Severe Asthma
Conditions
Brief summary
As Conditions of Approval of the PMA for the Alair System, the FDA requires Boston Scientific to generate data to assess the durability of the BT treatment effect as well as safety data in the intended use population in the United States.
Detailed description
This is a multicenter, open-label, single arm study designed to demonstrate durability of the treatment effect and to evaluate the short-term and longer-term safety profile of the Alair System in the United States in the intended use population (patients 18 years and older with severe persistent asthma).
Interventions
DEVICEAlair System
Treatment of airways with the Alair System
Sponsors
Boston Scientific Corporation
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Subject is an adult between the ages of 18 to 65 years. 2. Subject is able to read, understand, and sign a written Informed Consent to participate in the study and able to comply with the study protocol. 3. Subject has asthma and is taking regular maintenance medication that includes: 1. Inhaled corticosteroid (ICS) at a dosage greater than 1000μg beclomethasone per day or equivalent, AND long acting β2-agonist (LABA) at a dosage of ≥80μg per day Salmeterol or equivalent. 2. Other asthma medications such as leukotriene modifiers, or anti-IgE, are acceptable (Subjects on Xolair® must have been on Xolair for greater than 1 year). 3. Oral corticosteroids (OCS) at a dosage of up to, but not greater than 10mg per day are acceptable.\* 4. Subject has a pre-bronchodilator FEV1 of greater than or equal to 60% of predicted. 5. Subject is a non-smoker for 1 year or greater (if former smoker, less than 10 pack years total smoking history). 6. Subject is able to undergo outpatient (same day) bronchoscopy in the opinion of the investigator or per hospital guidelines. 7. Subject has at least 2 days of asthma symptoms in the last 4 weeks. 8. Subject has an AQLQ score during the baseline period of 6.25 or less. * NOTE: Subjects on a dosage regimen of 20mg OCS every other day may be included as this is equivalent to an average daily dosage of 10mg.
Exclusion criteria
1. Subject is participating in another clinical trial within 6 weeks of the Baseline Period involving respiratory intervention that could affect the outcome measures of this Study. 2. Over the last 7 days of a 4 week medication stable period, subject requirement for rescue medication use other than for prophylactic use for exercise exceeds an average of: 1. 8 puffs per day of short-acting bronchodilator, or 2. 4 puffs per day of long-acting rescue bronchodilator, or 3. 2 nebulizer treatments per day. At the discretion of the Principal Investigator, subjects considered as unstable on baseline medications may have medications adjusted and re-evaluated after a 4 week medication stabilization period. 3. Subject has a post-bronchodilator FEV1 of less than 65%. 4. Subject has a history of life-threatening asthma, defined by past intubation for asthma, or ICU admission for asthma within the prior 2 years. 5. Subject has 3 or more hospitalizations for exacerbations of asthma in the previous year. 6. Subject has had 4 or more infections of lower respiratory tract (LRTI) requiring antibiotics in the past 12 months. 7. Subject has had 4 or more pulses of systemic corticosteroids (tablets, suspension or injection) for asthma symptoms in the past 12 months. 8. Subject has a known sensitivity to medications required to perform bronchoscopy (such as lidocaine, atropine and benzodiazepines). 9. Subject has other respiratory diseases including emphysema, cystic fibrosis, vocal cord dysfunction, mechanical upper airway obstruction, Churg-Strauss syndrome, and allergic bronchopulmonary aspergillosis (asthma, immediate cutaneous reactivity to A. fumigatus, total serum IgE of \>1000ng/mL, elevated specific IgE and IgG to A. fumigatus with or without evidence of central bronchiectasis). 10. Subject has segmental atelectasis, lobar consolidation, significant or unstable pulmonary infiltrate, or pneumothorax, confirmed on x-ray. 11. Subject currently has clinically significant cardiovascular disease, including myocardial infarction, angina, cardiac dysfunction, cardiac dysrhythmia, conduction defect, cardiomyopathy, or stroke. 12. Subject has a known aortic aneurysm. 13. Subject has significant co-morbid illness such as cancer, renal failure, liver disease, or cerebral vascular disease. 14. Subject has uncontrolled hypertension (\>200mm Hg systolic or \>100mm Hg diastolic pressure). 15. Subject has an implanted electrical stimulation device (e.g., a pacemaker, cardiac defibrillator, or deep nerve or deep brain stimulator). 