Clinical Trials Register

Summary
EudraCT Number:	2020-003018-11
Sponsor's Protocol Code Number:	CQGE031E12301
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2021-08-18
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

2020-003018-11

A.3

Full title of the trial

A multi-center, randomized, double-blind, placebo controlled study to investigate the efficacy and safety of ligelizumab (QGE031) in the treatment of Chronic Inducible Urticaria (CINDU) in adolescents and adults inadequately controlled with H1-antihistamines

Többközpontú, randomizált, kettős vak, placebokontrollos vizsgálat a krónikus indukált csalánkiütés (CINDU) kezelésére alkalmazott ligelizumab (QGE031) hatásosságának és biztonságosságának értékelésére olyan serdülők és felnőttek kezelésére, akik csalánkiütése nem megfelelően kontrollált H1-antihisztaminok alkalmazása mellett

A.3.1

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

Study of efficacy and safety of ligelizumab in adolescents and adults with chronic inducible urticaria who remain symptomatic despite treatment with H1- antihistamines

A ligelizumab hatásosságának és biztonságosságának vizsgálata olyan serdülők és felnőttek krónikus, indukálható urtikáriájának kezelésére, akik H1-antihisztaminok alkalmazása ellenére is tüneteket mutatnak

A.4.1

Sponsor's protocol code number

CQGE031E12301

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 Hungary Kft.
B.5.2	Functional name of contact point	Public Information Desk
B.5.3	Address:
B.5.3.1	Street Address	Bartók Béla út 43-47.
B.5.3.2	Town/ city	Budapest
B.5.3.3	Post code	1114
B.5.3.4	Country	Hungary
B.5.4	Telephone number	00 36 1 457-6500
B.5.5	Fax number	00 36 1 457-6600
B.5.6	E-mail	infoph.hungary@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.3.1	Product name	Ligelizumab
D.3.2	Product code	QGE031
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	LIGELIZUMAB
D.3.9.2	Current sponsor code	QGE031
D.3.9.3	Other descriptive name	Anti-IgE antibody
D.3.9.4	EV Substance Code	SUB177843
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	120
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	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
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
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

Chronic Inducible Urticaria

E.1.1.1

Medical condition in easily understood language

Chronic Hives

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	10009869
E.1.2	Term	Cold urticaria
E.1.2	System Organ Class	10040785 - Skin and subcutaneous tissue disorders

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	10008675
E.1.2	Term	Cholinergic urticaria
E.1.2	System Organ Class	10040785 - Skin and subcutaneous tissue disorders

E.1.2 Medical condition or disease under investigation

E.1.2	Version	23.0
E.1.2	Level	LLT
E.1.2	Classification code	10012521
E.1.2	Term	Dermographism
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 superiority of ligelizumab versus placebo with regards to the change from baseline in response to a standardized provocation test for each CINDU subtype.

E.2.2

Secondary objectives of the trial

To demonstrate superiority of ligelizumab versus placebo with regard to proportion of participants with a complete response after standardized provocation test.
To demonstrate superiority of ligelizumab versus placebo in itch NRS following the provocation test.
To assess the safety of ligelizumab.

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. Participant’s parent’s or legal guardian’s signed informed consent and child’s assent, if appropriate, must be obtained before any assessment is performed.
3. Male and female participants ≥ 12 years of age at the time of screening.
4. Confirmed CINDU diagnosis (as per guidelines) for symptomatic dermographism, cold urticaria or cholinergic urticaria for ≥ 4 months (defined as onset of CINDU with supporting documentation (e.g medical record, clinical history, photographs)).
5. Diagnosis of CINDU (symptomatic dermographism, cold urticaria or cholinergic urticaria) inadequately controlled with H1-AH at local label approved doses at the time of randomization
6. Participants must be able to physically perform the protocol defined provocation test specific to the participant's CINDU.
7. Cholinergic urticaria participants must show sweating in performing the pulse-controlled ergometry test on day of randomization. Participants with anhidrosis must not be included.
8. Willing and able to complete a daily symptom eDiary as per protocol requirement and adhere to the study visit schedules.

