Clinical Trials Register

Summary
EudraCT Number:	2014-003384-38
Sponsor's Protocol Code Number:	R668-AD-1415
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-09-29
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2014-003384-38

A.3

Full title of the trial

A PHASE 3, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY
INVESTIGATING THE EFFICACY AND SAFETY OF MULTIPLE DUPILUMAB
DOSE REGIMENS ADMINISTERED AS MONOTHERAPY FOR MAINTAINING
TREATMENT RESPONSE IN PATIENTS WITH ATOPIC DERMATITIS

Studio di fase 3, randomizzato, in doppio cieco, controllato verso placebo per valutare l’efficacia e la sicurezza di regimi di dosaggio multipli di dupilumab somministrato in monoterapia per mantenere la risposta al trattamento in pazienti con dermatite atopica

A.3.1

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

A study to confirm the efficacy and safety of different dupilumab dose regimens in adults with atopic dermatitis (AD)

Studio per valutare l’efficacia e la sicurezza di regimi differenti di dosaggio di dupilumab somministrato in adulti con dermatite atopica (DA)

A.3.2

Name or abbreviated title of the trial where available

Liberty AD Solo - Continue

A.4.1

Sponsor's protocol code number

R668-AD-1415

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN12345678

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT12345678

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1234-1234-1234

A.5.4

Other Identifiers

Name:

IND 107969

Number:

IND 107969

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. - Stati Uniti d'America
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	REGN668/SAR231893
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	REGN668/SAR231893
D.3.9.3	Other descriptive name	DUPILUMAB
D.3.9.4	EV Substance Code	SUB179171
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.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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Atopic dermatitis

Dermatite atopica

E.1.1.1

Medical condition in easily understood language

Atopic dermatitis / Eczema

Dermatite atopica / 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	19.0
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 assess the ability of different dupilumab dose regimens, administered as monotherapy, to maintain the treatment response achieved after 16 weeks of initial treatment with dupilumab monotherapy compared to placebo

L’obiettivo primario dello studio è di valutare la capacità di diversi regimi di dosaggio di dupilumab, somministrato in monoterapia, di mantenere la risposta al trattamento ottenuta dopo 16 settimane di trattamento iniziale con dupilumab in monoterapia rispetto al placebo

E.2.2

Secondary objectives of the trial

The secondary objective of the study is to assess the safety of different dupilumab dose regimens administered as monotherapy over a period of
36 weeks

L’obiettivo secondario dello studio è di valutare la sicurezza di diversi regimi di dosaggio di dupilumab somministrato in monoterapia nell’arco di 36 settimane

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

A patient must meet the following criteria to be eligible for inclusion in the study:
1. Must have completed the treatment phase in 1 of the two 16-week initial treatment studies (R668-AD-1334 or R668-AD-1416).
2. Must have achieved at least 1 of the following 2 treatment success criteria:
IGA = 0 or 1 (clear or almost clear) at week 16 OR EASI-75 (at least 75% reduction in EASI score from baseline to week 16)
3. Must be willing and able to comply with clinic visits and study-related procedures
4. Must provide signed informed consent
5. Must be able to understand and complete study-related questionnaires

Il paziente deve soddisfare tutte le seguenti condizioni al fine di essere eligibile nello studio:
1. deve avere completato la fase di trattamento di 16 settimane di uno dei due studi di trattamento iniziali (R668-AD-1334 or R668-AD-1416)
2. deve avere raggiunto almeno uno dei due criteri di successo del trattamento seguenti:
Valutazione globale dello sperimentatore (Investigator’s Global Assessment, IGA) pari a 0 o 1 (scomparsa o quasi scomparsa) alla settimana 16 OPPURE un Eczema Area and Severity Index (EASI)-75 alla settimana 16 (riduzione di almeno il 75% nel punteggio EASI dal basale alla settimana 16).
3. deve manifestare la volontà e la possibilità di rispettare le visite e le procedure di studio
4. deve fornire consenso informato scritto
5. deve comprendere e completare i questionari relativi allo studio

