Trial Outcomes & Findings for Anti-ST2 (MSTT1041A) in COPD (COPD-ST2OP) (NCT NCT03615040)

NCT ID: NCT03615040

Last Updated: 2022-06-21

Results Overview

Where a COPD exacerbation is defined by symptomatic worsening of COPD requiring: * Use of systemic corticosteroids for at least 3 days; a single depot injectable dose of corticosteroids will be considered equivalent to a 3-day course of systemic corticosteroids; and/or * Use of antibiotics and/or * inpatient hospitalisation or death due to COPD

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 81 participants
• Primary outcome timeframe: 0-48 weeks
• Results posted on: 2022-06-21

Participant Flow

Recruitment at a single centre. Potential participants were identified by the research team using a variety of methods: database of previous COPD trial participants who consented to be contacted for future trials; respiratory outpatient clinics/acute admission unit; self-referrals; GP practices. Recruitment ran between 11 Oct 2018 and 05 Jul 2019.

Potential participants were assessed according to eligibility criteria at initial screening and provided written informed consent before commencing any trial-related procedures. Participants then entered a screening period for 7-14 days before randomisation. eligible to participate were randomised into a 48-week treatment period (anti-ST2/placebo).

Participant milestones

Measure	Anti-ST2 Anti-ST2 (MSTT1041A\*) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. Anti-ST2 was presented as sterile, clear, and colourless to slightly yellow liquid. Each sterile vial is filled with a 1 mL deliverable volume of 70 mg/mL. It was formulated with 15 mM sodium acetate, 9.0% (w/v) sucrose, 0.01% (w/v) polysorbate 20, pH 5.2. \*Official USAN name for MSTT1041A is now astegolimab	Placebo Placebo (no active component) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. Placebo for Anti-ST2 (MSTT1041A) was formulated with 10 mM sodium acetate, 9.0% (w/v) sucrose, 0.004% (w/v) polysorbate 20, pH 5.2, and was supplied in an identical vial configuration.
Overall Study STARTED	42	39
Overall Study COMPLETED	36	34
Overall Study NOT COMPLETED	6	5

Reasons for withdrawal

Measure	Anti-ST2 Anti-ST2 (MSTT1041A\*) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. Anti-ST2 was presented as sterile, clear, and colourless to slightly yellow liquid. Each sterile vial is filled with a 1 mL deliverable volume of 70 mg/mL. It was formulated with 15 mM sodium acetate, 9.0% (w/v) sucrose, 0.01% (w/v) polysorbate 20, pH 5.2. \*Official USAN name for MSTT1041A is now astegolimab	Placebo Placebo (no active component) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. Placebo for Anti-ST2 (MSTT1041A) was formulated with 10 mM sodium acetate, 9.0% (w/v) sucrose, 0.004% (w/v) polysorbate 20, pH 5.2, and was supplied in an identical vial configuration.
Overall Study Withdrawal by Subject	2	1
Overall Study Physician Decision	2	2
Overall Study Clinical diagnosis of lung cancer	1	0
Overall Study Clinical diagnosis of oesophageal cancer	1	0
Overall Study Death	0	2

Baseline Characteristics

Anti-ST2 (MSTT1041A) in COPD (COPD-ST2OP)

Baseline characteristics by cohort

Measure	Anti-ST2 n=42 Participants Anti-ST2 (MSTT1041A\*) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. Anti-ST2 was presented as sterile, clear, and colourless to slightly yellow liquid. Each sterile vial is filled with a 1 mL deliverable volume of 70 mg/mL. It was formulated with 15 mM sodium acetate, 9.0% (w/v) sucrose, 0.01% (w/v) polysorbate 20, pH 5.2. \*Official USAN name for MSTT1041A is now astegolimab	Placebo n=39 Participants Placebo (no active component) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. Placebo for Anti-ST2 (MSTT1041A) was formulated with 10 mM sodium acetate, 9.0% (w/v) sucrose, 0.004% (w/v) polysorbate 20, pH 5.2, and was supplied in an identical vial configuration.	Total n=81 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	12 Participants n=5 Participants	4 Participants n=7 Participants	16 Participants n=5 Participants
Age, Categorical >=65 years	30 Participants n=5 Participants	35 Participants n=7 Participants	65 Participants n=5 Participants
Age, Continuous	67.6 years STANDARD_DEVIATION 8.2 • n=5 Participants	70.8 years STANDARD_DEVIATION 6.2 • n=7 Participants	69.1 years STANDARD_DEVIATION 7.5 • n=5 Participants
Sex: Female, Male Female	17 Participants n=5 Participants	13 Participants n=7 Participants	30 Participants n=5 Participants
Sex: Female, Male Male	25 Participants n=5 Participants	26 Participants n=7 Participants	51 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	42 Participants n=5 Participants	39 Participants n=7 Participants	81 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	1 Participants n=5 Participants	0 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	41 Participants n=5 Participants	39 Participants n=7 Participants	80 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	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United Kingdom	42 participants n=5 Participants	39 participants n=7 Participants	81 participants n=5 Participants

PRIMARY outcome

Timeframe: 0-48 weeks

Population: An intention-to-treat population was used for the primary analysis and all participants were included in the analysis (n = 81). The primary analysis used observed data, meaning only observed exacerbations were used alongside the corresponding time period in the offset of log-time.

Where a COPD exacerbation is defined by symptomatic worsening of COPD requiring:

• Use of systemic corticosteroids for at least 3 days; a single depot injectable dose of corticosteroids will be considered equivalent to a 3-day course of systemic corticosteroids; and/or
• Use of antibiotics and/or
• inpatient hospitalisation or death due to COPD

Outcome measures

Measure	Anti-ST2 n=42 Participants Anti-ST2 (MSTT1041A) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. MSTT1041A: MSTT1041A (RO7187807; formerly made by Amgen \[AMG\] and referred to as AMG 282) is a novel biopharmaceutical that blocks signaling of interleukin (IL)-33, an inflammatory cytokine of the IL-1 family and member of the newly discovered "alarmin" class of molecules. IL-33 is released from airway epithelial cells in response to allergens, irritants, and infection. IL-33 release can trigger acute exacerbations in both asthma and COPD. MSTT1041A has the ability to block inflammation,prevent exacerbations, and improve lung function and quality of life. Anti-ST2 is presented as sterile, clear, and colourless to slightly yellow liquid. Each sterile vial is filled with a 1 mL deliverable volume of 70 mg/mL. It is formulated with 15 mM sodium acetate, 9.0% (w/v) sucrose, 0.01% (w/v) polysorbate 20, pH 5.2.	Placebo n=39 Participants Placebo (no active component) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. Placebo: Placebo for Anti-ST2 (MSTT1041A) is formulated with 10 mM sodium acetate, 9.0% (w/v) sucrose, 0.004% (w/v) polysorbate 20, pH 5.2, and is supplied in an identical vial configuration.
Number of Moderate to Severe Exacerbation (Defined as Requiring Treatment With Systemic Corticosteroids and/or Antibiotics in the Community or Hospital or Hospitalisation).	2.21 Exacerbations Standard Deviation 2.04	2.67 Exacerbations Standard Deviation 2.14

SECONDARY outcome

Timeframe: Weeks 0 , 4, 12, 24, 26, 48

Population: Safety population

Number of Participants with Adverse Events in the 48 Weeks of the Trial From First Dose

Outcome measures

Measure	Anti-ST2 n=42 Participants Anti-ST2 (MSTT1041A) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. MSTT1041A: MSTT1041A (RO7187807; formerly made by Amgen \[AMG\] and referred to as AMG 282) is a novel biopharmaceutical that blocks signaling of interleukin (IL)-33, an inflammatory cytokine of the IL-1 family and member of the newly discovered "alarmin" class of molecules. IL-33 is released from airway epithelial cells in response to allergens, irritants, and infection. IL-33 release can trigger acute exacerbations in both asthma and COPD. MSTT1041A has the ability to block inflammation,prevent exacerbations, and improve lung function and quality of life. Anti-ST2 is presented as sterile, clear, and colourless to slightly yellow liquid. Each sterile vial is filled with a 1 mL deliverable volume of 70 mg/mL. It is formulated with 15 mM sodium acetate, 9.0% (w/v) sucrose, 0.01% (w/v) polysorbate 20, pH 5.2.	Placebo n=39 Participants Placebo (no active component) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. Placebo: Placebo for Anti-ST2 (MSTT1041A) is formulated with 10 mM sodium acetate, 9.0% (w/v) sucrose, 0.004% (w/v) polysorbate 20, pH 5.2, and is supplied in an identical vial configuration.
Adverse Event Rate in the 48 Weeks of the Trial From First Dose	34 Participants	28 Participants

