Trial Outcomes & Findings for A Phase II, Randomized, Double-blind, Placebo-controlled Study to Assess MEDI3506 in Participants With COPD and Chronic Bronchitis (NCT NCT04631016)

Results Overview

The mean change from baseline in Pre-BD FEV1 at Week 12 (tozorakimab - placebo) estimated using a repeated measures mixed effects analysis of covariance measures was estimated. Data available from all visits up to and including Week 12, irrespective of whether the participant discontinued study drug or received reliever therapy was considered. FEV1 was measured by spirometry at clinic.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

137 participants

Primary outcome timeframe

Baseline (Day -35 to Day -28) through Week 12

Results posted on

2025-02-27

Participant Flow

The study was conducted at 47 centers in 12 countries (Australia, Canada, Czech Republic, Denmark, Germany, United Kingdom, Hungary, Israel, Poland, South Africa, Spain, and USA).

A total of 137 participants were randomized, of which 135 participants received at least one dose of study drug.

Participant milestones

Participant milestones
Measure	Tozorakimab Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).	Placebo Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.
Overall Study STARTED	69	68
Overall Study Treated	67	68
Overall Study COMPLETED	58	63
Overall Study NOT COMPLETED	11	5

Reasons for withdrawal

Reasons for withdrawal
Measure	Tozorakimab Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).	Placebo Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.
Overall Study Adverse Event	3	0
Overall Study Withdrawal by Subject	5	4
Overall Study Reason unspecified	1	0
Overall Study Failure to meet randomization criteria	2	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Tozorakimab n=67 Participants Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).	Placebo n=68 Participants Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.	Total n=135 Participants Total of all reporting groups
Age, Continuous	64.5 Years STANDARD_DEVIATION 8.3 • n=5 Participants	64.3 Years STANDARD_DEVIATION 6.1 • n=7 Participants	64.4 Years STANDARD_DEVIATION 7.22 • n=5 Participants
Sex: Female, Male Female	26 Participants n=5 Participants	27 Participants n=7 Participants	53 Participants n=5 Participants
Sex: Female, Male Male	41 Participants n=5 Participants	41 Participants n=7 Participants	82 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	66 Participants n=5 Participants	66 Participants n=7 Participants	132 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	64 Participants n=5 Participants	65 Participants n=7 Participants	129 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline (Day -35 to Day -28) through Week 12

Population: Intent-to-treat (ITT) population included all participants who received any study drug and were analyzed according to the treatment they actually received.

The mean change from baseline in Pre-BD FEV1 at Week 12 (tozorakimab - placebo) estimated using a repeated measures mixed effects analysis of covariance measures was estimated. Data available from all visits up to and including Week 12, irrespective of whether the participant discontinued study drug or received reliever therapy was considered. FEV1 was measured by spirometry at clinic.

Outcome measures

Outcome measures
Measure	Tozorakimab n=67 Participants Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).	Placebo n=68 Participants Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.
Change From Baseline to Week 12 in Pre-bronchodilator Forced Expiratory Volume in 1 Second (Pre-BD FEV1) as Measured in Clinic	0.019 Litre Standard Error 0.026	-0.005 Litre Standard Error 0.025

SECONDARY outcome

Timeframe: Post-dose at Study Weeks 2, 4, 12, 20, 24, 28, 32, and 36

Population: Pharmacokinetic (PK) evaluable population included participants who received at least 1 dose of tozorakimab and had at least 1 detectable post-treatment sample available. Number of participants analyzed (N) denotes the number of participants evaluated for this outcome measure. Number analyzed (n) denotes those participants who had adequate PK sample available at the specified time point.

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

Outcome measures

Outcome measures
Measure	Tozorakimab n=65 Participants Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).	Placebo Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.
Serum Tozorakimab Concentration Week 12	7548.78 μg/L Standard Deviation 6416.68	—
Serum Tozorakimab Concentration Week 20	10789.81 μg/L Standard Deviation 31903.70	—
Serum Tozorakimab Concentration Week 2	24604.70 μg/L Standard Deviation 43934.55	—
Serum Tozorakimab Concentration Week 4	8041.59 μg/L Standard Deviation 22355.66	—
Serum Tozorakimab Concentration Week 24	6410.05 μg/L Standard Deviation 4123.46	—
Serum Tozorakimab Concentration Week 28	7289.36 μg/L Standard Deviation 5331.35	—
Serum Tozorakimab Concentration Week 32	1483.19 μg/L Standard Deviation 1779.88	—
Serum Tozorakimab Concentration Week 36	420.13 μg/L Standard Deviation 701.12	—

SECONDARY outcome

Timeframe: Pre-dose at Study Weeks 0 (baseline) and post-dose at Study Weeks 2, 4, 12, 20, 24, 28, 32, and 36

Population: As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received. Here, number of participants analyzed (N) denotes those participants who had at least one post-baseline ADA assessment.

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.

Outcome measures

Outcome measures
Measure	Tozorakimab n=66 Participants Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).	Placebo n=65 Participants Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.
Number of Participants With Positive Anti-drug Antibodies (ADA) to Tozorakimab Treatment-induced ADA	1 Participants	0 Participants
Number of Participants With Positive Anti-drug Antibodies (ADA) to Tozorakimab Treatment-boosted ADA	0 Participants	0 Participants
Number of Participants With Positive Anti-drug Antibodies (ADA) to Tozorakimab Persistently positive ADA	0 Participants	0 Participants
Number of Participants With Positive Anti-drug Antibodies (ADA) to Tozorakimab Transiently positive ADA	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Day -35 to Day -28) through Week 28

Population: ITT population included all participants who received any study drug and were analyzed according to the treatment they actually received.

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.

Outcome measures

Outcome measures
Measure	Tozorakimab n=67 Participants Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).	Placebo n=68 Participants Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.
Number of Participants Experiencing First Chronic Obstructive Pulmonary Disease Composite Exacerbations (COPDCompEx) Event	28 Participants	36 Participants

SECONDARY outcome

Timeframe: Baseline (from evening of Study Day -14 to the morning of Study Day 1) through Week 12

Population: ITT population included all participants who received any study drug and were analyzed according to the treatment they actually received.

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.

Outcome measures

Outcome measures
Measure	Tozorakimab n=67 Participants Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).	Placebo n=68 Participants Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.
Change From Baseline to Week 12 in 4-weekly Mean Evaluating Respiratory Symptoms of COPD (E-RS:COPD) Total Score	-6.09 Units on a scale Standard Error 1.004	-6.06 Units on a scale Standard Error 0.962

SECONDARY outcome

Timeframe: Baseline (from evening of Study Day -14 to the morning of Study Day 1) through Week 12

Population: ITT population included all participants who received any study drug and were analyzed according to the treatment they actually received.

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.

Outcome measures

Outcome measures
Measure	Tozorakimab n=67 Participants Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).	Placebo n=68 Participants Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.
Change From Baseline to Week 12 in Mean Breathlessness, Cough and Sputum Scale (BCSS) Score (Over the Previous 4 Weeks)	-2.18 Units on a scale Standard Error 0.313	-2.18 Units on a scale Standard Error 0.298

SECONDARY outcome

Timeframe: Baseline (from evening of Study Day -14 to the morning of Study Day 1) through Week 12

Population: ITT population included all participants who received any study drug and were analyzed according to the treatment they actually received.

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.

Outcome measures

Outcome measures
Measure	Tozorakimab n=67 Participants Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).	Placebo n=68 Participants Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.
Change From Baseline to Week 12 in Cough Visual Analogue Scale (VAS) Score	-17.21 mm Standard Error 3.639	-17.70 mm Standard Error 3.483

SECONDARY outcome

Timeframe: Baseline (from evening of Study Day -14 to the morning of Study Day 1) through Week 12

Population: ITT population included all participants who received any study drug and were analyzed according to the treatment they actually received. Here, number of participants analyzed (N) denotes those participants who were evaluable at Week 12.

