AIR2 Extension Study to Demonstrate Longer-term (> 1 Year) Durability of Effectiveness

Study Overview
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Brief Summary
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The objective of this study is to evaluate durability of effectiveness (beyond one year) of the Alair System in patients with severe persistent asthma. The study will consist of Alair-group subjects who are currently in the follow-up phase (out to 5 years) of the AIR2 Trial (Protocol #04-02, clinicaltrials.gov number NCT00231114). Durability of the treatment effect will be evaluated by comparing the proportion of subjects who experience severe exacerbations during the first year after Alair treatment with the proportion of subjects who experience severe exacerbations during subsequent 12 month periods out to 5 years. All Alair group subjects in the AIR2 Trial are being followed out to 5 years as per the AIR2 Trial protocol. The data that are to be used to determine durability of effectiveness as described in the present protocol (Protocol #10-01) are being collected under the existing AIR2 Trial protocol (Protocol # 04-02). Study Hypothesis: An empirical demonstration of the durability of the treatment effect will be used to show that the proportion of subjects experiencing severe exacerbations for the first year compared with the proportions of subjects experiencing severe exacerbations in subsequent years do not get substantially worse. The primary statistical objective is to demonstrate that the proportion of subjects who experience severe exacerbations in the subsequent 12-month follow-up (for Year 2, Year 3, Year 4 and Year 5 [in 12-month periods]) is not statistically worse when compared with the proportion of first 12-months, which begins 6-weeks after the last Alair treatment. This objective will be met if the upper 95% confidence limit of the difference in proportions (i.e., the subsequent 12-month proportion minus the first 12-month proportion) is less than 20%.

Detailed Description
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This will be an open-label, single arm study designed to demonstrate the durability of effectiveness (beyond one year) of the Alair System in patients with severe persistent asthma. Durability of treatment effect will be evaluated by comparison of the proportion of subjects experiencing severe exacerbations during the first year after the Alair treatment to subsequent 12-month periods out to 5 years. The 12-month periods will begin 6 weeks post-last Alair bronchoscopy.

Official Title
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AIR2 Extension Study to Demonstrate Longer-term (> 1 Year) Durability of Effectiveness

Conditions
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Asthma

Intervention / Treatment
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* Device: Bronchial Thermoplasty with the Alair System


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All Alair group subjects who have participated in the AIR2 Trial (NCT00231114) and were not lost to follow-up at the end of the 12 month premarket visit, and those who are willing to comply with the study protocol and routine visits for the duration of the study will be included in the post-approval study Exclusion Criteria: None.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Alair Group<br>Subjects who underwent treatment with the Alair System in the AIR2 Trial (Protocol No. 04-02, NCT00231114) | Device: Bronchial Thermoplasty with the Alair System<br>* Bronchial Thermoplasty with the Alair System<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severe Exacerbations | The primary endpoint will be the proportion of subjects experiencing severe exacerbations during the first year after the Alair treatment compared to subsequent 12-month periods out to 5 years. This objective will be met if the upper 95% confidence limit of the difference in proportions (i.e., the subsequent 12-month proportion minus the first 12-month proportion) is less than 20%. Severe exacerbation is defined as treatment with oral or intravenous corticosteroids, OR a doubling of the baseline inhaled corticosteroid dose for at least 3 days, OR any temporary increase in the dosage of oral corticosteroids for a subject taking maintenance oral corticosteroids at entry into the AIR2 Trial (Protocol #04-02). | 12 month periods out to 5 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severe Exacerbations | Number of severe exacerbations per subject per year. Severe exacerbation is defined as treatment with oral or intravenous corticosteroids, OR a doubling of the baseline inhaled corticosteroid dose for at least 3 days, OR any temporary increase in the dosage of oral corticosteroids for a subject taking maintenance oral corticosteroids at entry into the AIR2 Trial (Protocol #04-02). | 12 Month periods out to 5 years | 
| Respiratory Adverse Events | Number of respiratory adverse events per subject per year. 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. | 12 Month periods out to 5 years | 
| Respiratory Adverse Events | Proportion of subjects experiencing one or more respiratory adverse event in each of the years 1 through 5 following the Alair treatment. 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. | 12 Month periods out to 5 years | 
| Emergency Room Visits for Respiratory Symptoms | Proportion of Subjects with Emergency Room Visits for Respiratory Symptoms | 12 Month periods out to 5 years | 
| Emergency Room (ER) Visits for Respiratory Symptoms | Number of Emergency Room Visits for Respiratory Symptoms per subject per year. | 12 Month periods out to 5 years | 
| Hospitalizations for Respiratory Symptoms | Proportion of subjects with hospitalizations for respiratory symptoms. | 12 Month periods out to 5 Years | 
| Hospitalizations for Respiratory Symptoms | Number of Hospitalizations for Respiratory Symptoms per subject per year. | 12 Month periods out to 5 years | 
| Pre-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Pre-Bronchodilator FEV1 (% Predicted) percentage changes from Baseline to the Year 1, Year 2, Year 3, Year 4, and Year 5. | 12 Month periods out to 5 years | 
| Post-Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) | Post-Bronchodilator FEV1 (% Predicted) percentage changes from Baseline to the Year 1, Year 2, Year 3, Year 4, and Year 5. | 12 Month periods out to 5 years |