Company: AstraZeneca (UK)
mechanism: monoclonal antibody. Tralokinumab is a human IgG4 monoclonal antibody that targets IL-13, a key cytokine that is believed to play a key role in the pathogenesis of asthma through the promotion of inflammation, airway hyper-responsiveness, mucus hyper-secretion, airway remodeling via fibrosis, increased IgE synthesis and mast cell activation.
severe, inadequately controlled asthma
area: Allergic diseases - Immunological diseases - Respiratory diseases
Country: Argentina, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, France, Germany, Italy, Japan, Republic of Korea, Mexico, The Netherlands, Peru, Philippines, Poland, Russian Federation,Slovakia, South Africa, Spain, UK, USA, Vietnam
- The ATMOSPHERE programme is comprised of 2,298 patients at 571 sites across 27 countries including the pivotal efficacy trials, STRATOS 1 and STRATOS 2, along with the TROPOS, MESOS and Japan Long-Term Safety (LTS) trials.
- STRATOS 1 and 2 are Phase III multicentre, randomised, double-blinded, parallel-group, placebo-controlled trials designed to evaluate the efficacy and safety of a regular, subcutaneous administration of tralokinumab for 52 weeks in adult and adolescent patients with severe asthma inadequately controlled despite treatment with ICS plus LABA.
- STRATOS2 is evaluating efficacy and safety of tralokinumab administered subcutaneously in subjects with uncontrolled asthma on inhaled corticosteroid plus long-acting ?2-agonist and having a history of asthma exacerbations. Approximately 770 subjects will be randomized globally. Subjects will receive tralokinumab, or placebo, administered via subcutaneous injection at the study site, over a 52-week treatment period. (NCT02194699)
- STRATOS1 is designed to evaluate efficacy and safety of tralokinumab administered subcutaneously in subjects with uncontrolled asthma on inhaled corticosteroid plus long-acting ?2-agonist and having a history of asthma exacerbations. Approximately 1140 subjects will be randomized globally. Subjects will receive tralokinumab, or placebo, administered via subcutaneous injection at the study site, over a 52-week treatment period. (NCT02161757)
- The third trial is a multicentre, randomized, double-blind,parallel group, placebo controlled, phase 3 study to evaluate the efficacy and safety of tralokinumab in reducing oral corticosteroid dependent asthma (NCT02281357).
- TROPOS is a Phase III multicentre, randomised, double-blinded, parallel-group, placebo-controlled trial for 40 weeks in adult and adolescent patients with severe asthma who require continuous treatment with ICS plus LABA, and chronic treatment with maintenance oral corticosteroid (OCS) therapy.
- MESOS is a Phase II multicentre, randomised, double-blinded, parallel group, placebo-controlled trial for 12 weeks in adults with uncontrolled asthma requiring continuous treatment with ICS, with or without other asthma controllers.
- Japan LTS is an open-label, multicentre trial to evaluate the safety of tralokinumab for 52 weeks in Japanese adults and adolescents with asthma inadequately controlled on ICS plus LABA.
- • On May 10, 2017, AstraZeneca and MedImmune, its global biologics research and development arm, announced that tralokinumab did not meet its primary endpoint of a significant reduction in the annual asthma exacerbation rate (AAER) in the overall population of severe, uncontrolled asthma patients, compared with placebo in STRATOS 1, the first of two pivotal Phase III trials.
- In a planned analysis, a clinically-relevant reduction in AAER was observed in a sub-population of patients with an elevated biomarker associated with increased IL-13 activity. This sub-group of patients will now be the focus for the future analysis of STRATOS 2, the second ongoing pivotal Phase III trial.
- AstraZeneca will now await the STRATOS 2 results in the second half of 2017 to explore the potential to treat a sub-group of uncontrolled asthma patients with tralokinumab.
- The safety and tolerability findings in STRATOS 1 were consistent with those observed in previous trials with tralokinumab. A full evaluation of the data is ongoing and the results will be submitted for presentation at a forthcoming medical meeting.
- Potential future regulatory submissions for tralokinumab will be dependent on the combined analysis of both STRATOS 1 and STRATOS 2, the two pivotal trials in the ATMOSPHERE clinical programme.
- • On October 30, 2014, a third trial has been added on Clinicaltrials.gov.
- • On August 14, 2014, AstraZeneca announced the start of the Phase III programme for tralokinumab, a potential treatment for patients with severe, inadequately controlled asthma, developed by MedImmune, the company’s global biologics research and development arm. The Phase III programme will evaluate the safety and effectiveness of tralokinumab in reducing the rate of asthma exacerbations (AER) in adults and adolescents with severe, inadequately controlled asthma despite receiving inhaled corticosteroids plus long-acting ?2-agonist. The programme will also assess the effect of tralokinumab on lung function, patient-reported asthma symptoms and quality of life, as well as investigate whether potential clinical biomarkers could identify patients who are more likely to respond to tralokinumab.
- Initiation of the Phase III programme is based on results from a Phase IIb study conducted by MedImmune. Results from that study were presented at the 2014 American Thoracic Society (ATS) International Conference in San Diego, California in May.The efficacy and safety of tralokinumab is also being investigated in an ongoing Phase II study in patients with mild-to-moderate idiopathic pulmonary fibrosis (IPF) over a 72-week treatment period.