SECONDARY outcome

Timeframe: Weeks 0 , 4, 12, 24, 26, 48

Population: Safety population

Number of Participants with Serious Adverse Events in the 48 Weeks of the Trial From First Dose

Outcome measures

Measure	Anti-ST2 n=42 Participants Anti-ST2 (MSTT1041A) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. MSTT1041A: MSTT1041A (RO7187807; formerly made by Amgen \[AMG\] and referred to as AMG 282) is a novel biopharmaceutical that blocks signaling of interleukin (IL)-33, an inflammatory cytokine of the IL-1 family and member of the newly discovered "alarmin" class of molecules. IL-33 is released from airway epithelial cells in response to allergens, irritants, and infection. IL-33 release can trigger acute exacerbations in both asthma and COPD. MSTT1041A has the ability to block inflammation,prevent exacerbations, and improve lung function and quality of life. Anti-ST2 is presented as sterile, clear, and colourless to slightly yellow liquid. Each sterile vial is filled with a 1 mL deliverable volume of 70 mg/mL. It is formulated with 15 mM sodium acetate, 9.0% (w/v) sucrose, 0.01% (w/v) polysorbate 20, pH 5.2.	Placebo n=39 Participants Placebo (no active component) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. Placebo: Placebo for Anti-ST2 (MSTT1041A) is formulated with 10 mM sodium acetate, 9.0% (w/v) sucrose, 0.004% (w/v) polysorbate 20, pH 5.2, and is supplied in an identical vial configuration.
Serious Adverse Event Rate in the 48 Weeks of the Trial From First Dose	12 Participants	16 Participants

SECONDARY outcome

Timeframe: Weeks 0, 4, 12, 24, 36, 48

Population: Modified ITT (available data)

Patient reported outcome (PRO). To evaluate health status; designed to measure health impairment in patients with asthma and COPD. It is in two parts. Part I produces the Symptoms score, and Part 2 the Activity and Impact scores. A Total score is also produced. The Total score is calculated by summing the weights to all the positive responses in each component. This score is then put onto the scale 0 to 100 by dividing by the Total possible sum (3201.9)- and times by 100. A score of 0 would represent the best health and a score of 100 would represent the worst possible state of the patient.

Outcome measures

Measure	Anti-ST2 n=42 Participants Anti-ST2 (MSTT1041A) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. MSTT1041A: MSTT1041A (RO7187807; formerly made by Amgen \[AMG\] and referred to as AMG 282) is a novel biopharmaceutical that blocks signaling of interleukin (IL)-33, an inflammatory cytokine of the IL-1 family and member of the newly discovered "alarmin" class of molecules. IL-33 is released from airway epithelial cells in response to allergens, irritants, and infection. IL-33 release can trigger acute exacerbations in both asthma and COPD. MSTT1041A has the ability to block inflammation,prevent exacerbations, and improve lung function and quality of life. Anti-ST2 is presented as sterile, clear, and colourless to slightly yellow liquid. Each sterile vial is filled with a 1 mL deliverable volume of 70 mg/mL. It is formulated with 15 mM sodium acetate, 9.0% (w/v) sucrose, 0.01% (w/v) polysorbate 20, pH 5.2.	Placebo n=39 Participants Placebo (no active component) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. Placebo: Placebo for Anti-ST2 (MSTT1041A) is formulated with 10 mM sodium acetate, 9.0% (w/v) sucrose, 0.004% (w/v) polysorbate 20, pH 5.2, and is supplied in an identical vial configuration.
St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score Baseline	60.1 score on a scale Standard Deviation 13.7	58.4 score on a scale Standard Deviation 17.6
St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score Week 4	56.7 score on a scale Standard Deviation 13.5	58.9 score on a scale Standard Deviation 16.5
St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score Week 12	56.9 score on a scale Standard Deviation 15.2	59.9 score on a scale Standard Deviation 18.2
St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score Week 24	56.6 score on a scale Standard Deviation 15.3	59.6 score on a scale Standard Deviation 17.9
St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score Week 36	59.5 score on a scale Standard Deviation 14.6	59.5 score on a scale Standard Deviation 17.0
St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score Week 48	57.7 score on a scale Standard Deviation 15.7	63.3 score on a scale Standard Deviation 17.2

SECONDARY outcome

Timeframe: Weeks 0, 4, 12, 24, 36, 48

Population: Modified ITT (available data)

Patient reported outcome (PRO). To evaluate health status: evaluation and rehabilitation education guidance on the respiratory and motor functions of patients with chronic obstructive pulmonary disease. CAT score is made by summing the score to eight questions on COPD. For each, the person with COPD picks the number between 0-5 that reflects their response. A zero indicates no effect on quality of life, whereas a 5 suggests a very significant effect.The CAT has a scoring range of 0-40, with 40 indicating the most severe COPD and 0 being the least severe COPD.

A change of 2 units suggests a meaningful difference. This test should be used in conjunction with the mMRC and forced expiratory volume in one second (FEV1) to determine COPD health assessment of participants.

Outcome measures

Measure	Anti-ST2 n=42 Participants Anti-ST2 (MSTT1041A) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. MSTT1041A: MSTT1041A (RO7187807; formerly made by Amgen \[AMG\] and referred to as AMG 282) is a novel biopharmaceutical that blocks signaling of interleukin (IL)-33, an inflammatory cytokine of the IL-1 family and member of the newly discovered "alarmin" class of molecules. IL-33 is released from airway epithelial cells in response to allergens, irritants, and infection. IL-33 release can trigger acute exacerbations in both asthma and COPD. MSTT1041A has the ability to block inflammation,prevent exacerbations, and improve lung function and quality of life. Anti-ST2 is presented as sterile, clear, and colourless to slightly yellow liquid. Each sterile vial is filled with a 1 mL deliverable volume of 70 mg/mL. It is formulated with 15 mM sodium acetate, 9.0% (w/v) sucrose, 0.01% (w/v) polysorbate 20, pH 5.2.	Placebo n=39 Participants Placebo (no active component) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. Placebo: Placebo for Anti-ST2 (MSTT1041A) is formulated with 10 mM sodium acetate, 9.0% (w/v) sucrose, 0.004% (w/v) polysorbate 20, pH 5.2, and is supplied in an identical vial configuration.
COPD Assessment Test (CAT) (Questionnaire) Week 0	22.1 score on a scale Standard Deviation 6.6	22.6 score on a scale Standard Deviation 5.7
COPD Assessment Test (CAT) (Questionnaire) Week 4	22.2 score on a scale Standard Deviation 5.5	21.7 score on a scale Standard Deviation 5.8
COPD Assessment Test (CAT) (Questionnaire) Week 12	22.0 score on a scale Standard Deviation 5.1	22.3 score on a scale Standard Deviation 6.9
COPD Assessment Test (CAT) (Questionnaire) Week 24	22.7 score on a scale Standard Deviation 6.9	22.1 score on a scale Standard Deviation 5.5
COPD Assessment Test (CAT) (Questionnaire) Week 36	22.7 score on a scale Standard Deviation 5.0	22.4 score on a scale Standard Deviation 6.0
COPD Assessment Test (CAT) (Questionnaire) Week 48	23.4 score on a scale Standard Deviation 6.0	23.6 score on a scale Standard Deviation 7.8

SECONDARY outcome

Timeframe: Screening, weeks 0, 4, 12, 24, 36, 48

Population: Modified ITT (available data)

Patient reported outcome (PRO). To evaluate respiratory breathlessness symptoms (Grade 0-4, with Grade 0 being breathlessness with strenuous exercise to Grade 4 being breathlessness for daily activities like dressing).

