Clinical Trials Register

Summary
EudraCT Number:	2018-000595-15
Sponsor's Protocol Code Number:	CZPL389A2203E1
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2020-02-20
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

France - ANSM

A.2

EudraCT number

2018-000595-15

A.3

Full title of the trial

A randomized, double blind, multicenter extension to CZPL389A2203 dose-ranging study to assess the short-term and long-term safety and efficacy of oral ZPL389 with concomitant or intermittent use of TCS and/or TCI in adult patients with atopic dermatitis (ZEST Extension)

Protocole d’extension de l’étude CZPL389A2203, dose-réponse, multicentrique, randomisée, en double aveugle, évaluant à court terme et à long terme la tolérance et l’efficacité de ZPL389 par voie orale avec une utilisation concomitante ou intermittente de dermocorticoïdes et/ou d’inhibiteurs de la calcineurine topiques chez des patients adultes atteints de dermatite atopique (Extension de l’étude ZEST)

A.3.1

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

A study to assess the safety and efficacy of ZPL389 with concomitant or intermittent use of TCS and/or TCI in atopic dermatitis patients

Etude évaluant a tolérance et l’efficacité de ZPL389 en utilisation concomitante ou intermittente de dermocorticoïdes et/ou d’inhibiteurs de la calcineurine topiques chez des patients adultes atteints de dermatite atopique

A.3.2

Name or abbreviated title of the trial where available

ZEST Extension

A.4.1

Sponsor's protocol code number

CZPL389A2203E1

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	Novartis Pharma AG
B.1.3.4	Country	Switzerland
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	Novartis Pharma AG
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis Pharma S.A.S
B.5.2	Functional name of contact point	Information&Communication Médicales
B.5.3	Address:
B.5.3.1	Street Address	8/10 rue Henry Sainte Claire Deville, CS 40150
B.5.3.2	Town/ city	Rueil-Malmaison
B.5.3.3	Post code	92563
B.5.3.4	Country	France
B.5.4	Telephone number	+33 1 5547 6600
B.5.5	Fax number	+33 1 5547 6100
B.5.6	E-mail	icm.phfr@novartis.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.3.2	Product code	ZPL389
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	adriforant
D.3.9.1	CAS number	2096455-87-5
D.3.9.2	Current sponsor code	ZPL389
D.3.9.3	Other descriptive name	ZPL-3893787
D.3.9.4	EV Substance Code	SUB179385
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	No
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.3.2	Product code	ZPL389
D.3.4	Pharmaceutical form	Capsule, hard
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	adriforant
D.3.9.1	CAS number	2096455-87-5
D.3.9.2	Current sponsor code	ZPL389
D.3.9.3	Other descriptive name	ZPL-3893787
D.3.9.4	EV Substance Code	SUB179385
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	No
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

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 atopique

E.1.1.1

Medical condition in easily understood language

chronic inflammatory skin disease

Maladie inflammatoire chronique de la peau

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	21.1
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

To assess the short-term and long-term safety of 30 mg o.d and 50 mg o.d ZPL389 with concomitant or intermittent use of TCS and/or TCI up to total of 32 weeks and 116 weeks of treatment.

Evaluer la sécurité d’emploi à court terme et à long terme de ZPL389 30 mg/jour et 50 mg/jour avec une utilisation concomitante ou intermittente des DC et/ou ICT jusqu'à 32 semaines et 116 semaines de traitement

E.2.2

Secondary objectives of the trial

To evaluate the efficacy of 30 mg o.d and 50 mg o.d ZPL389 with concomitant or intermittent use of TCS and/or TCI as assessed by IGA response over time.
To evaluate the efficacy of 30 mg o.d and 50 mg o.d ZPL389 with concomitant or intermittent use of TCS and/or TCI as assessed by EASI over time.

Evaluer l’efficacité de ZPL389 30 mg/jour et 50 mg/jour avec une utilisation concomitante ou intermittente des DC et/ou ICT, mesurée par l’évaluation globale du médecin-investigateur (IGA pour Investigator's Global Assessment) au cours de l’étude
Evaluer l’efficacité de ZPL389 30 mg/jour et 50 mg/jour avec une utilisation concomitante ou intermittente des DC et/ou ICT, mesurée par l’indice de l’étendue et de la sévérité de l’eczéma (EASI pour Eczema Area and Severity Index) au cours de l’étude

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Signed informed consent must be obtained before any assessment is performed.
2. Female and male subjects with atopic dermatitis who have participated in and completed 16 weeks of treatment in CZPL389A2203 study.
3. Willing and able to comply with scheduled visits, treatment plan, laboratory tests, diary
completion and other study procedures.

1. Le consentement éclairé doit être obtenu par écrit avant toute procédure liée à l’étude.
2. Patients de sexe masculin ou féminin atteints de dermatite atopique ayant participé à l’étude CZPL389A2203 et ayant terminé les 16 semaines de traitement.
3. Patient désireux et capable de se conformer aux visites prévues, au traitement, aux analyses biologiques, à la tenue d’un journal et aux autres procédures de l’étude.

