Asthma
Conditions
Brief summary
This is a prospective, active-controlled, randomized, open label, single-center, multiple dose, two-period crossover clinical trial to assess the efficacy, safety and pharmacokinetics of AQ001S compared to a budesonide inhalation suspension (comparator) in adults with mild asthma. Both treatments will be administered by nebulization.
Detailed description
Adults patients with mild asthma (18 to 65 years old), who are 'inhaled corticosteroid (ICS)'-naïve for minimum 60 days at Screening Visit will be enrolled in the study. The patients will be treated for 28 days. The primary endpoint will be assessed by a provocative concentration of methacholine that results in a 20% drop (PC20) in the first second forced expiratory volume (FEV1) as determined by methacholine challenge test. The pharmacokinetics (PK) endpoint, i.e. PK profile of budesonide in plasma, and pharmacodynamics (PD) endpoints, i.e. recording of symptom scores, use of reliever drugs as needed, biomarkers of airway inflammation and pulmonary function tests will be assessed during the study.
Interventions
DRUGAQ001S 0.125 mg/ml
administered by nebulization once daily
DRUGBudesonide 0.125 mg/ml inhalation suspension
administered by nebulization once daily
Sponsors
Aquilon Pharmaceuticals S.A.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Body mass index between 18.5 and 29 kg/m2. * Documented clinical diagnosis of stable, persistent, asthma for at least 3 months * Subjects who are ICS-naïve for minimum 60 days at Screening Visit. * 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. * Post-bronchodilator FEV1 at least 80% of the predicted, documented in the last year. * 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. * Female subjects of childbearing potential should have a negative pregnancy test at Screening Visit and use a highly effective method of contraception. * Reliable subjects who are willing to be available for the duration of the clinical trial and willing to comply with clinical trial procedures. * Subjects who have the ability to understand the requirements of the clinical trial. * Subjects who have given written informed consent.
Exclusion criteria
* Current smokers or recent (\< 8 weeks) ex-smokers or ex-smokers if \> 10 pack-years. * Pregnant or breastfeeding female subjects. * Inability to carry out pulmonary function testing. * FEV1 \< 70%. * History of near-fatal asthma and/or intensive care unit admission for asthma symptoms. * Exacerbations of asthma requiring oral steroids, hospitalization or change in asthma treatment in the previous three months. * Evidence of symptomatic chronic or acute respiratory infection in the previous 8 weeks. * Diagnosis of chronic obstructive pulmonary disease (COPD) or bronchiectasis. * Pulmonary malformations, tuberculosis, cystic fibrosis. * History of hypersensitivity or existing contraindication to budesonide or any other Investigational Medicinal Product (IMP) ingredients. * Untreated oral candidiasis. * Immunosuppressive treatment, including systemic corticosteroids (e.g., oral, parenteral, ocular, nasal), within 28 days before Screening Visit. * Use of ICS within 60 days before Screening Visit. * Use of anti-leukotrienes, immunoglobulins, beta-blockers, digitalis, amiodarone, antifungals, macrolides, antidepressants, monoamine oxidase inhibitors, antiretroviral drugs, cholinesterase inhibitors, histamine, theophylline, non-steroidal anti-inflammatory drugs, anticholinergic drugs, neuroleptics, curariform drugs, antihistaminic (anti-H1) drugs, calcium channel blockers, long acting beta2-antagonists, mast cell stabilizers (e.g. natrium cromoglycate). * History of alcohol or drug abuse. * Unstable or life-threatening cardiac disease * 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. * Diabetes mellitus. * Neuropsychiatric diseases. * Clinically relevant laboratory abnormalities at Screening Visit. * Blood or plasma donation within 30 days prior to Screening Visit. * 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. * Any surgical or medical condition which might significantly alter the absorption, distribution, metabolism, or excretion of drugs, or which may jeopardize the subject in case of participation in the clinical trial. * 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. * Human immunodeficiency virus (HIV) and severe acute respiratory syndrome (SARS)-CoV-2 infections. * Subjects who participated in an investigational trial within the 12 weeks prior to the start of the trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in PC20 After Each Treatment Period Assessed by Methacholine (MCh) Challenge Test | visit 1 (baseline) - visit 2 (at the end of Treatment Period 1) and visit 4 (end of Treatment Period 2) | At Visit 1 (baseline), Visit 2 (29-day treatment period 1) and Visit 4 (29-day treatment period 2), a MCh challenge test will be performed, i.e. up to the administration of a concentration of MCh provoking an FEV1 fall of 20% (PC20). FEV1 is measured by spirometry. The change in PC20 from baseline to the end of each period (two periods) was assessed. |
