COPD Exacerbation
Conditions
Keywords
COPD, Exacerbations, ST2 MAb, RG6149, MSTT1041A, Anti-ST2, Phase IIa, Placebo controlled
Brief summary
Chronic obstructive pulmonary disease (COPD) is a significant cause of morbidity and mortality worldwide. In contrast to other chronic diseases, COPD is increasing in prevalence and is projected to be the third-leading cause of death and disability worldwide by 2030. The costs to society for treating COPD are high, accounting for approximately 3.4% of the total health care budget of the European Union. Acute exacerbations of COPD (AECOPD) are responsible for a large portion of the economic burden of COPD. More than 500,000 hospitalisations and 100,000 deaths are attributed to AECOPD in the US each year. In addition to a substantial economic burden, AECOPD is also responsible for much of the morbidity and mortality from COPD. Interleukin-33 (IL-33) is an alarmin released from the epithelium following damage. IL-33 is an IL-1 family alarmin cytokine constitutively expressed at epithelial barrier surfaces where it is rapidly released from cells during tissue injury. IL-33 signals through a receptor complex of IL-1 receptor-like 1 (IL1RL1) (known as ST2) and IL-1 receptor accessory protein (IL1RAcP) to initiate MyD88-dependent inflammatory pathways. The role of the IL33/ST2 axis in COPD is uncertain. IL33 has been implicated in eosinophil recruitment to the airway and maturation in the bone marrow largely via its effects upon innate lymphoid cells. IL33 increased following experimental cold in asthma and thus might play a role in the consequent inflammatory response and possible susceptibility to secondary bacterial infection in obstructive lung disease. Both eosinophilic inflammation and viral infection drive COPD exacerbations and therefore targeting the IL33/ST2 axis might reduce COPD exacerbations. The main aim of this trial is to evaluate whether anti-ST2 will impact on airway inflammation in COPD and therefore reduce the frequency of exacerbations. For the purposes of this trial, exacerbations are defined as flare-ups of symptoms involving the use of healthcare resulting in treatment with steroids and/or antibiotics and/or hospitalisation or death due to COPD.
Detailed description
This is a single-centre, double-blind, placebo- controlled, parallel group, randomised controlled trial to assess the efficacy and safety of anti-ST2 compared to placebo, in patients with moderate to very severe COPD (GOLD II-IV). Anti-ST2 will be administered via subcutaneous injection once every 4 weeks (Week 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, and 44) during the 48-week treatment period. Participants will be followed up for 60 weeks (i.e. 48 week treatment period and 12 week follow-up), with secondary outcome measures at baseline, 4, 12, 24, 36, 48 and 60 weeks and at exacerbation events presenting prior to treatment initiation. After signing the informed consent at the initial visit, patients will enter a screening period which should last for up to 2 weeks unless extension of the screening period is necessary under certain circumstances. Patients who qualify to participate in the study will be randomised into a 48-week treatment period in which they will receive either 490 mg anti-ST2 or a matching placebo. Patients will be evaluated for an additional 12 weeks following completion of the randomised treatment period. Treatment groups will remain blinded until the 60-week follow-up period is completed, and trial database is locked. This trial is sponsored by the University of Leicester, coordinated by the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) - Respiratory and Leicester Clinical Trials Unit (LCTU) and funded by Genentech, Inc. The primary objective of the study is to evaluate the efficacy of anti-ST2 versus placebo on frequency of moderate-to-severe exacerbations (health care utilisation resulting in treatment with systemic corticosteroids and/or antibiotics or hospitalisation, respectively) as add-on to standard of care. Secondary objectives: another key objective is to assess the safety and tolerability of subcutaneous (SC) doses of anti-ST2 compared to placebo in adult patients with moderate to very severe COPD. Additionally, to assess the effects of anti-ST2 versus placebo both during stable visits and at the exacerbation events on the following: 1. Symptoms 2. Health status 3. Lung function 4. Inflammatory cell differentials i. Sputum cell count ii. Blood cell count 5. Airway morphometry 6. Pharmacogenomics Exploratory objectives include: 1. Systemic inflammation 2. Upper airway inflammation 3. Airway infection and ecology 4. Breath volatile organic compound profiling 5. Quantitative airway geometry and densitometry 6. Pharmacogenomics 7. Pharmacokinetics and ADA level 8. Pharmacogenomics response analysis in subgroups determined by SNPs for alleles associated with the IL33/ST2 axis. Subgroup objectives: 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) \[SGRQ-c\], and lung function \[FEV1\] in subgroups defined by baseline blood eosinophil count.
Interventions
DRUGMSTT1041A
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.
DRUGPlacebo
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.
Sponsors
Glenfield Hospital, Leicester
Genentech, Inc.
University of Leicester
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
A or B
Intervention model description
Single-centre, double-blinded, placebo-controlled, parallel group, randomised controlled trial
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Symptoms typical of COPD when stable (baseline mMRC dyspnoea score ≥ 2) 2. GOLD COPD stage 2-4 3. Smoking pack years ≥ 10 years 4. Age \> 40 years 5. Receiving standard-of-care drug therapy as per British Thoracic Society (BTS) guidance for COPD 6. A history of ≥ 2 moderate-to-severe exacerbations in the last 12 months. 7. Be able to give valid written consent; compliant with study procedures and study visits. 8. Able to understand written and spoken English
Exclusion criteria
1. Significant known respiratory disorders other than COPD that in the view of the investigator will affect the study 2. Patients whose treatment is considered palliative (life expectancy \<12 months) 3. Known hypersensitivity to the active substance of the investigational product (IP) or any of the excipients 4. Known history of anaphylaxis 5. Patients with a COPD exacerbation and/or pneumonia within the 4 weeks prior to visit 1 6. Have, in the opinion of investigator, uncontrolled co-morbid conditions, such as diabetes mellitus, hypertension and heart failure \[e.g. New York Heart Association (NYHA) class III (e.g. less than ordinary activity causes fatigue, palpitation, or dyspnoea), and class IV (e.g. Symptoms of heart failure at rest)\] that will affect the study. 7. Myocardial infarction, unstable angina or stroke within 12 month prior to screening 8. Diagnosis of malignancy within 5 years of visit 1 (except for excised localised carcinoma of skin not including malignant melanoma) 9. Clinically significant ECG changes, which in the opinion of investigator warrants further investigations 10. Laboratory abnormalities, which in the opinion of investigator warrants further investigations 11. Have, in the opinion of the investigator, evidence of alcohol, drug or solvent abuse. 12. Pregnant, breastfeeding, or lactating women. Women of child-bearing potential (i.e. not surgically sterilised or post- menopausal) must have a negative blood serum pregnancy test performed at the screening visit and must agree to use two methods of birth control, (one of which must be a barrier method). 13. Participation in an interventional clinical study within 3 months of visit 1 or receipt of any investigational medicinal product within 3 months or 5 half- lives. 14. Upon questioning the patient has blood born infection (e.g. HIV, hepatitis B or C)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Moderate to Severe Exacerbation (Defined as Requiring Treatment With Systemic Corticosteroids and/or Antibiotics in the Community or Hospital or Hospitalisation). | 0-48 weeks | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serious Adverse Event Rate in the 48 Weeks of the Trial From First Dose | Weeks 0 , 4, 12, 24, 26, 48 | Number of Participants with Serious Adverse Events in the 48 Weeks of the Trial From First Dose |