Outcome measures

Measure	Anti-ST2 n=42 Participants Anti-ST2 (MSTT1041A) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. MSTT1041A: MSTT1041A (RO7187807; formerly made by Amgen \[AMG\] and referred to as AMG 282) is a novel biopharmaceutical that blocks signaling of interleukin (IL)-33, an inflammatory cytokine of the IL-1 family and member of the newly discovered "alarmin" class of molecules. IL-33 is released from airway epithelial cells in response to allergens, irritants, and infection. IL-33 release can trigger acute exacerbations in both asthma and COPD. MSTT1041A has the ability to block inflammation,prevent exacerbations, and improve lung function and quality of life. Anti-ST2 is presented as sterile, clear, and colourless to slightly yellow liquid. Each sterile vial is filled with a 1 mL deliverable volume of 70 mg/mL. It is formulated with 15 mM sodium acetate, 9.0% (w/v) sucrose, 0.01% (w/v) polysorbate 20, pH 5.2.	Placebo n=39 Participants Placebo (no active component) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. Placebo: Placebo for Anti-ST2 (MSTT1041A) is formulated with 10 mM sodium acetate, 9.0% (w/v) sucrose, 0.004% (w/v) polysorbate 20, pH 5.2, and is supplied in an identical vial configuration.
Modified Medical Research Council (mMRC) Dyspnea Scale Week 4	2.0 score on a scale Interval 2.0 to 3.0	2.0 score on a scale Interval 2.0 to 3.0
Modified Medical Research Council (mMRC) Dyspnea Scale Week 0	2.0 score on a scale Interval 2.0 to 3.0	2.0 score on a scale Interval 2.0 to 3.0
Modified Medical Research Council (mMRC) Dyspnea Scale Week 12	2.0 score on a scale Interval 2.0 to 3.0	2.0 score on a scale Interval 2.0 to 3.0
Modified Medical Research Council (mMRC) Dyspnea Scale Week 24	2.0 score on a scale Interval 2.0 to 3.0	2.0 score on a scale Interval 1.0 to 3.0
Modified Medical Research Council (mMRC) Dyspnea Scale Week 36	2.0 score on a scale Interval 2.0 to 3.0	3.0 score on a scale Interval 2.0 to 3.0
Modified Medical Research Council (mMRC) Dyspnea Scale Week 48	2.0 score on a scale Interval 2.0 to 3.0	2.0 score on a scale Interval 1.5 to 3.5

SECONDARY outcome

Timeframe: Weeks 0, 4, 12, 24, 36, 48

Population: Modified ITT (available data)

Patient reported outcome (PRO). To evaluate respiratory symptoms. The participant is asked to place a mark (X) on the scale at the point that best describes their health currently. Minimum score 0mm (better outcome), maximum score 100mm (worse outcome) for each section of the scale (dyspnoea, cough, sputum). The Total VAS score is the sum of the 3 scales, thus the minimum score is 0 (best outcome) and the maximum 300 (worst outcome).

Outcome measures

Measure	Anti-ST2 n=42 Participants Anti-ST2 (MSTT1041A) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. MSTT1041A: MSTT1041A (RO7187807; formerly made by Amgen \[AMG\] and referred to as AMG 282) is a novel biopharmaceutical that blocks signaling of interleukin (IL)-33, an inflammatory cytokine of the IL-1 family and member of the newly discovered "alarmin" class of molecules. IL-33 is released from airway epithelial cells in response to allergens, irritants, and infection. IL-33 release can trigger acute exacerbations in both asthma and COPD. MSTT1041A has the ability to block inflammation,prevent exacerbations, and improve lung function and quality of life. Anti-ST2 is presented as sterile, clear, and colourless to slightly yellow liquid. Each sterile vial is filled with a 1 mL deliverable volume of 70 mg/mL. It is formulated with 15 mM sodium acetate, 9.0% (w/v) sucrose, 0.01% (w/v) polysorbate 20, pH 5.2.	Placebo n=39 Participants Placebo (no active component) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. Placebo: Placebo for Anti-ST2 (MSTT1041A) is formulated with 10 mM sodium acetate, 9.0% (w/v) sucrose, 0.004% (w/v) polysorbate 20, pH 5.2, and is supplied in an identical vial configuration.
Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores VAS Total Week 0	142.7 units on a scale Standard Deviation 54.6	143.8 units on a scale Standard Deviation 53.8
Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores VAS Total Week 4	129.3 units on a scale Standard Deviation 45.7	148.5 units on a scale Standard Deviation 61.2
Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores VAS Total Week 12	139.5 units on a scale Standard Deviation 50.3	140.0 units on a scale Standard Deviation 65.1
Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores VAS Total Week 24	131.0 units on a scale Standard Deviation 57.9	146.6 units on a scale Standard Deviation 55.1
Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores VAS Total Week 36	146.9 units on a scale Standard Deviation 51.9	147.6 units on a scale Standard Deviation 59.6
Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores VAS Total Week 48	140.7 units on a scale Standard Deviation 58.0	146.5 units on a scale Standard Deviation 70.0
Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores VAS Dyspnoea Week 0	52.5 units on a scale Standard Deviation 20.3	53.5 units on a scale Standard Deviation 22.1
Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores VAS Dyspnoea Week 4	50.1 units on a scale Standard Deviation 17.7	57.8 units on a scale Standard Deviation 20.6
Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores VAS Dyspnoea Week 12	55.2 units on a scale Standard Deviation 17.1	54.7 units on a scale Standard Deviation 25.4
Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores VAS Dyspnoea Week 24	46.5 units on a scale Standard Deviation 20.0	57.9 units on a scale Standard Deviation 22.6
Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores VAS Dyspnoea Week 36	56.0 units on a scale Standard Deviation 18.6	57.6 units on a scale Standard Deviation 22.5
Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores VAS Dyspnoea Week 48	58.8 units on a scale Standard Deviation 15.8	60.5 units on a scale Standard Deviation 21.8
Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores VAS Cough Week 0	49.7 units on a scale Standard Deviation 23.7	47.5 units on a scale Standard Deviation 22.7
Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores VAS Cough Week 4	41.3 units on a scale Standard Deviation 19.6	45.9 units on a scale Standard Deviation 25.5
Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores VAS Cough Week 12	44.2 units on a scale Standard Deviation 22.3	45.1 units on a scale Standard Deviation 24.6
Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores VAS Cough Week 24	47.6 units on a scale Standard Deviation 23.7	45.2 units on a scale Standard Deviation 21.9
Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores VAS Cough Week 36	48.4 units on a scale Standard Deviation 20.4	46.0 units on a scale Standard Deviation 25.1
Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores VAS Cough Week 48	40.4 units on a scale Standard Deviation 24.7	47.0 units on a scale Standard Deviation 29.6
Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores VAS Sputum production Week 0	40.5 units on a scale Standard Deviation 25.5	42.8 units on a scale Standard Deviation 24.5
Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores VAS Sputum production Week 4	37.9 units on a scale Standard Deviation 24.5	44.7 units on a scale Standard Deviation 27.0
Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores VAS Sputum production Week 12	40.1 units on a scale Standard Deviation 25.7	40.2 units on a scale Standard Deviation 28.7
Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores VAS Sputum production Week 24	36.9 units on a scale Standard Deviation 26.3	43.5 units on a scale Standard Deviation 24.3
Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores VAS Sputum production Week 36	42.6 units on a scale Standard Deviation 27.3	44.0 units on a scale Standard Deviation 26.2
Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores VAS Sputum production Week 48	41.5 units on a scale Standard Deviation 26.5	39.0 units on a scale Standard Deviation 27.6

SECONDARY outcome

Timeframe: Screening, week 12, 28, 36, 48

Population: Modified ITT (available data)

The sputum purulence colour card using the Bronko test has values of 0, 1, 2, 3, 4, 5 and 6. Lower scores indicate better health.