16. Subject has coagulopathy (INR \> 1.5). 17. Subject has any other medical condition that would make them inappropriate for study participation, in the Investigator's opinion.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subjects Experiencing Severe Exacerbations (Rates) | Year 1 vs. Year 2, 3, 4, 5 | The primary endpoint will be the proportion of subjects experiencing severe exacerbations during the subsequent 12-month (for Years 2, 3, 4, and 5) compared to the first 12-month after the Alair treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Respiratory Adverse Event Rates | Year 1-5 | A respiratory adverse event is defined as any sign, symptom, illness, clinically significant abnormal laboratory value, or other adverse medical event associated with the Respiratory System that appears or worsens in a subject during a clinical study, regardless of whether or not it is considered related to the procedure used as part of the protocol. |
| Subjects With Respiratory Adverse Events | Year 1-5 | A respiratory adverse event is defined as any sign, symptom, illness, clinically significant abnormal laboratory value, or other adverse medical event associated with the Respiratory System that appears or worsens in a subject during a clinical study, regardless of whether or not it is considered related to the procedure used as part of the protocol. |
| Emergency Room Visits for Respiratory Symptoms Rates | Year 1-5 | Emergency room visits for respiratory symptoms (rates of emergency room visits) |
| Subjects With Emergency Room Visits for Respiratory Symptoms | Year 1-5 | Subjects with Emergency room visits for respiratory symptoms |
| Hospitalizations for Respiratory Symptoms Rates | Year 1-5 | (# hospitalizations for respiratory symptoms / subject / year) |
| Rates of Severe Exacerbations | Year 1-5 | \# Severe exacerbations / subject / year |
| Respiratory Serious Adverse Events Rates | Year 1-5 | The rate of subjects with respiratory serious adverse events (SAEs) |
| Subjects With Respiratory Serious Adverse Events | Year 1-5 | Subjects with Respiratory Serious Adverse Events |
| Pre-bronchodilator FEV1 | Year 1-5 | % Predicted Pre-bronchodilator FEV1 |
| Post-bronchodilator FEV1 | Year 1-5 | % Predicted Post-bronchodilator FEV1 |
| Subjects With Hospitalizations for Respiratory Symptoms | Year 1-5 | Subjects with hospitalizations for respiratory symptoms |
Countries
Canada, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Alair Alair system
Alair System: Treatment of airways with the Alair System | 279 |
| Total | 279 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 4 |
| Overall Study | Lost to Follow-up | 31 |
| Overall Study | Physician Decision | 8 |
| Overall Study | Withdrawal by Subject | 14 |
Baseline characteristics
| Characteristic | Alair |
|---|---|
| Age, Continuous | 45.71 years |
| AQLQ | 4.03 AQLQ Score STANDARD_DEVIATION 1.28 |
| BMI | 32.2 kg/m2 |
| FEV1 - % Predicted Post-bronchodilator FEV1 | 85.8 % Predicted STANDARD_DEVIATION 13.6 |
| FEV1 - % Predicted Pre-bronchodilator FEV1 | 80.4 % Predicted STANDARD_DEVIATION 13.7 |
| Height | 167.4 cm |
| Prior 12 months - Event rates ER visits for asthma | 0.54 # events / subject STANDARD_DEVIATION 1.2 |
| Prior 12 months - Event rates Hospitalizations for asthma | 0.22 # events / subject STANDARD_DEVIATION 0.53 |
| Prior 12 months - Event rates Severe Exacerbations | 1.61 # events / subject STANDARD_DEVIATION 1.12 |
| Prior 12 months - % Subjects ER visits for asthma | 82 Participants |
| Prior 12 months - % Subjects Hospitalization for asthma | 45 Participants |
| Prior 12 months - % Subjects Severe Exacerbations | 217 Participants |
| Race/Ethnicity, Customized American Indian or Alaska native | 3 Participants |
| Race/Ethnicity, Customized Asian | 4 Participants |
| Race/Ethnicity, Customized Black, of African Heritage | 25 Participants |
| Race/Ethnicity, Customized Caucasian | 234 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 8 Participants |
| Race/Ethnicity, Customized Other | 5 Participants |
| Sex: Female, Male Female | 180 Participants |
| Sex: Female, Male Male | 99 Participants |
| Weight | 90.3 kg |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 4 / 279 |
| other Total, other adverse events | 268 / 279 |
| serious Total, serious adverse events | 130 / 279 |
Outcome results
Primary
Subjects Experiencing Severe Exacerbations (Rates)
The primary endpoint will be the proportion of subjects experiencing severe exacerbations during the subsequent 12-month (for Years 2, 3, 4, and 5) compared to the first 12-month after the Alair treatment.
