Study to Evaluate Efficacy & Safety of Tralokinumab in Subjects With Asthma Inadequately Controlled on Corticosteroids

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Multicentre, Randomized, Double-blind, Parallel Group, Placebo Controlled, 12-Week, Ph 2 Study to Evaluate the Effect of Tralokinumab on Airway Inflammation in Adults With Asthma Inadequately Controlled on Inhaled Corticosteroid (MESOS)

Conditions
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Asthma

Intervention / Treatment
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* Biological: Tralokinumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 to 75 years Documented physician-diagnosed asthma for at least 12 months prior to enrolment (v1) Documented treatment with an asthma controller regimen requiring treatment with ICS (minimum dose of ≥ 250 ug fluticasone propionate via dry powder inhaler equivalents total daily dose) alone or in combination ≥ 6 months and that has been taken at a stable dose for at least 1 month prior to enrolment (v1) Additional maintenance asthma controller medications must be given at a stable dose for at least 1 month prior to v1. At enrolment (v1) the subject must have a predicted normal value (PNV) for the pre-bronchodilator (BD) FEV1>50% and more than 1L. Post-BD reversibility in FEV1 of ≥12% and ≥200 mL at enrolment (v1). Exclusion Criteria: History of interstitial lung disease, chronic obstructive pulmonary disease (COPD), or other clinically significant lung disease other than asthma. History of anaphylaxis following any biologic therapy. Hepatitis B, C or HIV Pregnant or breastfeeding History of cancer Current tobacco smoking or a history of tobacco smoking for >10 pack-years. Previous receipt of tralokinumab

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tralokinumab Dose Regimen<br>Tralokinumab Subcutaneous Injection | Biological: Tralokinumab<br>* Subcutaneous Injection<br>|
| Placebo Comparator: Placebo Dose Regimen<br>Placebo Subcutaneous Injection | Other: Placebo<br>* Subcutaneous Injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | 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 | 

Secondary Outcome Measures

| Outcome Measure | 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. | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Respiratory Tract Disease, Asthma, Reactive Airways, Obstructive Tract Disease, Lung Diseases