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A Multicentre, Randomized, Double-blind, Parallel Group, Placebo Controlled, 12-Week, Phase 2 Study to Evaluate the Effect of Tralokinumab on Airway Inflammation in Adults with Asthma Inadequately Controlled on Inhaled Corticosteroid.
This is a multicentre, randomized, double-blind, parallel group, placebo-controlled, phase 2 study to designed evaluate the effect of a 300 mg dose of tralokinumab administered subcutaneously every 2 weeks on airway inflammation in adults with asthma inadequately controlled on inhaled corticosteroids (ICS) with or without other controllers. Approximately 80 subjects will be randomized. Subjects will receive tralokinumab, or placebo, administered via subcutaneous injection at the study site, over a 12 week treatment period.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tralokinumab Dose Regimen | Experimental | Tralokinumab Subcutaneous Injection |
|
| Placebo Dose Regimen | Placebo Comparator | Placebo Subcutaneous Injection |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tralokinumab | Biological | Subcutaneous Injection |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to Week 12, Expressed as a Ratio, in Number of Airway Submucosal Eosinophils | The number of airway submucosal eosinophils per millimetre squared (mm^2) was determined by microscopic evaluation of bronchoscopic biopsies. The ratio of post-randomisation value at Week 12 to baseline value was computed as (Week 12 value / baseline value). The change from baseline to Week 12 (ratio) in the number of airway submucosal eosinophils is presented as geometric mean ± standard deviation (SD) of log values. | Baseline (Week 0) and Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to Week 12, Expressed as a Ratio, in Number of Blood Eosinophils | The blood eosinophil count was obtained from the total and differential white blood cell counts. The ratio of post-randomisation value at Week 12 to baseline value was computed as (Week 12 value / baseline value). The change from baseline to Week 12 (ratio) in the number of blood eosinophils is presented as geometric mean ± SD of log values. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Christopher Brightling, MD | Institute for Lung Health, United Kingdom | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Vancouver | British Columbia | V5Z 1M9 | Canada | ||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35537502 | Derived | Diver S, Sridhar S, Khalfaoui LC, Russell RJ, Emson C, Griffiths JM, de Los Reyes M, Yin D, Colice G, Brightling CE. Feno differentiates epithelial gene expression clusters: Exploratory analysis from the MESOS randomized controlled trial. J Allergy Clin Immunol. 2022 Oct;150(4):830-840. doi: 10.1016/j.jaci.2022.04.024. Epub 2022 May 7. | |
| 29793857 |
| Label | URL |
|---|---|
| Related Info | View source |
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79 patients were randomised to receive investigational product (IP) and all those randomised received treatment.
First patient enrolled: 29 Sep 2015; Last patient last visit: 21 Jun 2017. Study performed at 14 sites in 3 countries. Patients maintained on currently prescribed inhaled corticosteroid (≥250 micrograms fluticasone dry powder formulation equivalents total daily dose) + any additional maintenance asthma controller medication throughout the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Tralo 300 mg Q2W | Tralokinumab 300 milligrams (mg) administered subcutaneously every 2 weeks (Q2W) over a 12-week treatment period (up to 6 doses). |
| FG001 | Placebo | Placebo administered subcutaneously Q2W over a 12-week treatment period (up to 6 doses). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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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 | Jan 15, 2016 | Jan 7, 2019 |
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| Placebo |
| Other |
Subcutaneous Injection |
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| Baseline (Week 0) and Week 12 |
| Change From Baseline to Week 12, Expressed as a Ratio, in Number of Differential Sputum Eosinophils | Sputum induction was performed to obtain satisfactory samples of sputum originating from the airways. The ratio of post-randomisation value at Week 12 to baseline value was computed as (Week 12 value / baseline value). The change from baseline to Week 12 (ratio) in the number of eosinophils in induced sputum is presented as geometric mean ± SD of log values. | Baseline (Week 0) and Week 12 |
| Change From Baseline to Week 12, Expressed as a Ratio, in Blood Free Eosinophil Cationic Protein (ECP) Concentrations | ECP concentrations were determined to assess evidence of activation of eosinophils in blood. The ratio of post-randomisation value at Week 12 to baseline value was computed as (Week 12 value / baseline value). The change from baseline to Week 12 (ratio) in blood free ECP concentrations is presented as geometric mean ± SD of log values. | Baseline (Week 0) and Week 12 |