Outcome measures

Measure	Anti-ST2 n=42 Participants Anti-ST2 (MSTT1041A) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. MSTT1041A: MSTT1041A (RO7187807; formerly made by Amgen \[AMG\] and referred to as AMG 282) is a novel biopharmaceutical that blocks signaling of interleukin (IL)-33, an inflammatory cytokine of the IL-1 family and member of the newly discovered "alarmin" class of molecules. IL-33 is released from airway epithelial cells in response to allergens, irritants, and infection. IL-33 release can trigger acute exacerbations in both asthma and COPD. MSTT1041A has the ability to block inflammation,prevent exacerbations, and improve lung function and quality of life. Anti-ST2 is presented as sterile, clear, and colourless to slightly yellow liquid. Each sterile vial is filled with a 1 mL deliverable volume of 70 mg/mL. It is formulated with 15 mM sodium acetate, 9.0% (w/v) sucrose, 0.01% (w/v) polysorbate 20, pH 5.2.	Placebo n=39 Participants Placebo (no active component) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. Placebo: Placebo for Anti-ST2 (MSTT1041A) is formulated with 10 mM sodium acetate, 9.0% (w/v) sucrose, 0.004% (w/v) polysorbate 20, pH 5.2, and is supplied in an identical vial configuration.
Sputum Purulence Colour Card Week 0	3.0 score on a scale Interval 2.0 to 4.0	3.0 score on a scale Interval 2.0 to 4.0
Sputum Purulence Colour Card Week 12	3.0 score on a scale Interval 2.0 to 4.0	3.0 score on a scale Interval 2.0 to 4.0
Sputum Purulence Colour Card Week 24	3.0 score on a scale Interval 2.0 to 4.0	3.0 score on a scale Interval 2.0 to 4.0
Sputum Purulence Colour Card Week 36	3.0 score on a scale Interval 2.0 to 4.0	3.0 score on a scale Interval 2.0 to 4.5
Sputum Purulence Colour Card Week 48	4.0 score on a scale Interval 2.0 to 6.0	4.0 score on a scale Interval 2.0 to 6.0

SECONDARY outcome

Timeframe: Week 0 and Week 48

Population: Modified ITT (available data)

To assess lung function. The participant will take a maximum inhalation, release maximum exhalation and then continue to exhale afterwards. They will then be treated with a bronchodilator. The spirometry test is then repeated to determine how much the bronchodilator medication helped with breathing. FEV1/FVC ratio will be calculated.

Outcome measures

Measure	Anti-ST2 n=8 Participants Anti-ST2 (MSTT1041A) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. MSTT1041A: MSTT1041A (RO7187807; formerly made by Amgen \[AMG\] and referred to as AMG 282) is a novel biopharmaceutical that blocks signaling of interleukin (IL)-33, an inflammatory cytokine of the IL-1 family and member of the newly discovered "alarmin" class of molecules. IL-33 is released from airway epithelial cells in response to allergens, irritants, and infection. IL-33 release can trigger acute exacerbations in both asthma and COPD. MSTT1041A has the ability to block inflammation,prevent exacerbations, and improve lung function and quality of life. Anti-ST2 is presented as sterile, clear, and colourless to slightly yellow liquid. Each sterile vial is filled with a 1 mL deliverable volume of 70 mg/mL. It is formulated with 15 mM sodium acetate, 9.0% (w/v) sucrose, 0.01% (w/v) polysorbate 20, pH 5.2.	Placebo n=5 Participants Placebo (no active component) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. Placebo: Placebo for Anti-ST2 (MSTT1041A) is formulated with 10 mM sodium acetate, 9.0% (w/v) sucrose, 0.004% (w/v) polysorbate 20, pH 5.2, and is supplied in an identical vial configuration.
Pre and Post Bronchodilator (BD) Spirometry - FEV1/FVC Ratio Pre BD FEV1/FVC ratio Week 0	49.0 Ratio Standard Deviation 14.1	46.6 Ratio Standard Deviation 18.6
Pre and Post Bronchodilator (BD) Spirometry - FEV1/FVC Ratio Pre BD FEV1/FVC ratio Week 48	51.0 Ratio Standard Deviation 15.5	40.2 Ratio Standard Deviation 9.6

SECONDARY outcome

Timeframe: Screening, Weeks 4, 12, 24, 36, 48

Population: Modified ITT (available data)

To assess lung function. FEV1 is the volume of air that can forcibly be blown out in first 1 second, after full inspiration. Post BD Forced Expiratory Volume in 1 Second (FEV1)

Outcome measures

Measure	Anti-ST2 n=42 Participants Anti-ST2 (MSTT1041A) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. MSTT1041A: MSTT1041A (RO7187807; formerly made by Amgen \[AMG\] and referred to as AMG 282) is a novel biopharmaceutical that blocks signaling of interleukin (IL)-33, an inflammatory cytokine of the IL-1 family and member of the newly discovered "alarmin" class of molecules. IL-33 is released from airway epithelial cells in response to allergens, irritants, and infection. IL-33 release can trigger acute exacerbations in both asthma and COPD. MSTT1041A has the ability to block inflammation,prevent exacerbations, and improve lung function and quality of life. Anti-ST2 is presented as sterile, clear, and colourless to slightly yellow liquid. Each sterile vial is filled with a 1 mL deliverable volume of 70 mg/mL. It is formulated with 15 mM sodium acetate, 9.0% (w/v) sucrose, 0.01% (w/v) polysorbate 20, pH 5.2.	Placebo n=39 Participants Placebo (no active component) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. Placebo: Placebo for Anti-ST2 (MSTT1041A) is formulated with 10 mM sodium acetate, 9.0% (w/v) sucrose, 0.004% (w/v) polysorbate 20, pH 5.2, and is supplied in an identical vial configuration.
Post BD Forced Expiratory Volume in 1 Second (FEV1) Week 0	1.21 Litres Standard Deviation 0.46	1.14 Litres Standard Deviation 0.48
Post BD Forced Expiratory Volume in 1 Second (FEV1) Week 4	1.21 Litres Standard Deviation 0.46	1.09 Litres Standard Deviation 0.46
Post BD Forced Expiratory Volume in 1 Second (FEV1) Week 12	1.22 Litres Standard Deviation 0.48	1.14 Litres Standard Deviation 0.52
Post BD Forced Expiratory Volume in 1 Second (FEV1) Week 24	1.17 Litres Standard Deviation 0.43	1.10 Litres Standard Deviation 0.50
Post BD Forced Expiratory Volume in 1 Second (FEV1) Week 36	1.23 Litres Standard Deviation 0.47	1.09 Litres Standard Deviation 0.52
Post BD Forced Expiratory Volume in 1 Second (FEV1) Week 48	1.30 Litres Standard Deviation 0.50	1.09 Litres Standard Deviation 0.57

SECONDARY outcome

Timeframe: Week 0 and week 48

Population: Modified ITT (available data)

To assess lung function, i.e. the functional residual capacity of the lungs. The participant sits inside an airtight box, inhales or exhales to a particular volume (usually FRC), and then a shutter drops across their breathing tube. The participant makes respiratory efforts against the closed shutter, causing their chest volume to expand and decompressing the air in their lungs. The increase in their chest volume slightly reduces the box volume (the non-person volume of the box) and thus slightly increases the pressure in the box. Total Lung Capacity and Residual Volume measured.

Outcome measures

Measure	Anti-ST2 n=19 Participants Anti-ST2 (MSTT1041A) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. MSTT1041A: MSTT1041A (RO7187807; formerly made by Amgen \[AMG\] and referred to as AMG 282) is a novel biopharmaceutical that blocks signaling of interleukin (IL)-33, an inflammatory cytokine of the IL-1 family and member of the newly discovered "alarmin" class of molecules. IL-33 is released from airway epithelial cells in response to allergens, irritants, and infection. IL-33 release can trigger acute exacerbations in both asthma and COPD. MSTT1041A has the ability to block inflammation,prevent exacerbations, and improve lung function and quality of life. Anti-ST2 is presented as sterile, clear, and colourless to slightly yellow liquid. Each sterile vial is filled with a 1 mL deliverable volume of 70 mg/mL. It is formulated with 15 mM sodium acetate, 9.0% (w/v) sucrose, 0.01% (w/v) polysorbate 20, pH 5.2.	Placebo n=16 Participants Placebo (no active component) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. Placebo: Placebo for Anti-ST2 (MSTT1041A) is formulated with 10 mM sodium acetate, 9.0% (w/v) sucrose, 0.004% (w/v) polysorbate 20, pH 5.2, and is supplied in an identical vial configuration.
Body Plethysmography ('Body Box') Total Lung Capacity and Residual Volume Total Lung Capacity Week 0	7.5 Litres Standard Deviation 1.6	7.5 Litres Standard Deviation 1.4
Body Plethysmography ('Body Box') Total Lung Capacity and Residual Volume Total Lung Capacity Week 48	7.6 Litres Standard Deviation 1.5	7.6 Litres Standard Deviation 1.5
Body Plethysmography ('Body Box') Total Lung Capacity and Residual Volume Residual Volume Week 0	4.5 Litres Standard Deviation 1.5	4.7 Litres Standard Deviation 1.5
Body Plethysmography ('Body Box') Total Lung Capacity and Residual Volume Residual Volume Week 48	4.8 Litres Standard Deviation 1.6	5.0 Litres Standard Deviation 1.4

SECONDARY outcome

Timeframe: Weeks 0, 4, 12, 24, 36, 48

Population: Modified ITT (available data)

To assess inflammation at exacerbation events. White blood cells, eosinophils and neutrophils will be measured.