| St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score | Weeks 0, 4, 12, 24, 36, 48 | 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. |
| COPD Assessment Test (CAT) (Questionnaire) | Weeks 0, 4, 12, 24, 36, 48 | 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. |
| Modified Medical Research Council (mMRC) Dyspnea Scale | Screening, weeks 0, 4, 12, 24, 36, 48 | 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). |
| Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores | Weeks 0, 4, 12, 24, 36, 48 | 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). |
| Sputum Purulence Colour Card | Screening, week 12, 28, 36, 48 | 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. |
| Pre and Post Bronchodilator (BD) Spirometry - FEV1/FVC Ratio | Week 0 and Week 48 | 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. |
| Post BD Forced Expiratory Volume in 1 Second (FEV1) | Screening, Weeks 4, 12, 24, 36, 48 | 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) |
| Body Plethysmography ('Body Box') Total Lung Capacity and Residual Volume | Week 0 and week 48 | 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. |
| Blood Inflammatory Cell Differentials | Weeks 0, 4, 12, 24, 36, 48 | To assess inflammation at exacerbation events. White blood cells, eosinophils and neutrophils will be measured. |
| Sputum Inflammatory Cell Differentials: Eosinophils | Weeks 0, 4, 12, 24, 36, 48 | To assess inflammation at exacerbation events. Eosinophils cells will be measured. |
| Pre and Post Bronchodilator (BD) Spirometry- FEV1 and FVC | Week 0 and Week 48 | 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. |
| Pre and Post Bronchodilator (BD) Spirometry- FEV1 Predicted and FVC Predicted | Week 0 and Week 48 | 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. |
| Body Plethysmography ('Body Box') - Residual Volume/Total Lung Capacity Ratio | Week 0 and week 48 | 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. |
| Sputum Inflammatory Cell Differentials: Macrophages | Weeks 0, 4, 12, 24, 36, 48 | To assess inflammation at exacerbation events. Sputum inflammatory cell differentials: Macrophages |
| Sputum Inflammatory Cell Differentials: Epithelium | Weeks 0, 4, 12, 24, 36, 48 | To assess inflammation at exacerbation events. Epithelium cells will be measured. |
| Adverse Event Rate in the 48 Weeks of the Trial From First Dose | Weeks 0 , 4, 12, 24, 26, 48 | Number of Participants with Adverse Events in the 48 Weeks of the Trial From First Dose |
Other
| Measure | Time frame | Description |
|---|---|---|
| Blood Biomarkers [Exploratory Outcome] | Screening, weeks 4, 12, 24, 36, 48 | Various biomarkers of inflammation will be measured in blood. |
| Cell Subset Analysis Including But Not Restricted to Exploration of ILC2 Cells [Exploratory Outcome] | Screening, weeks 4, 12, 24, 36, 48 | ILC2 cells will be analysed using plasma for biomarkers. |
| Urine Biomarkers of Inflammation [Exploratory Outcome] | Screening, weeks 0, 4, 12, 24, 36, 48 | Various biomarkers of inflammation will be measured in urine. |
| Mediator Profiling (Biomarkers) [Exploratory Outcome] | Weeks 0, 4, 12, 24, 36, 48 | Mediators of inflammation in blood, sputum and urine will be assessed. |
| Nasosorption [Exploratory Outcome] | 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. |
| Nasal Epithelial Sampling [Exploratory Outcome] | 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. |
| Breath Volatile Organic Compound (VOC) Profiling [Exploratory Outcome] | 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. |
| Microbiomics [Exploratory Outcome] | 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. |
| Targeted qPCR (Bacteria and Viruses) for Common Airway Pathogens [Exploratory Outcome] | 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. |
| Pharmacogenomics Response Analysis in Subgroups Determined by SNPs for Alleles Associated With the IL33/ST2 Axis. [Exploratory Outcome] | 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. |
| Baseline Blood Eosinophil Count [Subgroup Objective] | 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. |
| St George's Respiratory Questionnaire for COPD Patients (SGRQ-c) [Subgroup Objective] | 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. |
| FEV1 [Subgroup Objective] | 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. |
| Sputum Mediator Profiling (Biomarkers) [Exploratory Outcome] | Weeks 0, 4, 12, 24, 36, 48 | Various biomarkers of inflammation will be measured in sputum. |
| Non-contrast Thoracic CT Derived Outcomes [Exploratory Outcome] | 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. |
Countries
United Kingdom
Participant flow
Recruitment details
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.
Pre-assignment details
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).
Participants by arm
| Arm | Count |
|---|---|
| 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 | 42 |
| 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. | 39 |
| Total | 81 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Clinical diagnosis of lung cancer | 1 | 0 |
| Overall Study | Clinical diagnosis of oesophageal cancer | 1 | 0 |
| Overall Study | Death | 0 | 2 |
| Overall Study | Physician Decision | 2 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Anti-ST2 | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 30 Participants | 35 Participants | 65 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 4 Participants | 16 Participants |
| Age, Continuous | 67.6 years STANDARD_DEVIATION 8.2 | 70.8 years STANDARD_DEVIATION 6.2 | 69.1 years STANDARD_DEVIATION 7.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 42 Participants | 39 Participants | 81 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 41 Participants | 39 Participants | 80 Participants |
| Region of Enrollment United Kingdom | 42 participants | 39 participants | 81 participants |
| Sex: Female, Male Female | 17 Participants | 13 Participants | 30 Participants |
| Sex: Female, Male Male | 25 Participants | 26 Participants | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 42 | 2 / 39 |
| other Total, other adverse events | 34 / 42 | 28 / 39 |
| serious Total, serious adverse events | 12 / 42 | 16 / 39 |
Outcome results
Primary
Number of Moderate to Severe Exacerbation (Defined as Requiring Treatment With Systemic Corticosteroids and/or Antibiotics in the Community or Hospital or Hospitalisation).
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
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Anti-ST2 | 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 |
| Placebo | Number of Moderate to Severe Exacerbation (Defined as Requiring Treatment With Systemic Corticosteroids and/or Antibiotics in the Community or Hospital or Hospitalisation). | 2.67 Exacerbations | Standard Deviation 2.14 |
Comparison: A generalised linear model (assuming neg. binomial distribution) was used. The model includes the number of exacerbations during the 48 week treatment as an outcome with explanatory variables of treatment arm \& number of exacerbations in the 12 months prior to the trial (stratification factor), and log-time on trial (in weeks) as an offset. The offset, allows for different lengths of time in the trial. Only observed exacerbations were used alongside the corresponding time period in the offset.p-value: 0.19595% CI: [0.53, 1.14]t-test, 2 sided
Secondary
Adverse Event Rate in the 48 Weeks of the Trial From First Dose
Number of Participants with Adverse Events in the 48 Weeks of the Trial From First Dose
Time frame: Weeks 0 , 4, 12, 24, 26, 48
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Anti-ST2 | Adverse Event Rate in the 48 Weeks of the Trial From First Dose | 34 Participants |
| Placebo | Adverse Event Rate in the 48 Weeks of the Trial From First Dose | 28 Participants |
Secondary
Blood Inflammatory Cell Differentials
To assess inflammation at exacerbation events. White blood cells, eosinophils and neutrophils will be measured.
