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| ID | Type | Description | Link |
|---|---|---|---|
| 2018-000919-24 | EudraCT Number | ||
| GB40568 | Other Grant/Funding Number | Genentech | |
| U1111-1210-1335 | Other Identifier | WHO Universal Trial Number | |
| 244758 | Other Identifier | IRAS Number | |
| 18/EM/0189 | Other Identifier | East Midlands - Leicester South Research Ethics Committee |
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| Name | Class |
|---|---|
| Glenfield Hospital, Leicester | OTHER |
| Genentech, Inc. | INDUSTRY |
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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.
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:
Exploratory objectives include:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Anti-ST2 | Experimental | Anti-ST2 (MSTT1041A) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. |
|
| Placebo | Placebo Comparator | Placebo (no active component) received as subcutaneous injection by infusion pump at 490mg every 4 weeks over a 48 week treatment period. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MSTT1041A | Drug | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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:
| 0-48 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | Weeks 0 , 4, 12, 24, 26, 48 |
| Serious Adverse Event Rate in the 48 Weeks of the Trial From First Dose |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Screening and week 48 |
| Sputum Mediator Profiling (Biomarkers) [Exploratory Outcome] |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Christopher Brightling, Prof | University of Leicester | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Biomedical Research Centre- Respiratory, Glenfield Hospital | Leicester | Leicestershire | LE3 9QP | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35339234 | Derived | Yousuf AJ, Mohammed S, Carr L, Yavari Ramsheh M, Micieli C, Mistry V, Haldar K, Wright A, Novotny P, Parker S, Glover S, Finch J, Quann N, Brookes CL, Hobson R, Ibrahim W, Russell RJ, John C, Grimbaldeston MA, Choy DF, Cheung D, Steiner M, Greening NJ, Brightling CE. Astegolimab, an anti-ST2, in chronic obstructive pulmonary disease (COPD-ST2OP): a phase 2a, placebo-controlled trial. Lancet Respir Med. 2022 May;10(5):469-477. doi: 10.1016/S2213-2600(21)00556-7. Epub 2022 Mar 24. |
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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).
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.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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:
| 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. | Posted | Mean | Standard Deviation | Exacerbations | 0-48 weeks |
|
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal pain | Gastrointestinal disorders | MedDRA version 20 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA version 20 | Systematic Assessment |
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Professor Chris Brightling | University of Leicester | +44 116 250 2704 | ceb17@le.ac.uk |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 7, 2020 | Nov 10, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 11, 2021 | Nov 10, 2021 | SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Apr 1, 2019 | Nov 10, 2021 | ICF_002.pdf |
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| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
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| ID | Term |
|---|---|
| C000711667 | astegolimab |
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Single-centre, double-blinded, placebo-controlled, parallel group, randomised controlled trial
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A or B
|
|
| Placebo | Drug | 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 Participants with Serious Adverse Events in the 48 Weeks of the Trial From First Dose |
| Weeks 0 , 4, 12, 24, 26, 48 |
| 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. | Weeks 0, 4, 12, 24, 36, 48 |
| 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. | Weeks 0, 4, 12, 24, 36, 48 |
| 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). | Screening, weeks 0, 4, 12, 24, 36, 48 |
| 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). | Weeks 0, 4, 12, 24, 36, 48 |
| 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. | Screening, week 12, 28, 36, 48 |
| 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. | Week 0 and Week 48 |
| 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) | Screening, Weeks 4, 12, 24, 36, 48 |
| 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. | Week 0 and week 48 |
| Blood Inflammatory Cell Differentials | To assess inflammation at exacerbation events. White blood cells, eosinophils and neutrophils will be measured. | Weeks 0, 4, 12, 24, 36, 48 |
| Sputum Inflammatory Cell Differentials: Eosinophils | To assess inflammation at exacerbation events. Eosinophils cells will be measured. | Weeks 0, 4, 12, 24, 36, 48 |
| 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. | Week 0 and Week 48 |
| 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. | Week 0 and Week 48 |
| 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. | Week 0 and week 48 |
| Sputum Inflammatory Cell Differentials: Macrophages | To assess inflammation at exacerbation events. Sputum inflammatory cell differentials: Macrophages | Weeks 0, 4, 12, 24, 36, 48 |
| Sputum Inflammatory Cell Differentials: Epithelium | To assess inflammation at exacerbation events. Epithelium cells will be measured. | Weeks 0, 4, 12, 24, 36, 48 |
Various biomarkers of inflammation will be measured in sputum. |
| Weeks 0, 4, 12, 24, 36, 48 |
| Blood Biomarkers [Exploratory Outcome] | Various biomarkers of inflammation will be measured in blood. | Screening, weeks 4, 12, 24, 36, 48 |
| Cell Subset Analysis Including But Not Restricted to Exploration of ILC2 Cells [Exploratory Outcome] | ILC2 cells will be analysed using plasma for biomarkers. | Screening, weeks 4, 12, 24, 36, 48 |
| Urine Biomarkers of Inflammation [Exploratory Outcome] | Various biomarkers of inflammation will be measured in urine. | Screening, weeks 0, 4, 12, 24, 36, 48 |
