Clinical Trials Register

Summary
EudraCT Number:	2016-004997-16
Sponsor's Protocol Code Number:	R668-AD-1652
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:	2017-11-03
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

Czechia - SUKL

A.2

EudraCT number

2016-004997-16

A.3

Full title of the trial

A randomized, double-blind, placebo-controlled study to investigate the efficacy and safety of dupilumab administered concomitantly with topical corticosteroids in patients, ≥6 years to <12 years of age, with severe atopic dermatitis

PIP number: P/069/2017

Randomizovaná, dvojitě zaslepená, placebem kontrolovaná studie pro hodnocení účinnosti a bezpečnosti přípravku dupilumabu podávaného současně s lokálními kortikosteroidy u pacientů ve věku od 6 let včetně do 12 let s těžkou atopickou dermatitidou

A.3.1

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

A randomized study to investigate the efficacy and safety of dupilumab administered with topical corticosteroids in patients ≥6 to <12 years with severe atopic dermatitis

A.4.1

Sponsor's protocol code number

R668-AD-1652

A.5.4

Other Identifiers

Name:

IND Number

Number:

107969

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/219/2016

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 Trial Information
B.5.3	Address:
B.5.3.1	Street Address	777 Old Saw Mill River Road
B.5.3.2	Town/ city	Tarrytown, NY
B.5.3.3	Post code	10591
B.5.3.4	Country	United States
B.5.6	E-mail	clinicaltrials@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	Yes
D.2.1.1.1	Trade name	Dupixent
D.2.1.1.2	Name of the Marketing Authorisation holder	Regeneron Pharmaceuticals, Inc.
D.2.1.2	Country which granted the Marketing Authorisation	United States
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 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	SAR231893/REGN668
D.3.9.3	Other descriptive name	DUPILUMAB
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)	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/REGN668
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.3.9.1	CAS number	1190264-60-8
D.3.9.2	Current sponsor code	SAR231893/REGN668
D.3.9.3	Other descriptive name	DUPILUMAB
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	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)	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
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
D.8.4	Route of administration of the placebo	Subcutaneous use
D.8 Placebo: 3
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

Atopic Dermatitis

E.1.1.1

Medical condition in easily understood language

Atopic Dermatitis / Eczema

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	20.0
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

To demonstrate the efficacy of dupilumab administered concomitantly with topical corticosteroids (TCS) in patients ≥6 years to <12 years of age with severe atopic dermatitis (AD).

E.2.2

Secondary objectives of the trial

To assess the safety of dupilumab administered concomitantly with TCS in patients ≥6 years to <12 years of age with severe AD.

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

1. Pharmacogenomic sub-study.

E.3

Principal inclusion criteria

1. Male or female ≥6 to <12 years of age at time of screening visit
2. Diagnosis of AD according to the American Academy of Dermatology consensus criteria (Eichenfield 2003) at screening visit
3. Chronic AD diagnosed at least 1 year prior to the screening visit
4. IGA = 4 at screening and baseline visits
5. EASI ≥21 at the screening and baseline visits
6. BSA ≥15% at screening and baseline visits
7. Documented recent history (within 6 months before the baseline visit) of inadequate response to topical AD medication(s)
8. At least 11 (of a total of 14) applications of a stable dose of topical emollient (moisturizer) twice daily during the 7 consecutive days immediately before the baseline visit

E.4

Principal exclusion criteria

1. Participation in a prior dupilumab clinical study
2. Treatment with a systemic investigational drug before the baseline visit
3. Treatment with a topical investigational drug within 2 weeks prior to the baseline visit
4. Treatment with crisabarole within 2 weeks prior to the baseline visit
5. History of important side effects of medium potency topical corticosteroids (eg, intolerance to treatment, hypersensitivity reactions, significant skin atrophy, systemic effects), as assessed by the investigator or patient’s treating physician
6. Treatment with a TCI within 2 weeks prior to the baseline visit
7. Having used any of the following treatments within 4 weeks before the baseline visit, or any condition that, in the opinion of the investigator, is likely to require such treatment(s) during the first 4 weeks of study treatment:
a. Immunosuppressive/immunomodulating drugs (eg, systemic corticosteroids, cyclosporine, mycophenolate-mofetil, interferon gamma, Janus kinase inhibitors, azathioprine, methotrexate, etc.)
b. Phototherapy for AD
8. Treatment with biologics, as follows:
a. Any cell-depleting agents including but not limited to rituximab: within 6 months before the baseline visit, or until lymphocyte and CD 19+ lymphocyte count returns to normal, whichever is longer
b. Other biologics: within 5 half-lives (if known) or 16 weeks before the baseline visit, whichever is longer
9. Treatment with a live (attenuated) vaccine within 4 weeks before the baseline visit
10. Body weight <15 kg at baseline
11. Initiation of treatment of AD with prescription moisturizers or moisturizers containing additives such as ceramide, hyaluronic acid, urea, or filaggrin degradation products during the screening period (patients may continue using stable doses of such moisturizers if initiated before the screening visit)
12. Regular use (more than 2 visits per week) of a tanning booth/parlor within 8 weeks of the baseline visit
13. Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiprotozoals, or antifungals within 2 weeks before the baseline visit
14. Established diagnosis of a primary immunodeficiency disorder
15. History of past or current tuberculosis or other mycobacterial infection
16. Known history of human immunodeficiency virus (HIV) infection or HIV seropositivity at the screening visit
17. Established diagnosis of hepatitis B viral infection at the time of screening or is positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) at the time of screening
18. Established diagnosis of hepatitis C viral infection at the time of screening or is positive for hepatitis C antibody at the screening visit
19. On current treatment for hepatic disease including but not limited to acute or chronic hepatitis, cirrhosis, or hepatic failure, or has evidence of liver disease as indicated by persistent (confirmed by repeated tests ≥2 weeks apart) elevated transaminases (alanine aminotransferase [ALT] and/or aspartate aminotransferase [AST]) more than 3 times the upper limit of normal (ULN) during the screening period
20. Presence of any 1 or more of the following abnormalities in laboratory test results at screening:
• Platelets ≤100 × 103/μL
• Neutrophils <1.5 × 103/μL
• Creatine phosphokinase (CPK) >5 × ULN
• Serum creatinine >1.5 × ULN
21. Presence of skin comorbidities that may interfere with study assessments. This includes, but is not limited to, conditions like scabies, seborrheic dermatitis, cutaneous T cell lymphoma, psoriasis, etc.
22. History of malignancy before the baseline visit
23. Diagnosed active endoparasitic infections; suspected or high risk of endoparasitic infection, unless clinical and (if necessary) laboratory assessment have ruled out active infection before randomization
24. Severe concomitant illness(es) that, in the investigator’s judgment, would adversely affect the patient’s participation in the study.