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.

Outcome measures

Outcome measures
Measure	Tozorakimab n=62 Participants Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).	Placebo n=64 Participants Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.
Change From Baseline to Week 12 in Saint George's Respiratory Questionnaire (SGRQ) Total Score	-9.177 Units on a scale Standard Error 2.116	-8.273 Units on a scale Standard Error 2.029

SECONDARY outcome

Timeframe: Baseline (from evening of Study Day -14 to the morning of Study Day 1) through Week 12

Population: ITT population included all participants who received any study drug and were analyzed according to the treatment they actually received. Here, number of participants analyzed (N) denotes those participants who were evaluable at Week 12.

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.

Outcome measures

Outcome measures
Measure	Tozorakimab n=62 Participants Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).	Placebo n=65 Participants Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.
Percentage of Participants With a Decrease in SGRQ Total Score of >= 4 Points From Baseline to Week 12	61.3 Percentage of Participants Interval 0.62 to 1.58	61.5 Percentage of Participants

SECONDARY outcome

Timeframe: Baseline (Study Day 1) and Week 12

Population: ITT population included all participants who received any study drug and were analyzed according to the treatment they actually received. Here, number of participants analyzed (N) denotes those participants who were evaluable at Week 12.

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.

Outcome measures

Outcome measures
Measure	Tozorakimab n=64 Participants Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).	Placebo n=66 Participants Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.
Change From Baseline to Week 12 in Airwave Oscillometry (AO) Parameters R5	0.015 kPa*s/L Standard Error 0.032	-0.030 kPa*s/L Standard Error 0.030
Change From Baseline to Week 12 in Airwave Oscillometry (AO) Parameters R5-R20	0.008 kPa*s/L Standard Error 0.013	-0.014 kPa*s/L Standard Error 0.013
Change From Baseline to Week 12 in Airwave Oscillometry (AO) Parameters R20	0.006 kPa*s/L Standard Error 0.024	-0.017 kPa*s/L Standard Error 0.023

SECONDARY outcome

Timeframe: Baseline (Study Day 1) and Week 12

Population: ITT population included all participants who received any study drug and were analyzed according to the treatment they actually received. Here, number of participants analyzed (N) denotes those participants who were evaluable at Week 12.

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.

Outcome measures

Outcome measures
Measure	Tozorakimab n=64 Participants Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).	Placebo n=66 Participants Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.
Change From Baseline to Week 12 in AO Parameter-Area Under the Reactance Curve (AX)	-0.081 kPa/L Standard Error 0.375	-0.267 kPa/L Standard Error 0.360

SECONDARY outcome

Timeframe: Baseline (Day -21 to Day -7) and Week 12

Population: ITT population included all participants who received any study drug and were analyzed according to the treatment they actually received. Here, number of participants analyzed (N) denotes those participants who were evaluable at Week 12.

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.

Outcome measures

Outcome measures
Measure	Tozorakimab n=58 Participants Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).	Placebo n=61 Participants Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.
Ratio to Baseline in Daily, Night-time, and Awake Time Cough Frequency at Week 12 Night-time cough frequency	1.03 Ratio to baseline Interval 0.62 to 1.7	0.61 Ratio to baseline Interval 0.38 to 0.98
Ratio to Baseline in Daily, Night-time, and Awake Time Cough Frequency at Week 12 Awake time cough frequency	0.89 Ratio to baseline Interval 0.74 to 1.07	0.84 Ratio to baseline Interval 0.71 to 0.99
Ratio to Baseline in Daily, Night-time, and Awake Time Cough Frequency at Week 12 Daily cough frequency	0.89 Ratio to baseline Interval 0.74 to 1.07	0.83 Ratio to baseline Interval 0.7 to 0.99

SECONDARY outcome

Timeframe: Baseline (Week -5 to -4) through Week 28 post-dose

Population: ITT population included all participants who received any study drug and were analyzed according to the treatment they actually received. Here, number of participants analyzed (N) denotes those participants who were evaluable at Week 28.