Outcome measures

Measure	Anti-ST2 n=42 Participants Anti-ST2 (MSTT1041A) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. MSTT1041A: MSTT1041A (RO7187807; formerly made by Amgen \[AMG\] and referred to as AMG 282) is a novel biopharmaceutical that blocks signaling of interleukin (IL)-33, an inflammatory cytokine of the IL-1 family and member of the newly discovered "alarmin" class of molecules. IL-33 is released from airway epithelial cells in response to allergens, irritants, and infection. IL-33 release can trigger acute exacerbations in both asthma and COPD. MSTT1041A has the ability to block inflammation,prevent exacerbations, and improve lung function and quality of life. Anti-ST2 is presented as sterile, clear, and colourless to slightly yellow liquid. Each sterile vial is filled with a 1 mL deliverable volume of 70 mg/mL. It is formulated with 15 mM sodium acetate, 9.0% (w/v) sucrose, 0.01% (w/v) polysorbate 20, pH 5.2.	Placebo n=39 Participants Placebo (no active component) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. Placebo: Placebo for Anti-ST2 (MSTT1041A) is formulated with 10 mM sodium acetate, 9.0% (w/v) sucrose, 0.004% (w/v) polysorbate 20, pH 5.2, and is supplied in an identical vial configuration.
Blood Inflammatory Cell Differentials White Blood Cell Count Week 0	8.2 10^9 *cells* per litre Standard Error 0.045	8.0 10^9 *cells* per litre Standard Error 0.046
Blood Inflammatory Cell Differentials White Blood Cell Count Week 4	7.5 10^9 *cells* per litre Standard Error 0.035	7.5 10^9 *cells* per litre Standard Error 0.037
Blood Inflammatory Cell Differentials White Blood Cell Count Week 12	8.0 10^9 *cells* per litre Standard Error 0.043	7.7 10^9 *cells* per litre Standard Error 0.047
Blood Inflammatory Cell Differentials White Blood Cell Count Week 24	7.8 10^9 *cells* per litre Standard Error 0.047	7.6 10^9 *cells* per litre Standard Error 0.050
Blood Inflammatory Cell Differentials White Blood Cell Count Week 36	8.0 10^9 *cells* per litre Standard Error 0.046	7.3 10^9 *cells* per litre Standard Error 0.048
Blood Inflammatory Cell Differentials White Blood Cell Count Week 48	7.5 10^9 *cells* per litre Standard Error 0.058	8.0 10^9 *cells* per litre Standard Error 0.065
Blood Inflammatory Cell Differentials Eosinophil Count Week 0	0.21 10^9 *cells* per litre Standard Error 0.107	0.20 10^9 *cells* per litre Standard Error 0.111
Blood Inflammatory Cell Differentials Eosinophil Count Week 4	0.15 10^9 *cells* per litre Standard Error 0.105	0.22 10^9 *cells* per litre Standard Error 0.111
Blood Inflammatory Cell Differentials Eosinophil Count Week 12	0.13 10^9 *cells* per litre Standard Error 0.105	0.20 10^9 *cells* per litre Standard Error 0.116
Blood Inflammatory Cell Differentials Eosinophil Count week 24	0.12 10^9 *cells* per litre Standard Error 0.096	0.21 10^9 *cells* per litre Standard Error 0.099
Blood Inflammatory Cell Differentials Eosinophil Count Week 36	0.11 10^9 *cells* per litre Standard Error 0.106	0.20 10^9 *cells* per litre Standard Error 0.111
Blood Inflammatory Cell Differentials Eosinophil Count week 48	0.10 10^9 *cells* per litre Standard Error 0.143	0.17 10^9 *cells* per litre Standard Error 0.160
Blood Inflammatory Cell Differentials Neutrophil Count Week 0	5.6 10^9 *cells* per litre Standard Error 0.062	5.1 10^9 *cells* per litre Standard Error 0.064
Blood Inflammatory Cell Differentials Neutrophil Count Week 4	4.9 10^9 *cells* per litre Standard Error 0.046	4.9 10^9 *cells* per litre Standard Error 0.049
Blood Inflammatory Cell Differentials Neutrophil Count Week 12	5.4 10^9 *cells* per litre Standard Error 0.053	5.2 10^9 *cells* per litre Standard Error 0.059
Blood Inflammatory Cell Differentials Neutrophil Count Week 24	5.4 10^9 *cells* per litre Standard Error 0.059	5.0 10^9 *cells* per litre Standard Error 0.061
Blood Inflammatory Cell Differentials Neutrophil Count Week 36	5.6 10^9 *cells* per litre Standard Error 0.056	4.9 10^9 *cells* per litre Standard Error 0.059
Blood Inflammatory Cell Differentials Neutrophil Count Week 48	5.3 10^9 *cells* per litre Standard Error 0.079	5.5 10^9 *cells* per litre Standard Error 0.089

SECONDARY outcome

Timeframe: Weeks 0, 4, 12, 24, 36, 48

Population: Modified ITT (available data)

To assess inflammation at exacerbation events. Eosinophils cells will be measured.

Outcome measures

Measure	Anti-ST2 n=31 Participants Anti-ST2 (MSTT1041A) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. MSTT1041A: MSTT1041A (RO7187807; formerly made by Amgen \[AMG\] and referred to as AMG 282) is a novel biopharmaceutical that blocks signaling of interleukin (IL)-33, an inflammatory cytokine of the IL-1 family and member of the newly discovered "alarmin" class of molecules. IL-33 is released from airway epithelial cells in response to allergens, irritants, and infection. IL-33 release can trigger acute exacerbations in both asthma and COPD. MSTT1041A has the ability to block inflammation,prevent exacerbations, and improve lung function and quality of life. Anti-ST2 is presented as sterile, clear, and colourless to slightly yellow liquid. Each sterile vial is filled with a 1 mL deliverable volume of 70 mg/mL. It is formulated with 15 mM sodium acetate, 9.0% (w/v) sucrose, 0.01% (w/v) polysorbate 20, pH 5.2.	Placebo n=34 Participants Placebo (no active component) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. Placebo: Placebo for Anti-ST2 (MSTT1041A) is formulated with 10 mM sodium acetate, 9.0% (w/v) sucrose, 0.004% (w/v) polysorbate 20, pH 5.2, and is supplied in an identical vial configuration.
Sputum Inflammatory Cell Differentials: Eosinophils Eosinophil count (%) Week 0	1.42 Percentage of Eosinophils in sputum Standard Error 0.254	1.63 Percentage of Eosinophils in sputum Standard Error 0.242
Sputum Inflammatory Cell Differentials: Eosinophils Eosinophil count (%) Week 4	0.43 Percentage of Eosinophils in sputum Standard Error 0.188	1.69 Percentage of Eosinophils in sputum Standard Error 0.185
Sputum Inflammatory Cell Differentials: Eosinophils Eosinophil count (%) Week 12	0.41 Percentage of Eosinophils in sputum Standard Error 0.168	1.67 Percentage of Eosinophils in sputum Standard Error 0.190
Sputum Inflammatory Cell Differentials: Eosinophils Eosinophil count (%) Week 24	0.44 Percentage of Eosinophils in sputum Standard Error 0.191	1.69 Percentage of Eosinophils in sputum Standard Error 0.209
Sputum Inflammatory Cell Differentials: Eosinophils Eosinophil count (%) Week 36	0.47 Percentage of Eosinophils in sputum Standard Error 0.212	1.94 Percentage of Eosinophils in sputum Standard Error 0.236
Sputum Inflammatory Cell Differentials: Eosinophils Eosinophil count (%) Week 48	0.33 Percentage of Eosinophils in sputum Standard Error 0.232	1.24 Percentage of Eosinophils in sputum Standard Error 0.243

SECONDARY outcome

Timeframe: Week 0 and Week 48

Population: Modified ITT (available data)

To assess lung function. The participant will take a maximum inhalation, release maximum exhalation and then continue to exhale afterwards. They will then be treated with a bronchodilator. The spirometry test is then repeated to determine how much the bronchodilator medication helped with breathing. FEV1 and FVC will be measured.