| Incidence of Treatment-Emergent Adverse Events | Over the treatment period, from the informed consent signature up to the end of second 29-day treatment period | Incidence of Treatment-Emergent Adverse Events as assessed by collection of (Serious) Adverse Events |
Countries
Belgium
Participant flow
Recruitment details
Cross-over part of the study (treatment period 1) - Washout period of 2 weeks - Cross-over part of the study (treatment period 2)
Participants by arm
| Arm | Count |
|---|---|
| Sequence A: AQ001S - Comparator AQ001S budesonide solution was administered for 29 (+2) days once daily (treatment period 1). Following a wash-out period of 14 (+2) days, the comparator (budesonide suspension) was administered for 29 (+2) days once daily (treatment period 2). | 11 |
| Sequence B: Comparator - AQ001S The comparator (budesonide suspension) was administered for 29 (+2) days once daily (treatment period 1). Following a washout period of 14 (+2) days, AQ001S budesonide solution was administered for 29 (+2) days once daily (treatment period 2). | 12 |
| Total | 23 |
Baseline characteristics
| Characteristic | Sequence A: AQ001S - Comparator | Sequence B: Comparator - AQ001S | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 12 Participants | 23 Participants |
| Age, Continuous | 36.3 years STANDARD_DEVIATION 11.2 | 29.1 years STANDARD_DEVIATION 9.9 | 32.5 years STANDARD_DEVIATION 10.9 |
| Body Mass Index (BMI) | 24.38 kg/m² STANDARD_DEVIATION 2.91 | 24.24 kg/m² STANDARD_DEVIATION 3.86 | 24.31 kg/m² STANDARD_DEVIATION 3.36 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 12 Participants | 23 Participants |
| Region of Enrollment Belgium | 11 participants | 12 participants | 23 participants |
| Sex: Female, Male Female | 4 Participants | 8 Participants | 12 Participants |
| Sex: Female, Male Male | 7 Participants | 4 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 23 |
| other Total, other adverse events | 4 / 23 | 2 / 23 |
| serious Total, serious adverse events | 0 / 23 | 0 / 23 |
Outcome results
Primary
Change From Baseline in PC20 After Each Treatment Period Assessed by Methacholine (MCh) Challenge Test
At Visit 1 (baseline), Visit 2 (29-day treatment period 1) and Visit 4 (29-day treatment period 2), a MCh challenge test will be performed, i.e. up to the administration of a concentration of MCh provoking an FEV1 fall of 20% (PC20). FEV1 is measured by spirometry. The change in PC20 from baseline to the end of each period (two periods) was assessed.
Time frame: visit 1 (baseline) - visit 2 (at the end of Treatment Period 1) and visit 4 (end of Treatment Period 2)
Population: The efficacy population encompasses all subjects that completed both treatment periods and for which the primary efficacy parameter PC20 was available at baseline (visit 1) and after both treatment periods (visit 2 and visit 4).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| AQ001S 0.125 mg/ml | Change From Baseline in PC20 After Each Treatment Period Assessed by Methacholine (MCh) Challenge Test | 3.7 mg/mL |
| Budesonide Inhalation Suspension 0.125 mg/ml | Change From Baseline in PC20 After Each Treatment Period Assessed by Methacholine (MCh) Challenge Test | 1.2 mg/mL |
Comparison: The primary efficacy endpoint is the change from baseline in PC20 after each treatment period (baseline is defined at Visit 1).~For primary efficacy analysis, the mean PC20 changes from baseline between AQ001S and the comparator were compared by analysis of covariance (ANCOVA) for crossover design. A p-value was calculated for the difference of the parameter between AQ001S and the comparator.~Additionally, an adjusted 95%-CI for the mean difference was obtained by the ANCOVA.p-value: 0.00081395% CI: [106.42, 306.48]ANCOVA
Primary
Incidence of Treatment-Emergent Adverse Events
Incidence of Treatment-Emergent Adverse Events as assessed by collection of (Serious) Adverse Events
Time frame: Over the treatment period, from the informed consent signature up to the end of second 29-day treatment period
Population: The safety population includes all randomized subjects who received at least one dose of the study medication (AQ001S or comparator).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| AQ001S 0.125 mg/ml | Incidence of Treatment-Emergent Adverse Events | All-Cause Mortality | 0 events |
| AQ001S 0.125 mg/ml | Incidence of Treatment-Emergent Adverse Events | Serious Adverse Events | 0 events |
| AQ001S 0.125 mg/ml | Incidence of Treatment-Emergent Adverse Events | Other (not including serious) Adverse Events | 3 events |
| Budesonide Inhalation Suspension 0.125 mg/ml | Incidence of Treatment-Emergent Adverse Events | All-Cause Mortality | 0 events |
| Budesonide Inhalation Suspension 0.125 mg/ml | Incidence of Treatment-Emergent Adverse Events | Serious Adverse Events | 0 events |
| Budesonide Inhalation Suspension 0.125 mg/ml | Incidence of Treatment-Emergent Adverse Events | Other (not including serious) Adverse Events | 10 events |