| Mediator Profiling (Biomarkers) [Exploratory Outcome] | Mediators of inflammation in blood, sputum and urine will be assessed. | Weeks 0, 4, 12, 24, 36, 48 |
| 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. | Screening, Weeks 12, 24, 36, 48 |
| 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. | Screening, weeks 12, 24, 36, 48 |
| 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. | Screening, Weeks 12, 24, 36, 48 |
| 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. | Weeks 0, 4, 12, 24, 36, 48 |
| 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. | Weeks 0, 4, 12, 24, 36, 48 |
| 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. | Baseline and week 48 |
| 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. | Screening, weeks 4, 12, 24, 36, 48 |
| 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. | Weeks 0, 4, 12, 24, 36, 48 |
| 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. | Weeks 0 and 48 |
| Clinical diagnosis of lung cancer |
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| Clinical diagnosis of oesophageal cancer |
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| Death |
|
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | 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.
| OG001 | Placebo | 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. |
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| 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 | Safety population | Posted | Count of Participants | Participants | Weeks 0 , 4, 12, 24, 26, 48 |
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|
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| 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 | Safety population | Posted | Count of Participants | Participants | Weeks 0 , 4, 12, 24, 26, 48 |
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| 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. | Modified ITT (available data) | Posted | Mean | Standard Deviation | score on a scale | Weeks 0, 4, 12, 24, 36, 48 |
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|
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| 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. | Modified ITT (available data) | Posted | Mean | Standard Deviation | score on a scale | Weeks 0, 4, 12, 24, 36, 48 |
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| 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). | Modified ITT (available data) | Posted | Median | Inter-Quartile Range | score on a scale | Screening, weeks 0, 4, 12, 24, 36, 48 |
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| 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). | Modified ITT (available data) | Posted | Mean | Standard Deviation | units on a scale | Weeks 0, 4, 12, 24, 36, 48 |
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| 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. | Modified ITT (available data) | Posted | Median | Inter-Quartile Range | score on a scale | Screening, week 12, 28, 36, 48 |
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| 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. | Modified ITT (available data) | Posted | Mean | Standard Deviation | Ratio | Week 0 and Week 48 |
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| 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) | Modified ITT (available data) | Posted | Mean | Standard Deviation | Litres | Screening, Weeks 4, 12, 24, 36, 48 |
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| 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. | Modified ITT (available data) | Posted | Mean | Standard Deviation | Litres | Week 0 and week 48 |
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| Secondary | Blood Inflammatory Cell Differentials | To assess inflammation at exacerbation events. White blood cells, eosinophils and neutrophils will be measured. | Modified ITT (available data) | Posted | Geometric Mean | Standard Error | 10^9 *cells* per litre | Weeks 0, 4, 12, 24, 36, 48 |
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| Secondary | Sputum Inflammatory Cell Differentials: Eosinophils | To assess inflammation at exacerbation events. Eosinophils cells will be measured. | Modified ITT (available data) | Posted | Geometric Mean | Standard Error | Percentage of Eosinophils in sputum | Weeks 0, 4, 12, 24, 36, 48 |
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| 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. | Not Posted | Screening and week 48 | Participants |
| Other Pre-specified | Sputum Mediator Profiling (Biomarkers) [Exploratory Outcome] | Various biomarkers of inflammation will be measured in sputum. | Not Posted | Weeks 0, 4, 12, 24, 36, 48 | Participants |
| Other Pre-specified | Blood Biomarkers [Exploratory Outcome] | Various biomarkers of inflammation will be measured in blood. | Not Posted | Screening, weeks 4, 12, 24, 36, 48 | Participants |
| 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. | Not Posted | Screening, weeks 4, 12, 24, 36, 48 | Participants |
| Other Pre-specified | Urine Biomarkers of Inflammation [Exploratory Outcome] | Various biomarkers of inflammation will be measured in urine. | Not Posted | Screening, weeks 0, 4, 12, 24, 36, 48 | Participants |
| Other Pre-specified | Mediator Profiling (Biomarkers) [Exploratory Outcome] | Mediators of inflammation in blood, sputum and urine will be assessed. | Not Posted | Weeks 0, 4, 12, 24, 36, 48 | Participants |
| 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. | Not Posted | Screening, Weeks 12, 24, 36, 48 | Participants |
| 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. | Not Posted | Screening, weeks 12, 24, 36, 48 | Participants |
| 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. | Not Posted | Screening, Weeks 12, 24, 36, 48 | Participants |
| 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. | Not Posted | Weeks 0, 4, 12, 24, 36, 48 | Participants |
| 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. | Not Posted | Weeks 0, 4, 12, 24, 36, 48 | Participants |
| 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. | Not Posted | Baseline and week 48 | Participants |
| 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. | Not Posted | Screening, weeks 4, 12, 24, 36, 48 | Participants |