Outcome measures

Measure	Anti-ST2 n=8 Participants Anti-ST2 (MSTT1041A) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. MSTT1041A: MSTT1041A (RO7187807; formerly made by Amgen \[AMG\] and referred to as AMG 282) is a novel biopharmaceutical that blocks signaling of interleukin (IL)-33, an inflammatory cytokine of the IL-1 family and member of the newly discovered "alarmin" class of molecules. IL-33 is released from airway epithelial cells in response to allergens, irritants, and infection. IL-33 release can trigger acute exacerbations in both asthma and COPD. MSTT1041A has the ability to block inflammation,prevent exacerbations, and improve lung function and quality of life. Anti-ST2 is presented as sterile, clear, and colourless to slightly yellow liquid. Each sterile vial is filled with a 1 mL deliverable volume of 70 mg/mL. It is formulated with 15 mM sodium acetate, 9.0% (w/v) sucrose, 0.01% (w/v) polysorbate 20, pH 5.2.	Placebo n=5 Participants Placebo (no active component) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. Placebo: Placebo for Anti-ST2 (MSTT1041A) is formulated with 10 mM sodium acetate, 9.0% (w/v) sucrose, 0.004% (w/v) polysorbate 20, pH 5.2, and is supplied in an identical vial configuration.
Pre and Post Bronchodilator (BD) Spirometry- FEV1 and FVC Pre BD FEV1 Week 0	1.43 Litres Standard Deviation 0.43	0.94 Litres Standard Deviation 0.33
Pre and Post Bronchodilator (BD) Spirometry- FEV1 and FVC Pre BD FEV1 Week 48	1.43 Litres Standard Deviation 0.49	0.86 Litres Standard Deviation 0.15
Pre and Post Bronchodilator (BD) Spirometry- FEV1 and FVC Pre BD FVC Week 0	2.97 Litres Standard Deviation 0.89	2.17 Litres Standard Deviation 0.34
Pre and Post Bronchodilator (BD) Spirometry- FEV1 and FVC Pre BD FVC Week 48	2.88 Litres Standard Deviation 0.94	2.20 Litres Standard Deviation 0.36

SECONDARY outcome

Timeframe: Week 0 and Week 48

Population: Modified ITT (available data)

To assess lung function. The participant will take a maximum inhalation, release maximum exhalation and then continue to exhale afterwards. They will then be treated with a bronchodilator. The spirometry test is then repeated to determine how much the bronchodilator medication helped with breathing. FEV1 % predicted and FVC % predicted will be measured.

Outcome measures

Measure	Anti-ST2 n=8 Participants Anti-ST2 (MSTT1041A) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. MSTT1041A: MSTT1041A (RO7187807; formerly made by Amgen \[AMG\] and referred to as AMG 282) is a novel biopharmaceutical that blocks signaling of interleukin (IL)-33, an inflammatory cytokine of the IL-1 family and member of the newly discovered "alarmin" class of molecules. IL-33 is released from airway epithelial cells in response to allergens, irritants, and infection. IL-33 release can trigger acute exacerbations in both asthma and COPD. MSTT1041A has the ability to block inflammation,prevent exacerbations, and improve lung function and quality of life. Anti-ST2 is presented as sterile, clear, and colourless to slightly yellow liquid. Each sterile vial is filled with a 1 mL deliverable volume of 70 mg/mL. It is formulated with 15 mM sodium acetate, 9.0% (w/v) sucrose, 0.01% (w/v) polysorbate 20, pH 5.2.	Placebo n=5 Participants Placebo (no active component) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. Placebo: Placebo for Anti-ST2 (MSTT1041A) is formulated with 10 mM sodium acetate, 9.0% (w/v) sucrose, 0.004% (w/v) polysorbate 20, pH 5.2, and is supplied in an identical vial configuration.
Pre and Post Bronchodilator (BD) Spirometry- FEV1 Predicted and FVC Predicted Pre BD FEV1 predicted (%) Week 0	55.9 Percent predicted Standard Deviation 17.1	39.6 Percent predicted Standard Deviation 10.4
Pre and Post Bronchodilator (BD) Spirometry- FEV1 Predicted and FVC Predicted Pre BD FEV1 predicted (%) Week 48	56.5 Percent predicted Standard Deviation 19.9	38.2 Percent predicted Standard Deviation 8.3
Pre and Post Bronchodilator (BD) Spirometry- FEV1 Predicted and FVC Predicted Pre BD predicted FVC (%) Week 0	88.5 Percent predicted Standard Deviation 16.6	75.6 Percent predicted Standard Deviation 16.7
Pre and Post Bronchodilator (BD) Spirometry- FEV1 Predicted and FVC Predicted Pre BD predicted FVC (%) Week 48	85.8 Percent predicted Standard Deviation 22.8	79.2 Percent predicted Standard Deviation 28.5

SECONDARY outcome

Timeframe: Week 0 and week 48

Population: Modified ITT (available data)

To assess lung function, i.e. the functional residual capacity of the lungs. The participant sits inside an airtight box, inhales or exhales to a particular volume (usually FRC), and then a shutter drops across their breathing tube. The participant makes respiratory efforts against the closed shutter, causing their chest volume to expand and decompressing the air in their lungs. The increase in their chest volume slightly reduces the box volume (the non-person volume of the box) and thus slightly increases the pressure in the box. Residual Volume/Total Lung Capacity ratio will be calculated. RV/TLC ratio: this is the residual volume (RV) to total lung capacity (TLC). It is calculated as a percentage as follows: RV/TLC ×100.

Outcome measures

Measure	Anti-ST2 n=19 Participants Anti-ST2 (MSTT1041A) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. MSTT1041A: MSTT1041A (RO7187807; formerly made by Amgen \[AMG\] and referred to as AMG 282) is a novel biopharmaceutical that blocks signaling of interleukin (IL)-33, an inflammatory cytokine of the IL-1 family and member of the newly discovered "alarmin" class of molecules. IL-33 is released from airway epithelial cells in response to allergens, irritants, and infection. IL-33 release can trigger acute exacerbations in both asthma and COPD. MSTT1041A has the ability to block inflammation,prevent exacerbations, and improve lung function and quality of life. Anti-ST2 is presented as sterile, clear, and colourless to slightly yellow liquid. Each sterile vial is filled with a 1 mL deliverable volume of 70 mg/mL. It is formulated with 15 mM sodium acetate, 9.0% (w/v) sucrose, 0.01% (w/v) polysorbate 20, pH 5.2.	Placebo n=16 Participants Placebo (no active component) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. Placebo: Placebo for Anti-ST2 (MSTT1041A) is formulated with 10 mM sodium acetate, 9.0% (w/v) sucrose, 0.004% (w/v) polysorbate 20, pH 5.2, and is supplied in an identical vial configuration.
Body Plethysmography ('Body Box') - Residual Volume/Total Lung Capacity Ratio Residual Volume/Total Lung Capacity ratio (%) Week 0	59.8 percentage (RV of TLC) Standard Deviation 9.5	61.3 percentage (RV of TLC) Standard Deviation 11.5
Body Plethysmography ('Body Box') - Residual Volume/Total Lung Capacity Ratio Residual Volume/Total Lung Capacity ratio (%) Week 48	61.1 percentage (RV of TLC) Standard Deviation 11.2	65.2 percentage (RV of TLC) Standard Deviation 9.7

SECONDARY outcome

Timeframe: Weeks 0, 4, 12, 24, 36, 48

Population: Modified ITT (available data)

To assess inflammation at exacerbation events. Sputum inflammatory cell differentials: Macrophages

