Clinical Trials Register

Summary
EudraCT Number:	2021-000014-42
Sponsor's Protocol Code Number:	AQ-PRO-013
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:	2021-02-18
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

Belgium - FPS Health-DGM

A.2

EudraCT number

2021-000014-42

A.3

Full title of the trial

A randomized, double-blind, placebo-controlled, parallel, trial to determine the safety and efficacy of inhaled AQ001S in the management of acute COVID-19 symptoms

Étude clinique interventionnelle prospective, randomisée, en double aveugle, contrôlée par placebo, en parallèle afin d’évaluer l'innocuité et l'efficacité d’une solution pour inhalation contenant du budésonide (AQ001S) dans la gestion des symptômes aigus liés au COVID-19

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 and efficacy of a liquid for inhalation of budesonide (AQ001S) to treat adults with COVID-19 related respiratory disease.

Etude de la sécurité et de l'efficacité d'un liquide pour inhalation de budésonide dans le traitement de troubles respiratoires liés au COVID-19.

A.3.2

Name or abbreviated title of the trial where available

SIROCCO 1

A.4.1

Sponsor's protocol code number

AQ-PRO-013

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	Aquilon Pharmaceuticals
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	4000
B.5.3.4	Country	Belgium
B.5.4	Telephone number	3242292800
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
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	Yes
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	Inhalation use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

COVID-19 related respiratory disease

Troubles respiratoires liés au COVID-19

E.1.1.1

Medical condition in easily understood language

COVID-19 related respiratory disease

Troubles respiratoires liés au COVID-19

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	23.0
E.1.2	Level	LLT
E.1.2	Classification code	10084270
E.1.2	Term	SARS-CoV-2 acute respiratory disease
E.1.2	System Organ Class	100000004862

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 safety of AQ001S in the management of acute COVID-19 symptoms
To assess the efficacy of AQ001S in the management of acute COVID-19 symptoms
To assess the effects of AQ001S on pharmacodynamic (PD) parameters related to COVID-19

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patient admitted to hospital due to the severity of his/her confirmed or suspected COVID-19 disease.
2. Positive virus test for SARS-CoV-2 using RT-PCR (nasal swab).
3. Patient with COVID-19 clinical progression scale score ≥ 4 (hospitalized; no oxygen therapy).
4. Male or female, ≥18 years of age at the time of consent.
5. Patients who have given written informed consent.
6. Reliable patients who are willing to be available for the duration of the clinical trial and willing to comply with clinical trial procedures.
7. Patients who have the ability to understand the requirements of the clinical trial.
8. Female patients of childbearing potential (women of childbearing potential, WOCBP) should have a negative pregnancy test at Screening Visit.
9. Female patients of childbearing potential (women of childbearing potential, WOCBP) using a highly effective method of contraception (i.e., pregnancy rate of < 1% per year) on a stable regimen, for at least 28 days, and pursuing this contraception during the trial and for 28 days after the last administration of the IMP. The highly effective methods of contraception must be one of the following: combined estrogen and progestogen hormonal contraception with inhibition of ovulation, progestogen-only hormonal contraception associated with inhibition of ovulation, intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, vasectomized partner, or agreement on continuous abstinence from heterosexual intercourse.

E.4

Principal exclusion criteria

1. Intensive care patients
2. Inability to use a nebulizer with a mouthpiece.
3. History of hypersensitivity to corticosteroid or to any of the excipients in the drug preparation.
4. Untreated oral candidiasis.
5. Evidence of symptomatic chronic or acute respiratory infection other than COVID-19 in the previous 8 weeks.
6. Proven diagnosis of asthma or bronchiectasis.
7. Proven diagnosis of COPD treated with ongoing ICS and/or corticosteroid treatment within 3 months prior to randomization.
8. Pulmonary malformations, tuberculosis, cystic fibrosis.
9. History or presence of severe hepatic impairment (i.e. alanine transaminase (ALT) and aspartate transaminase (AST) greater than 15 times the upper limit of normal)
10. History or presence of severe renal impairment (considered as clinically significant according to the investigator’s discretion (i.e., stage 4 (DFR=15-29 mL/min)).
11. Anticipated transfer to another hospital within 72 hours.
12. Use of ICS, at a strength at least equivalent to 200 µg of beclomethasone per day, within 7 days before Screening Visit.
13. Female patients who are breast-feeding, lactating, pregnant or intending to become pregnant.
14. Any condition, including findings in the patients' medical history or in the pre-randomization study assessments that, in the opinion of the Investigator, constitute a risk or a contraindication for the participation of the patient into the study or that could interfere with the study objectives, conduct or evaluation.
15. Current or previous participation in another clinical trial where the patient has received a dose of an IMP containing small molecules within 30 days or 5 half-lives (whichever is longer) prior to entry into this study or containing biologicals within 3 months prior to entry into this study.