| 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. | Not Posted | Weeks 0, 4, 12, 24, 36, 48 | Participants |
| 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. | Not Posted | Weeks 0 and 48 | Participants |
| 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. | Modified ITT (available data) | Posted | Mean | Standard Deviation | Litres | Week 0 and Week 48 |
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| 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. | Modified ITT (available data) | Posted | Mean | Standard Deviation | Percent predicted | Week 0 and Week 48 |
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| 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. | Modified ITT (available data) | Posted | Mean | Standard Deviation | percentage (RV of TLC) | Week 0 and week 48 |
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| Secondary | Sputum Inflammatory Cell Differentials: Macrophages | To assess inflammation at exacerbation events. Sputum inflammatory cell differentials: Macrophages | Modified ITT (available data) | Posted | Geometric Mean | Standard Error | Percentage of Macrophage in sputum | Weeks 0, 4, 12, 24, 36, 48 |
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| Secondary | Sputum Inflammatory Cell Differentials: Epithelium | To assess inflammation at exacerbation events. Epithelium cells will be measured. | Modified ITT (available data) | Posted | Geometric Mean | Standard Error | Percentage of Epithelium in sputum | Weeks 0, 4, 12, 24, 36, 48 |
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| 0 |
| 42 |
| 12 |
| 42 |
| 34 |
| 42 |
| EG001 | 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. | 2 | 39 | 16 | 39 | 28 | 39 |
| Adenoma of the bowel | Gastrointestinal disorders | MedDRA version 20 | Systematic Assessment |
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| Blood transfusion (anaemia) | Blood and lymphatic system disorders | MedDRA version 20 | Systematic Assessment |
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| Chest infection/infective exacerbation of bronchiectasis | Respiratory, thoracic and mediastinal disorders | MedDRA version 20 | Systematic Assessment |
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| Clinical diagnosis of lung cancer | Respiratory, thoracic and mediastinal disorders | MedDRA version 20 | Systematic Assessment |
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| Community acquired pneumonia | Respiratory, thoracic and mediastinal disorders | MedDRA version 20 | Systematic Assessment |
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| Descending aorta thrombosis | Cardiac disorders | MedDRA version 20 | Systematic Assessment |
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| Elective surgery (transurethral resection of the prostate) | Renal and urinary disorders | MedDRA version 20 | Systematic Assessment |
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| Epididymo-orchitis | Reproductive system and breast disorders | MedDRA version 20 | Systematic Assessment |
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| Flu-like illness (viral infection) | Respiratory, thoracic and mediastinal disorders | MedDRA version 20 | Systematic Assessment |
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| Fractured neck of femur | Musculoskeletal and connective tissue disorders | MedDRA version 20 | Systematic Assessment |
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| Gastrointestinal symptoms | Gastrointestinal disorders | MedDRA version 20 | Systematic Assessment |
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| Gout | Musculoskeletal and connective tissue disorders | MedDRA version 20 | Systematic Assessment |
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| Heart failure | Cardiac disorders | MedDRA version 20 | Systematic Assessment |
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| Hospital acquired pneumonia | Respiratory, thoracic and mediastinal disorders | MedDRA version 20 | Systematic Assessment |
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| Infective exacerbation of bronchiectasis | Respiratory, thoracic and mediastinal disorders | MedDRA version 20 | Systematic Assessment |
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| Left scaphoid fracture | Musculoskeletal and connective tissue disorders | MedDRA version 20 | Systematic Assessment |
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| Oesophageal cancer | Gastrointestinal disorders | MedDRA version 20 | Systematic Assessment |
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| Pneumonia | Respiratory, thoracic and mediastinal disorders | MedDRA version 20 | Systematic Assessment |
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| Pneumonia and type 2 respiratory failure | Reproductive system and breast disorders | MedDRA version 20 | Systematic Assessment |
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| Prostatitis | Renal and urinary disorders | MedDRA version 20 | Systematic Assessment |
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| Resection of prostate | Renal and urinary disorders | MedDRA version 20 | Systematic Assessment |
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| Right pneumothorax | Respiratory, thoracic and mediastinal disorders | MedDRA version 20 | Systematic Assessment |
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| Right thrombosed popliteal aneurysm | Cardiac disorders | MedDRA version 20 | Systematic Assessment |
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| Shortness of breath | Respiratory, thoracic and mediastinal disorders | MedDRA version 20 | Systematic Assessment |
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| Small bowel obstruction | Gastrointestinal disorders | MedDRA version 20 | Systematic Assessment |
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| Suspected UTI | Renal and urinary disorders | MedDRA version 20 | Systematic Assessment |
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| Syncopal episode | Cardiac disorders | MedDRA version 20 | Systematic Assessment |
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| Type 2 respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA version 20 | Systematic Assessment |
