Please select the outcome measures that correspond to the clinical trial below.
Title: MEA115575: A Randomised, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study of Mepolizumab Adjunctive Therapy to Reduce Steroid Use in Subjects With Severe Refractory Asthma
Brief Summary: 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.


Options:
A: Number of Participants With the Indicated Percent Reduction From Baseline in Oral Corticosteroid (OCS) Dose During Weeks 20 to 24 While Maintaining Asthma Control (Baseline; Weeks 20 to 24)
B: Frequency of Clinical Asthma Exacerbations (CAEs) During 12 Months of Treatment (Day 1 to Week 52); Frequency of Each of the Two Criteria for Clinical Asthma Exacerbations (CAEs) (Day 1 to Week 52)
C: Maximum Observed Serum Concentration (Cmax) for CAT-354 After First Dose (Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21); Maximum Observed Serum Concentration (Cmax) for CAT-354 After Second Dose (Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 28; Day 35); Maximum Observed Serum Concentration (Cmax) for CAT-354 After Third Dose (Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 56; Day 63, 84, 105 and 147); Area Under the Serum Concentration Time Curve From Time Zero to Last Measurable Concentration (AUC[0 - t]) for CAT-354 After First Dose (Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21); Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC[0 - Infinity]) for CAT-354 After First Dose (Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21); Apparent Terminal Elimination Phase Half-Life (t[1/2]el) for CAT-354 After First Dose (Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21); Clearance (CL) for CAT-354 After First Dose (Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21); Volume of Distribution (Vd) for CAT-354 After First Dose (Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0; Day 4, 7, 14 and 21); Observed Serum Drug Concentration for CAT-354 28 Days (C28) After First Dose (Pre-dose on Day 28); Observed Serum Drug Concentration for CAT-354 28 Days (C28) After Second Dose (Pre-dose on Day 56); Observed Serum Concentration for CAT-354 28 Days (C28) After Third Dose (Day 84); Accumulation Ratio (R0) for CAT-354 (Pre-dose, 10 minutes and 12 hours post-end of infusion on Day 0 and 56; Pre-dose on Day 28; Day 4, 7, 14, 21, 63 and 84)
D: Evaluate the safety and tolerability of MEDI-563 in adults with atopic asthma and evaluate the effects of MEDI-563 on eosinophil counts in airway mucosal biopsies 28 days after completion of dosing in adults with atopic asthma. (Study Day 84 or Day 140 - (dose-driven))

Answer: A