| Change From Baseline to Week 12, Expressed as a Ratio, in Sputum Free ECP Concentrations | ECP concentrations were determined to assess evidence of activation of eosinophils in sputum. The ratio of post-randomisation value at Week 12 to baseline value was computed as (Week 12 value / baseline value). The change from baseline to Week 12 (ratio) in sputum free ECP concentrations is presented as geometric mean ± SD of log values. | Baseline (Week 0) and Week 12 |
| Montreal |
| Quebec |
| H4A 3J1 |
| Canada |
| Research Site | Québec | Quebec | G1V 4G5 | Canada |
| Research Site | Aalborg | 9000 | Denmark |
| Research Site | Århus C | 8000 | Denmark |
| Research Site | Hvidovre | 2650 | Denmark |
| Research Site | København NV | 2400 | Denmark |
| Research Site | Odense C | 5000 | Denmark |
| Research Site | Belfast | BT12 6BA | United Kingdom |
| Research Site | Glasgow | G12 OYN | United Kingdom |
| Research Site | Leicester | LE3 9QP | United Kingdom |
| Research Site | London | United Kingdom |
| Research Site | Manchester | M23 9QZ | United Kingdom |
| Research Site | Nottingham | NG5 1PB | United Kingdom |
| Research Site | Southampton | SO16 6YD | United Kingdom |
| Russell RJ, Chachi L, FitzGerald JM, Backer V, Olivenstein R, Titlestad IL, Ulrik CS, Harrison T, Singh D, Chaudhuri R, Leaker B, McGarvey L, Siddiqui S, Wang M, Braddock M, Nordenmark LH, Cohen D, Parikh H, Colice G, Brightling CE; MESOS study investigators. Effect of tralokinumab, an interleukin-13 neutralising monoclonal antibody, on eosinophilic airway inflammation in uncontrolled moderate-to-severe asthma (MESOS): a multicentre, double-blind, randomised, placebo-controlled phase 2 trial. Lancet Respir Med. 2018 Jul;6(7):499-510. doi: 10.1016/S2213-2600(18)30201-7. Epub 2018 May 21. |
| 29536781 | Derived | Panettieri RA Jr, Wang M, Braddock M, Bowen K, Colice G. Tralokinumab for the treatment of severe, uncontrolled asthma: the ATMOSPHERE clinical development program. Immunotherapy. 2018 Mar 1;10(6):473-490. doi: 10.2217/imt-2017-0191. Epub 2018 Mar 14. |
| Related Info | View source |
| COMPLETED |
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| NOT COMPLETED |
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All patients in the full analysis set (FAS) and who received any IP (tralokinumab or placebo) were included in the baseline analysis.
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| ID | Title | Description |
|---|---|---|
| BG000 | Tralo 300 mg Q2W | Tralokinumab 300 mg administered subcutaneously Q2W over a 12-week treatment period (up to 6 doses). |
| BG001 | Placebo | Placebo administered subcutaneously Q2W over a 12-week treatment period (up to 6 doses). |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race (NIH/OMB) | Count of Participants | Participants |
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| 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 | Change From Baseline to Week 12, Expressed as a Ratio, in Number of Airway Submucosal Eosinophils | The number of airway submucosal eosinophils per millimetre squared (mm^2) was determined by microscopic evaluation of bronchoscopic biopsies. The ratio of post-randomisation value at Week 12 to baseline value was computed as (Week 12 value / baseline value). The change from baseline to Week 12 (ratio) in the number of airway submucosal eosinophils is presented as geometric mean ± standard deviation (SD) of log values. | The FAS included all randomised patients who received any IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analyses. | Posted | Geometric Mean | Standard Deviation | Ratio | Baseline (Week 0) and Week 12 |
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| Secondary | Change From Baseline to Week 12, Expressed as a Ratio, in Number of Blood Eosinophils | The blood eosinophil count was obtained from the total and differential white blood cell counts. The ratio of post-randomisation value at Week 12 to baseline value was computed as (Week 12 value / baseline value). The change from baseline to Week 12 (ratio) in the number of blood eosinophils is presented as geometric mean ± SD of log values. | The FAS included all randomised patients who received any IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analyses. | Posted | Geometric Mean | Standard Deviation | Ratio | Baseline (Week 0) and Week 12 |
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| Secondary | Change From Baseline to Week 12, Expressed as a Ratio, in Number of Differential Sputum Eosinophils | Sputum induction was performed to obtain satisfactory samples of sputum originating from the airways. The ratio of post-randomisation value at Week 12 to baseline value was computed as (Week 12 value / baseline value). The change from baseline to Week 12 (ratio) in the number of eosinophils in induced sputum is presented as geometric mean ± SD of log values. | The FAS included all randomised patients who received any IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analyses. | Posted | Geometric Mean | Standard Deviation | Ratio | Baseline (Week 0) and Week 12 |
