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

• ClinicalTrials.gov Identifier: NCT02449473
• Recruitment Status: Completed
• First Posted: May 20, 2015
• Results First Posted: January 8, 2019
• Last Update Posted: January 8, 2019
• Sponsor: AstraZeneca
• Information provided by (Responsible Party): AstraZeneca

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Asthma	Biological: Tralokinumab; Other: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 79 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: September 29, 2015
• Actual Primary Completion Date: June 21, 2017
• Actual Study Completion Date: June 21, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline to Week 12, Expressed as a Ratio, in Number of Airway Submucosal Eosinophils [ Time Frame: Baseline (Week 0) and Week 12 ]
   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.

Secondary Outcome Measures :

1. Change From Baseline to Week 12, Expressed as a Ratio, in Number of Blood Eosinophils [ Time Frame: Baseline (Week 0) and Week 12 ]
   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.
2. Change From Baseline to Week 12, Expressed as a Ratio, in Number of Differential Sputum Eosinophils [ Time Frame: Baseline (Week 0) and Week 12 ]
   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.
3. Change From Baseline to Week 12, Expressed as a Ratio, in Blood Free Eosinophil Cationic Protein (ECP) Concentrations [ Time Frame: Baseline (Week 0) and Week 12 ]
   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.
4. Change From Baseline to Week 12, Expressed as a Ratio, in Sputum Free ECP Concentrations [ Time Frame: Baseline (Week 0) and Week 12 ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

Canada, British Columbia

Research Site

Vancouver, British Columbia, Canada, V5Z 1M9

Canada, Quebec

Research Site

Montreal, Quebec, Canada, H4A 3J1

Canada

Research Site

Quebec, Canada, G1V 4G5

Denmark

Research Site

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

United Kingdom

Research Site

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

Sponsors and Collaborators

AstraZeneca

Investigators

• Principal Investigator: Christopher Brightling, MD; Institute for Lung Health, United Kingdom

  Study Documents (Full-Text)

Documents provided by AstraZeneca:

Study Protocol  [PDF] January 15, 2016

Statistical Analysis Plan  [PDF] July 28, 2017

More Information

Additional Information:

Related Info 

Related Info 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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. Review.

• Responsible Party: AstraZeneca
• ClinicalTrials.gov Identifier: NCT02449473
• Other Study ID Numbers: D2210C00014
• First Posted: May 20, 2015
• Results First Posted: January 8, 2019
• Last Update Posted: January 8, 2019
• Last Verified: January 2019

Keywords provided by AstraZeneca:

Asthma; Reactive Airways; Respiratory Tract Disease; Obstructive Tract Disease; Lung Diseases

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases