Clinical Trials Register

Summary
EudraCT Number:	2017-002473-19
Sponsor's Protocol Code Number:	PNEU-ASTHMA-02
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-06-24
Trial 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

France - ANSM

A.2

EudraCT number

2017-002473-19

A.3

Full title of the trial

PREDICTIVE FACTORS AND MAGNITUDE OF RESPONSE TO OMALIZUMAB AND MEPOLIZUMAB IN ALLERGIC AND EOSINOPHILIC SEVERE ASTHMA: PREDICTUMAB, AN OPEN-LABEL, CONTROLLED, RANDOMIZED MULTINATIONAL PRAGMATIC TRIAL

A.3.1

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

Predictive factors of response to omalizumab and mepolizumab in asthma.

A.4.1

Sponsor's protocol code number

PNEU-ASTHMA-02

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	Cliniques Universitaires Saint-Luc
B.1.3.4	Country	Belgium
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Cliniques Universitaires Saint-Luc
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Cliniques Universitaires Saint-Luc
B.5.2	Functional name of contact point	Pneumology Unit
B.5.3	Address:
B.5.3.1	Street Address	Avenue Hippocrate 10
B.5.3.2	Town/ city	Bruxelles
B.5.3.3	Post code	1200
B.5.3.4	Country	Belgium
B.5.4	Telephone number	003227642866
B.5.6	E-mail	charles.pilette@uclouvain.be

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	Yes
D.2.1.1.1	Trade name	NUCALA
D.2.1.1.2	Name of the Marketing Authorisation holder	GlaxoSmithKline Trading Services Limited
D.2.1.2	Country which granted the Marketing Authorisation	Ireland
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.3.4	Pharmaceutical form	Powder for concentrate for solution for injection/infusion
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	NUCALA
D.3.9.1	CAS number	196078-29-2
D.3.9.2	Current sponsor code	Pneu-asthma-002
D.3.9.3	Other descriptive name	MEPOLIZUMAB
D.3.9.4	EV Substance Code	SUB21650
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	100
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)	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	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	Yes
D.2.1.1.1	Trade name	XOLAIR
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Europharm Limited
D.2.1.2	Country which granted the Marketing Authorisation	Ireland
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	XOLAIR
D.3.4	Pharmaceutical form	Powder and solvent for solution for injection/infusion
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	OMALIZUMAB
D.3.9.1	CAS number	242138-07-4
D.3.9.2	Current sponsor code	Pneu-asthma-02
D.3.9.4	EV Substance Code	SUB12543MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	75
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)	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	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

Adult patients (18-90 years old) with severe asthma and eligible for both XOLAIR and NUCALA therapies, and agreeing on participating (signature of a written informed consent).

E.1.1.1

Medical condition in easily understood language

Adults with asthma

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

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 compare the rate and magnitude of response to omalizumab and mepolizumab in patients with severe allergic and eosinophilic asthma, in terms of annual rate of severe exacerbations (primary outcome).

E.2.2

Secondary objectives of the trial

To determine theranostic features, i.e. clinical features and blood/urine/mucosal (nasal, sputum) biomarkers able to predict a better response to omalizumab or mepolizumab in severe asthma patients eligible to both therapies.
To compare effects of omalizumab and mepolizumab on secondary outcomes, i.e. asthma symptom scores (ACT, ACQ6), asthma-related quality of life (AQLQ), lung function (FEV1), and nasal symptoms (VAS and, for nasal polyps, endoscopic scoring).
To record the baseline clinical characteristics of severe asthma patients eligible to both biotherapies, as compared to those eligible to omalizumab according to the PERSIST study.
To compare, in responders, effects of omalizumab and mepolizumab on clinical and biological features, in particular blood (and sputum) eosinophils.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