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| Urosepsis | Renal and urinary disorders | MedDRA version 20 | Systematic Assessment |
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| Ventricular tachycardia | Cardiac disorders | MedDRA version 20 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA version 20 | Systematic Assessment |
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| Cellulitis | Infections and infestations | MedDRA version 20 | Systematic Assessment |
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| Chest pain | General disorders | MedDRA version 20 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA version 20 | Systematic Assessment |
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| Dyspepsia | Gastrointestinal disorders | MedDRA version 20 | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA version 20 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA version 20 | Systematic Assessment |
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| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA version 20 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA version 20 | Systematic Assessment |
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| Hypertension | Vascular disorders | MedDRA version 20 | Systematic Assessment |
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| Lethargy | General disorders | MedDRA version 20 | Systematic Assessment |
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| Malaise | General disorders | MedDRA version 20 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA version 20 | Systematic Assessment |
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| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA version 20 | Systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA version 20 | Systematic Assessment |
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| Oral pain | Gastrointestinal disorders | MedDRA version 20 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA version 20 | Systematic Assessment |
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| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA version 20 | Systematic Assessment |
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| Pulmonary mass | Respiratory, thoracic and mediastinal disorders | MedDRA version 20 | Systematic Assessment |
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| Skin infection | Infections and infestations | MedDRA version 20 | Systematic Assessment |
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| Toothache | Gastrointestinal disorders | MedDRA version 20 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA version 20 | Systematic Assessment |
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| Viral upper respiratory tract infection | Infections and infestations | MedDRA version 20 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA version 20 | Systematic Assessment |
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Not provided
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Not provided
| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| Week 4 |
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| Week 24 |
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| Week 36 |
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| Week 48 |
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| Week 4 |
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| Week 12 |
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| Week 24 |
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| Week 36 |
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| Week 48 |
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| Week 4 |
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| Week 12 |
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| Week 24 |
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| Week 36 |
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| Week 48 |
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| 0.95 |
| Superiority |
| Wilcoxon Rank sum test of mMRC dyspnoea Week 24 | Wilcoxon (Mann-Whitney) | 0.78 | Superiority |
| Wilcoxon Rank sum test of mMRC dyspnoea Week 36 | Wilcoxon (Mann-Whitney) | 0.88 | Superiority |
| Wilcoxon Rank sum test of mMRC dyspnoea Week 48 | Wilcoxon (Mann-Whitney) | 0.78 | Superiority |
| VAS Total Week 4 |
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| VAS Total Week 12 |
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| VAS Total Week 24 |
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| VAS Total Week 36 |
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| VAS Total Week 48 |
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| VAS Dyspnoea Week 0 |
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| VAS Dyspnoea Week 4 |
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| VAS Dyspnoea Week 12 |
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| VAS Dyspnoea Week 24 |
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| VAS Dyspnoea Week 36 |
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| VAS Dyspnoea Week 48 |
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| VAS Cough Week 0 |
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| VAS Cough Week 4 |
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| VAS Cough Week 12 |
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| VAS Cough Week 24 |
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| VAS Cough Week 36 |
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| VAS Cough Week 48 |
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| VAS Sputum production Week 0 |
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| VAS Sputum production Week 4 |
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| VAS Sputum production Week 12 |
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| VAS Sputum production Week 24 |
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| VAS Sputum production Week 36 |
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| VAS Sputum production Week 48 |
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VAS Dyspnoea |
| Mixed Models Analysis |
| 0.083 |
Using mixed effect linear model with explanatory variables treatment, number of exacerbations in the 12 months prior to the trial (stratification), visit time point (as categorical variable) and baseline score as fixed effects. |
