Clinical trial NCT02449473: Study to Evaluate Efficacy & Safety of Tralokinumab in Subjects With Asthma Inadequately Controlled on Corticosteroids
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Asthma
Keywords: Asthma
Reactive Airways
Respiratory Tract Disease
Obstructive Tract Disease
Lung Diseases
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2015-05-20
Enrollment: 79
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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

Primary outcomes:
measure: Change From Baseline to Week 12, Expressed as a Ratio, in Number of Airway Submucosal Eosinophils
timeFrame: Baseline (Week 0) and Week 12
Secondary outcomes:
measure: Change From Baseline to Week 12, Expressed as a Ratio, in Number of Blood Eosinophils
timeFrame: Baseline (Week 0) and Week 12
measure: Change From Baseline to Week 12, Expressed as a Ratio, in Number of Differential Sputum Eosinophils
timeFrame: Baseline (Week 0) and Week 12
measure: Change From Baseline to Week 12, Expressed as a Ratio, in Blood Free Eosinophil Cationic Protein (ECP) Concentrations
timeFrame: Baseline (Week 0) and Week 12
measure: Change From Baseline to Week 12, Expressed as a Ratio, in Sputum Free ECP Concentrations
timeFrame: Baseline (Week 0) and Week 12
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Quebec
country: Canada
facility: Research Site
city: Hvidovre
country: Denmark
facility: Research Site
city: København NV
country: Denmark
facility: Research Site
city: Odense C
country: Denmark
facility: Research Site
city: Ålborg
country: Denmark
facility: Research Site
city: Århus C
country: Denmark
facility: Research Site
city: Belfast
country: United Kingdom
facility: Research Site
city: Glasgow
country: United Kingdom
facility: Research Site
city: Leicester
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Manchester
country: United Kingdom
facility: Research Site
city: Nottingham
country: United Kingdom
facility: Research Site
city: Southampton
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Institute for Lung Health, United Kingdom
name: Christopher Brightling, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.