Time frame: Weeks 0, 4, 12, 24, 36, 48
Population: Modified ITT (available data)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Anti-ST2 | Blood Inflammatory Cell Differentials | Eosinophil Count week 24 | 0.12 10^9 *cells* per litre | Standard Error 0.096 |
| Anti-ST2 | Blood Inflammatory Cell Differentials | White Blood Cell Count Week 36 | 8.0 10^9 *cells* per litre | Standard Error 0.046 |
| Anti-ST2 | Blood Inflammatory Cell Differentials | Eosinophil Count Week 36 | 0.11 10^9 *cells* per litre | Standard Error 0.106 |
| Anti-ST2 | Blood Inflammatory Cell Differentials | White Blood Cell Count Week 12 | 8.0 10^9 *cells* per litre | Standard Error 0.043 |
| Anti-ST2 | Blood Inflammatory Cell Differentials | Eosinophil Count week 48 | 0.10 10^9 *cells* per litre | Standard Error 0.143 |
| Anti-ST2 | Blood Inflammatory Cell Differentials | White Blood Cell Count Week 48 | 7.5 10^9 *cells* per litre | Standard Error 0.058 |
| Anti-ST2 | Blood Inflammatory Cell Differentials | Neutrophil Count Week 0 | 5.6 10^9 *cells* per litre | Standard Error 0.062 |
| Anti-ST2 | Blood Inflammatory Cell Differentials | Eosinophil Count Week 0 | 0.21 10^9 *cells* per litre | Standard Error 0.107 |
| Anti-ST2 | Blood Inflammatory Cell Differentials | Neutrophil Count Week 4 | 4.9 10^9 *cells* per litre | Standard Error 0.046 |
| Anti-ST2 | Blood Inflammatory Cell Differentials | White Blood Cell Count Week 4 | 7.5 10^9 *cells* per litre | Standard Error 0.035 |
| Anti-ST2 | Blood Inflammatory Cell Differentials | Neutrophil Count Week 12 | 5.4 10^9 *cells* per litre | Standard Error 0.053 |
| Anti-ST2 | Blood Inflammatory Cell Differentials | Eosinophil Count Week 4 | 0.15 10^9 *cells* per litre | Standard Error 0.105 |
| Anti-ST2 | Blood Inflammatory Cell Differentials | Neutrophil Count Week 24 | 5.4 10^9 *cells* per litre | Standard Error 0.059 |
| Anti-ST2 | Blood Inflammatory Cell Differentials | White Blood Cell Count Week 24 | 7.8 10^9 *cells* per litre | Standard Error 0.047 |
| Anti-ST2 | Blood Inflammatory Cell Differentials | Neutrophil Count Week 36 | 5.6 10^9 *cells* per litre | Standard Error 0.056 |
| Anti-ST2 | Blood Inflammatory Cell Differentials | Eosinophil Count Week 12 | 0.13 10^9 *cells* per litre | Standard Error 0.105 |
| Anti-ST2 | Blood Inflammatory Cell Differentials | Neutrophil Count Week 48 | 5.3 10^9 *cells* per litre | Standard Error 0.079 |
| Anti-ST2 | Blood Inflammatory Cell Differentials | White Blood Cell Count Week 0 | 8.2 10^9 *cells* per litre | Standard Error 0.045 |
| Placebo | Blood Inflammatory Cell Differentials | Neutrophil Count Week 48 | 5.5 10^9 *cells* per litre | Standard Error 0.089 |
| Placebo | Blood Inflammatory Cell Differentials | White Blood Cell Count Week 0 | 8.0 10^9 *cells* per litre | Standard Error 0.046 |
| Placebo | Blood Inflammatory Cell Differentials | White Blood Cell Count Week 4 | 7.5 10^9 *cells* per litre | Standard Error 0.037 |
| Placebo | Blood Inflammatory Cell Differentials | White Blood Cell Count Week 12 | 7.7 10^9 *cells* per litre | Standard Error 0.047 |
| Placebo | Blood Inflammatory Cell Differentials | White Blood Cell Count Week 24 | 7.6 10^9 *cells* per litre | Standard Error 0.05 |
| Placebo | Blood Inflammatory Cell Differentials | White Blood Cell Count Week 36 | 7.3 10^9 *cells* per litre | Standard Error 0.048 |
| Placebo | Blood Inflammatory Cell Differentials | Eosinophil Count Week 0 | 0.20 10^9 *cells* per litre | Standard Error 0.111 |
| Placebo | Blood Inflammatory Cell Differentials | Eosinophil Count Week 4 | 0.22 10^9 *cells* per litre | Standard Error 0.111 |
| Placebo | Blood Inflammatory Cell Differentials | Eosinophil Count Week 12 | 0.20 10^9 *cells* per litre | Standard Error 0.116 |
| Placebo | Blood Inflammatory Cell Differentials | Eosinophil Count week 24 | 0.21 10^9 *cells* per litre | Standard Error 0.099 |
| Placebo | Blood Inflammatory Cell Differentials | Eosinophil Count Week 36 | 0.20 10^9 *cells* per litre | Standard Error 0.111 |
| Placebo | Blood Inflammatory Cell Differentials | Eosinophil Count week 48 | 0.17 10^9 *cells* per litre | Standard Error 0.16 |
| Placebo | Blood Inflammatory Cell Differentials | Neutrophil Count Week 0 | 5.1 10^9 *cells* per litre | Standard Error 0.064 |
| Placebo | Blood Inflammatory Cell Differentials | Neutrophil Count Week 4 | 4.9 10^9 *cells* per litre | Standard Error 0.049 |
| Placebo | Blood Inflammatory Cell Differentials | Neutrophil Count Week 12 | 5.2 10^9 *cells* per litre | Standard Error 0.059 |
| Placebo | Blood Inflammatory Cell Differentials | Neutrophil Count Week 24 | 5.0 10^9 *cells* per litre | Standard Error 0.061 |
| Placebo | Blood Inflammatory Cell Differentials | Neutrophil Count Week 36 | 4.9 10^9 *cells* per litre | Standard Error 0.059 |
| Placebo | Blood Inflammatory Cell Differentials | White Blood Cell Count Week 48 | 8.0 10^9 *cells* per litre | Standard Error 0.065 |
Comparison: White blood cell countp-value: 0.73695% CI: [0.95, 1.07]Mixed Models Analysis
Comparison: Eosinophil Countp-value: <0.00195% CI: [0.51, 0.69]Mixed Models Analysis
Comparison: Neutrophil Countp-value: 0.67895% CI: [0.93, 1.13]Mixed Models Analysis
Secondary
Body Plethysmography ('Body Box') - Residual Volume/Total Lung Capacity Ratio
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.