E.4

Principal exclusion criteria

A patient who meets any of the following criteria will be excluded from the study:
1. Receipt of rescue medication for AD in the initial treatment study
2. Any conditions that require permanent discontinuation of study treatment in either initial
treatment study
3. Planned or anticipated major surgical procedure during the patient's participation in this study
4. Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed
during this study
Birth control exclusion criterion # 5is listed in protocol section 4.2.2

Il paziente che soddisfi una delle seguenti condizioni sarà escluso dallo studio:
1. assunzione -nello studio iniziale di trattamento- di rescue medication (farmaco di soccorso) per trattamento di dermatite atopica
2. qualsiasi condizione che richieda l’interruzione definitiva del trattamento in entrambi gli studi iniziali di trattamento
3. rilevante procedura chirurgica (pianificata o anticipata) durante la partecipazione del paziente al presente studio
4. donne in gravidanza o in allattamento o donne che pianifichino una gravidanza o un allattamento durante lo studio
Sistemi di controllo delle nascite (criterio di esclusione #5) come specificato nel protocollo, paragrafo 4.2.2

E.5 End points

E.5.1

Primary end point(s)

Proportion of patients with IGA scores of 0 or 1 (clear or almost clear) at week 36. For the EMA and EMA Reference Market countries only, the co-primary efficacy endpoint is: EASI-75: Proportion of patients with EASI-75 (≥75% improvement) at week 36 compared to the baseline EASI in the initial treatment study (R668-AD-1334 or R668-AD-1416)

Proporzione di pazienti con punteggi IGA pari a 0 o 1 (scomparsa o quasi scomparsa) alla settimana 36. Per EMA e per i Paesi che fanno riferimento a EMA l'endpoint co-primario è: EASI-75: Proporzione di pazienti con EASI-75 (≥75% di miglioramento) alla settimana 36 rispetto all’EASI basale negli studi di trattamento iniziali (R668-AD-1334 o R668-AD-1416)

E.5.1.1

Timepoint(s) of evaluation of this end point

The primary endpoint will be determined at week 36

Settimana 36

E.5.2

Secondary end point(s)

EASI-75: Proportion of patients with EASI-75 (≥75% improvement) at week 36 compared to the baseline EASI in the initial treatment study (R668-AD-1334 or R668-AD-1416). Change in SCORAD from baseline to week 36. Percent of patients whose Pruritus NRS increased by 3 or more points from baseline to week 36

EASI-75: Proporzione di pazienti con EASI-75 (≥75% di miglioramento) alla settimana 36 rispetto all’EASI basale nello studio di trattamento iniziale (R668 AD-1334 o R668-AD-1416) Variazione dell’indice SCORAD dal basale alla settimana 36 Percentuale di pazienti la cui intensità massima del prurito secondo la Scala di valutazione numerica (Numerical Rating Scale, NRS) è aumentata di 3 o più punti dal basale alla settimana 36

E.5.2.1

Timepoint(s) of evaluation of this end point

The secondary endpoints will be determined from baseline to week 36

Dalla visita al Basale alla settimana 36

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

128

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

European Union

Hong Kong

Japan

Korea, Republic of

Singapore

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 in follow up phase (week 48)

LVLS nella fase di follow-up (settimana 48)

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:

400

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

346

F.4.2.2

In the whole clinical trial

440

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 the treatment period may be eligible to enroll in an open-label extension (OLE) study starting at week 36. Patients who
do not transition into the OLE study before week 48 will undergo an additional follow-up visit at week 40 and a final (end-of-study) visit at week 48.

I pazienti che completeranno il trattamento potranno essere eligibili per partecipare a uno studio di estensione in aperto che partirà alla settimana 36. I pazienti che non prenderanno parte a questo studio in aperto prima della settimana 48, saranno sottoposti a una visita di follow-up aggiuntiva alla settimana 40 e ad una visita finale (fine dello studio) alla settimana 48.

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

2015-04-24

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-03-26

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-10-18

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