Clinical Trials Register

Summary
EudraCT Number:	2019-002849-38
Sponsor's Protocol Code Number:	AQ-PRO-005
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-03-04
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2019-002849-38

A.3

Full title of the trial

A prospective, active-controlled, randomized, open label, single-center, multiple dose, two-period crossover clinical trial to assess the safety, pharmacodynamics, pharmacokinetics, and preliminary efficacy assessment of a budesonide inhalation solution (AQ001S) compared to a budesonide inhalation suspension (comparator)

Etude clinique interventionnelle prospective, contrôlée, randomisée, ouverte, monocentrique, à doses répétées, croisée (2 périodes), afin d’évaluer la sécurité, la pharmacodynamie, la pharmacocinétique et l’efficacité préliminaire d’une solution pour inhalation contenant du budésonide (AQ001S) en comparaison à une suspension pour inhalation contenant du budésonide (comparateur).

A.3.1

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

A clinical study to assess the safety, systemic exposure and efficacy of a liquid for inhalation of budesonide (AQ001S) to treat asthma.

étude de la sécurité, de l’exposition systémique et de l’efficacité d’un liquide pour inhalation de budésonide dans le traitement de l’asthme

A.3.2

Name or abbreviated title of the trial where available

BOREAS

A.4.1

Sponsor's protocol code number

AQ-PRO-005

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	Aquilon Pharmaceuticals
B.1.3.4	Country	Belgium
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	Walloon Region (SPW-EER)
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	Aquilon Pharmaceuticals
B.5.2	Functional name of contact point	Clinical Operations
B.5.3	Address:
B.5.3.1	Street Address	Quai de la Boverie 59
B.5.3.2	Town/ city	Liege
B.5.3.3	Post code	4020
B.5.3.4	Country	Belgium
B.5.4	Telephone number	32042292800
B.5.6	E-mail	clinops@aquilonpharma.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	Budesonide inhalation solution 0.125 mg/ml
D.3.2	Product code	AQ001S 0.125 mg/ml
D.3.4	Pharmaceutical form	Inhalation solution
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	BUDESONIDE
D.3.9.1	CAS number	51333-22-3
D.3.9.2	Current sponsor code	budesonide
D.3.9.3	Other descriptive name	16α,17α -butylidenedioxy-11β,21-dihydroxypregna-1,4-diene-3,20-dione; 16α,17-[(1RS)-butylidenebis(oxy)]-11β,21-dihydroxypregna-1,4-diene-3,20-dion
D.3.9.4	EV Substance Code	SUB05955MIG
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	0.125
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	Yes
D.2.1.1.1	Trade name	Nebbud 0.25 mg/2 ml zawiesina do nebulizacji
D.2.1.1.2	Name of the Marketing Authorisation holder	Teva Pharmaceuticals Polska Sp. z o.o.
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	Nebbud 0.25 mg/2 ml
D.3.4	Pharmaceutical form	Inhalation solution
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
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.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10003555
E.1.2	Term	Asthma bronchial
E.1.2	System Organ Class	100000004855

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Assess the safety of AQ001S 0.125 mg/ml, compare the primary pharmacodynamics, i.e. the bronchoprotection, of AQ001S 0.125 mg/ml with the comparator.

E.2.2

Secondary objectives of the trial

To compare 1) the pharmacokinetics and 2) secondary PD/efficacy of AQ001S 0.125 mg/ml with the comparator.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subjects aged between 18 and 65 years, inclusive.
2. Body mass index ≤ 30 kg/m2.
3. Documented clinical diagnosis of stable, persistent, asthma for at least 3 months, i.e.:
• for whom forced expiratory volume in one second (FEV1) ≥ 70% of predicted, and
• treated with as-needed reliever medication (short-acting beta2-agonist-containing medication) only.
4. Subjects who are ICS-naïve for minimum 60 days at Screening Visit.
5. Positive methacholine (MCh) challenge test (concentration of MCh provoking an FEV1 fall of 20% [PC20] < 8 mg/ml or dose of MCh provoking an FEV1 fall of 20% [PD20] < 0.2 mg) in the last year.
6. Post-bronchodilator FEV1 at least 80% of the predicted, documented in the last year.
7. Clinical laboratory test results, 12-lead electrocardiogram (ECG), blood pressure and heart rate (supine) within normal reference range or judged to be not clinically significant by the Investigator.
8. Female subjects of childbearing potential should have a negative pregnancy test at Screening Visit.
9. Female subjects of childbearing potential using a highly effective method of contraception for at least 28 days and pursuing this contraception during the trial and for 28 days after the last administration of the investigational medicinal product (IMP).