o Signed informed consent form (ICF),
o Age >18+ years (18-90 years old) at time of signing ICF,
o Able to comply with the study protocol, in the investigator’s judgment,
o Documented physician-diagnosed asthma ,
o and eligible to omalizumab and mepolizumab and who have not yet received any of these therapies. Eligibility criteria to omalizumab or mepolizumab are defined by all of these characteristics :
 patients with severe asthma remaining uncontrolled despite optimal, high-dose inhaled ICS therapy and LABA; (alternative add-on medication could consist of LTRA or low-dose theophylline),
  2 severe exacerbations in the previous year (as defined by requiring oral or injective corticosteroids for 3 days or a doubled dose for cortico-dependent patients, or by emergency room visit or hospitalisation for asthma),
 impaired lung function (FEV1 < 80% predicted),
 increased serum total IgE between 76 and 700 kU/L (but a range of 30 to 1.300 kU/L also applicable in countries other than Belgium, such as France according to EMA and national rules),
 allergic background evidenced by specific IgE  0.35 kU/L and/or skin prick-test reactivity to at least one perennial allergen,
 and blood eosinophils  300/L in at least two samples, just before initiation and during the previous year.

E.4

Principal exclusion criteria

o History of evidence of drug/substance abuse that would pose a risk to patient safety, interfere with the conduct of study, have an impact on the study results, or affect the patient’s ability to participate in the study, in the opinion of the investigator,
o Difficult to treat asthma and others severe respiratory diseases,
o Patient already currently/actively enrolled in a clinical therapeutic trial (testing another drug); the concomitant inclusion in a Registry, which may include biosampling, is not an exclusion criterion,
o Protected subjects (sous tutelle or curatelle), patients who are unable to express their consent, subjects who are deprived of liberty, subjects who are hospitalized without consent, subjects who are admitted in a health-care or social institute with another aim than that of the research, inclusion in an emergency situation, patient who is subject to a court order;
o Pregnant, post-partum or lactating women;
o Known sensitivity to any of the active substances or their excipients to be administered during the study;
o Active malignancy or malignancy in remission over less than 5 years.

E.5 End points

E.5.1

Primary end point(s)

The primary criterion for judgment will be the rate of severe exacerbation during one year in patients on omalizumab vs mepolizumab, in the overall population.
An additional primary criterion will be the rate of response to
omalizumab vs that for mepolizumab, in the overall and stratified population(s).

E.5.1.1

Timepoint(s) of evaluation of this end point

The definition of response (at 4 or 6 months versus baseline, and further at 22 or 24 months vs baseline).

E.5.2

Secondary end point(s)

Clinical features and biomarkers (or array signatures) analyzed in blood, mucosal and urine
samples will be tested for their putative ability to predict a better response to oma- or
mepolizumab (theranostic value). The candidate features are age at (severe) disease onset and
presence of nasal polyps or aspirin hypersensitivity as well as serum specific/total IgE ratio and
blood eosinophil levels.
Asthma-related outcomes other than exacerbations – i.e. disease control reflected by ACT
(Annex 1 : Asthma Control Test – ACT) and ACQ6 (Annex 2 : Asthma Control Questionnaire – ACQ),
asthma-related quality of life questionnaire reflected by AQLQ (Annex 3 : Asthma Quality of Life
Questionnaire - AQLQ), lung function reflected by FEV1 % predicted and absolute change - as
well as nasal symptoms (VAS and, for nasal polyps, endoscopic scoring) will be assessed in the
oma- and mepolizumab groups, in the overall and stratified populations.
The clinical characteristics of the study population will be recorded, as well as the effects of
both biologics on biological markers such as blood (and sputum) eosinophils or FeNO.

E.5.2.1

Timepoint(s) of evaluation of this end point

up to 24 months

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

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

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)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

Yes

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

Yes

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

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

E.8.6.2

Trial being conducted completely outside of the EEA

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

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:

145

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

219

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

252

F.4.2

For a multinational trial

F.4.2.1

In the EEA

364

F.4.2.2

In the whole clinical trial

364

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)

les patients poursuivront le traitement à l'étude après la fin de l'étude

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

2020-08-10

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-09-07

P. End of Trial
P.	End of Trial Status	Ongoing

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