Time frame: Week 0 and week 48
Population: Modified ITT (available data)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Anti-ST2 | 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 |
| Anti-ST2 | 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 |
| Placebo | Body Plethysmography ('Body Box') - Residual Volume/Total Lung Capacity Ratio | Residual Volume/Total Lung Capacity ratio (%) Week 0 | 61.3 percentage (RV of TLC) | Standard Deviation 11.5 |
| Placebo | Body Plethysmography ('Body Box') - Residual Volume/Total Lung Capacity Ratio | Residual Volume/Total Lung Capacity ratio (%) Week 48 | 65.2 percentage (RV of TLC) | Standard Deviation 9.7 |
Comparison: Residual Volume/Total Lung Capacity ratio.p-value: 0.20195% CI: [-7.53, 1.65]ANCOVA
Secondary
Body Plethysmography ('Body Box') Total Lung Capacity and Residual Volume
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.
Time frame: Week 0 and week 48
Population: Modified ITT (available data)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Anti-ST2 | Body Plethysmography ('Body Box') Total Lung Capacity and Residual Volume | Residual Volume Week 0 | 4.5 Litres | Standard Deviation 1.5 |
| Anti-ST2 | Body Plethysmography ('Body Box') Total Lung Capacity and Residual Volume | Total Lung Capacity Week 0 | 7.5 Litres | Standard Deviation 1.6 |
| Anti-ST2 | Body Plethysmography ('Body Box') Total Lung Capacity and Residual Volume | Total Lung Capacity Week 48 | 7.6 Litres | Standard Deviation 1.5 |
| Anti-ST2 | Body Plethysmography ('Body Box') Total Lung Capacity and Residual Volume | Residual Volume Week 48 | 4.8 Litres | Standard Deviation 1.6 |
| Placebo | Body Plethysmography ('Body Box') Total Lung Capacity and Residual Volume | Residual Volume Week 48 | 5.0 Litres | Standard Deviation 1.4 |
| Placebo | Body Plethysmography ('Body Box') Total Lung Capacity and Residual Volume | Residual Volume Week 0 | 4.7 Litres | Standard Deviation 1.5 |
| Placebo | Body Plethysmography ('Body Box') Total Lung Capacity and Residual Volume | Total Lung Capacity Week 48 | 7.6 Litres | Standard Deviation 1.5 |
| Placebo | Body Plethysmography ('Body Box') Total Lung Capacity and Residual Volume | Total Lung Capacity Week 0 | 7.5 Litres | Standard Deviation 1.4 |
Comparison: Total Lung Capacityp-value: 0.90595% CI: [-0.46, 0.52]ANCOVA
Comparison: Residual Volumep-value: 0.77595% CI: [-0.62, 0.47]ANCOVA
Secondary
COPD Assessment Test (CAT) (Questionnaire)
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.
Time frame: Weeks 0, 4, 12, 24, 36, 48
Population: Modified ITT (available data)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Anti-ST2 | COPD Assessment Test (CAT) (Questionnaire) | Week 4 | 22.2 score on a scale | Standard Deviation 5.5 |
| Anti-ST2 | COPD Assessment Test (CAT) (Questionnaire) | Week 24 | 22.7 score on a scale | Standard Deviation 6.9 |
| Anti-ST2 | COPD Assessment Test (CAT) (Questionnaire) | Week 12 | 22.0 score on a scale | Standard Deviation 5.1 |
| Anti-ST2 | COPD Assessment Test (CAT) (Questionnaire) | Week 36 | 22.7 score on a scale | Standard Deviation 5 |
| Anti-ST2 | COPD Assessment Test (CAT) (Questionnaire) | Week 48 | 23.4 score on a scale | Standard Deviation 6 |
| Anti-ST2 | COPD Assessment Test (CAT) (Questionnaire) | Week 0 | 22.1 score on a scale | Standard Deviation 6.6 |
| Placebo | COPD Assessment Test (CAT) (Questionnaire) | Week 48 | 23.6 score on a scale | Standard Deviation 7.8 |
| Placebo | COPD Assessment Test (CAT) (Questionnaire) | Week 0 | 22.6 score on a scale | Standard Deviation 5.7 |
| Placebo | COPD Assessment Test (CAT) (Questionnaire) | Week 4 | 21.7 score on a scale | Standard Deviation 5.8 |
| Placebo | COPD Assessment Test (CAT) (Questionnaire) | Week 12 | 22.3 score on a scale | Standard Deviation 6.9 |
| Placebo | COPD Assessment Test (CAT) (Questionnaire) | Week 24 | 22.1 score on a scale | Standard Deviation 5.5 |
| Placebo | COPD Assessment Test (CAT) (Questionnaire) | Week 36 | 22.4 score on a scale | Standard Deviation 6 |
Comparison: Calculated using mixed effect linear model with dependent variable of the outcome at baseline and follow-up time points (Week 4, 12, 24, 36, 48); explanatory variables of treatment arm, number of exacerbations in the 12 months prior to the trial (stratification factor), visit time point (as categorical variable), baseline score; an interaction term between treatment and visit as fixed effects; and patient identification as a random effect.p-value: 0.46995% CI: [-0.91, 2]Mixed Models Analysis
Secondary
Modified Medical Research Council (mMRC) Dyspnea Scale
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).