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

Outcome measures

Outcome measures
Measure	Tozorakimab n=31 Participants Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).	Placebo n=35 Participants Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.
Change From Baseline in Pre-BD FEV1 and Post-BD FEV1 Through Week 28 in Participants With Extent of Emphysema < 10% Pre-BD FEV1	0.031 Litre Standard Error 0.057	0.006 Litre Standard Error 0.049
Change From Baseline in Pre-BD FEV1 and Post-BD FEV1 Through Week 28 in Participants With Extent of Emphysema < 10% Post-BD FEV1	-0.039 Litre Standard Error 0.071	-0.018 Litre Standard Error 0.059

SECONDARY outcome

Timeframe: Baseline (Week -5 to -4) through Week 28 post-dose

Population: ITT population included all participants who received any study drug and were analyzed according to the treatment they actually received. Here, number of participants analyzed (N) denotes those participants who were evaluable at Week 28.

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

Outcome measures

Outcome measures
Measure	Tozorakimab n=29 Participants Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).	Placebo n=29 Participants Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.
Change From Baseline in Pre-BD FEV1 and Post-BD FEV1 Through Week 28 in Participants With Extent of Emphysema >= 10% Pre-BD FEV1 Week 28	-0.015 Litre Standard Error 0.036	-0.068 Litre Standard Error 0.034
Change From Baseline in Pre-BD FEV1 and Post-BD FEV1 Through Week 28 in Participants With Extent of Emphysema >= 10% Post-BD FEV1 Week 28	0.074 Litre Standard Error 0.044	-0.053 Litre Standard Error 0.042

SECONDARY outcome

Timeframe: Baseline (Week -5 to -4) through Week 28 post-dose

Population: ITT population included all participants who received any study drug and were analyzed according to the treatment they actually received. Here, number of participants analyzed (N) denotes those participants who were evaluable at Week 28.

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

Outcome measures

Outcome measures
Measure	Tozorakimab n=31 Participants Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).	Placebo n=35 Participants Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.
Change From Baseline in Pre-BD and Post-BD Forced Vital Capacity (FVC) Through Week 28 in Participants With Extent of Emphysema < 10% Post-BD FVC Week 28	-0.121 Litre Standard Error 0.114	0.046 Litre Standard Error 0.096
Change From Baseline in Pre-BD and Post-BD Forced Vital Capacity (FVC) Through Week 28 in Participants With Extent of Emphysema < 10% Pre-BD FVC Week 28	-0.143 Litre Standard Error 0.105	-0.056 Litre Standard Error 0.093

SECONDARY outcome

Timeframe: Baseline (Week -5 to -4) through Week 28 post-dose

Population: ITT population included all participants who received any study drug and were analyzed according to the treatment they actually received. Here, number of participants analyzed (N) denotes those participants who were evaluable at Week 28.

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

Outcome measures

Outcome measures
Measure	Tozorakimab n=29 Participants Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).	Placebo n=29 Participants Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.
Change From Baseline in Pre-BD and Post-BD FVC Through Week 28 in Participants With Extent of Emphysema >= 10% Pre-BD FVC Week 28	0.089 Litre Standard Error 0.086	-0.121 Litre Standard Error 0.084
Change From Baseline in Pre-BD and Post-BD FVC Through Week 28 in Participants With Extent of Emphysema >= 10% Post-BD FVC Week 28	0.081 Litre Standard Error 0.081	-0.094 Litre Standard Error 0.077

SECONDARY outcome

Timeframe: Day 1 through 253 days (maximum observed duration)

Population: As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.

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.

Outcome measures

Outcome measures
Measure	Tozorakimab n=67 Participants Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).	Placebo n=68 Participants Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), and TEAEs of Special Interest (TEAESIs) Any TEAEs	53 Participants	50 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), and TEAEs of Special Interest (TEAESIs) Any TESAEs	14 Participants	9 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Treatment Emergent Serious Adverse Events (TESAEs), and TEAEs of Special Interest (TEAESIs) Any TEAESIs	33 Participants	24 Participants

SECONDARY outcome

Timeframe: Day 1 through 253 days (maximum observed duration)

Population: As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.

