This study will evaluate the efficacy and safety of astegolimab compared with placebo in participants with chronic obstructive pulmonary disease (COPD) who are former or current smokers and have a history of frequent exacerbations.

Inclusion Criteria

• Documented COPD diagnosis for ≥ 12 months
• History of frequent exacerbations, defined as having had 2 or more moderate or severe COPD exacerbations within 12 months prior to screening
• Post-bronchodilator FEV1 ≥ 20% and < 80% of predicted at screening
• Post-bronchodilator FEV1/FVC < 0.70 at screening
• Modified Medical Research Council (dyspnea scale) (mMRC) score ≥ 2
• Current tobacco smoker or former smoker with a history of smoking ≥ 10 pack-years
• On optimized COPD maintenance therapy as defined below for ≥ 12 months prior to screening, and stable on current therapy for at least 4 weeks prior to screening: Inhaled corticosteroid (ICS) plus long-acting beta-agonist (LABA), Long-acting muscarinic antagonist (LAMA) plus LABA, ICS plus LAMA plus LABA
• Chest X-ray or computed tomography (CT) scan within 6 months prior to screening or chest X-ray during the screening period that confirms the absence of clinically significant lung disease besides COPD

Exclusion Criteria

• Current documented diagnosis of asthma
• History of clinically significant pulmonary disease other than COPD
• Diagnosis of 1-antitrypsin deficiency
• History of long-term treatment with oxygen at > 4.0 liters/minute
• Lung volume reduction surgery or procedure within 12 months prior to screening
• Individuals participating in, or scheduled for, an intensive COPD rehabilitation program (participants who are in the maintenance phase of a rehabilitation program are eligible)
• History of lung transplant
• Any infection that resulted in hospital admission for ≥ 24 hours and/or treatment with oral, IV, or IM antibiotics within 4 weeks prior to or during screening
• Upper or lower respiratory tract infection within 4 weeks prior to or during screening
• Treatment with oral, IV, or IM corticosteroids within 4 weeks prior to initiation of study drug
• Initiation of or change in non-biologic immunomodulatory or immunosuppressive therapy within 3 months prior to screening
• Unstable cardiac disease, myocardial infarction, or New York Heart Association Class III or IV heart failure within 12 months prior to screening

For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data\_sharing