Time frame: Screening, weeks 0, 4, 12, 24, 36, 48
Population: Modified ITT (available data)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Anti-ST2 | Modified Medical Research Council (mMRC) Dyspnea Scale | Week 24 | 2.0 score on a scale |
| Anti-ST2 | Modified Medical Research Council (mMRC) Dyspnea Scale | Week 36 | 2.0 score on a scale |
| Anti-ST2 | Modified Medical Research Council (mMRC) Dyspnea Scale | Week 12 | 2.0 score on a scale |
| Anti-ST2 | Modified Medical Research Council (mMRC) Dyspnea Scale | Week 0 | 2.0 score on a scale |
| Anti-ST2 | Modified Medical Research Council (mMRC) Dyspnea Scale | Week 4 | 2.0 score on a scale |
| Anti-ST2 | Modified Medical Research Council (mMRC) Dyspnea Scale | Week 48 | 2.0 score on a scale |
| Placebo | Modified Medical Research Council (mMRC) Dyspnea Scale | Week 4 | 2.0 score on a scale |
| Placebo | Modified Medical Research Council (mMRC) Dyspnea Scale | Week 24 | 2.0 score on a scale |
| Placebo | Modified Medical Research Council (mMRC) Dyspnea Scale | Week 0 | 2.0 score on a scale |
| Placebo | Modified Medical Research Council (mMRC) Dyspnea Scale | Week 48 | 2.0 score on a scale |
| Placebo | Modified Medical Research Council (mMRC) Dyspnea Scale | Week 12 | 2.0 score on a scale |
| Placebo | Modified Medical Research Council (mMRC) Dyspnea Scale | Week 36 | 3.0 score on a scale |
Comparison: Wilcoxon Rank sum test of mMRC dyspnoea Week 4p-value: 0.9Wilcoxon (Mann-Whitney)
Comparison: Wilcoxon Rank sum test of mMRC dyspnoea Week 12p-value: 0.95Wilcoxon (Mann-Whitney)
Comparison: Wilcoxon Rank sum test of mMRC dyspnoea Week 24p-value: 0.78Wilcoxon (Mann-Whitney)
Comparison: Wilcoxon Rank sum test of mMRC dyspnoea Week 36p-value: 0.88Wilcoxon (Mann-Whitney)
Comparison: Wilcoxon Rank sum test of mMRC dyspnoea Week 48p-value: 0.78Wilcoxon (Mann-Whitney)
Secondary
Post BD Forced Expiratory Volume in 1 Second (FEV1)
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)
Time frame: Screening, Weeks 4, 12, 24, 36, 48
Population: Modified ITT (available data)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Anti-ST2 | Post BD Forced Expiratory Volume in 1 Second (FEV1) | Week 0 | 1.21 Litres | Standard Deviation 0.46 |
| Anti-ST2 | Post BD Forced Expiratory Volume in 1 Second (FEV1) | Week 24 | 1.17 Litres | Standard Deviation 0.43 |
| Anti-ST2 | Post BD Forced Expiratory Volume in 1 Second (FEV1) | Week 36 | 1.23 Litres | Standard Deviation 0.47 |
| Anti-ST2 | Post BD Forced Expiratory Volume in 1 Second (FEV1) | Week 4 | 1.21 Litres | Standard Deviation 0.46 |
| Anti-ST2 | Post BD Forced Expiratory Volume in 1 Second (FEV1) | Week 48 | 1.30 Litres | Standard Deviation 0.5 |
| Anti-ST2 | Post BD Forced Expiratory Volume in 1 Second (FEV1) | Week 12 | 1.22 Litres | Standard Deviation 0.48 |
| Placebo | Post BD Forced Expiratory Volume in 1 Second (FEV1) | Week 48 | 1.09 Litres | Standard Deviation 0.57 |
| Placebo | Post BD Forced Expiratory Volume in 1 Second (FEV1) | Week 12 | 1.14 Litres | Standard Deviation 0.52 |
| Placebo | Post BD Forced Expiratory Volume in 1 Second (FEV1) | Week 0 | 1.14 Litres | Standard Deviation 0.48 |
| Placebo | Post BD Forced Expiratory Volume in 1 Second (FEV1) | Week 4 | 1.09 Litres | Standard Deviation 0.46 |
| Placebo | Post BD Forced Expiratory Volume in 1 Second (FEV1) | Week 24 | 1.10 Litres | Standard Deviation 0.5 |
| Placebo | Post BD Forced Expiratory Volume in 1 Second (FEV1) | Week 36 | 1.09 Litres | Standard Deviation 0.52 |
Comparison: mixed effect linear model with explanatory variables of treatment arm, number of exacerbations in the 12 months prior to the trial (stratification factor), visit time point (as categorical variable), baseline score and patient identification as a random effect to account for repeated measures over time was fitted for each outcome. Adjusted mean difference between treatment arms with 95% confidence interval and p-value were reported. In the modified ITT population.p-value: 0.09495% CI: [-0.01, 0.09]Mixed Models Analysis
Secondary
Pre and Post Bronchodilator (BD) Spirometry- FEV1 and FVC
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.
Time frame: Week 0 and Week 48
Population: Modified ITT (available data)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Anti-ST2 | Pre and Post Bronchodilator (BD) Spirometry- FEV1 and FVC | Pre BD FEV1 Week 0 | 1.43 Litres | Standard Deviation 0.43 |
| Anti-ST2 | Pre and Post Bronchodilator (BD) Spirometry- FEV1 and FVC | Pre BD FEV1 Week 48 | 1.43 Litres | Standard Deviation 0.49 |
| Anti-ST2 | Pre and Post Bronchodilator (BD) Spirometry- FEV1 and FVC | Pre BD FVC Week 0 | 2.97 Litres | Standard Deviation 0.89 |
| Anti-ST2 | Pre and Post Bronchodilator (BD) Spirometry- FEV1 and FVC | Pre BD FVC Week 48 | 2.88 Litres | Standard Deviation 0.94 |
| Placebo | Pre and Post Bronchodilator (BD) Spirometry- FEV1 and FVC | Pre BD FVC Week 48 | 2.20 Litres | Standard Deviation 0.36 |
| Placebo | Pre and Post Bronchodilator (BD) Spirometry- FEV1 and FVC | Pre BD FEV1 Week 0 | 0.94 Litres | Standard Deviation 0.33 |
| Placebo | Pre and Post Bronchodilator (BD) Spirometry- FEV1 and FVC | Pre BD FVC Week 0 | 2.17 Litres | Standard Deviation 0.34 |
| Placebo | Pre and Post Bronchodilator (BD) Spirometry- FEV1 and FVC | Pre BD FEV1 Week 48 | 0.86 Litres | Standard Deviation 0.15 |
Comparison: Pre BD FVC (litres): Analysis of covariance (ANCOVA) adjusting for the baseline valuep-value: 0.36295% CI: [-0.14, 0.35]ANCOVA
Comparison: Pre BD FVC (litre):Analysis of covariance (ANCOVA) adjusting for the baseline valuep-value: 0.71395% CI: [-0.61, 0.44]ANCOVA
Secondary
Pre and Post Bronchodilator (BD) Spirometry - FEV1/FVC Ratio
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.
Time frame: Week 0 and Week 48
Population: Modified ITT (available data)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Anti-ST2 | Pre and Post Bronchodilator (BD) Spirometry - FEV1/FVC Ratio | Pre BD FEV1/FVC ratio Week 0 | 49.0 Ratio | Standard Deviation 14.1 |
| Anti-ST2 | Pre and Post Bronchodilator (BD) Spirometry - FEV1/FVC Ratio | Pre BD FEV1/FVC ratio Week 48 | 51.0 Ratio | Standard Deviation 15.5 |
| Placebo | Pre and Post Bronchodilator (BD) Spirometry - FEV1/FVC Ratio | Pre BD FEV1/FVC ratio Week 0 | 46.6 Ratio | Standard Deviation 18.6 |
| Placebo | Pre and Post Bronchodilator (BD) Spirometry - FEV1/FVC Ratio | Pre BD FEV1/FVC ratio Week 48 | 40.2 Ratio | Standard Deviation 9.6 |
Comparison: Pre BD FEV1/FVC ratio: Analysis of covariance (ANCOVA) adjusting for the baseline valuep-value: 0.06995% CI: [-0.83, 18.97]ANCOVA
Secondary
Pre and Post Bronchodilator (BD) Spirometry- FEV1 Predicted and FVC Predicted
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.