| Mean Difference (Net) |
| -4.9 |
| 2-Sided |
| 95 |
| -10.6 |
| 0.7 |
| Superiority |
| VAS Cough | Mixed Models Analysis | 0.546 | Using mixed effect linear model with explanatory variables treatment, number of exacerbations in the 12 months prior to the trial (stratification), visit time point (as categorical variable) and baseline score as fixed effects. | Mean Difference (Net) | -2.1 | 2-Sided | 95 | -8.9 | 4.7 | Superiority |
| VAS Sputum production | Mixed Models Analysis | 0.527 | Using mixed effect linear model with explanatory variables treatment, number of exacerbations in the 12 months prior to the trial (stratification), visit time point (as categorical variable) and baseline score as fixed effects. | Mean Difference (Net) | -1.9 | 2-Sided | 95 | -7.8 | 4.0 | Superiority |
| Week 12 |
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| Week 24 |
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| Week 36 |
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| Week 48 |
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| 0.52 |
| Superiority |
| sputum purulence colour card Week 36 | Wilcoxon (Mann-Whitney) | 0.82 | Superiority |
| sputum purulence colour card Week 48 | Wilcoxon (Mann-Whitney) | 0.95 | Superiority |
| Week 4 |
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| Week 12 |
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| Week 24 |
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| Week 36 |
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| Week 48 |
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| Residual Volume Week 0 |
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| Residual Volume Week 48 |
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Residual Volume |
| ANCOVA |
| 0.775 |
To compare change from baseline to 48 weeks (pre and post treatment measurements), analysis of covariance (ANCOVA) model with baseline value as a covariate was fitted. Adjusted mean difference with 95% confidence interval and p-value were reported. |
| Mean Difference (Final Values) |
| -0.08 |
| 2-Sided |
| 95 |
| -0.62 |
| 0.47 |
| Superiority |
| White Blood Cell Count Week 4 |
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| White Blood Cell Count Week 12 |
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| White Blood Cell Count Week 24 |
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| White Blood Cell Count Week 36 |
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| White Blood Cell Count Week 48 |
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| Eosinophil Count Week 0 |
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| Eosinophil Count Week 4 |
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| Eosinophil Count Week 12 |
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| Eosinophil Count week 24 |
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| Eosinophil Count Week 36 |
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| Eosinophil Count week 48 |
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| Neutrophil Count Week 0 |
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| Neutrophil Count Week 4 |
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| Neutrophil Count Week 12 |
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| Neutrophil Count Week 24 |
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| Neutrophil Count Week 36 |
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| Neutrophil Count Week 48 |
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Eosinophil Count |
| Mixed Models Analysis |
| <0.001 |
Outcome was log transformed Explanatory variables: treatment arm, number of exacerbations in the 12 months prior to the trial (stratification factor), log BL value, visit time point (categorical) and patient identification (random effect). |
| Geometric mean ratio |
| 0.59 |
| 2-Sided |
| 95 |
| 0.51 |
| 0.69 |
| Superiority |
| Neutrophil Count | Mixed Models Analysis | 0.678 | Outcome was log transformed Explanatory variables: treatment arm, number of exacerbations in the 12 months prior to the trial (stratification factor), log BL value, visit time point (categorical) and patient identification (random effect). | Geometric mean ratio | 1.02 | 2-Sided | 95 | 0.93 | 1.13 | Superiority |
| Eosinophil count (%) Week 4 |
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| Eosinophil count (%) Week 12 |
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| Eosinophil count (%) Week 24 |
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| Eosinophil count (%) Week 36 |
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| Eosinophil count (%) Week 48 |
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| Pre BD FVC Week 0 |
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| Pre BD FVC Week 48 |
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| ANCOVA |
| 0.713 |
| Mean Difference (Final Values) |
| -0.09 |
| 2-Sided |
| 95 |
| -0.61 |
| 0.44 |
| Superiority |
| Pre BD predicted FVC (%) Week 0 |
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| Pre BD predicted FVC (%) Week 48 |
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| ANCOVA |
| 0.214 |
| Mean Difference (Final Values) |
| -10.4 |
| 2-Sided |
| 95 |
| -27.9 |
| 7.1 |
| Superiority |
| Macrophage count in sputum (%) Week 4 |
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| Macrophage count in sputum (%) Week 12 |
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| Macrophage count in sputum (%) Week 24 |
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| Macrophage count in sputum (%) Week 36 |
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| Macrophage count in sputum (%) Week 48 |
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| Epithelium count (%) Week 4 |
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| Epithelium count (%) Week 12 |
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| Epithelium count (%) Week 24 |
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| Epithelium count (%) Week 36 |
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| Epithelium count (%) Week 48 |
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