Clinical Trials Register

Summary
EudraCT Number:	2019-003801-90
Sponsor's Protocol Code Number:	EFC16460
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:	2020-02-24
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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2019-003801-90

A.3

Full title of the trial

A randomized, double blind, placebo-controlled, multi-center, parallel group study to evaluate the efficacy and safety of dupilumab in patients with prurigo nodularis who are inadequately controlled on topical prescription therapies or when those therapies are not advisable

Randomizált, kettős vak, placebo-kontrollos, többcentrikus, párhuzamos csoportos vizsgálat a dupilumab hatásosságának és biztonságosságának kiértékelése olyan prurigo nodularis-ban szenvedő betegek körében, akik a vényköteles helyi kezelésekkel nem megfelelően kontrolláltak, vagy akiknek az ilyen terápiák nem javasoltak

A.3.1

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

Study of dupilumab for the treatment of patients with prurigo nodularis, inadequately controlled on topical prescription therapies or when those therapies are not advisable

A dupilumab vizsgálata olyan prurigo nodularisban (krónikus viszkető bőrbetegségben) szenvedő betegek kezelése terén, akiknél a helyileg alkalmazott vényköteles kezelések nem nyújtanak megfelelő kontrollt a betegségre, vagy ha ezek a terápiák nem javallottak

A.3.2

Name or abbreviated title of the trial where available

LIBERTY-PN PRIME2

A.4.1

Sponsor's protocol code number

EFC16460

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	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	n.a.
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.5.4	Telephone number	+361505 0050
B.5.5	Fax number	+361505 2917
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.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

Prurigo Nodularis

E.1.1.1

Medical condition in easily understood language

Prurigo Nodularis

Viszkető bőrbetegség

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	PT
E.1.2	Classification code	10029263
E.1.2	Term	Neurodermatitis
E.1.2	System Organ Class	10040785 - Skin and subcutaneous tissue 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 demonstrate the efficacy of dupilumab on itch response in patients with prurigo nodularis (PN), inadequately controlled on topical prescription therapy or when those therapies are not advisable

Annak igazolása, hogy a dupilumab hatásos választ ad a viszketésre a PN-ben szenvedő betegeknél, akiknél a helyileg alkalmazott vényköteles kezelések nem voltak hatásosak vagy ellenjavalltak.

E.2.2

Secondary objectives of the trial

To demonstrate the efficacy of dupilumab on additional itch endpoints in patients with PN, inadequately controlled on topical prescription therapy or when those therapies are not advisable
To demonstrate efficacy of dupilumab on skin lesions of PN
To demonstrate the improvement in health-related quality of life
To evaluate safety outcome measures
To evaluate immunogenicity of dupilumab

Annak igazolása, hogy a dupilumab hatásos a kiegészítő viszketési végpontok esetén a PN-ben szenvedő betegeknél, akiknél a helyileg alkalmazott vényköteles kezelések nem voltak hatásosak vagy ellenjavalltak.
A dupilumab hatásosságának igazolása a PN bőrléziók esetében.
Az egészséggel kapcsolatos életminőség (HRQoL) javulásának bemutatása
A biztonságossági kimeneteli mérések értékelése.
A dupilumab immunogenitásának értékelése.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Must be 18 to 80 years of age, at the time of signing the informed consent.
With a clinical diagnosis of PN defined by all of the following:
- Diagnosed by a dermatologist for at least 3 months before the Screening visit
- On the WI-NRS ranging from 0 to 10, patients must have an average worst itch score of ≥7 in the 7 days prior to Day1.
- Patients must have a minimum of 20 PN lesions in total on both legs, and/or both arms and/or trunk, at Screening visit and Day 1
- History of failing a 2-week course of medium-to-high potency topical corticosteroids (TCS) or when TCS are not medically advisable
- Have applied a stable dose of topical emollient (mositurizer) once or twice daily for at least the 7 consecutive days immediately before Day 1
Must be willing and able to complete a daily symptom eDiary for the duration of the study

E.4

Principal exclusion criteria

Participants are excluded from the study if any of the following criteria apply:
- Presence of skin morbidities other than PN and mild atopic dermatitis that may interfere with the assessment of the study outcomes
- PN secondary to medications
- PN secondary to medical conditions such as neuropathy or psychiatric disease
- A documented atopic dermatitis severity of moderate to severe within 6 months before or at the Screening visit
- Severe concomitant illness(es) under poor control that, in the investigator’s judgment, would adversely affect the patient’s participation in the study
- Severe renal conditions (eg, patients with uremia and/or on dialysis)
- Participants with uncontrolled thyroid disease.
- Active tuberculosis or non-tuberculous mycobacterial infection, or a history of incompletely treated tuberculosis unless documented adequately treated
- 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.
- Active chronic or acute infection (except HIV) requiring treatment with systemic antibiotics, antivirals, antiprotozoals, or antifungals within 2 weeks before the screening visit
- Known or suspected immunodeficiency
-Active malignancy or history of malignancy within 5 years before the baseline visit, except completely treated in situ carcinoma of the cervix, completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin.

E.5 End points

E.5.1

Primary end point(s)

Improvement (reduction) in worst-itch numeric rating scale (WI-NRS) by ≥ 4 from baseline to Week 12

A legrosszabb viszketés numerikus besorolási skálán (WI-NRS) ≥4 értékű javulást (csökkenést) elérő résztvevők aránya a kiindulástól a 12. hétig.