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).

Outcome measures

Outcome measures
Measure	Tozorakimab n=67 Participants Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).	Placebo n=68 Participants Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.
Number of Participants With Abnormal Vital Signs Reported as TEAEs Hypotension	1 Participants	0 Participants
Number of Participants With Abnormal Vital Signs Reported as TEAEs Dyspnoea	2 Participants	3 Participants
Number of Participants With Abnormal Vital Signs Reported as TEAEs Hypertension	2 Participants	3 Participants
Number of Participants With Abnormal Vital Signs Reported as TEAEs Pyrexia	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 1 through 253 days (maximum observed duration)

Population: As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.

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.

Outcome measures

Outcome measures
Measure	Tozorakimab n=67 Participants Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).	Placebo n=68 Participants Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Haematuria	2 Participants	0 Participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Anaemia	0 Participants	1 Participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Hypercholesterolaemia	0 Participants	1 Participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Hyperuricaemia	0 Participants	1 Participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Hypertransaminasaemia	1 Participants	0 Participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs SARS-CoV-2 test positive	2 Participants	0 Participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Hyperthyroidism	0 Participants	1 Participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Hypothyroidism	1 Participants	0 Participants
Number of Participants With Abnormal Clinical Laboratory Parameters Reported as TEAEs Urinary tract infection	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Day 1 through 253 days (maximum observed duration)

Population: As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.

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

Outcome measures

Outcome measures
Measure	Tozorakimab n=67 Participants Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).	Placebo n=68 Participants Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.
Number of Participants With Abnormal Electrocardiograms (ECGs) Reported as TEAEs	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Week -3 to -1) through Week 28

Population: As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received. Here, number of participants analyzed (N) denotes those participants who were evaluable at Week 28.

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

Outcome measures

Outcome measures
Measure	Tozorakimab n=56 Participants Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).	Placebo n=60 Participants Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.
Change From Baseline in Left Ventricular Ejection Fraction (LVEF) as Measured by Echocardiogram	0.9 Ratio Standard Deviation 5.78	0.2 Ratio Standard Deviation 4.61

SECONDARY outcome

Timeframe: Baseline (Day -35 to Day -28) through Week 28

Population: As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received. Here, number of participants analyzed (N) denotes those participants who were evaluable at Week 28.

Change in NT-proBNP Level from baseline is reported.

Outcome measures

Outcome measures
Measure	Tozorakimab n=58 Participants Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).	Placebo n=61 Participants Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.
Change From Baseline in N-terminal Pro-brain Natriuretic Peptide (NT-proBNP) Level	4.051 pmol/L Standard Deviation 17.937	1.948 pmol/L Standard Deviation 14.280

SECONDARY outcome

Timeframe: Day 1 through 253 days (maximum observed duration)

Population: As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.

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

Outcome measures

Outcome measures
Measure	Tozorakimab n=67 Participants Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).	Placebo n=68 Participants Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.
Number of Participants With Coronavirus Disease 2019 (COVID-19) Related AEs and SAEs COVID-19 related AEs	17 Participants	14 Participants
Number of Participants With Coronavirus Disease 2019 (COVID-19) Related AEs and SAEs COVID-19 related SAEs	1 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline (Week 0) through Week 28

Population: As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received. Here, number of participants analyzed (N) denotes the number of participants who were SARS-CoV-2 serum negative at baseline and had at least one post-baseline result.

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

Outcome measures

Outcome measures
Measure	Tozorakimab n=6 Participants Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).	Placebo n=7 Participants Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.
Number of Participants Seropositive for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)	6 Participants	6 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline (Week -5 to -4) to Weeks 12 and 28 post-dose

Population: ITT population included all participants who received any study drug and were analyzed according to the treatment they actually received. Here, number of participants analyzed (N) denotes those participants who were included in the analysis.

