Clinical Trials Register

Summary
EudraCT Number:	2018-001543-30
Sponsor's Protocol Code Number:	R3500-AD-1798
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2019-02-14
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2018-001543-30

A.3

Full title of the trial

A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE 2A STUDY TO ASSESS THE EFFICACY AND SAFETY OF REGN3500 MONOTHERAPY AND COMBINATION OF REGN3500 PLUS DUPILUMAB IN ADULT PATIENTS WITH MODERATE-TO-SEVERE ATOPIC DERMATITIS

A.3.1

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

A Safety and Efficacy Study in Adult Patients with Moderate to Severe Atopic Dermatitis

A.4.1

Sponsor's protocol code number

R3500-AD-1798

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 Trial Management
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	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	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	REGN3500
D.3.4	Pharmaceutical form	Lyophilisate for 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	REGN3500
D.3.9.3	Other descriptive name	REGN3500
D.3.9.4	EV Substance Code	SUB182669
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)	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	Yes
D.2.1.1.1	Trade name	Dupixent
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi-Aventis Groupe
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	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.3.9.2	Current sponsor code	REGN668
D.3.9.3	Other descriptive name	SAR231893
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Lyophilisate for 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 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

E.1.1.1

Medical condition in easily understood language

Moderate to Severe Atopic Dermatitis

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

The primary objective of the study is to evaluate the efficacy of REGN3500 monotherapy compared with placebo treatment in adult patients with
moderate-to-severe atopic dermatitis (AD).

E.2.2

Secondary objectives of the trial

-To evaluate the efficacy of REGN3500 in combination with dupilumab compared with placebo treatment in adult patients with moderate-to-severe AD
-To assess the safety, tolerability, and immunogenicity of subcutaneous (SC) doses of REGN3500 monotherapy and REGN3500 in combination with dupilumab in adult patients with moderate-to-severe AD
-To evaluate the pharmacokinetics (PK) of REGN3500 monotherapy and REGN3500 in combination with dupilumab in adult patients with moderate-to-severe AD

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Male or female, 18 to 75 years
2. Chronic AD, according to American Academy of Dermatology Consensus Criteria (Eichenfield, 2014), that has been present for at least 3 years before the screening visit
3. EASI score ≥16 at the screening and baseline visits
4. IGA score ≥3 (on the 0 to 4 IGA scale, in which 3 is moderate and 4 is severe) at screening and baseline visits
5. ≥10% BSA of AD involvement at the screening and baseline visits
6. Baseline peak Pruritus NRS score for maximum itch intensity ≥4
7. Documented recent history (within 6 months before the screening visit) of inadequate response to topical AD medication(s) or for whom topical treatments are medically inadvisable (eg, intolerance, because of important side effects, or safety risks).
8. Have applied a stable dose of topical bland emollient (moisturizer) at least twice daily for at least the 7 consecutive days immediately before randomization
9. Willing and able to comply with all clinic visits and study-related procedures
10. Provide informed consent signed by study patient or legally acceptable representative
11. Able to understand and complete study-related questionnaires