E.5 End points

E.5.1

Primary end point(s)

The safety will be evaluated collecting the following information:
• Adverse events and serious adverse events
• General tolerability: vital signs, ECG, physical examination (including signs of hypercorticism and adrenal suppression)
• Laboratory parameters: hematology, biochemistry and urinalysis
• Safety and tolerability - respiratory rate
• Safety and tolerability - oxygen saturation
• Local tolerability:
o Increased bronchial irritability
o Paradoxical bronchospasm
o Oropharyngeal examination (e.g. vocal cord myopathy, fungal infection)

The efficacy will be evaluated collecting the following information:
• Change in the COVID-19 clinical progression scale from baseline (Visit 2) to Day 7±2, Day 14±2, Day 28±2.
• changes in COVID-19 clinical endpoints from baseline (Visit 2) to Day 28 ±2 (Visit 5):
o Time to discharge,
o Time to ICU admission,
o Length of ICU stay,
o Time to hospital readmission.
o Length of hospital readmission
o Time to mechanical ventilation
o Occurrence of death within 60 days
• Change in mMRC (Modified Medical Research Council) Dyspnea Scale from baseline (Visit 2) at Day 28±2
• Changes in the pulmonary function (Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), FEV1/FVC ratio, SpO2, FiO2 and SpO2/FiO2 ratio) from baseline (Visit 2) to Day 28±2
• Changes in the diffusion capacity for carbon monoxide (DLCO) from baseline (Visit 2) to Day 28±2
• Changes in the pulmonary CT Scan from baseline (Visit 2) to Day 28±2

The PD will be evaluated collecting the following information:
• Changes in the systemic inflammatory and cardiovascular biomarkers from baseline (Visit 2) to Day 7±2, Day 14±2, Day 28±2:
o Inflammatory markers: IL-1 β, IL-4, IL-6, IL-10, IL-17A, IL-17F, IL-21, IL-22, IL-23, IL-25, IL-31, IL-33, TNFα, ferritin, CRP, d-dimer, neutrophil count, macrophage count, lymphocyte count, eosinophil count, Neutrophil Extracellular Trap (NET) production, IFN-γ, sCD40L
o Cardiovascular markers: Troponin, CK, MMPs (MMP1, MMP9, MMP8, MMP12, MMP13)
• Changes in IgE, IgA and IgG rates from baseline (Visit 2) to Day 28±2

E.5.1.1

Timepoint(s) of evaluation of this end point

At visits 2 (Baseline), 3 (Week 1), 4 (Week 2) and 5 (Day 28). See Endpoint description for more information.
Efficacy: change from baseline
Safety: descriptive comparison with baseline

E.5.2

Secondary end point(s)

• Assesssment of 6-minute walking test (6MWT) results at Day 28±2
• Changes in nocturnal oximetry from baseline (Visit 2) to Day 28±2
• Changes in Saint-Georges’ questionnaire from baseline (Visit 2) to Day 28±2
• Change in VAS chest pain from baseline (Visit 2) to Day 7±2, Day 14±2, Day 28±2
• Changes in ACQ-5 quality of life questionnaire from baseline (Visit 2) to Day 7±2, Day 14±2, Day 28±2.
• Measurement of the level of circulating exosomes in blood at baseline (Visit 2) and Day 7±2, Day 14±2, Day 28±2.

E.5.2.1

Timepoint(s) of evaluation of this end point

At visits 2 (Baseline), 3 (Week 1), 4 (Week 2) and 5 (Day 28). See Endpoint description for more information.

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

Yes

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

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

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

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)

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.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 standard of care treatment for COVID-19.

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

2021-04-19

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2021-04-24

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2022-12-18

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