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

Serum concentration of tozorakimab collected over time are reported. The lower limit of quantification (LLOQ) for tozorakimab was considered to be 10 μg/L.

Number of participants with positive ADA to tozorakimab are reported. Treatment-induced ADA positive is defined as ADA negative at baseline and positive at post-baseline assessment. Treatment-boosted ADA positive is defined as ADA positive at baseline and boosted (>= 4 fold) the pre-existing titre during the study period. Persistent positive is defined as ADA negative at baseline and positive at >= 2 post-baseline assessments (with >= 16 weeks between first and last positive) or ADA positive at last post-baseline assessment. Transiently positive is defined as ADA negative at baseline and at least one post-baseline ADA positive measurement and not fulfilling the conditions for persistently positive.

The COPDCompEx combines exacerbations with events defined from participant e-Diaries and peak expiratory flow (PEF). COPDCompEx defined exacerbations included episodes leading to one or more of the following: hospitalization, emergency room visit, treatment with systemic corticosteroids (injected and/or oral), or treatment with antibiotics. Diary COPDCompEx events are defined by threshold and slope criteria being met for >= 2 consecutive days using the following diary and home spirometry variables: overall symptom rating, night-time awakenings due to symptoms, reliever medication use, PEF.

Change from baseline to Week 12 in 4-weekly mean E-RS:COPD total score is reported. The E-RS™:COPD is an 11-item electronic patient reported outcome (ePRO) questionnaires developed to evaluate the severity of respiratory symptoms of COPD including breathlessness (5 items; score range: 0 to 17), cough and sputum (3 items; score range: 0 to 11), and chest symptoms (3 items; score range: 0 to 12). The ePRO was completed every day at home and at site visits. Summation of E-RS:COPD item responses produced a total score ranging from 0 to 40, with higher scores indicating greater severity. The 4-weekly mean will be calculated as the sum of all non-missing daily scores over the 28-day evaluation period, divided by the number of non-missing daily scores.

Change from baseline to Week 12 in mean BCSS score (over the previous 4 weeks) is reported. The BCSS was a 3-item daily diary that assesses the severity of the 3 symptoms: breathlessness, sputum, and cough, each on a 5-point Likert scale ranging from 0 (no symptoms) to 4 (severe symptoms). Item scores were summed to yield a total score ranging from 0 to 12; wherein higher total score indicated more severe symptoms. The BCSS was captured each evening via eDiary. The 4-weekly mean BCSS score was calculated as the sum of all non-missing daily scores over the 28-dayevaluation period, divided by the number of non-missing daily scores.

Change from baseline to Week 12 in cough VAS score is reported. Participants were asked to complete a cough severity VAS (100 mm linear scale marked with a horizontal line by the participant, with 0 mm representing ''no cough'' and 100 mm representing "worst cough") that measured subjective assessment by the participant of the prior 24 hrs for severity of cough symptoms. It was completed each evening in the eDiary. The 4-weekly mean cough VAS score was calculated as the sum of all non-missing daily scores over the 28-day evaluation period, divided by the number of non-missing daily scores.

Change from baseline to Week 12 in SGRQ total score is reported. The SGRQ was a 50-item electronic PRO instrument developed to measure the health status of participants with airway obstruction diseases and is divided into 2 parts. Part 1 consisted 8 items pertaining to the severity of respiratory symptoms in the preceding 4 weeks; Part 2 consisted 42 items related to the daily activity and psychosocial impacts of the individual's respiratory condition. The SGRQ yielded a total score and three domain scores (symptoms, activity, and impacts). The total score indicated the impact of disease on overall health status, which was expressed as a percentage of overall impairment, in which 100 represents the worst possible health status and 0 indicates the best possible health status. The domain scores range from 0 to 100, with higher scores indicative of greater impairment.

Percentage of participants with a decrease in SGRQ total score of >= 4 points from baseline to Week 12 is reported. The SGRQ was a 50-item electronic PRO instrument developed to measure the health status of participants with airway obstruction diseases and is divided into 2 parts. Part 1 consisted 8 items pertaining to the severity of respiratory symptoms in the preceding 4 weeks; Part 2 consisted 42 items related to the daily activity and psychosocial impacts of individual's respiratory condition. SGRQ yielded a total score and three domain scores (symptoms, activity, and impacts). Total score indicated the impact of disease on overall health status, which was expressed as a percentage of overall impairment, in which 100 represents worst possible health status and 0 indicates best possible health status. The domain scores range from 0 to 100, with higher scores indicative of greater impairment. A change of 4 units/points is associated with a minimum clinically important difference.

Change from baseline to Week 12 in AO parameters including frequency dependence of resistance at 5-20 Hz (R5-R20) and respiratory resistance at 5 Hz (R5; total airway resistance) and 20 Hz (R20; resistance of large airways) is reported. AO is a non-invasive lung function test assessed using an AO device. It is assessed during quiet, tidal breathing with no participant effort required, by superimposing a multi-frequency oscillation onto the participant's natural breathing. AO device uses a vibrating mesh to generate a multifrequency sinusoidal pseudorandom noise (PRN) signal. The AO markers; respiratory resistance at 5 Hz (R5) and 20 Hz (R20) and difference between resistance at 5 and 20Hz (R5-R20; resistance in small airways) are recorded. These markers measure peripheral airway resistance.

Change from baseline to Week 12 in AO Parameter-Area Under the Reactance Curve (AX) is reported. AO is a non-invasive lung function test assessed using an AO device. It is assessed during quiet, tidal breathing with no participant effort required, by superimposing a multi-frequency oscillation onto the participant's natural breathing.

Ratio to baseline in daily, night-time, and awake time cough frequency at Week 12 is reported. Objective cough frequency was measured using an ambulatory cough monitoring (ACM) which was fitted and worn by the participants for approximately 24 hours after the visits. Daily cough frequency as full average hourly cough of the full duration of recording, night time cough frequency as sleep average hourly cough of the duration of recording at night, and awake time cough frequency as awake average hourly cough of the full duration of recording minus sleep recording will be derived from the recording.

Change from baseline in pre-BD FEV1 and post-BD FEV1 through Week 28 in participants with extent of emphysema < 10% is reported.

Change from baseline in pre-BD FEV1 and post-BD FEV1 through Week 28 in participants with extent of emphysema >= 10% is reported.

Change from baseline in pre-BD and post-BD FVC through Week 28 in participants with extent of emphysema < 10% is reported.

Change from baseline in pre-BD and post-BD FVC through Week 28 in participants with extent of emphysema >= 10% is reported.

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Adverse event of special interest (AESI) are AEs of scientific and medical interest specific to understanding of tozorakimab and requires close monitoring. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug.

Number of participants with abnormal vital signs reported as TEAEs are reported. Abnormal vital signs are defined as any abnormal finding in the vital sign parameters (oral or tympanic temperature, diastolic blood pressure, systolic blood pressure, heart [pulse] rate, and respiratory rate).

Number of participants with abnormal clinical laboratory parameters reported as TEAEs are reported. Abnormal clinical laboratory parameters defined as any abnormal finding during analysis of clinical chemistry, hematology, endocrinology, and urinalysis.

Number of participants with abnormal ECGs reported as TEAEs are reported.

Change from baseline in LVEF as measured by echocardiogram is reported.

Change in NT-proBNP Level from baseline is reported.

The number of participants with COVID-19 related AEs and SAEs are reported.

Number of participants who were seronegative at baseline and who had positive SARS-Cov-2 serology result at the end of study is reported.