E.4

Principal exclusion criteria

1. Prior participation in a REGN3500 (anti-IL-33) or dupilumab (anti-IL-4Rα) clinical study; past treatment with or current treatment with dupilumab
2. Body mass index <16 kg/m2
3. Treatment with an investigational drug within 8 weeks or within 5 half-lives (if known), whichever is longer, before the baseline visit
4. 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: Immunosuppressive/immunomodulating drugs (eg, systemic corticosteroids, cyclosporine, mycophenolate-mofetil, IFN-γ, Janus kinase inhibitors, azathioprine, methotrexate, etc) Phototherapy for AD
5. Treatment with TCS, TCI, or topical crisaborole within 1 week before the baseline visit
6. Treatment with biologics as follows: Any cell-depleting agents including but not limited to rituximab: within 6 months before the baseline visit, or until lymphocyte count returns to normal, whichever is longer Other biologics: within 5 half-lives (if known) or 16 weeks prior to baseline visit, whichever is longer
7. 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
8. Regular use (more than 2 visits per week) of a tanning booth/parlor within 4 weeks of the baseline visit
9. Planned or anticipated use of any prohibited medications and procedures during study treatment
10. Treatment with a live (attenuated) vaccine within 12 weeks before the baseline visit
11. Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiparasitics, antiprotozoals, or antifungals within 2 weeks before the baseline visit, or superficial skin infections within 1 week before the baseline visit
12. Known or suspected history of immunosuppression, including history of invasive opportunistic infections (eg, tuberculosis [TB], histoplasmosis, listeriosis, coccidioidomycosis, pneumocystosis, aspergillosis) despite infection resolution: or unusually frequent, recurrent, or prolonged infections, per investigator judgment
13. History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening
14. Positive with hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), or hepatitis C virus antibody (HCV Ab) at the screening visit
15. At baseline, presence of any conditions listed as criteria for study drug discontinuation
16. Presence of skin comorbidities that may interfere with study assessments
17. History of cancer, with the exceptions of: Patients with adequately treated basal cell carcinoma or carcinoma in situ of the
cervix. Patients with other malignancies that have been successfully treated for >10 years prior to screening where, in the judgement of both the investigator and the treating physician, appropriate follow-up has revealed no evidence of recurrence through time of screening.
18. 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
19. History of alcohol or drug abuse within 2 years of the screening visit
20. Severe concomitant illness(es) that, in the investigator’s judgment, would adversely affect the patient’s participation in the study.
21. Any other medical or psychological condition (including relevant laboratory abnormalities at screening) that, in the opinion of the investigator, may suggest a new and/or insufficiently understood disease, may present an unreasonable risk to the study patient as a result of his/her participation in this clinical study, may make patient’s participation unreliable, or may interfere with study assessments. The specific justification for patients excluded under this criterion will be noted in study documents
22. Planned or anticipated major surgical procedure during the patient’s participation in this study
23. Patient is a member of the investigational team or his/her immediate family
24. Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study
25. Women of childbearing potential (WOCBP) who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 20 weeks after the last dose of study drug.
26. Known sensitivity to doxycycline and/or tetracycline or to any of the components of the investigational product formulation
27. Patients who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities will be excluded from this study (as required by country regulations).

E.5 End points

E.5.1

Primary end point(s)

The primary endpoint in the study is the percent change in EASI score from baseline to week 16.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 16

E.5.2

Secondary end point(s)

Efficacy:
-Proportion of patients achieving EASI-50, EASI-75, and EASI-90 (≥50%, ≥75%, and ≥90% improvement from baseline) at week 16
-Absolute change in EASI score from baseline to week 16
-Proportion of patients with both an Investigator’s Global Assesssment (IGA) score of 0 or 1 (on a 5-point scale) and a reduction from baseline of ≥2 points at week 16
-Change (absolute and percent) from baseline to week 16 in weekly average of daily peak Pruritus Numerical Rating Scale (NRS)
-Proportion of patients with improvement (reduction) of weekly average of daily peak Pruritus NRS ≥4 from baseline at week 16
-Time to onset of effect on pruritus during the 16-week treatment period (≥4-point reduction of weekly average of daily peak Pruritus NRS from baseline)
-Percent change from baseline to week 16 in SCORing Atopic Dermatitis (SCORAD)
-Change from baseline to week 16 in percent body surface area (BSA) of AD involvement
Safety:
-Incidence of treatment-emergent adverse events (TEAEs) from baseline through end of treatment (week 16)
-Incidence of treatment-emergent serious adverse events (SAEs) from baseline through end of treatment (week 16)
-Incidence of treatment-emergent adverse events of special interest (AESIs) from baseline through end of treatment (week 16)
-Incidence of TEAEs from baseline through end of study (week 36)
-Incidence of treatment-emergent SAEs from baseline through end of study (week 36)
-Incidence of treatment-emergent AESIs from baseline through end of study (week 36)
PK:
-Concentrations of functional REGN3500 and functional dupilumab in serum by treatment regimen at each assessment time point from baseline to end of study (week 36)

E.5.2.1

Timepoint(s) of evaluation of this end point

Week 16 (efficacy) and Week 36 (safety and PK)

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

Yes

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)

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

Belgium

Czech Republic

Germany

Korea, Republic of

Netherlands

Poland

Spain

Taiwan

United States

E.8.7

Trial has a data monitoring committee

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

The end of the study is defined as the date on which last subject completes the 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:

250

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

132

F.4.2.2

In the whole clinical trial

280

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

2019-02-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-06-17

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-07-28

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