A Phase II, Randomized, Double-blind, Placebo-controlled Study to Assess MEDI3506 in Participants With COPD and Chronic Bronchitis

This is a research study to determine the efficacy and safety of investigational drug MEDI3506 for the treatment of adult participants with Chronic Obstructive Pulmonary Disease and Chronic Bronchitis.

Study D9180C00002 is a Phase II, randomised, double-blind, placebo-controlled, parallel group, proof of concept study to evaluate the efficacy and safety of MEDI3506 in adult participants with moderate to severe Chronic Obstructive Pulmonary Disease and Chronic Bronchitis.

Approximately 85 sites globally will participate in this study. Approximately 144 participants will be randomized to 2 treatment groups in a 1:1 ratio to receive MEDI3506 or placebo.

Eligibility Criteria:
Inclusion Criteria:

* Provision of informed consent.
* Participant must be 40 to 80 years of age inclusive, at the time of signing the informed consent form (ICF).
* Participants who are current or ex-smokers with a tobacco history of \>= 10 pack-years.
* Participants who have a documented history of COPD for at least 1 year.
* Participants who have a post-BD FEV1/FVC \< 0.70 and a post-BD FEV1 \>= 20% and \< 80% predicted normal value at screening. Centralized spirometry will be used for this criteria assessment.
* Participants who have a physician confirmed participant history of chronic bronchitis as defined as presence of cough and sputum on most days for \>= 3 months/year in at least the 2 year period immediately prior to study visit 1 (SV1) (Screening).
* Participants who have an average BCSS score of \>= 2 in cough and \>= 2 in sputum domains assessed over 14 days preceding SV3.
* Participants who have a documented stable regimen of dual therapy or triple therapy for \>= 3 months prior to enrolment; there should have been no change in treatment after the previous exacerbation prior to entering into the study. Where dual therapy consists of inhaled corticosteroids (ICS) + long-acting beta 2 agonist (LABA) or LABA + long-acting muscarinic receptor antagonist (LAMA), and triple therapy consists of ICS + LABA + LAMA.
* Participants who have a documented history of \>= 1 moderate or severe AECOPD requiring systemic corticosteroids and/or antibiotics for at least 3 days duration (or 1 injection of depot formulation), or hospitalization for reason of AECOPD in the previous 24 months.
* Body mass index within the range 18 to 40 kg/m\^2 (inclusive).
* Female participants of childbearing potential, must have negative pregnancy tests.
* Male and female participants must follow protocol contraceptive guidance.

Exclusion Criteria:

* Participants with a positive diagnostic nucleic acid test for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at screening. Participants with mild or asymptomatic disease could be rescreened.
* Participants with a significant coronavirus disease 2019 (COVID-19) illness within 6 months of enrolment.
* As judged by the investigator, any evidence of any active medical or psychiatric condition or other reason which in the investigator's opinion makes it undesirable for the participant to participate in the study.
* Current or past diagnosis of asthma which persisted beyond age of 25 years.
* Clinically important pulmonary disease other than COPD, radiological findings, and/or laboratory findings suggestive of a respiratory disease other than COPD that is contributing to the participant's respiratory symptoms.
* Increased pre-BD FEV1 at randomization visit (SV3) compared to Screening SV1 of \>= 400 mL or \>= 25% of SV1 FEV1.
* Any other clinically relevant abnormal findings on physical examination, laboratory testing; or chest CT scan, which in the opinion of the investigator or medical monitor may compromise the safety of the participant in the study or interfere with evaluation of the study intervention or reduce the participant's ability to participate in the study.

Chest CT scan findings requiring further investigation or repeat CT surveillance before SV14.

* A family history of heart failure.
* A LVEF \< 45% measured by echocardiogram.
* History of a clinically significant infection (viral, bacterial, or fungal) within 4 weeks.
* History of, or a reason to believe a participant has a history of, drug or alcohol abuse within the past 2 years prior to screening.
* Participants with a recent history of, or who have a positive test for, infective hepatitis or unexplained jaundice, or participants who have been treated for hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
* Evidence of active or untreated latent tuberculosis (TB).
* Change in smoking status in 12 weeks prior to enrolment or intention to change smoking status between enrolment and end of follow-up.
* Participants currently receiving background therapy that is not approved by regulatory authorities in the country of study for COPD are not eligible for the study.
* History of treatment with cardiotoxic medications (eg, as part of cancer therapy) including thiazolidinedione's.
* Treatment with broad spectrum antibiotic within 4 weeks prior to randomization (Day 1).
* Receiving any of the prohibited concomitant medications as specified in the clinical study protocol (CSP).
* Inability to perform technically acceptable spirometry.

Additional inclusion and exclusion criteria's applies.