E.4

Principal exclusion criteria

1. Inability to use TCS and/or TCI concomitantly or intermittently due to history of
important side effects of topical medication (e.g., intolerance to treatment, hypersensitivity reactions, significant skin atrophy, systemic effects), as assessed by the investigator or subject’s treating physician.
2. Subjects who met any study and/or treatment discontinuation criteria during the
CZPL389A2203 study (Section 9.1).
3. Any skin disease that, in the opinion of the investigator, would confound the diagnosis or evaluation of AD disease activity (e.g., Netherton Syndrome, Cutaneous T-Cell
Lymphoma, extensive contact dermatitis, chronic actinic dermatitis)
4. Subjects taking medications prohibited by the protocol (see Section 6.2.2)
5. Pregnant or nursing (lactating) women
6. Women of child-bearing potential (WOCBP), defined as all women physiologically
capable of becoming pregnant, unless they use required methods of contraception during
dosing and for 4 weeks after stopping of investigational medication.
7. Sexually active males unless they use a condom during intercourse while taking drug and for 4 weeks after stopping investigational medication and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent
delivery of the drug via seminal fluid.

1. Patients ne pouvant pas utiliser de façon concomitante ou intermittente les DC et/ou ICT à cause d’effets indésirables préalables importants (par ex. intolérance au traitement, réactions d’hypersensibilité, atrophie de la peau significative, effets systémiques), selon le jugement du médecin-investigateur ou du médecin traitant du patient.
2. Patients ayant rempli tout critère d’arrêt de l’étude et/ou du traitement pendant l’étude CZPL389A2203.
3. Toute maladie de la peau qui, selon le médecin-investigateur, pourrait interférer avec le diagnostic ou l’évaluation de l’activité de la dermatite atopique (par ex. syndrome de Netherton, lymphome cutané à cellules T, dermatite de contact généralisée, dermatite séborrhéique chronique).
4. Patients recevant des traitements non autorisés par le protocole.
5. Femmes enceintes ou qui allaitent.
6. Femmes en mesure d’avoir des enfants, c.-à-d. toutes les femmes physiologiquement aptes à être enceintes, sauf si elles utilisent une méthode de contraception très efficace pendant toute la période de traitement et les 4 semaines qui suivent l’arrêt du traitement à l’étude.
7. Les hommes ayant des rapports sexuels doivent accepter d’utiliser un préservatif pendant les rapports sexuels au cours de la période de traitement et pendant les 4 semaines qui suivent l’arrêt du traitement à l’étude et de ne pas concevoir d’enfant pendant cette période. L’usage du préservatif est également nécessaire pour les hommes vasectomisés afin d’empêcher la transmission du traitement à l’étude via le liquide séminal.

E.5 End points

E.5.1

Primary end point(s)

• Frequency of AEs at Week 32 (short-term) and Week 116 (long-term).

• Fréquence des évènements indésirables à la Semaine 32 (court terme) et à la Semaine 116 (long terme)

E.5.1.1

Timepoint(s) of evaluation of this end point

at week 32 and week 116

Aux semaines 32 et 116

E.5.2

Secondary end point(s)

IGA score over time (absolute and relative frequencies from core study baseline). IGA response is defined as achievement of an IGA score of 0 or 1 with a 2-point reduction from
core study baseline without use of confounding therapy (e.g. rescue medication) up to the
assessment time point.
EASI score over time (absolute and percent change from core study baseline). EASI-50/EASI-75 response over time: EASI-50/EASI-75 response is defined as achieving ≥50%/≥ 75% improvement (reduction) in EASI score compared to baseline without use of confounding therapy (e.g. rescue medication) up to the assessment time point.

• Score IGA au cours de l’étude (valeur absolue et pourcentage de variation par rapport à la baseline de l’étude principale). La réponse IGA est définie par un score IGA de 0 ou 1 avec une diminution de 2 points par rapport à la baseline de l’étude principale sans l’utilisation d’un traitement pouvant influencer le résultat (par ex. médicament de secours) jusqu’au moment de l’évaluation
• Score EASI au cours de l’étude (valeur absolue et pourcentage de variation par rapport à la baseline de l’étude principale). La réponse EASI-50/EASI-75 est définie par une amélioration (diminution) de ≥ 50 %/≥ 75 % du score EASI par rapport à la baseline de l’étude principale sans l’utilisation d’un traitement pouvant influencer le résultat (par ex. médicament de secours) jusqu’au moment de l’évaluation

E.5.2.1

Timepoint(s) of evaluation of this end point

Over time

Au cours de l'étude

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)

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

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

different dosage of the same product

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

Argentina

Belgium

Canada

Czech Republic

Estonia

Finland

France

Germany

Hungary

Iceland

Japan

Latvia

Lithuania

Netherlands

Poland

Russian Federation

Slovakia

Spain

Taiwan

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

Study completion is defined as when the last subject finishes their Study Completion visit and any repeat assessments associated with
this visit have been documented and followed-up appropriately by the Investigator

La fin d'étude est définie par le dernier patient qui fait la visite de fin d'étude et que toute évaluation associées à cette visite soit documentée et que l'investigateur a fait le suivi adéquate.

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:

286

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

218

F.4.2.2

In the whole clinical trial

306

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

2020-04-23

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-03-16

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2020-08-25

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