Outcome measures

Measure	Anti-ST2 n=31 Participants Anti-ST2 (MSTT1041A) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. MSTT1041A: MSTT1041A (RO7187807; formerly made by Amgen \[AMG\] and referred to as AMG 282) is a novel biopharmaceutical that blocks signaling of interleukin (IL)-33, an inflammatory cytokine of the IL-1 family and member of the newly discovered "alarmin" class of molecules. IL-33 is released from airway epithelial cells in response to allergens, irritants, and infection. IL-33 release can trigger acute exacerbations in both asthma and COPD. MSTT1041A has the ability to block inflammation,prevent exacerbations, and improve lung function and quality of life. Anti-ST2 is presented as sterile, clear, and colourless to slightly yellow liquid. Each sterile vial is filled with a 1 mL deliverable volume of 70 mg/mL. It is formulated with 15 mM sodium acetate, 9.0% (w/v) sucrose, 0.01% (w/v) polysorbate 20, pH 5.2.	Placebo n=34 Participants Placebo (no active component) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. Placebo: Placebo for Anti-ST2 (MSTT1041A) is formulated with 10 mM sodium acetate, 9.0% (w/v) sucrose, 0.004% (w/v) polysorbate 20, pH 5.2, and is supplied in an identical vial configuration.
Sputum Inflammatory Cell Differentials: Macrophages Macrophage count in sputum (%) Week 0	8.9 Percentage of Macrophage in sputum Standard Error 0.205	9.6 Percentage of Macrophage in sputum Standard Error 0.196
Sputum Inflammatory Cell Differentials: Macrophages Macrophage count in sputum (%) Week 4	8.6 Percentage of Macrophage in sputum Standard Error 0.211	11.0 Percentage of Macrophage in sputum Standard Error 0.208
Sputum Inflammatory Cell Differentials: Macrophages Macrophage count in sputum (%) Week 12	9.0 Percentage of Macrophage in sputum Standard Error 0.190	9.8 Percentage of Macrophage in sputum Standard Error 0.216
Sputum Inflammatory Cell Differentials: Macrophages Macrophage count in sputum (%) Week 24	9.2 Percentage of Macrophage in sputum Standard Error 0.222	12.3 Percentage of Macrophage in sputum Standard Error 0.244
Sputum Inflammatory Cell Differentials: Macrophages Macrophage count in sputum (%) Week 36	8.1 Percentage of Macrophage in sputum Standard Error 0.213	9.7 Percentage of Macrophage in sputum Standard Error 0.237
Sputum Inflammatory Cell Differentials: Macrophages Macrophage count in sputum (%) Week 48	6.9 Percentage of Macrophage in sputum Standard Error 0.286	11.4 Percentage of Macrophage in sputum Standard Error 0.300

SECONDARY outcome

Timeframe: Weeks 0, 4, 12, 24, 36, 48

Population: Modified ITT (available data)

To assess inflammation at exacerbation events. Epithelium cells will be measured.

Outcome measures

Measure	Anti-ST2 n=31 Participants Anti-ST2 (MSTT1041A) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. MSTT1041A: MSTT1041A (RO7187807; formerly made by Amgen \[AMG\] and referred to as AMG 282) is a novel biopharmaceutical that blocks signaling of interleukin (IL)-33, an inflammatory cytokine of the IL-1 family and member of the newly discovered "alarmin" class of molecules. IL-33 is released from airway epithelial cells in response to allergens, irritants, and infection. IL-33 release can trigger acute exacerbations in both asthma and COPD. MSTT1041A has the ability to block inflammation,prevent exacerbations, and improve lung function and quality of life. Anti-ST2 is presented as sterile, clear, and colourless to slightly yellow liquid. Each sterile vial is filled with a 1 mL deliverable volume of 70 mg/mL. It is formulated with 15 mM sodium acetate, 9.0% (w/v) sucrose, 0.01% (w/v) polysorbate 20, pH 5.2.	Placebo n=34 Participants Placebo (no active component) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. Placebo: Placebo for Anti-ST2 (MSTT1041A) is formulated with 10 mM sodium acetate, 9.0% (w/v) sucrose, 0.004% (w/v) polysorbate 20, pH 5.2, and is supplied in an identical vial configuration.
Sputum Inflammatory Cell Differentials: Epithelium Epithelium count (%) Week 0	1.51 Percentage of Epithelium in sputum Standard Error 0.255	1.59 Percentage of Epithelium in sputum Standard Error 0.243
Sputum Inflammatory Cell Differentials: Epithelium Epithelium count (%) Week 4	1.34 Percentage of Epithelium in sputum Standard Error 0.257	2.06 Percentage of Epithelium in sputum Standard Error 0.253
Sputum Inflammatory Cell Differentials: Epithelium Epithelium count (%) Week 12	1.14 Percentage of Epithelium in sputum Standard Error 0.243	1.91 Percentage of Epithelium in sputum Standard Error 0.276
Sputum Inflammatory Cell Differentials: Epithelium Epithelium count (%) Week 24	1.56 Percentage of Epithelium in sputum Standard Error 0.284	1.44 Percentage of Epithelium in sputum Standard Error 0.311
Sputum Inflammatory Cell Differentials: Epithelium Epithelium count (%) Week 36	1.03 Percentage of Epithelium in sputum Standard Error 0.266	1.26 Percentage of Epithelium in sputum Standard Error 0.296
Sputum Inflammatory Cell Differentials: Epithelium Epithelium count (%) Week 48	1.56 Percentage of Epithelium in sputum Standard Error 0.435	1.21 Percentage of Epithelium in sputum Standard Error 0.456

OTHER_PRE_SPECIFIED outcome

Timeframe: Screening and week 48

Quantitative measures of airway geometry and densitometry. Mean lung density expiratory/inspiratory [MLD E/I] (small airway), % wall area [WA] and LA (larger airways) will be measured.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 0, 4, 12, 24, 36, 48

Various biomarkers of inflammation will be measured in sputum.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Screening, weeks 4, 12, 24, 36, 48

Various biomarkers of inflammation will be measured in blood.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Screening, weeks 4, 12, 24, 36, 48

ILC2 cells will be analysed using plasma for biomarkers.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Screening, weeks 0, 4, 12, 24, 36, 48

Various biomarkers of inflammation will be measured in urine.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 0, 4, 12, 24, 36, 48

Mediators of inflammation in blood, sputum and urine will be assessed.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Screening, Weeks 12, 24, 36, 48

To assess upper airway inflammation. This is a non-invasive method to sample nasal mucosal lining fluid using a synthetic absorptive matrix (SAM) of low protein binding. The SAM is advanced up the lumen of the nasal cavity, and then the outside of the nose is gently pressed to oppose the SAM against the nasal mucosa for 30 seconds.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Screening, weeks 12, 24, 36, 48

To assess airway upper inflammation. Nasal epithelial cells will be sampled from the anterior nares using either a polyester swab or a cytology brush with the standard collection method - cytology brush sampling from beneath the inferior turbinate. This test is optional for participants.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Screening, Weeks 12, 24, 36, 48

To assess inflammation. PTR-MS, ADVION and ReCIVA will be used to measure gaseous molecules found in the breath that are from inside and outside the lungs. We aim to collect these molecule and analyse them to see if there are any changes in a persons breath that could be linked to the metabolic health, before, during and after taking the drug or placebo.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 0, 4, 12, 24, 36, 48

To assess airway infection and ecology. We will analyse the microbes in patients' lungs using their sputum samples and profile the effect of treatment on these microbes.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 0, 4, 12, 24, 36, 48

To assess airway infection and ecology. We will analyse the microbes in patients' lungs and profile the effect of treatment on these microbes.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and week 48

To evaluate the rate of protocol-defined COPD exacerbations through 48 weeks treatment period, patient reported outcomes (PROs), and lung functions, by subgroup outcomes.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Screening, weeks 4, 12, 24, 36, 48

To evaluate the efficacy of anti-ST2 versus placebo on the outcome rate of protocol-defined COPD exacerbations through 48 weeks treatment period, patient reported outcomes (PROs) and lung function in subgroups defined by baseline blood eosinophil count.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 0, 4, 12, 24, 36, 48

To evaluate the efficacy of anti-ST2 versus placebo on the outcome rate of protocol-defined COPD exacerbations through 48 weeks treatment period, patient reported outcomes (PROs) and lung function in subgroups defined by baseline blood eosinophil count.

Outcome measures

Outcome data not reported

OTHER_PRE_SPECIFIED outcome

Timeframe: Weeks 0 and 48

To evaluate the efficacy of anti-ST2 versus placebo on the outcome rate of protocol-defined COPD exacerbations through 48 weeks treatment period, patient reported outcomes (PROs) and lung function in subgroups defined by baseline blood eosinophil count.