E.5.1.1

Timepoint(s) of evaluation of this end point

Baseline to Week 12

A kiindulástól a 12. hétig

E.5.2

Secondary end point(s)

1 - Proportion of participants with improvement (reduction) in worst-itch numeric rating scale (WI-NRS) by ≥4 from baseline to Week 24
2 - Time to onset of effect on pruritus ; Time to onset of effect on pruritus as measured by proportion of participants with an improvement (reduction) in WI-NRS by ≥4 from baseline during the 24-week treatment period
3 - Change from baseline in WI-NRS ; Change from baseline in WI-NRS at Week 12 and Week 24
4 - Percent change from baseline in WI-NRS ; Percent change from baseline in WI-NRS at Week 12 and Week 24
5 - Percent change from baseline in WI-NRS over time ; Percent change from baseline in WI-NRS over time until Week 24
6 - Proportion of participants with WI-NRS reduction ≥ 4 over time ; Proportion of participants with WI-NRS reduction ≥ 4 over time until Week 24
7 - Onset of action in change from baseline in WI-NRS ; Onset of action in change from baseline in WI-NRS (first p<0.05 difference from placebo in the daily WI-NRS that remains significant at subsequent measurements) until Week 12
8 - Proportion of participants with Investigator’s Global Assessment 0/1 score for PN-stage ; Proportion of participants with Investigator’s Global Assessment 0/1 score for PN-Stage (IGA PN-S) at Week 4, Week 8, Week 12, and Week 24.
9 - Change from baseline in IGA PN-S score ; Change from baseline in IGA PN-S score at Week 4, Week 8, Week 12 and Week 24
10 - Proportion of participants with Investigator’s Global Assessment 0/1 score for PN-Assess ; Proportion of participants with Investigator’s Global Assessment 0/1 score for PN-Assess (IGA PN-A) at Week 4, Week8, Week 12, and Week 24
11 - Change from baseline in health-related quality-of-life ; Change from baseline in health-related quality-of-life, as measured by Dermatology Life Quality Index (DLQI) to Week 12 and Week 24
12 - Adverse Events ; Percentage of participants experiencing treatment-emergent adverse events (TEAEs) or serious adverse events (SAEs) from baseline through Week 24
13 - Immunogenicity ; Incidence of treatment-emergent antidrug antibodies (ADA) against dupilumab over time

1 - A WI-NRS skálán ≥4 értékű javulást (csökkentést) elérő résztvevők aránya a kiindulástól a 24. hétig.
2 - A prurituszra gyakorolt hatás megjelenésének ideje a résztvevők arányában mérve, akik a WI-NRS skálán ≥4 értékű javulást (csökkenést) mutatnak a kiinduláshoz képest a 24 hetes kezelési időszakban.
3 - A WI-NRS alapján kimutatott változás a kiindulási szinthez képest a 12. és a 24. héten.
4 - A WI-NRS alapján kimutatott százalékos változás a kiindulási szinthez képest a 12. és a 24. héten.
5 - A WI-NRS százalékos változása a kiinduláshoz képest az idő múlásával, a 24. hétig.
6 - Azon résztvevők aránya, akiknél a WI-NRS csökkenése ≥4 az idő múlásával, a 24. hétig.
7 - A WI-NRS skálán a kiindulási értékhez viszonyított eltérés kezdete (a napi WI-NRS skálán az első p <0,05 különbség a placebóhoz képest, amely a következő méréseknél is szignifikáns marad) a 12. hétig
8 - A 4. és 8., a 12. és a 24. héten a PN-stádium esetén a vizsgáló globális értékelése szerint 0/1 (IGA PN-S) pontszámot elérő résztvevők aránya.
9 - Eltérés az IGA PN-S pontszám kiindulási értékétől a 4., a 8., a 12. és a 24. héten.
10 - A 4. és 8., a 12. és a 24. héten a PN-stádium esetén a vizsgáló globális értékelése szerint 0/1 (IGA PN-A) pontszámot elérő résztvevők aránya.
11 - Eltérés a HRQoL kiindulási értékétől, a Dermatology Life Quality Index (DLQI) alapján mérve, a 12. és a 24. hétig.
12 - A kezelésből eredő nemkívánatos eseményeket (TEAE) vagy súlyos nemkívánatos eseményeket (SAE) tapasztalt résztvevők százalékos aránya a kiindulástól a 24. hétig.
13 - A kezelés során a dupilumabbal szemben kialakult gyógyszerellenes antitestek (ADA) előfordulása az idő függvényében.

E.5.2.1

Timepoint(s) of evaluation of this end point

1, 12, 13 : Baseline to Week 24
2, 5, 6 : Baseline to overtime until Week 24
3, 4, 11 : Baseline to Week 12 and Week 24
7 : Baseline to overtime until Week 12
8, 9, 10 : Baseline to Week 4, Week 8, Week 12, and Week 24

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

Yes

E.6.11

Pharmacogenomic

Yes

E.6.12

Pharmacoeconomic

Yes

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

Information not present in EudraCT

E.8.4

The trial involves multiple sites in the Member State concerned

Information not present in EudraCT

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

Chile

France

Hungary

Italy

Portugal

Spain

Taiwan

United Kingdom

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

LVLS

Utolsó alany utolsó vizit

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

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:

102

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

111

F.4.2.2

In the whole clinical trial

175

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

2020-03-26

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-03-24

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-11-22

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