Time frame: Week 0 and Week 48
Population: Modified ITT (available data)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Anti-ST2 | 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 |
| Anti-ST2 | 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 |
| Anti-ST2 | 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 |
| Anti-ST2 | 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 |
| Placebo | Pre and Post Bronchodilator (BD) Spirometry- FEV1 Predicted and FVC Predicted | Pre BD predicted FVC (%) Week 48 | 79.2 Percent predicted | Standard Deviation 28.5 |
| Placebo | Pre and Post Bronchodilator (BD) Spirometry- FEV1 Predicted and FVC Predicted | Pre BD FEV1 predicted (%) Week 0 | 39.6 Percent predicted | Standard Deviation 10.4 |
| Placebo | Pre and Post Bronchodilator (BD) Spirometry- FEV1 Predicted and FVC Predicted | Pre BD predicted FVC (%) Week 0 | 75.6 Percent predicted | Standard Deviation 16.7 |
| Placebo | Pre and Post Bronchodilator (BD) Spirometry- FEV1 Predicted and FVC Predicted | Pre BD FEV1 predicted (%) Week 48 | 38.2 Percent predicted | Standard Deviation 8.3 |
Comparison: Pre FEV1 predicted: Analysis of covariance (ANCOVA) adjusting for the baseline valuep-value: 0.71195% CI: [-8.63, 12.2]ANCOVA
Comparison: Pre BD FVC predicted (%): Analysis of covariance (ANCOVA) adjusting for the baseline valuep-value: 0.21495% CI: [-27.9, 7.1]ANCOVA
Secondary
Serious Adverse Event Rate in the 48 Weeks of the Trial From First Dose
Number of Participants with Serious Adverse Events in the 48 Weeks of the Trial From First Dose
Time frame: Weeks 0 , 4, 12, 24, 26, 48
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Anti-ST2 | Serious Adverse Event Rate in the 48 Weeks of the Trial From First Dose | 12 Participants |
| Placebo | Serious Adverse Event Rate in the 48 Weeks of the Trial From First Dose | 16 Participants |
Secondary
Sputum Inflammatory Cell Differentials: Eosinophils
To assess inflammation at exacerbation events. Eosinophils cells will be measured.
Time frame: Weeks 0, 4, 12, 24, 36, 48
Population: Modified ITT (available data)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Anti-ST2 | Sputum Inflammatory Cell Differentials: Eosinophils | Eosinophil count (%) Week 0 | 1.42 Percentage of Eosinophils in sputum | Standard Error 0.254 |
| Anti-ST2 | Sputum Inflammatory Cell Differentials: Eosinophils | Eosinophil count (%) Week 4 | 0.43 Percentage of Eosinophils in sputum | Standard Error 0.188 |
| Anti-ST2 | Sputum Inflammatory Cell Differentials: Eosinophils | Eosinophil count (%) Week 12 | 0.41 Percentage of Eosinophils in sputum | Standard Error 0.168 |
| Anti-ST2 | Sputum Inflammatory Cell Differentials: Eosinophils | Eosinophil count (%) Week 24 | 0.44 Percentage of Eosinophils in sputum | Standard Error 0.191 |
| Anti-ST2 | Sputum Inflammatory Cell Differentials: Eosinophils | Eosinophil count (%) Week 36 | 0.47 Percentage of Eosinophils in sputum | Standard Error 0.212 |
| Anti-ST2 | Sputum Inflammatory Cell Differentials: Eosinophils | Eosinophil count (%) Week 48 | 0.33 Percentage of Eosinophils in sputum | Standard Error 0.232 |
| Placebo | Sputum Inflammatory Cell Differentials: Eosinophils | Eosinophil count (%) Week 36 | 1.94 Percentage of Eosinophils in sputum | Standard Error 0.236 |
| Placebo | Sputum Inflammatory Cell Differentials: Eosinophils | Eosinophil count (%) Week 0 | 1.63 Percentage of Eosinophils in sputum | Standard Error 0.242 |
| Placebo | Sputum Inflammatory Cell Differentials: Eosinophils | Eosinophil count (%) Week 24 | 1.69 Percentage of Eosinophils in sputum | Standard Error 0.209 |
| Placebo | Sputum Inflammatory Cell Differentials: Eosinophils | Eosinophil count (%) Week 4 | 1.69 Percentage of Eosinophils in sputum | Standard Error 0.185 |
| Placebo | Sputum Inflammatory Cell Differentials: Eosinophils | Eosinophil count (%) Week 48 | 1.24 Percentage of Eosinophils in sputum | Standard Error 0.243 |
| Placebo | Sputum Inflammatory Cell Differentials: Eosinophils | Eosinophil count (%) Week 12 | 1.67 Percentage of Eosinophils in sputum | Standard Error 0.19 |
Comparison: Eosinophil countp-value: <0.00195% CI: [0.19, 0.33]Mixed Models Analysis
Secondary
Sputum Inflammatory Cell Differentials: Epithelium
To assess inflammation at exacerbation events. Epithelium cells will be measured.
Time frame: Weeks 0, 4, 12, 24, 36, 48
Population: Modified ITT (available data)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Anti-ST2 | Sputum Inflammatory Cell Differentials: Epithelium | Epithelium count (%) Week 0 | 1.51 Percentage of Epithelium in sputum | Standard Error 0.255 |
| Anti-ST2 | Sputum Inflammatory Cell Differentials: Epithelium | Epithelium count (%) Week 4 | 1.34 Percentage of Epithelium in sputum | Standard Error 0.257 |
| Anti-ST2 | Sputum Inflammatory Cell Differentials: Epithelium | Epithelium count (%) Week 12 | 1.14 Percentage of Epithelium in sputum | Standard Error 0.243 |
| Anti-ST2 | Sputum Inflammatory Cell Differentials: Epithelium | Epithelium count (%) Week 24 | 1.56 Percentage of Epithelium in sputum | Standard Error 0.284 |
| Anti-ST2 | Sputum Inflammatory Cell Differentials: Epithelium | Epithelium count (%) Week 36 | 1.03 Percentage of Epithelium in sputum | Standard Error 0.266 |
| Anti-ST2 | Sputum Inflammatory Cell Differentials: Epithelium | Epithelium count (%) Week 48 | 1.56 Percentage of Epithelium in sputum | Standard Error 0.435 |
| Placebo | Sputum Inflammatory Cell Differentials: Epithelium | Epithelium count (%) Week 36 | 1.26 Percentage of Epithelium in sputum | Standard Error 0.296 |
| Placebo | Sputum Inflammatory Cell Differentials: Epithelium | Epithelium count (%) Week 0 | 1.59 Percentage of Epithelium in sputum | Standard Error 0.243 |
| Placebo | Sputum Inflammatory Cell Differentials: Epithelium | Epithelium count (%) Week 24 | 1.44 Percentage of Epithelium in sputum | Standard Error 0.311 |
| Placebo | Sputum Inflammatory Cell Differentials: Epithelium | Epithelium count (%) Week 4 | 2.06 Percentage of Epithelium in sputum | Standard Error 0.253 |
| Placebo | Sputum Inflammatory Cell Differentials: Epithelium | Epithelium count (%) Week 48 | 1.21 Percentage of Epithelium in sputum | Standard Error 0.456 |
| Placebo | Sputum Inflammatory Cell Differentials: Epithelium | Epithelium count (%) Week 12 | 1.91 Percentage of Epithelium in sputum | Standard Error 0.276 |