Time frame: Year 1 vs. Year 2, 3, 4, 5
Population: Primary Endpoint - the proportion of subjects experiencing severe exacerbations during the subsequent 12-month (for Years 2, 3, 4, and 5) compared to the first 12-month after the Alair treatment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Year 1 | Subjects Experiencing Severe Exacerbations (Rates) | 132 Participants |
| Year 2 | Subjects Experiencing Severe Exacerbations (Rates) | 118 Participants |
| Year 3 | Subjects Experiencing Severe Exacerbations (Rates) | 118 Participants |
| Year 4 | Subjects Experiencing Severe Exacerbations (Rates) | 106 Participants |
| Year 5 | Subjects Experiencing Severe Exacerbations (Rates) | 97 Participants |
Comparison: Comparison of Years 1 and 295% CI: [-0.1251, 0.0497]
Comparison: Comparison of Years 1 and 395% CI: [-0.1197, 0.0565]
Comparison: Comparison of Years 1 and 495% CI: [-0.1444, 0.0329]
Comparison: Comparison of Years 1 and 595% CI: [-0.1661, 0.013]
Secondary
Emergency Room Visits for Respiratory Symptoms Rates
Emergency room visits for respiratory symptoms (rates of emergency room visits)
Time frame: Year 1-5
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Year 1 | Emergency Room Visits for Respiratory Symptoms Rates | .31 # ER Visit / subject / year | Standard Deviation 0.87 |
| Year 2 | Emergency Room Visits for Respiratory Symptoms Rates | .24 # ER Visit / subject / year | Standard Deviation 0.8 |
| Year 3 | Emergency Room Visits for Respiratory Symptoms Rates | .21 # ER Visit / subject / year | Standard Deviation 0.65 |
| Year 4 | Emergency Room Visits for Respiratory Symptoms Rates | .17 # ER Visit / subject / year | Standard Deviation 0.56 |
| Year 5 | Emergency Room Visits for Respiratory Symptoms Rates | .13 # ER Visit / subject / year | Standard Deviation 0.49 |
Secondary
Hospitalizations for Respiratory Symptoms Rates
(# hospitalizations for respiratory symptoms / subject / year)
Time frame: Year 1-5
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Year 1 | Hospitalizations for Respiratory Symptoms Rates | 0.13 # Hospitalizations / subject / year | Standard Deviation 0.5 |
| Year 2 | Hospitalizations for Respiratory Symptoms Rates | 0.11 # Hospitalizations / subject / year | Standard Deviation 0.47 |
| Year 3 | Hospitalizations for Respiratory Symptoms Rates | 0.11 # Hospitalizations / subject / year | Standard Deviation 0.47 |
| Year 4 | Hospitalizations for Respiratory Symptoms Rates | 0.05 # Hospitalizations / subject / year | Standard Deviation 0.28 |
| Year 5 | Hospitalizations for Respiratory Symptoms Rates | 0.06 # Hospitalizations / subject / year | Standard Deviation 0.31 |
Secondary
Post-bronchodilator FEV1
% Predicted Post-bronchodilator FEV1
Time frame: Year 1-5
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Year 1 | Post-bronchodilator FEV1 | 93.1 % Predicted | Standard Deviation 13.9 |
| Year 2 | Post-bronchodilator FEV1 | 92.3 % Predicted | Standard Deviation 14.1 |
| Year 3 | Post-bronchodilator FEV1 | 91.8 % Predicted | Standard Deviation 14.2 |
| Year 4 | Post-bronchodilator FEV1 | 91.1 % Predicted | Standard Deviation 14.4 |
| Year 5 | Post-bronchodilator FEV1 | 91.0 % Predicted | Standard Deviation 14.3 |
Secondary
Pre-bronchodilator FEV1
% Predicted Pre-bronchodilator FEV1
Time frame: Year 1-5
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Year 1 | Pre-bronchodilator FEV1 | 89.6 % Predicted | Standard Deviation 14.5 |
| Year 2 | Pre-bronchodilator FEV1 | 89.3 % Predicted | Standard Deviation 14.6 |
| Year 3 | Pre-bronchodilator FEV1 | 87.7 % Predicted | Standard Deviation 14.9 |
| Year 4 | Pre-bronchodilator FEV1 | 88.5 % Predicted | Standard Deviation 13.8 |
| Year 5 | Pre-bronchodilator FEV1 | 87.4 % Predicted | Standard Deviation 14.6 |
Secondary
Rates of Severe Exacerbations
\# Severe exacerbations / subject / year
Time frame: Year 1-5
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Year 1 | Rates of Severe Exacerbations | 0.93 # Severe Exacerbations / subject / year | Standard Deviation 1.35 |
| Year 2 | Rates of Severe Exacerbations | .92 # Severe Exacerbations / subject / year | Standard Deviation 1.21 |
| Year 3 | Rates of Severe Exacerbations | .77 # Severe Exacerbations / subject / year | Standard Deviation 1.01 |
| Year 4 | Rates of Severe Exacerbations | .84 # Severe Exacerbations / subject / year | Standard Deviation 1.23 |
| Year 5 | Rates of Severe Exacerbations | .72 # Severe Exacerbations / subject / year | Standard Deviation 1.13 |
Secondary
Respiratory Adverse Event Rates
A respiratory adverse event is defined as any sign, symptom, illness, clinically significant abnormal laboratory value, or other adverse medical event associated with the Respiratory System that appears or worsens in a subject during a clinical study, regardless of whether or not it is considered related to the procedure used as part of the protocol.