E.4

Principal exclusion criteria

1. Use of other investigational drugs within 5 half-lives of enrollment, or within 30 days for small molecules prior to the screening visit or until the expected pharmacodynamic effect has returned to baseline for biologics, whichever is longer.
2. History of hypersensitivity to any of the study drugs or its components or to drugs of similar classes (i.e. to murine, chimeric or human antibodies) or to the provocation test or items used in provocation tests
3. Participants who have any concomitant CSU at screening
4. Participants who have a familial form (e.g familial cold autoinflammatory syndrome, familial cold urticaria) of the target CINDU that is being considered for the participant's inclusion in this study
5. Participants having a more defined other form of inducible urticaria than the target CINDU that is being considered for the participant's inclusion in this study
6. Diseases, other than chronic inducible urticaria, with urticarial or angioedema symptoms such as urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa) and hereditary or acquired angioedema (eg, due to C1 inhibitor deficiency).
7. Any other skin disease associated with chronic itching that might influence, in the investigator’s opinion, the study evaluations and results (eg, atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, etc.) or skin diseases associated with only wheals and no itch e.g asymptomatic dermographism
8. Prior exposure to ligelizumab, omalizumab or other anti-IgE therapies
9. Female participants, including adolescent females of 12 to less than 18 years of age, of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during dosing of study treatment

E.5 End points

E.5.1

Primary end point(s)

Symptomatic Dermographism
Change from baseline in Total Fric Score (TFS) at Week 12 in response to FricTest® 4.0
Cold Urticaria
Change from baseline in critical temperature threshold (CTT) at Week 12 in response to the TempTest® 4.0
Cholinergic Urticaria
Change from baseline in itch numerical rating scale (NRS) at Week 12 in response to the pulse-controlled ergometry test.

E.5.1.1

Timepoint(s) of evaluation of this end point

Week 12

E.5.2

Secondary end point(s)

Symptomatic Dermographism
Proportion of participants with complete response in FricTest® at Week 12

Change from baseline in itch NRS following provocation test at Week 12, in participants with itch NRS > 0 at baseline

Cold Urticaria
Proportion of participants with complete response in TempTest® at Week 12
Change from baseline in itch NRS following provocation test at Week 12, in participants with itch NRS > 0 at baseline

Cholinergic Urticaria
Proportion of participants with itch NRS=0 following the pulse-controlled ergometry test at Week 12
Proportion of participants with physician global assessment of severity of hives=0 following the pulse-controlled ergometry test at Week 12

Safety endpoints will include but not be limited to:
•Occurrence of treatment emergent adverse events (serious and non-serious) during the study
•Occurrence of treatment emergent adverse events during the study leading to discontinuation of study treatment
•Occurrence of treatment emergent adverse events of interest listed as either identified or potential risks, during the study
•Changes in safety parameters

E.5.2.1

Timepoint(s) of evaluation of this end point

At 12 Weeks and 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

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

E.6.12

Pharmacoeconomic

E.6.13

Others

Yes

E.6.13.1

Other scope of the trial description

To assess immunogenicity (IG) of ligelizumab

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

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

Brazil

Canada

Chile

China

India

Israel

Jordan

Korea, Republic of

Lebanon

Malaysia

Philippines

Russian Federation

Singapore

South Africa

Taiwan

Thailand

Turkey

United States

Vietnam

Austria

Bulgaria

Finland

France

Germany

Hungary

Italy

Netherlands

Poland

Romania

Slovakia

Slovenia

Spain

United Kingdom

Argentina

Greece

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

LVLS

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

Yes

F.1.1

Number of subjects for this age range:

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)

Yes

F.1.1.6.1

Number of subjects for this age range:

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

325

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

162

F.4.2.2

In the whole clinical trial

428

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)

Participants may be eligible for post-trial access after completion of the study

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

2021-10-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-09-17

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2022-08-09

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