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)

Inclusion Criteria 1. Must have given written informed consent (signed and dated) and any authorizations required by local law and be able to comply with all study requirements 2. Males or females. Aged 40-70 inclusive at the time of informed consent 3. Females must be non-pregnant and non-lactating, and either surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy, bilateral oophorectomy) or postmenopausal 4. BMI \< 35.0 kg/m\^2 5. Participants with a diagnosis of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS) 1. Ability to perform acceptable and reproducible spirometry 2. Post-bronchodilator (4 puffs of albuterol) spirometry at Screening demonstrating the following: i. FEV1/ forced vital capacity (FVC) ratio of \< 0.70 ii. FEV1 ≥ 50% and ≤ 90% of predicted normal 6. Clinically stable COPD in the 4 weeks prior to Screening (Visit 1) 7. Current and former smokers with smoking history of ≥ 20 pack years 8. Meet SGRQ definition of CB 9. CAT score ≥ 10 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