Asthma Intervention Research 2 (AIR2) Trial

Safety and Effectiveness of the Alair® System for the Treatment of Asthma: A Multicenter Randomized Clinical Trial(Asthma Intervention Research (AIR2) Trial)

The objective of this randomized, double blind, sham-controlled study is to demonstrate the safety and effectiveness of the Alair System in a population of subjects with severe asthma who are still symptomatic despite being managed on conventional therapy of high doses of inhaled corticosteroids and long-acting β2-agonists.

The primary efficacy endpoint will be the difference between Study groups in the change in Asthma Quality of Life Questionnaire (AQLQ) score from Baseline and the average score from the 6-, 9-, and 12-month follow-up visits.

All other outcome measures assessed at 12 months post-treatment.

This will be a multicenter, randomized, double-blind, sham-controlled study comparing the effects of treatment with the Alair System to conventional therapy of inhaled corticosteroids (ICS) and long-acting β2-agonists (LABA).

A Bayesian adaptive approach to sample size selection is used with a randomization scheme of 2:1 (two Alair Group Subjects for every one Control Group Subject).

Inclusion Criteria:

• Subject is an adult between the ages of 18 to 65 years.
• Subject has asthma and is taking regular maintenance medication that includes Inhaled corticosteroid (ICS) AND long acting ß2-agonist (LABA).
• Subject has a Pre-bronchodilator Forced Expiratory Volume in one second (FEV1) of greater than or equal to 60% of predicted after medication stabilization during the Baseline Period.
• Subject has a PC20 < 8 mg/ml per methacholine inhalation test using standardized methods. PC20 is a provocative concentration of Provocholine® (a brand of methacholine chloride) resulting in a drop of FEV1 of 20% or more from Baseline.
• Subject has at least two days of asthma symptoms during the 4-weeks of the Baseline Diary Period.
• Subject is a non-smoker for 1 year or greater (if former smoker, less than 10 pack years total smoking history).

Exclusion Criteria:

• Subject has a Post-bronchodilator FEV1 of less than 65%.
• Subject has 3 or more hospitalizations for exacerbations of asthma in the previous year; OR a history of life-threatening asthma, defined by past intubations for asthma, or ICU admission for asthma within the prior 24 months.
• Subject has a history of recurrent lower respiratory tract infections requiring antibiotics (more than 3 in the past 12 months).
• Subject has a history of recurrent oral steroid use for asthma (4 or more pulses of oral steroids in the past 12 months).
• Subject has a known sensitivity to medications required to perform bronchoscopy (such as lidocaine, atropine and benzodiazepines).
• Subject has known systemic hypersensitivity or contraindication to Methacholine chloride or other parasympathomimetic agents.
• Subject has other medical criteria.