Clinical Trials

Date: 2016-03-05

Type of information: Presentation of results at a congress

phase: 3

Announcement: presentation of results at the American Academy of Allergy, Asthma & Immunology annual meeting

Company: GSK (UK)

Product: mepolizumab

Action mechanism:

• monoclonal antibody. Mepolizumab is an investigational fully humanised IgG monoclonal antibody specific for interleukin 5 (IL-5) which is in development for severe refractory asthma in patients who exacerbate despite high-dose inhaled (ICS) or oral corticosteroids (OCS) and long-acting beta-2 agonist use. IL-5 is a cytokine which regulates the growth, activation and survival of eosinophils (white blood cells) and provides an essential signal for the movement of eosinophils from the bone marrow into the lung. Mepolizumab binds to human IL-5, stopping it from binding to its receptor on the surface of eosinophils. Inhibiting IL-5 binding in this manner reduces blood, tissue and sputum eosinophil levels, which in turn reduces the frequency of exacerbations. Mepolizumab is not approved for use anywhere in the world.

Disease: eosinophilic asthma

Therapeutic area: Allergic diseases - Inflammatory diseases - Respiratory diseases

Country:

Trial details:

• The Phase III programme includes two key studies: MENSA STUDY - MEA115588: A 32-week multicentre, randomised, double-blind, double-dummy, placebo-controlled study in patients with severe uncontrolled refractory asthma. The primary endpoint of the study is to evaluate the efficacy of mepolizumab 75 mg intravenous (i.v.) and 100 mg subcutaneous (SC) every 4 weeks versus placebo on the frequency of clinically significant exacerbations in patients with severe refractory asthma. This study will evaluate two dose regimens of mepolizumab [75mg intravenous (i.v.) or 100mg subcutaneous (SC) every 4 weeks] compared with placebo over a 32 week treatment period in subjects with severe refractory asthma with elevated blood eosinophils. Efficacy will be measured by a reduction in the frequency of asthma exacerbations. Additional efficacy assessments will include measurements of lung function, symptom scores, and quality of life. Safety will be assessed by clinical laboratory samples, ECGs, immunogenicity and adverse events. This study is intended to replicate the Phase IIb/III study MEA112997. Subjects in MEA115588, who meet all eligibility criteria at screening visit, will enter the run-in period. Those subjects that are not able/eligible to be randomised at the end of the 6 week run-in period will be deemed run-in failures. Subjects will remain on their current maintenance therapy throughout the run-in, double-blind treatment administration and follow-up periods. Subjects who meet the randomisation eligibility criteria will be randomised in a 1:1:1 ratio to receive one of the following treatments every 4 weeks for a total of 8 doses: Mepolizumab 75 miligram (mg) i.v. and placebo SC, or Mepolizumab 100 mg SC and placebo i.v. or Placebo i.v. and placebo SC. Subjects that receive all 8 doses of double-blind treatment, and meet the eligibility criteria for the Open-Label Extension (OLE) Study, will be offered the opportunity to participate in the OLE trial.
• SIRIUS STUDY - MEA115575: A 24-week randomised, double-blind, placebo-controlled, parallel-group, multicentre study to evaluate the use of mepolizumab 100mg subcutaneous adjunctive therapy every 4 weeks to reduce steroid use in patients with severe refractory asthma. This is a randomised, double-blind, placebo-controlled, parallel-group, multicenter study of mepolizumab in comparison with placebo in reducing Oral Corticosteroid (OCS) use in subjects with severe refractory asthma. The study consists of four phases, OCS Optimisation Phase (Week -8 to Week 0), and the double-blind treatment period divided into an Induction Phase (Week 0 to Week 4), OCS Reduction Phase (Week 5 upto Week 20) followed by Maintenance Phase (Week 20 to Week 24). During the Optimisation Phase the investigator will adjust the OCS (prednisone/prednisolone) dose according to the Optimisation titration schedule based on a review of Asthma Control Questionnaire (ACQ)-5 score and exacerbation. In the Induction Phase subjects will be randomized 1:1 (approximately 60 per arm) to receive either mepolizumab (100 mg) administered subcutaneously (SC) or placebo every 4 weeks in addition to their existing maintenance asthma therapy with the lowest dose of OCS from Optimisation Phase. The Induction Phase will allow sufficient time for those subjects randomised to the mepolizumab arm to achieve a decrease in the eosinophilic inflammation prior to the reduction in OCS. During the Reduction Phase, subjects will continue receiving 100 mg mepolizumab/placebo every 4 weeks and the OCS dose reduction will be done every 4 weeks using the reduction titration schedule based on a review of eDiary parameters recorded by the subject, the subjects’ exacerbation history, and a review of the signs and symptoms of adrenal insufficiency. In the Maintenance Phase subjects will be maintained without any further OCS dose adjustment. Subjects who complete the 24 week double-blind period and meet the eligibility criteria, will be offered the opportunity to participate in an open label extension (OLE) study otherwise they will return for a Follow-up Visit 12 weeks after their last dose of double blind study treatment. At each clinic visit, adverse events, safety labs, spirometery parameters and exacerbations will be assessed. The pharmacokinetic samples will be collected in the beginning of the treatment, prior to last dose, at the end of study (exit visit) and the follow up. The Phase III programme also includes safety extension trials that will further assess treatment of subsequent asthma attacks in mepolizumab-naive as well as previously-treated patients.
• (NCT01691521 and NCT01691508)

Latest news:

Is general: Yes