E.5 End points

E.5.1

Primary end point(s)

1. Proportion of patients with EASI-75 (≥75% improvement from baseline) at week 16
2. Proportion of patients with IGA 0 or 1 (on a 5-point scale) at week 16

E.5.1.1

Timepoint(s) of evaluation of this end point

Ad 1: at week 16
Ad 2: at week 16

E.5.2

Secondary end point(s)

Key secondary endpoints
1. Percent change in EASI score from baseline to week 16
2. Percent change from baseline to week 16 in weekly average of daily worst itch score

Other secondary endpoints:
1. Change from baseline to week 16 in weekly average of daily worst itch score
2. Proportion of patients with EASI-50 at week 16
3. Proportion of patients with EASI-90 at week 16
4. Change from baseline to week 16 in percent Body Surface Area (BSA) affected by AD
5. Percent change from baseline to week 16 in SCORing AD (SCORAD)
6. Proportion of patients with improvement (reduction) of weekly average of daily worst itch score ≥4 from baseline at week 16
7. Proportion of patients with improvement (reduction) of weekly average of daily worst itch score ≥3 from baseline at week 16
8. Time to onset of effect on pruritus during the 16-week treatment period (≥4 point reduction of weekly average of daily worst itch score from baseline)
9. Time to onset of effect on pruritus during the 16-week treatment period (≥3 point reduction of weekly average of daily worst itch score from baseline)
10. Change from baseline to week 16 in Children’s Dermatology Life Quality Index (CDLQI)
11. Change from baseline to week 16 in Patient Oriented Eczema Measure (POEM)
12. Change from baseline to week 16 in Dermatitis Family Index (DFI)
13. Change from baseline to week 16 in Patient-Reported Outcomes Measurement Information System (PROMIS) pediatric anxiety short form scale score
14. Change from baseline to week 16 in PROMIS pediatric depressive symptoms short form scale score
15. Topical treatment for AD – proportion of TCS medication-free days from baseline to week 16
16. Mean weekly dose of TCS in grams for low and medium potency TCS from baseline to week 16
17. Mean weekly dose of TCS in grams for high potency TCS from baseline to week 16
18. Incidence of skin-infection treatment-emergent adverse events (TEAEs) (excluding herpetic infections) through week 16
19. Incidence of serious TEAEs through week 16

E.5.2.1

Timepoint(s) of evaluation of this end point

The key secondary endpoints:
Ad 1: from baseline to week 16
Ad 2: baseline to week 16

Other secondary endpoints:
Ad 1: from baseline to week 16
Ad 2: at week 16
Ad 3: at week 16
Ad 4: from baseline to week 16
Ad 5: from baseline to week 16
Ad 6: from baseline to week 16
Ad 7: from baseline to week 16
Ad 8: from baseline to week 16
Ad 9: from baseline to week 16
Ad 10: from baseline to week 16
Ad 11: from baseline to week 16
Ad 12: from baseline to week 16
Ad 13: from baseline to week 16
Ad 14: from baseline to week 16
Ad 15: from baseline to week 16
Ad 16: from baseline to week 16
Ad 17: from baseline to week 16
Ad 18: through week 16
Ad 19: through week 16

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

Yes

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)

Yes

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

Canada

Czech Republic

Germany

Poland

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 Visit Last Subject

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:

330

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:

330

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

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

156

F.4.2.2

In the whole clinical trial

330

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)

Eligible patients may have a chance to participate in Open-Label Extension

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

2018-02-02

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-02-09

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2019-09-09

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