A Study to Assess the Safety, Tolerability, and Efficacy of ION-827359 in Participants With Mild to Moderate Chronic Obstructive Pulmonary Disease (COPD) With Chronic Bronchitis (CB)

Exclusion Criteria

• •1. Clinically significant abnormalities in medical history (e.g., previous acute coronary syndrome within 6 months of screening, congestive heart failure, major surgery within 3 months of Screening) or physical examination
• •2. Screening laboratory results as follows, or any other clinically significant abnormalities in screening laboratory values that would render a subject unsuitable for inclusion
• •1. Urine protein/creatinine (P/C) ratio ≥ 0.3 mg/mg. In the event of P/C ratio above this threshold eligibility may be confirmed by a quantitative total urine protein measurement of \< 300 mg/24 hr
• •2. Positive test (including trace) for blood on urinalysis. In the event of a positive test eligibility may be confirmed with urine microscopy showing ≤ 5 red blood cells per high power field
• •3. alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, alkaline phosphatase (ALP), serum creatinine, blood urea nitrogen (BUN) \> 1.5 × upper limit of normal (ULN)
• •4. Platelet count \< LLN
• •5. Serum potassium \> 5.2 mmol/L
• •6. Estimated GFR \< 60 mL/min (as determined by the Cockcroft-Gault Equation for creatinine clearance)
• •7. A positive PCR test for SARS-CoV-2 at any time prior to randomization
• •3. Any active infection requiring systemic antiviral or antimicrobial therapy that will not be completed prior to first day Study Drug product is administered to the participant (Study Day 1)
• •4. Unwillingness to comply with study procedures, including follow-up, as specified by this protocol, or unwillingness to cooperate fully with the Investigator
• •5. Clinically important pulmonary disease other than COPD
• •6. Asthma as a primary or main diagnosis according to the Global Initiative for Asthma (GINA) guidelines (GINA 2011) or other accepted guidelines. Participants with a past medical history of asthma (e.g. childhood or adolescence) may be included
• •7. Treatment with systemic corticosteroids and/or antibiotics, and/or hospitalization for a COPD exacerbation within 4 weeks prior to enrolment (Visit 1)
• •8. Acute upper or lower respiratory infection requiring antibiotics or antiviral medication within 4 weeks prior to enrolment (Visit 1)
• •9. Long term oxygen therapy (LTOT)
• •10. Participants participating in, or scheduled for, an intensive (active) COPD rehabilitation program (participants who are in the maintenance phase of a rehabilitation program are eligible to take part)
• •11. Concomitant medication restrictions: Oral anticoagulants, oral steroids (e.g. prednisone or Medrol), theophylline, chronic azithromycin, or roflumilast
• •12. Have any other conditions, which, in the opinion of the Investigator would make the subject unsuitable for inclusion, or could interfere with the subject participating in or completing the Study