Outcome measures

Outcome data not reported

Adverse Events

Anti-ST2

Serious events: 12 serious events

Other events: 34 other events

Deaths: 0 deaths

Placebo

Serious events: 16 serious events

Other events: 28 other events

Deaths: 2 deaths

Serious adverse events

Measure	Anti-ST2 n=42 participants at risk Anti-ST2 (MSTT1041A\*) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. Anti-ST2 was presented as sterile, clear, and colourless to slightly yellow liquid. Each sterile vial is filled with a 1 mL deliverable volume of 70 mg/mL. It was formulated with 15 mM sodium acetate, 9.0% (w/v) sucrose, 0.01% (w/v) polysorbate 20, pH 5.2. \*Official USAN name for MSTT1041A is now astegolimab	Placebo n=39 participants at risk Placebo (no active component) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. Placebo for Anti-ST2 (MSTT1041A) was formulated with 10 mM sodium acetate, 9.0% (w/v) sucrose, 0.004% (w/v) polysorbate 20, pH 5.2, and was supplied in an identical vial configuration.
Gastrointestinal disorders Abdominal pain	2.4% 1/42 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	2.6% 1/39 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Gastrointestinal disorders Adenoma of the bowel	0.00% 0/42 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	2.6% 1/39 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Blood and lymphatic system disorders Blood transfusion (anaemia)	2.4% 1/42 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	0.00% 0/39 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Respiratory, thoracic and mediastinal disorders Chest infection/infective exacerbation of bronchiectasis	0.00% 0/42 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	2.6% 1/39 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Respiratory, thoracic and mediastinal disorders Clinical diagnosis of lung cancer	2.4% 1/42 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	0.00% 0/39 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Respiratory, thoracic and mediastinal disorders Community acquired pneumonia	7.1% 3/42 • Number of events 3 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	2.6% 1/39 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Cardiac disorders Descending aorta thrombosis	0.00% 0/42 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	2.6% 1/39 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Renal and urinary disorders Elective surgery (transurethral resection of the prostate)	2.4% 1/42 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	0.00% 0/39 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Reproductive system and breast disorders Epididymo-orchitis	0.00% 0/42 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	2.6% 1/39 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Respiratory, thoracic and mediastinal disorders Flu-like illness (viral infection)	2.4% 1/42 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	0.00% 0/39 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Musculoskeletal and connective tissue disorders Fractured neck of femur	0.00% 0/42 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	2.6% 1/39 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Gastrointestinal disorders Gastrointestinal symptoms	2.4% 1/42 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	0.00% 0/39 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Musculoskeletal and connective tissue disorders Gout	2.4% 1/42 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	0.00% 0/39 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Cardiac disorders Heart failure	0.00% 0/42 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	2.6% 1/39 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Respiratory, thoracic and mediastinal disorders Hospital acquired pneumonia	0.00% 0/42 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	5.1% 2/39 • Number of events 2 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Respiratory, thoracic and mediastinal disorders Infective exacerbation of bronchiectasis	0.00% 0/42 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	2.6% 1/39 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Musculoskeletal and connective tissue disorders Left scaphoid fracture	0.00% 0/42 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	2.6% 1/39 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Gastrointestinal disorders Oesophageal cancer	2.4% 1/42 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	0.00% 0/39 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Respiratory, thoracic and mediastinal disorders Pneumonia	0.00% 0/42 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	10.3% 4/39 • Number of events 4 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Reproductive system and breast disorders Pneumonia and type 2 respiratory failure	0.00% 0/42 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	2.6% 1/39 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Renal and urinary disorders Prostatitis	0.00% 0/42 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	2.6% 1/39 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Renal and urinary disorders Resection of prostate	2.4% 1/42 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	0.00% 0/39 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Respiratory, thoracic and mediastinal disorders Right pneumothorax	0.00% 0/42 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	2.6% 1/39 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Cardiac disorders Right thrombosed popliteal aneurysm	0.00% 0/42 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	2.6% 1/39 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Respiratory, thoracic and mediastinal disorders Shortness of breath	0.00% 0/42 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	2.6% 1/39 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Gastrointestinal disorders Small bowel obstruction	2.4% 1/42 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	0.00% 0/39 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Renal and urinary disorders Suspected UTI	0.00% 0/42 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	2.6% 1/39 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Cardiac disorders Syncopal episode	0.00% 0/42 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	2.6% 1/39 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Respiratory, thoracic and mediastinal disorders Type 2 respiratory failure	2.4% 1/42 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	0.00% 0/39 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Renal and urinary disorders Urosepsis	0.00% 0/42 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	2.6% 1/39 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Cardiac disorders Ventricular tachycardia	0.00% 0/42 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	2.6% 1/39 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.

Other adverse events

Measure	Anti-ST2 n=42 participants at risk Anti-ST2 (MSTT1041A\*) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. Anti-ST2 was presented as sterile, clear, and colourless to slightly yellow liquid. Each sterile vial is filled with a 1 mL deliverable volume of 70 mg/mL. It was formulated with 15 mM sodium acetate, 9.0% (w/v) sucrose, 0.01% (w/v) polysorbate 20, pH 5.2. \*Official USAN name for MSTT1041A is now astegolimab	Placebo n=39 participants at risk Placebo (no active component) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. Placebo for Anti-ST2 (MSTT1041A) was formulated with 10 mM sodium acetate, 9.0% (w/v) sucrose, 0.004% (w/v) polysorbate 20, pH 5.2, and was supplied in an identical vial configuration.
Musculoskeletal and connective tissue disorders Arthralgia	4.8% 2/42 • Number of events 3 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	2.6% 1/39 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Musculoskeletal and connective tissue disorders Back pain	9.5% 4/42 • Number of events 5 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	7.7% 3/39 • Number of events 4 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Infections and infestations Cellulitis	0.00% 0/42 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	5.1% 2/39 • Number of events 2 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
General disorders Chest pain	11.9% 5/42 • Number of events 5 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	10.3% 4/39 • Number of events 4 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Gastrointestinal disorders Diarrhoea	11.9% 5/42 • Number of events 7 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	2.6% 1/39 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Gastrointestinal disorders Dyspepsia	2.4% 1/42 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	5.1% 2/39 • Number of events 2 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Injury, poisoning and procedural complications Fall	0.00% 0/42 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	5.1% 2/39 • Number of events 3 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
General disorders Fatigue	0.00% 0/42 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	5.1% 2/39 • Number of events 2 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Respiratory, thoracic and mediastinal disorders Haemoptysis	0.00% 0/42 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	5.1% 2/39 • Number of events 2 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Nervous system disorders Headache	23.8% 10/42 • Number of events 20 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	12.8% 5/39 • Number of events 9 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Vascular disorders Hypertension	7.1% 3/42 • Number of events 3 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	2.6% 1/39 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
General disorders Lethargy	4.8% 2/42 • Number of events 2 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	5.1% 2/39 • Number of events 2 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
General disorders Malaise	4.8% 2/42 • Number of events 2 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	2.6% 1/39 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Gastrointestinal disorders Nausea	4.8% 2/42 • Number of events 2 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	2.6% 1/39 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Musculoskeletal and connective tissue disorders Neck pain	9.5% 4/42 • Number of events 5 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	0.00% 0/39 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
General disorders Oedema peripheral	2.4% 1/42 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	5.1% 2/39 • Number of events 2 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Gastrointestinal disorders Oral pain	2.4% 1/42 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	5.1% 2/39 • Number of events 2 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	4.8% 2/42 • Number of events 2 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	2.6% 1/39 • Number of events 2 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Musculoskeletal and connective tissue disorders Pain in extremity	2.4% 1/42 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	5.1% 2/39 • Number of events 2 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Respiratory, thoracic and mediastinal disorders Pulmonary mass	7.1% 3/42 • Number of events 3 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	5.1% 2/39 • Number of events 2 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Infections and infestations Skin infection	0.00% 0/42 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	5.1% 2/39 • Number of events 2 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Gastrointestinal disorders Toothache	9.5% 4/42 • Number of events 4 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	2.6% 1/39 • Number of events 1 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Infections and infestations Urinary tract infection	14.3% 6/42 • Number of events 11 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	2.6% 1/39 • Number of events 2 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Infections and infestations Viral upper respiratory tract infection	7.1% 3/42 • Number of events 5 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	10.3% 4/39 • Number of events 6 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.
Gastrointestinal disorders Vomiting	11.9% 5/42 • Number of events 5 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.	2.6% 1/39 • Number of events 2 • Adverse event data occurring from the point of randomisation until the final trial visit following follow-up (or 100 days post cessation of trial treatment (if discontinued early), were recorded throughout the 48 week treatment period and 12 week post-trial follow-up.

Additional Information

Professor Chris Brightling

University of Leicester

Phone: +44 116 250 2704

Email: ceb17@le.ac.uk

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place