Time frame: Year 1-5
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Year 1 | Respiratory Adverse Event Rates | 1.70 # Resp. AE / subject / year | Standard Deviation 1.95 |
| Year 2 | Respiratory Adverse Event Rates | 1.52 # Resp. AE / subject / year | Standard Deviation 1.66 |
| Year 3 | Respiratory Adverse Event Rates | 1.28 # Resp. AE / subject / year | Standard Deviation 1.42 |
| Year 4 | Respiratory Adverse Event Rates | 1.35 # Resp. AE / subject / year | Standard Deviation 1.63 |
| Year 5 | Respiratory Adverse Event Rates | 1.22 # Resp. AE / subject / year | Standard Deviation 1.92 |
Secondary
Respiratory Serious Adverse Events Rates
The rate of subjects with respiratory serious adverse events (SAEs)
Time frame: Year 1-5
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Year 1 | Respiratory Serious Adverse Events Rates | 0.14 # Respiratory SAEs / subect / year | Standard Deviation 0.5 |
| Year 2 | Respiratory Serious Adverse Events Rates | 0.11 # Respiratory SAEs / subect / year | Standard Deviation 0.37 |
| Year 3 | Respiratory Serious Adverse Events Rates | 0.10 # Respiratory SAEs / subect / year | Standard Deviation 0.41 |
| Year 4 | Respiratory Serious Adverse Events Rates | 0.06 # Respiratory SAEs / subect / year | Standard Deviation 0.33 |
| Year 5 | Respiratory Serious Adverse Events Rates | 0.06 # Respiratory SAEs / subect / year | Standard Deviation 0.28 |
Secondary
Subjects With Emergency Room Visits for Respiratory Symptoms
Subjects with Emergency room visits for respiratory symptoms
Time frame: Year 1-5
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Year 1 | Subjects With Emergency Room Visits for Respiratory Symptoms | 48 Participants |
| Year 2 | Subjects With Emergency Room Visits for Respiratory Symptoms | 37 Participants |
| Year 3 | Subjects With Emergency Room Visits for Respiratory Symptoms | 32 Participants |
| Year 4 | Subjects With Emergency Room Visits for Respiratory Symptoms | 28 Participants |
| Year 5 | Subjects With Emergency Room Visits for Respiratory Symptoms | 18 Participants |
Secondary
Subjects With Hospitalizations for Respiratory Symptoms
Subjects with hospitalizations for respiratory symptoms
Time frame: Year 1-5
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Year 1 | Subjects With Hospitalizations for Respiratory Symptoms | 21 Participants |
| Year 2 | Subjects With Hospitalizations for Respiratory Symptoms | 19 Participants |
| Year 3 | Subjects With Hospitalizations for Respiratory Symptoms | 18 Participants |
| Year 4 | Subjects With Hospitalizations for Respiratory Symptoms | 8 Participants |
| Year 5 | Subjects With Hospitalizations for Respiratory Symptoms | 11 Participants |
Secondary
Subjects With Respiratory Adverse Events
A respiratory adverse event is defined as any sign, symptom, illness, clinically significant abnormal laboratory value, or other adverse medical event associated with the Respiratory System that appears or worsens in a subject during a clinical study, regardless of whether or not it is considered related to the procedure used as part of the protocol.
Time frame: Year 1-5
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Year 1 | Subjects With Respiratory Adverse Events | 184 Participants |
| Year 2 | Subjects With Respiratory Adverse Events | 165 Participants |
| Year 3 | Subjects With Respiratory Adverse Events | 155 Participants |
| Year 4 | Subjects With Respiratory Adverse Events | 141 Participants |
| Year 5 | Subjects With Respiratory Adverse Events | 133 Participants |
Secondary
Subjects With Respiratory Serious Adverse Events
Subjects with Respiratory Serious Adverse Events
Time frame: Year 1-5
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Year 1 | Subjects With Respiratory Serious Adverse Events | 26 Participants |
| Year 2 | Subjects With Respiratory Serious Adverse Events | 25 Participants |
| Year 3 | Subjects With Respiratory Serious Adverse Events | 17 Participants |
| Year 4 | Subjects With Respiratory Serious Adverse Events | 10 Participants |
| Year 5 | Subjects With Respiratory Serious Adverse Events | 11 Participants |