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

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)

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Other: Placebo; Biological: Tralokinumab

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G1V 4G5
    • Research Site
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Research Site
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • Research Site
• Denmark
  • Hvidovre, Denmark, 2650
    • Research Site
  • København NV, Denmark, 2400
    • Research Site
  • Odense C, Denmark, 5000
    • Research Site
  • Ålborg, Denmark, 9000
    • Research Site
  • Århus C, Denmark, 8000
    • Research Site
• United Kingdom
  • Belfast, United Kingdom, BT12 6BA
    • Research Site
  • Glasgow, United Kingdom, G12 OYN
    • Research Site
  • Leicester, United Kingdom, LE3 9QP
    • Research Site
  • London, United Kingdom
    • Research Site
  • Manchester, United Kingdom, M23 9QZ
    • Research Site
  • Nottingham, United Kingdom, NG5 1PB
    • Research Site
  • Southampton, United Kingdom, SO16 6YD
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18 to 75 years
2. Documented physician-diagnosed asthma for at least 12 months prior to enrolment (v1)
3. 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)
4. Additional maintenance asthma controller medications must be given at a stable dose for at least 1 month prior to v1.
5. At enrolment (v1) the subject must have a predicted normal value (PNV) for the pre-bronchodilator (BD) FEV1>50% and more than 1L.
6. Post-BD reversibility in FEV1 of ≥12% and ≥200 mL at enrolment (v1).

Exclusion Criteria:

1. History of interstitial lung disease, chronic obstructive pulmonary disease (COPD), or other clinically significant lung disease other than asthma.
2. History of anaphylaxis following any biologic therapy.
3. Hepatitis B, C or HIV
4. Pregnant or breastfeeding
5. History of cancer
6. Current tobacco smoking or a history of tobacco smoking for >10 pack-years.
7. Previous receipt of tralokinumab

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tralokinumab Dose Regimen; Tralokinumab Subcutaneous Injection	Biological: Tralokinumab; Subcutaneous Injection
Placebo Comparator: Placebo Dose Regimen; Placebo Subcutaneous Injection	Other: Placebo; Subcutaneous Injection

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Christopher Brightling, MD, Institute for Lung Health, United Kingdom

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): September 29, 2015
• Primary Completion (Actual): June 21, 2017
• Study Completion (Actual): June 21, 2017

Study Registration Dates

• First Submitted: May 18, 2015
• First Submitted That Met QC Criteria: May 18, 2015
• First Posted (Estimate): May 20, 2015

Study Record Updates

• Last Update Posted (Actual): January 8, 2019
• Last Update Submitted That Met QC Criteria: January 7, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: Asthma; Lung Diseases; Respiratory Tract Disease; Reactive Airways; Obstructive Tract Disease
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: D2210C00014