Comparison: Epithelium countp-value: 0.21595% CI: [0.54, 1.15]Mixed Models Analysis
Secondary
Sputum Inflammatory Cell Differentials: Macrophages
To assess inflammation at exacerbation events. Sputum inflammatory cell differentials: Macrophages
Time frame: Weeks 0, 4, 12, 24, 36, 48
Population: Modified ITT (available data)
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Anti-ST2 | Sputum Inflammatory Cell Differentials: Macrophages | Macrophage count in sputum (%) Week 0 | 8.9 Percentage of Macrophage in sputum | Standard Error 0.205 |
| Anti-ST2 | Sputum Inflammatory Cell Differentials: Macrophages | Macrophage count in sputum (%) Week 4 | 8.6 Percentage of Macrophage in sputum | Standard Error 0.211 |
| Anti-ST2 | Sputum Inflammatory Cell Differentials: Macrophages | Macrophage count in sputum (%) Week 12 | 9.0 Percentage of Macrophage in sputum | Standard Error 0.19 |
| Anti-ST2 | Sputum Inflammatory Cell Differentials: Macrophages | Macrophage count in sputum (%) Week 24 | 9.2 Percentage of Macrophage in sputum | Standard Error 0.222 |
| Anti-ST2 | Sputum Inflammatory Cell Differentials: Macrophages | Macrophage count in sputum (%) Week 36 | 8.1 Percentage of Macrophage in sputum | Standard Error 0.213 |
| Anti-ST2 | Sputum Inflammatory Cell Differentials: Macrophages | Macrophage count in sputum (%) Week 48 | 6.9 Percentage of Macrophage in sputum | Standard Error 0.286 |
| Placebo | Sputum Inflammatory Cell Differentials: Macrophages | Macrophage count in sputum (%) Week 36 | 9.7 Percentage of Macrophage in sputum | Standard Error 0.237 |
| Placebo | Sputum Inflammatory Cell Differentials: Macrophages | Macrophage count in sputum (%) Week 0 | 9.6 Percentage of Macrophage in sputum | Standard Error 0.196 |
| Placebo | Sputum Inflammatory Cell Differentials: Macrophages | Macrophage count in sputum (%) Week 24 | 12.3 Percentage of Macrophage in sputum | Standard Error 0.244 |
| Placebo | Sputum Inflammatory Cell Differentials: Macrophages | Macrophage count in sputum (%) Week 4 | 11.0 Percentage of Macrophage in sputum | Standard Error 0.208 |
| Placebo | Sputum Inflammatory Cell Differentials: Macrophages | Macrophage count in sputum (%) Week 48 | 11.4 Percentage of Macrophage in sputum | Standard Error 0.3 |
| Placebo | Sputum Inflammatory Cell Differentials: Macrophages | Macrophage count in sputum (%) Week 12 | 9.8 Percentage of Macrophage in sputum | Standard Error 0.216 |
Comparison: Macrophage countp-value: 0.11495% CI: [0.52, 1.07]Mixed Models Analysis
Secondary
Sputum Purulence Colour Card
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.
Time frame: Screening, week 12, 28, 36, 48
Population: Modified ITT (available data)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Anti-ST2 | Sputum Purulence Colour Card | Week 12 | 3.0 score on a scale |
| Anti-ST2 | Sputum Purulence Colour Card | Week 36 | 3.0 score on a scale |
| Anti-ST2 | Sputum Purulence Colour Card | Week 24 | 3.0 score on a scale |
| Anti-ST2 | Sputum Purulence Colour Card | Week 48 | 4.0 score on a scale |
| Anti-ST2 | Sputum Purulence Colour Card | Week 0 | 3.0 score on a scale |
| Placebo | Sputum Purulence Colour Card | Week 48 | 4.0 score on a scale |
| Placebo | Sputum Purulence Colour Card | Week 0 | 3.0 score on a scale |
| Placebo | Sputum Purulence Colour Card | Week 12 | 3.0 score on a scale |
| Placebo | Sputum Purulence Colour Card | Week 24 | 3.0 score on a scale |
| Placebo | Sputum Purulence Colour Card | Week 36 | 3.0 score on a scale |
Comparison: sputum purulence colour card Week 12p-value: 0.84Wilcoxon (Mann-Whitney)
Comparison: sputum purulence colour card Week 24p-value: 0.52Wilcoxon (Mann-Whitney)
Comparison: sputum purulence colour card Week 36p-value: 0.82Wilcoxon (Mann-Whitney)
Comparison: sputum purulence colour card Week 48p-value: 0.95Wilcoxon (Mann-Whitney)
Secondary
St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score
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.
Time frame: Weeks 0, 4, 12, 24, 36, 48
Population: Modified ITT (available data)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Anti-ST2 | St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score | Baseline | 60.1 score on a scale | Standard Deviation 13.7 |
| Anti-ST2 | St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score | Week 4 | 56.7 score on a scale | Standard Deviation 13.5 |
| Anti-ST2 | St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score | Week 12 | 56.9 score on a scale | Standard Deviation 15.2 |
| Anti-ST2 | St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score | Week 24 | 56.6 score on a scale | Standard Deviation 15.3 |
| Anti-ST2 | St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score | Week 36 | 59.5 score on a scale | Standard Deviation 14.6 |
| Anti-ST2 | St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score | Week 48 | 57.7 score on a scale | Standard Deviation 15.7 |
| Placebo | St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score | Week 36 | 59.5 score on a scale | Standard Deviation 17 |
| Placebo | St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score | Baseline | 58.4 score on a scale | Standard Deviation 17.6 |
| Placebo | St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score | Week 24 | 59.6 score on a scale | Standard Deviation 17.9 |
| Placebo | St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score | Week 4 | 58.9 score on a scale | Standard Deviation 16.5 |
| Placebo | St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score | Week 48 | 63.3 score on a scale | Standard Deviation 17.2 |
| Placebo | St George's Respiratory Questionnaire for COPD Patients (SGRQ-C) Total Score | Week 12 | 59.9 score on a scale | Standard Deviation 18.2 |
Comparison: Calculated using mixed effect linear model with dependent variable of the outcome at baseline and follow-up time points (Week 4, 12, 24, 36, 48); explanatory variables of treatment arm, number of exacerbations in the 12 months prior to the trial (stratification factor), visit time point (as categorical variable), baseline score; an interaction term between treatment and visit as fixed effects; and patient identification as a random effect.p-value: 0.03995% CI: [-6.4, -0.2]Mixed Models Analysis
Secondary
Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores
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).
