A Multicenter, Randomized, Sham-controlled Study to Evaluate Safety and Efficacy After Treatment with the Nuvaira™ Lung Denervation System in Patients with Chronic Obstructive Pulmonary Disease (COPD)

• Subject ≥40 years of age at the time of consent;

• Women of child bearing potential must not be pregnant, evidenced by a negative pregnancy test (blood or urine) pre-treatment, or lactating and agree not to become pregnant for the duration of the study;

• Smoking history of at least 10 pack years;

• Not smoking or using any other inhaled substance (e.g., cigarettes, vaping, cannabis, pipes) for a minimum of 2 months prior to consent and agrees to not start for the duration of the study;

• Subject has received a flu vaccination within the 12 months prior to the procedure or agrees to obtain vaccination once it becomes available and agrees to annual vaccinations for the duration of the study;

• Resting SpO2 ≥89% on room air at the time of screening;

• CAT score ≥10 at the time of screening;

• Diagnosis of COPD with 25%≤ FEV1 ≤80% of predicted, PaCO2 ˂ 50 (if FEV1 ˂30%) and FEV1/FVC \<70% (post-bronchodilator);

• Documented history of ≥ 2 moderate COPD exacerbations or ≥ 1 severe COPD exacerbation leading to hospitalization in the 12 months prior to consent with at least one exacerbation occurring while the subject was on optimal medical care (taking LAMA and a LABA, or scheduled SABA or SAMA instead of either a LAMA or LABA, not both, as regular respiratory maintenance medication);

• Subject is on optimal medical care at the time of consent;

• If subject has participated in a formal pulmonary rehabilitation program recently, program completion must have occurred ≥3 months prior to consent; if in a maintenance program, subject agrees to continue their current program through their 12-month follow-up visit;

• Subject is a candidate for bronchoscopy in the opinion of the physician or per hospital guidelines and is able to discontinue blood thinning medication peri-procedurally;

• The subject is able and agrees to complete all protocol required baseline and follow-up tests and assessments including taking certain medications (e.g., azithromycin, prednisolone/prednisone);

• Subject has provided written informed consent using a form that has been reviewed and approved by the Institutional Review Board (IRB)/Ethics Committee (EC).