Clinical Trials Register

Summary
EudraCT Number:	2018-000595-15
Sponsor's Protocol Code Number:	CZPL389A2203E1
National Competent Authority:	Slovakia - SIDC (Slovak)
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2019-09-12
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

Slovakia - SIDC (Slovak)

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)

Randomizovaná dvojito zaslepená multicentrická extenzia klinického skúšania CZPL389A2203 so stanovením dávky, na zhodnotenie krátkodobej a dlhodobej bezpečnosti a účinnosti perorálneho lieku ZPL389 pri súbežnej alebo intermitentnej liečbe lokálnymi kortikosteroidmi a/alebo lokálnymi inhibítormi kalcineurínu u dospelých pacientov s atopickou dermatitídou (extenzia klinického skúšania 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

Klinické skúšanie na zhodnotenie bezpečnosti a účinnosti ZPL389 pri súbežnej alebo intermitentnej liečbe lokálnymi kortikosteroidmi a/alebo lokálnymi inhibítormi kalcineurínu u pacientov s atopickou dermatitídou

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 Slovakia s.r.o.
B.5.2	Functional name of contact point	DRA information desk
B.5.3	Address:
B.5.3.1	Street Address	Žižkova 22/B
B.5.3.2	Town/ city	Bratislava
B.5.3.3	Post code	SK-811 02
B.5.3.4	Country	Slovakia
B.5.4	Telephone number	+421 2 50706116
B.5.5	Fax number	+421 2 50706100
B.5.6	E-mail	dra.slovakia@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

E.1.1.1

Medical condition in easily understood language

chronic inflammatory skin disease

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.

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.

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

Title: Actigraphy substudy
Objective: To explore the effect of ZPL389 on sleep disturbance and/or nocturnal scratching as measured by actigraphy in a subset of subjects

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.

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 active 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.

E.5 End points

E.5.1

Primary end point(s)

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

E.5.1.1

Timepoint(s) of evaluation of this end point

at week 32 and week 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.

E.5.2.1

Timepoint(s) of evaluation of this end point

Over time

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

Austria

Belgium

Canada

Estonia

Finland

Germany

Iceland

Japan

Netherlands

Poland

Russian Federation

Slovakia

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

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:

215

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

164

F.4.2.2

In the whole clinical trial

230

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

2019-11-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-09-17

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

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