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| Secondary | Change From Baseline to Week 12, Expressed as a Ratio, in Blood Free Eosinophil Cationic Protein (ECP) Concentrations | ECP concentrations were determined to assess evidence of activation of eosinophils in blood. The ratio of post-randomisation value at Week 12 to baseline value was computed as (Week 12 value / baseline value). The change from baseline to Week 12 (ratio) in blood free ECP concentrations is presented as geometric mean ± SD of log values. | The FAS included all randomised patients who received any IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analyses. | Posted | Geometric Mean | Standard Deviation | Ratio | Baseline (Week 0) and Week 12 |
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| Secondary | Change From Baseline to Week 12, Expressed as a Ratio, in Sputum Free ECP Concentrations | ECP concentrations were determined to assess evidence of activation of eosinophils in sputum. The ratio of post-randomisation value at Week 12 to baseline value was computed as (Week 12 value / baseline value). The change from baseline to Week 12 (ratio) in sputum free ECP concentrations is presented as geometric mean ± SD of log values. | The FAS included all randomised patients who received any IP, irrespective of their protocol adherence and continued participation in the study. Only patients with data available at the timepoints of testing were included in the analyses. | Posted | Geometric Mean | Standard Deviation | Ratio | Baseline (Week 0) and Week 12 |
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12 weeks
Data is reported for adverse events during the treatment period (onset date ≥ the first day of IP and ≤ the last day of IP + 2 weeks). Patient population was the safety analysis set which included all patients who received any IP, classified according to the treatment they actually received.
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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 | Tralo 300 mg Q2W | Tralokinumab 300 mg administered subcutaneously Q2W over a 12-week treatment period (up to 6 doses). | 0 | 39 | 0 | 39 | 30 | 39 |
| EG001 | Placebo | Placebo administered subcutaneously Q2W over a 12-week treatment period (up to 6 doses). | 0 | 40 | 1 | 40 | 27 | 40 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Viral upper respiratory tract infection | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA 20.0 | Systematic Assessment |
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| Headache | Nervous system disorders | MedDRA 20.0 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Rash | Skin and subcutaneous tissue disorders | MedDRA 20.0 | Systematic Assessment |
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| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 20.0 | Systematic Assessment |
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| Injection site erythema | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Injection site pain | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Injection site pruritus | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Injection site swelling | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Non-cardiac chest pain | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 20.0 | Systematic Assessment |
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| Weight increased | Investigations | MedDRA 20.0 | Systematic Assessment |
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| Procedural pain | Injury, poisoning and procedural complications | MedDRA 20.0 | Systematic Assessment |
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| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
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| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA 20.0 | Systematic Assessment |
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The results for differential sputum eosinophils and sputum free ECP levels should be viewed cautiously due to the small sample size and wide variability in results for sputum analyses.
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Clinical Lead | AstraZeneca | +1 301-398-0582 | ClinicalTrialTransparency@astrazeneca.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 28, 2017 | Jan 7, 2019 | SAP_001.pdf |
| ID | Term |
|---|---|
| D001249 | Asthma |
| D012140 | Respiratory Tract Diseases |
| D008171 | Lung Diseases |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D008173 | Lung Diseases, Obstructive |
| D012130 | Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| C574065 | tralokinumab |
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| Male |
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| Asian |
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| Native Hawaiian or Other Pacific Islander |
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| Black or African American |
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| White |
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| More than one race |
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| Unknown or Not Reported |
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