Clinical Trials Register

Summary
EudraCT Number:	2019-001762-14
Sponsor's Protocol Code Number:	69765
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2020-07-29
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Netherlands - Competent Authority

A.2

EudraCT number

2019-001762-14

A.3

Full title of the trial

Evaluation of the anti-inflammatory effects of glycopyrronium added to indacaterol/mometasone on the allergen-induced late asthmatic response

Een gerandomiseerd, dubbelblind, cross-over onderzoek naar het effect van Glycopyrronium toegevoegd aan Mometason en Indacaterol op een door allergeen veroorzaakte late astmatische ontstekingsreactie bij patiënten met astma

A.3.1

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

Anti-inflammatory effects of Glycopyrronium

Ontstekingsremmend effect Glycopyrronium

A.3.2

Name or abbreviated title of the trial where available

Anti-inflammatory effects of Glycopyrronium

A.4.1

Sponsor's protocol code number

69765

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	University Medical Center Groningen
B.1.3.4	Country	Netherlands
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	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	University Medical Center Groningen
B.5.2	Functional name of contact point	Maarten van den Berge
B.5.3	Address:
B.5.3.1	Street Address	Hanzeplein 1
B.5.3.2	Town/ city	Groningen
B.5.3.3	Post code	9713 GZ
B.5.3.4	Country	Netherlands
B.5.4	Telephone number	0031503615260
B.5.5	Fax number	0031503619320
B.5.6	E-mail	m.van.den.berge@umcg.nl

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
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	QMF149
D.3.4	Pharmaceutical form	Inhalation powder
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	mometasone
D.3.9.1	CAS number	105102-22-5
D.3.9.2	Current sponsor code	MF
D.3.9.3	Other descriptive name	MOMETASONE FUROATE
D.3.9.4	EV Substance Code	SUB03318MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	160
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Indacaterol
D.3.9.1	CAS number	753498-25-8
D.3.9.3	Other descriptive name	INDACATEROL MALEATE
D.3.9.4	EV Substance Code	SUB30300
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
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	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.3.1	Product name	QVM149
D.3.4	Pharmaceutical form	Inhalation powder
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	MOMETASONE
D.3.9.1	CAS number	105102-22-5
D.3.9.3	Other descriptive name	MF
D.3.9.4	EV Substance Code	SUB09045MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	80
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	indacaterol
D.3.9.1	CAS number	753498-25-8
D.3.9.3	Other descriptive name	INDACATEROL MALEATE
D.3.9.4	EV Substance Code	SUB30300
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	150
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	GLYCOPYRRONIUM
D.3.9.1	CAS number	51186-83-5
D.3.9.3	Other descriptive name	glycopyrrolate
D.3.9.4	EV Substance Code	SUB02381MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(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

Asthma

E.1.1.1

Medical condition in easily understood language

Asthma

E.1.1.2

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

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 assess the anti-inflammatory effects of Indacaterol/glycopyrronium/Mometasone (QVM) versus Indacaterol/Mometasone (QMF) on the allergen-induced late asthmatic response in patients with asthma.

E.2.2

Secondary objectives of the trial

Change from baseline after allergen challenge (V7/V10 vs V4 results) of:
• Cell differential counts in blood and sputum 24 hours after allergen challenge.
• Bronchial and alveolar nitric oxide.
• Multiple Breath Nitrogen Washout (Lung Clearance Index (LCI), Scond, Sacin).
• Lung function (FEV1, FEV1/FVC, FEF25, FEF50, FEF75, FEF25-75).
• Body plethysmography (RV (% predicted), RV/TLC % predicted).
• Impulse Oscillometry. Resistance (R5, R20, R5-20) and Reactance at 5 Hertz (IOS).
• Genome-wide mRNA and miRNA expression in sputum and in epithelial cells derived from nasal epithelial brushes.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Signed informed consent must be obtained prior to participation in the study.
2. Male and female adult patients aged between 18 and 65 years old.
3. Patients with a diagnosis of asthma for at least 6 months prior to Visit 1 with current asthma severity of step 1-3 (GINA 2018).
4. Patients with presence of allergy against house dust mite, cat or grass pollen.
5. PC20 methacholine ≤ 8 mg/ml.
6. Drop in FEV1 > 20% during the early asthmatic response and drop in FEV1 > 15% during the late asthmatic response, i.e. between 3-8 hours after allergen challenge.
7. Patients able to produce sputum of sufficient quality for evaluation of cell differential counts 24 hours after the baseline allergen challenge at Visit 3.

E.4

Principal exclusion criteria

1. Patients who have a smoking history ≥ 10 pack-years (Note: 1 pack is equivalent to 20 cigarettes. 10 pack years = 1 pack/day x 10 years or ½ pack/day x 20 years). Ex-smokers are eligible for inclusion if they quit smoking for at least 6 months prior to Visit 1.
2. Patients diagnosed with Chronic Obstructive Pulmonary Disease (COPD).
3. Patients with severe airway obstruction at baseline, FEV1 <70% of predicted or < 1.5 liters.
4. Patients who have had an asthma attack/exacerbation requiring systemic steroids or hospitalization or emergency room visit within 6 weeks of Visit 1. If patients experience an asthma attack/exacerbation requiring systemic steroids or hospitalization or emergency room visit, they may be re-screened 6 weeks after recovery from the exacerbation.
5. Patients who have had a respiratory tract infection or clinical significant asthma worsening as defined by Investigator within 4 weeks prior to Visit 1. Patients may be re-screened 4 weeks after recovery from their respiratory tract infection or asthma worsening.
6. Patients who have ever required intubation for a severe asthma attack/exacerbation.
7. Patients who have a clinical condition which is likely to be worsened by ICS administration (e.g. glaucoma, cataract and fragility fractures) who are according to investigator’s medical judgment at risk participating in the study.
8. Patients treated with a LAMA for asthma within 3 months prior to Visit 1.

E.5 End points

E.5.1

Primary end point(s)

• Reduction in the percentage of sputum eosinophils 24 hours after allergen challenge at the end of each treatment period vs baseline (V7/V10 vs V4 results).

E.5.1.1

Timepoint(s) of evaluation of this end point

End of study only

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

End of study

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

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)

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

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

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

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

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

LVLS2

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

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:

F.1.3

Elderly (>=65 years)

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

F.3.3.1

Women of childbearing potential not using contraception