Time frame: Weeks 0, 4, 12, 24, 36, 48
Population: Modified ITT (available data)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Anti-ST2 | 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 |
| Anti-ST2 | 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 |
| Anti-ST2 | 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 |
| Anti-ST2 | 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 |
| Anti-ST2 | 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 |
| Anti-ST2 | 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 |
| Anti-ST2 | 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 |
| Anti-ST2 | 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 |
| Anti-ST2 | 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 |
| Anti-ST2 | 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 |
| Anti-ST2 | 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 |
| Anti-ST2 | 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 |
| Anti-ST2 | 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 |
| Anti-ST2 | 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 |
| Anti-ST2 | 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 |
| Anti-ST2 | 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 |
| Anti-ST2 | 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 |
| Anti-ST2 | 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 |
| Anti-ST2 | 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 |
| Anti-ST2 | 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 |
| Anti-ST2 | 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 |
| Anti-ST2 | 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 |
| Anti-ST2 | 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 |
| Anti-ST2 | 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 |
| Placebo | Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores | VAS Sputum production Week 48 | 39.0 units on a scale | Standard Deviation 27.6 |
| Placebo | Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores | VAS Cough Week 4 | 45.9 units on a scale | Standard Deviation 25.5 |
| Placebo | Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores | VAS Cough Week 48 | 47.0 units on a scale | Standard Deviation 29.6 |
| Placebo | Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores | VAS Sputum production Week 4 | 44.7 units on a scale | Standard Deviation 27 |
| Placebo | Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores | VAS Sputum production Week 12 | 40.2 units on a scale | Standard Deviation 28.7 |
| Placebo | Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores | VAS Total Week 0 | 143.8 units on a scale | Standard Deviation 53.8 |
| Placebo | Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores | VAS Total Week 4 | 148.5 units on a scale | Standard Deviation 61.2 |
| Placebo | Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores | VAS Total Week 12 | 140.0 units on a scale | Standard Deviation 65.1 |
| Placebo | Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores | VAS Total Week 24 | 146.6 units on a scale | Standard Deviation 55.1 |
| Placebo | Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores | VAS Total Week 36 | 147.6 units on a scale | Standard Deviation 59.6 |
| Placebo | Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores | VAS Total Week 48 | 146.5 units on a scale | Standard Deviation 70 |
| Placebo | Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores | VAS Dyspnoea Week 0 | 53.5 units on a scale | Standard Deviation 22.1 |
| Placebo | Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores | VAS Dyspnoea Week 12 | 54.7 units on a scale | Standard Deviation 25.4 |
| Placebo | Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores | VAS Dyspnoea Week 24 | 57.9 units on a scale | Standard Deviation 22.6 |
| Placebo | Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores | VAS Dyspnoea Week 36 | 57.6 units on a scale | Standard Deviation 22.5 |
| Placebo | Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores | VAS Dyspnoea Week 48 | 60.5 units on a scale | Standard Deviation 21.8 |
| Placebo | Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores | VAS Cough Week 0 | 47.5 units on a scale | Standard Deviation 22.7 |
| Placebo | Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores | VAS Cough Week 12 | 45.1 units on a scale | Standard Deviation 24.6 |
| Placebo | Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores | VAS Cough Week 24 | 45.2 units on a scale | Standard Deviation 21.9 |
| Placebo | Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores | VAS Cough Week 36 | 46.0 units on a scale | Standard Deviation 25.1 |
| Placebo | Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores | VAS Sputum production Week 0 | 42.8 units on a scale | Standard Deviation 24.5 |
| Placebo | Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores | VAS Sputum production Week 24 | 43.5 units on a scale | Standard Deviation 24.3 |
| Placebo | Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores | VAS Sputum production Week 36 | 44.0 units on a scale | Standard Deviation 26.2 |
| Placebo | Visual Analogue Score (VAS) Total and Individual Dyspnoea, Cough, Sputum Production (100mm) Scores | VAS Dyspnoea Week 4 | 57.8 units on a scale | Standard Deviation 20.6 |
Comparison: VAS totalp-value: 0.23695% CI: [-24.9, 6.2]Mixed Models Analysis
Comparison: VAS Dyspnoeap-value: 0.08395% CI: [-10.6, 0.7]Mixed Models Analysis
Comparison: VAS Coughp-value: 0.54695% CI: [-8.9, 4.7]Mixed Models Analysis
Comparison: VAS Sputum productionp-value: 0.52795% CI: [-7.8, 4]Mixed Models Analysis
Other Pre-specified
Baseline Blood Eosinophil Count [Subgroup Objective]
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.
Time frame: Screening, weeks 4, 12, 24, 36, 48
Other Pre-specified
Blood Biomarkers [Exploratory Outcome]
Various biomarkers of inflammation will be measured in blood.
Time frame: Screening, weeks 4, 12, 24, 36, 48
Other Pre-specified
Breath Volatile Organic Compound (VOC) Profiling [Exploratory Outcome]
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.
Time frame: Screening, Weeks 12, 24, 36, 48
Other Pre-specified
Cell Subset Analysis Including But Not Restricted to Exploration of ILC2 Cells [Exploratory Outcome]
ILC2 cells will be analysed using plasma for biomarkers.
Time frame: Screening, weeks 4, 12, 24, 36, 48
Other Pre-specified
FEV1 [Subgroup Objective]
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.
Time frame: Weeks 0 and 48
Other Pre-specified
Mediator Profiling (Biomarkers) [Exploratory Outcome]
Mediators of inflammation in blood, sputum and urine will be assessed.
Time frame: Weeks 0, 4, 12, 24, 36, 48
Other Pre-specified
Microbiomics [Exploratory Outcome]
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.
Time frame: Weeks 0, 4, 12, 24, 36, 48
Other Pre-specified
Nasal Epithelial Sampling [Exploratory Outcome]
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.
Time frame: Screening, weeks 12, 24, 36, 48
Other Pre-specified
Nasosorption [Exploratory Outcome]
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.
Time frame: Screening, Weeks 12, 24, 36, 48
Other Pre-specified
Non-contrast Thoracic CT Derived Outcomes [Exploratory Outcome]
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.
Time frame: Screening and week 48
Other Pre-specified
Pharmacogenomics Response Analysis in Subgroups Determined by SNPs for Alleles Associated With the IL33/ST2 Axis. [Exploratory Outcome]
To evaluate the rate of protocol-defined COPD exacerbations through 48 weeks treatment period, patient reported outcomes (PROs), and lung functions, by subgroup outcomes.
Time frame: Baseline and week 48
Other Pre-specified
Sputum Mediator Profiling (Biomarkers) [Exploratory Outcome]
Various biomarkers of inflammation will be measured in sputum.
Time frame: Weeks 0, 4, 12, 24, 36, 48
Other Pre-specified
St George's Respiratory Questionnaire for COPD Patients (SGRQ-c) [Subgroup Objective]
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.
Time frame: Weeks 0, 4, 12, 24, 36, 48
Other Pre-specified
Targeted qPCR (Bacteria and Viruses) for Common Airway Pathogens [Exploratory Outcome]
To assess airway infection and ecology. We will analyse the microbes in patients' lungs and profile the effect of treatment on these microbes.
Time frame: Weeks 0, 4, 12, 24, 36, 48
Other Pre-specified
Urine Biomarkers of Inflammation [Exploratory Outcome]
Various biomarkers of inflammation will be measured in urine.
Time frame: Screening, weeks 0, 4, 12, 24, 36, 48