.
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	Regeneron Pharmaceuticals, Inc
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	Regeneron Pharmaceuticals, Inc.
B.5.2	Functional name of contact point	Clinical Trials information
B.5.3	Address:
B.5.3.1	Street Address	777 Old Saw Mill River Road
B.5.3.2	Town/ city	Tarrytown
B.5.3.3	Post code	NY 10591
B.5.3.4	Country	United States
B.5.6	E-mail	clinicaltrial@regeneron.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/REGN668
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.3.9.1	CAS number	1190264-60-8
D.3.9.2	Current sponsor code	Dupilumab
D.3.9.3	Other descriptive name	REGN668/SAR231893
D.3.9.4	EV Substance Code	SUB128559
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/REGN668
D.3.4	Pharmaceutical form	Solution for infusion 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.3.9.1	CAS number	1190264-60-8
D.3.9.2	Current sponsor code	DUPILUMAB
D.3.9.3	Other descriptive name	REGN668/SAR231893
D.3.9.4	EV Substance Code	SUB130625
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
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 infusion 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

Moderate to severe atopic dermatitis (AD).

E.1.1.1

Medical condition in easily understood language

Moderate to severe atopic dermatitis (AD).

E.1.1.2

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.1
E.1.2	Level	LLT
E.1.2	Classification code	10003639
E.1.2	Term	Atopic dermatitis
E.1.2	System Organ Class	100000004858

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The primary objective of the study is to demonstrate the efficacy of dupilumab administered concomitantly with TCS through week 16 in adult patients with moderate-to-severe AD.

E.2.2

Secondary objectives of the trial

-Evaluate long-term efficacy of dupilumab when administered
concomitantly with TCS for up to 52 weeks.
-Evaluate the long-term safety of dupilumab when administered
concomitantly with TCS for up to 52 weeks.

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

Optional Genomics Sub-study.
- Blood for DNA extraction should be collected on day 1/baseline (predose), but may be collected at any study visit.
- The purpose of the genomic analyses is to identify genomic
associations with clinical or biomarker response to IL-4R/13R
modulation, atopic disease risk, prognosis and progression, or other
clinical outcome measures.

E.3

Principal inclusion criteria

1. Male or female, 18 years or older
2. Chronic AD, (according to the American Academy of Dermatology
Consensus Criteria),that has been present for at least 3 years before the
screening visit.
3. Patients with documented recent history (within 6 months before the
screening visit) of inadequate response to a sufficient course of
outpatient treatment with topical AD medication(s).

E.4

Principal exclusion criteria

1. Prior treatment with dupilumab
2. Important side effects of topical medication (eg, intolerance to
treatment, hypersensitivity reactions, significant skin atrophy, systemic
effects), as assessed by the investigator or patient's treating physician.
3. At baseline visit >= 30% of the total lesional surface located on areas
of thin skin that cannot be safely treated with medium or higher potency
TCS (eg, face, neck, intertriginous areas, genital areas, areas of skin
atrophy)
4. Recent treatment (within specific time windows before the baseline
visit) with systemic corticosteroids, immunosuppressive agents, topical
corticosteroids and calcineurin inhibitors, live (attenuated) vaccine,
other investigational drugs
5. History of human immunodeficiency virus (HIV) infection
6. HIV or viral hepatitis positive serology at screening
7. Known or suspected immunosuppresion
8. Recent infections requiring antiinfectious treatment
9. Recent history or high risk of clinical endoparasitoses, unless clinical
and (if necessary) laboratory assessment have ruled out active infection
before randomization
10. High risk populations (low life expectancy, severe concomitant
diseases, etc.)
11. Pregnant or breast-feeding women
12. Patients of reproductive potential and sexually active who are
unwilling to use adequate contraceptive methods.

E.5 End points

E.5.1

Primary end point(s)

-Proportion of patients with EASI-75 response (reduction of EASI
score by >=75% from baseline) at week 16
-Proportion of patients with both an IGA 0 or 1 (on a 5-point scale)
and a reduction from baseline of >=2 points at week 16

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 16

E.5.2

Secondary end point(s)

Key Secondary Endpoints:
Percent change from baseline to week 16 in weekly average of peak
daily Pruritus Numerical Rating Scale (NRS)
Proportion of patients with improvement (reduction) in weekly average
of peak daily Pruritus NRS >=4 from baseline to week 16.
Proportion of patients with IGA 0 or 1 and a reduction from baseline of
>=2 points at week 52.
Proportion of patients with EASI-75 response at week 52.
Proportion of patients with improvement (reduction) in weekly average
of peak daily Pruritus NRS >=3 from baseline to week 16.
Percent change from baseline to week 52 in weekly average of peak
daily Pruritus NRS.
Other Secondary Endpoints:
Percent change in EASI score from baseline to week 16.
Change from baseline to week 16 in percent BSA.
Percent change in SCORing Atopic Dermatitis (SCORAD) from baseline to
week 16.
Percent change from baseline to week 16 in Global Individual Signs
Score (GISS) (erythema, infiltration/papulation, excoriations,
lichenification).
Change from baseline to week 16 in Dermatology Life Quality Index
(DLQI).
Change from baseline to week 16 in Hospital Anxiety and Depression
Scale (HADS).
Change from baseline to week 16 in Patient Oriented Eczema Measure
(POEM).
Reduction in topical AD medication use through week 16 (determined by
the amount of TCS and/or topical calcineurin inhibitors (TCI) used since
previous visit in weight).
Proportion of patients with improvement (reduction) in weekly average
of peak daily Pruritus NRS >=3 from baseline to week 52.
Proportion of patients with improvement (reduction) in weekly average
of peak daily Pruritus NRS >=4 from baseline to week 52.
Percent change in EASI score from baseline to week 52.
Change from baseline to week 52 in percent BSA.
Percent Change in SCORAD from baseline to week 52.
Percent Change from baseline to week 52 in GISS (erythema, infiltration
/papulation, excoriations, lichenification).
Change from baseline to week 2 in weekly average of peak daily Pruritus
NRS.
Number of flares through week 52.
Change from baseline to week 52 in DLQI.
Change from baseline to week 52 in POEM.
Change from baseline to week 52 in HADS.
Incidence of skin-infection treatment-emergent adverse events (TEAEs)
requiring systemic treatment from baseline through week 56.
Incidence of serious TEAEs through week 56.
Incidence of TEAEs leading to study drug discontinuation from baseline
through week 56.

E.5.2.1

Timepoint(s) of evaluation of this end point

1), 2), 3) Week 16
4), 5) Week 52
6) Week 16
7) Week 52
8) to 15) Week 16
16) to 21) Week 52
22) Week 2
23) to 26) Week 52
27) to 29) Week 56

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

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

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

121

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

Australia

Canada

Croatia

Czech Republic

France

Germany

Guadeloupe

Hungary

Italy

Japan

Korea, Republic of

Latvia

Netherlands

New Zealand

Poland

Romania

Russian Federation

Spain

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

Last Patient Last Visit

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:

594

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

106

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

Information not present in EudraCT

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

299

F.4.2.2

In the whole clinical trial

700

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 may be eligible to enroll in an openlabel 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

2014-05-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-06-12

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-10-19

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