E.4

Principal exclusion criteria

1. Current smokers or recent (< 8 weeks) ex-smokers or ex-smokers if > 10 pack-years.
2. FEV1 < 70%.
3. History of near-fatal asthma and/or intensive care unit admission for asthma symptoms.
4. Exacerbations of asthma requiring oral steroids, hospitalization or change in asthma treatment in the previous three months.
5. Evidence of symptomatic chronic or acute respiratory infection in the previous 8 weeks.
6. Diagnosis of chronic obstructive pulmonary disease (COPD) or bronchiectasis.
7. Pulmonary malformations, tuberculosis, cystic fibrosis.
8. Untreated oral candidiasis.
9. Immunosuppressive treatment, including systemic corticosteroids (e.g., oral, parenteral, ocular, nasal), within 28 days before Screening Visit.
10. Unstable or life-threatening cardiac disease
11. History or presence of prolonged QT interval (> 470 ms), or any other clinically significant ECG abnormalities as judged by the Investigator based on 12-lead ECG recordings at Screening Visit.
12. Diabetes mellitus.
13. Neuropsychiatric diseases.
14. History or presence of malignancy of any system organ class (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years prior to Screening Visit, regardless of whether there is evidence of local recurrence or metastases.
15. History or presence of any other clinically relevant disease of any major system organ class (e.g. cardiovascular, pulmonary, renal, hepatic, gastrointestinal, reproductive, endocrinological, neurological, psychiatric or orthopedic disease) as judged by the Investigator.

E.5 End points

E.5.1

Primary end point(s)

Safety:
The safety will be evaluated collecting the following information:
- Adverse events and serious adverse events, including asthma exacerbations
- General tolerability: vital signs, ECG, physical examination
- Laboratory parameters: hematology, biochemistry and urinalysis
- Local tolerability:
o Increased bronchial irritability
o Paradoxical bronchospasm
o Oropharyngeal examination (e.g. vocal cord myopathy, fungal infection)
- Forced expiratory volume at 1 second (FEV1) and forced vital capacity (FVC), measured by spirometry
- Assessment of hypothalamic pituitary adrenocortical (HPA) axis function: urinary cortisol/creatinine ratio in first waking urine
Pharmacodynamics (PD):
Bronchoprotection: Change from baseline in PC20, i.e. the concentration of methacholine provoking an FEV1 fall of 20%, as determined by methacholine challenge test.

E.5.1.1

Timepoint(s) of evaluation of this end point

Safety: After each treatment period (descriptive comparison with baseline)
PD: After each treatment period (change from baseline)

E.5.2

Secondary end point(s)

PD/efficacy:
The secondary PD/efficacy will be evaluated using the following parameters:
- Bronchoprotection and bronchodilation will be investigated by airway volume (av) and lobe volume (lv) measured by functional respiratory imaging (FRI) using computed tomography (CT) scans after Pre-CT scan MCh challenge.
- Symptom scores will be recorded using day- and night-time asthma symptom scoring and validated asthma-specific questionnaires (included in trial subject diary).
- Use of as-needed reliever medication (as reported in trial subject diary).
- Airway inflammation PD biomarkers: fractional concentration of exhaled nitric oxide (FeNO) and blood eosinophil count.
- FEV1 and forced inspiratory vital capacity (FIVC), measured by spirometry.
Pharmacokinetics (PK):
The PK endpoint, i.e. the PK profile of budesonide in plasma, will be evaluated through the following PK parameters, calculated for each treatment period:
- Start of treatment period:
o single dose 24-hour PK parameters at the time of the first scheduled IMP administration (15 time points): Cmax, tmax, Clast, tlast, AUC0-inf, AUC0-last, AUC0-6h, CL/F, V/F, λz and t1/2z.
- End of treatment period:
o single time point PK prior to the penultimate scheduled IMP administration: Cthrough.
o abridged PK at the time of the last scheduled IMP administration (7 time points): Cmax, tmax, Clast, tlast, and AUC0-last, AUC0-6h.

E.5.2.1

Timepoint(s) of evaluation of this end point

PD/Efficacy: After each treatment period (changes form baseline)
PK: as described in PK endpoint

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

E.6.7

Pharmacodynamic

Information not present in EudraCT

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

Yes

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

Yes

E.7.1.1

First administration to humans

Yes

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)

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

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

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

Yes

E.8.2.3.1

Comparator description

Nebbud 0.25 mg/2 ml

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

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

30 (+2) days after LVLS, in order to monitor safety after the last IMP administration

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

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

Information not present in EudraCT

F.3.3.4

Nursing women

Information not present in EudraCT

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.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)

Subsequent therapy will be the expected normal treatment of asthma.

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

2020-09-08

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	Completed
P.	Date of the global end of the trial	2022-12-21

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