NCT01691508

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

Completed Phase 3 Results posted Last updated 21 March 2017

What this trial tests

Phase 3 trial testing Mepolizumab in Asthma in 135 participants. Completed in 1 December 2013.

Timeline

1 October 2012

Primary endpoint
1 December 2013

1 December 2013

Quick facts

Lead sponsor	GlaxoSmithKline
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	135
Start date	1 October 2012
Primary completion	1 December 2013
Estimated completion	1 December 2013
Sites	47 locations across United States, Australia, Canada, Czechia, France, Germany, Mexico, Netherlands

Drugs / interventions tested

• Mepolizumab (MEPOLIZUMAB) — full drug profile →
• Placebo
• OCS (prednisone/prednisolone) — full drug profile →

Conditions studied

• Asthma — all drugs for Asthma →

Sponsor

GlaxoSmithKline — full company profile →

Who can join

12 and older, any sex, with Asthma. Patients with the condition only — healthy volunteers not accepted.

What's being measured

Primary outcomes are the specific endpoints the trial is designed to prove or disprove.

• Number of Participants With the Indicated Percent Reduction From Baseline in Oral Corticosteroid (OCS) Dose During Weeks 20 to 24 While Maintaining Asthma Control
  Time frame: Baseline; Weeks 20 to 24
  Baseline (BL) dose was the prescribed optimized prednisone/prednisolone dose following the OCS Optimization Phase. Maintenance (MN) dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). The percent reduction of OCS dose during weeks 20 to 24 compared to BL dose was calculated as: 100 x (BL dose minus MN dose)/BL dose. Asthma control between weeks 20 and

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma.
   Bel EH, Wenzel SE, Thompson PJ, Prazma CM, et al · · 2014 · cited 1132× · PMID 25199060 · DOI 10.1056/nejmoa1403291
2. Long-term Efficacy and Safety of Mepolizumab in Patients With Severe Eosinophilic Asthma: A Multi-center, Open-label, Phase IIIb Study.
   Lugogo N, Domingo C, Chanez P, Leigh R, et al · · 2016 · cited 197× · PMID 27553751 · DOI 10.1016/j.clinthera.2016.07.010
3. Antibodies to watch in 2015.
   Reichert JM. · · 2015 · cited 117× · PMID 25484055 · DOI 10.4161/19420862.2015.988944
4. Real-world mepolizumab in the prospective severe asthma REALITI-A study: initial analysis.
   Harrison T, Canonica GW, Chupp G, Lee J, et al · · 2020 · cited 101× · PMID 32817259 · DOI 10.1183/13993003.00151-2020
5. Treatment response with mepolizumab in severe eosinophilic asthma patients with previous omalizumab treatment.
   Magnan A, Bourdin A, Prazma CM, Albers FC, et al · · 2016 · cited 74× · PMID 27087007 · DOI 10.1111/all.12914
6. Targeted anti-inflammatory therapeutics in asthma and chronic obstructive lung disease.
   Durham AL, Caramori G, Chung KF, Adcock IM. · · 2016 · cited 74× · PMID 26334389 · DOI 10.1016/j.trsl.2015.08.004
7. From DREAM to REALITI-A and beyond: Mepolizumab for the treatment of eosinophil-driven diseases.
   Pavord ID, Bel EH, Bourdin A, Chan R, et al · · 2022 · cited 61× · PMID 34402066 · DOI 10.1111/all.15056
8. Eosinophilic Asthma: Pathophysiology and Therapeutic Horizons.
   Hussain M, Liu G. · · 2024 · cited 60× · PMID 38474348 · DOI 10.3390/cells13050384