Change from baseline in post-BD FEV1 to Weeks 12 and 28 is reported.

Outcome measures

Outcome measures
Measure	Tozorakimab n=65 Participants Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).	Placebo n=67 Participants Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.
Change From Baseline in Post-BD FEV1 To Weeks 12 and 28 Week 28	0.021 Litre Standard Error 0.036	-0.049 Litre Standard Error 0.033
Change From Baseline in Post-BD FEV1 To Weeks 12 and 28 Week 12	0.041 Litre Standard Error 0.036	-0.025 Litre Standard Error 0.033

Adverse Events

Tozorakimab

Serious events: 14 serious events

Other events: 40 other events

Deaths: 0 deaths

Placebo

Serious events: 9 serious events

Other events: 39 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Tozorakimab n=67 participants at risk Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).	Placebo n=68 participants at risk Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.
Nervous system disorders Headache	11.9% 8/67 • Number of events 10 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.	4.4% 3/68 • Number of events 3 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	38.8% 26/67 • Number of events 53 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.	39.7% 27/68 • Number of events 56 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.
General disorders Injection site erythema	14.9% 10/67 • Number of events 25 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.	0.00% 0/68 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.
Infections and infestations Covid-19	20.9% 14/67 • Number of events 15 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.	20.6% 14/68 • Number of events 14 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.
Infections and infestations Nasopharyngitis	4.5% 3/67 • Number of events 4 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.	10.3% 7/68 • Number of events 12 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.

Additional Information

Global Clinical Lead

AstraZeneca Clinical Study Information Center

Phone: +1-877-240-9479

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.
Publication restrictions are in place

Restriction type: OTHER

Measure	Tozorakimab n=67 participants at risk Participants received 7 doses of subcutaneous (SC) tozorakimab Dose Level 1 injection once every 4 weeks (Q4W).	Placebo n=68 participants at risk Participants received 7 doses of SC placebo injection matched to tozorakimab once Q4W.
Injury, poisoning and procedural complications Acetabulum fracture	1.5% 1/67 • Number of events 1 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.	0.00% 0/68 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.
Injury, poisoning and procedural complications Wrist fracture	1.5% 1/67 • Number of events 1 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.	0.00% 0/68 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.
Metabolism and nutrition disorders Dehydration	1.5% 1/67 • Number of events 1 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.	0.00% 0/68 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.
Musculoskeletal and connective tissue disorders Osteoarthritis	1.5% 1/67 • Number of events 1 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.	0.00% 0/68 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.00% 0/67 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.	1.5% 1/68 • Number of events 1 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.00% 0/67 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.	1.5% 1/68 • Number of events 1 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Transitional cell carcinoma	1.5% 1/67 • Number of events 1 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.	0.00% 0/68 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.
Nervous system disorders Transient ischaemic attack	1.5% 1/67 • Number of events 1 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.	0.00% 0/68 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	9.0% 6/67 • Number of events 6 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.	8.8% 6/68 • Number of events 6 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.
Gastrointestinal disorders Pancreatitis	1.5% 1/67 • Number of events 1 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.	0.00% 0/68 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.
Infections and infestations Covid-19	1.5% 1/67 • Number of events 1 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.	0.00% 0/68 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.
Infections and infestations Influenza	1.5% 1/67 • Number of events 1 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.	0.00% 0/68 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.
Infections and infestations Lower respiratory tract infection	1.5% 1/67 • Number of events 1 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.	0.00% 0/68 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.
Infections and infestations Pneumonia bacterial	0.00% 0/67 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.	1.5% 1/68 • Number of events 1 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.
Infections and infestations Pneumonia pseudomonal	0.00% 0/67 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.	1.5% 1/68 • Number of events 1 • Day 1 through 253 days (maximum observed duration) As-treated population included all participants who received any study drug and were analyzed according to the treatment they actually received.