Mepolizumab Steroid-Sparing Study in Subjects With Severe Refractory Asthma
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
1 other identifier
interventional
135
10 countries
47
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_3 asthma
Started Oct 2012
47 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 20, 2012
CompletedFirst Posted
Study publicly available on registry
September 24, 2012
CompletedStudy Start
First participant enrolled
October 1, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2013
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2013
CompletedResults Posted
Study results publicly available
January 26, 2016
CompletedMarch 23, 2017
March 1, 2017
1.2 years
September 20, 2012
November 5, 2015
March 21, 2017
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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 (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 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. The percent reduction of OCS was categorized as: 90 to 100%; 75 to \<90%; 50 to \<75%; \>0 to \<50%; no decrease in prednisone dose, or lack of asthma control, or withdrawal (WD) from treatment. Analysis was performed using a proportional odds model with terms for treatment group, region, duration of OCS use at BL (\<5 years vs. \>=5 years) and BL OCS dose.
Baseline; Weeks 20 to 24
Secondary Outcomes (4)
Number of Participants Who Achieved a Reduction of >=50% in Their Daily Oral Corticosteroid (OCS) Dose Compared With Baseline Dose, During Weeks 20 to 24 While Maintaining Asthma Control
Baseline; Weeks 20 to 24
Number of Participants Who Achieved a Reduction of Their Daily OCS Dose to <=5.0 mg During Weeks 20 to 24 While Maintaining Asthma Control
Weeks 20 to 24
Number of Participants Who Achieved a Total Reduction of OCS Dose During Weeks 20 to 24 While Maintaining Asthma Control
Weeks 20 to 24
Median Percentage Change From Baseline in Daily OCS Dose During Weeks 20 to 24 While Maintaining Asthma Control
Baseline; Weeks 20 to 24
Study Arms (2)
Mepolizumab
EXPERIMENTALMepolizumab 100 mg subcutaneous once every 4 weeks upto Week 20
Placebo
EXPERIMENTALPlacebo subcutaneous once every 4 weeks upto Week 20
Interventions
Mepolizumab is a fully humanised Immunoglobulin G antibody (IgG1, kappa) with human heavy and light chain frameworks.
Eligibility Criteria
You may qualify if:
- Informed Consent and Study Compliance: Subjects must be able to give written informed consent prior to participation in the study, which will include the ability to comply with the requirements and restrictions listed in the consent form.
- Systemic Corticosteroids: Requirement for regular treatment with maintenance systemic corticosteroids in the 6 months prior to Visit 1 and using a stable oral corticosteroid dose for 4 weeks prior to Visit 1. Subjects must be taking 5.0 to 35 mg/day of prednisone or equivalent at Visit 1 and must agree to switch to study required prednisone/prednisolone as their oral corticosteroid and use it per protocol for the duration of the study.
- Inhaled Corticosteroids: Requirement for regular treatment with high dose inhaled corticosteroid in the 6 months prior to Visit 1. For 18 years of age and older: inhaled corticosteroid (ICS) dose must be \>=880 microgram (µg)/day fluticasone propionate (FP) (ex-actuator) or equivalent daily. For ICS/ long acting beta2 agonist (LABA) combination preparations, the highest approved maintenance dose in the local country will meet this ICS criterion. For ages 12 to 17: ICS dose must be \>=440 μg/day FP (ex-actuator) or equivalent daily.
- Controller Medication: Current treatment with an additional controller medication for at least 3 months OR documentation of having used and failed an additional controller medication for at least 3 successive months during the prior 12 months \[e.g., LABA, leukotriene receptor antagonist (LTRA), or theophylline\].
- Eosinophilic Asthma: Prior documentation of eosinophilic asthma or high likelihood of eosinophilic asthma.
- FEV1: Persistent airflow obstruction as indicated by a pre-bronchodilator FEV1 \<80% predicted.
- Asthma: Evidence of asthma indicated by airway reversibility, hyperresponsiveness or airway variability.
You may not qualify if:
- Smoking history: Current smokers or former smokers with a smoking history of \>=10 pack years.
- Concurrent Respiratory Disease: Presence of a clinically important lung condition other than asthma.
- Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior screening
- Liver Disease: Unstable liver disease
- Cardiovascular: Subjects who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment.
- Other Concurrent Medical Conditions: Subjects who have known, pre-existing, clinically significant endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, haematological or any other system abnormalities that are uncontrolled with standard treatment.
- Eosinophilic Diseases: Subjects with other conditions that could lead to elevated eosinophils such as Hypereosiniophilic Syndromes, including Churg-Strauss Syndrome, or Eosinophilic Esophaghitis. Subjects with a known, pre-existing parasitic infestation within 6 months prior to Visit 1 are also to be excluded.
- ECG: ECG assessment QTcF \>=450 milliseconds (msec) or QTcF \>= 480 msec for subjects with Bundle Branch Block.
- Immunodeficiency: A known immunodeficiency (e.g. human immunodeficiency virus - HIV), other than that explained by the use of corticosteroids taken as therapy for asthma.
- Omalizumab Use: Subjects who have received omalizumab \[Xolair\] within 130 days of Visit 1.
- Other Monoclonal Antibodies: Subjects who have received any monoclonal antibody (other than Xolair) to treat inflammatory disease within 5 half-lives of Visit 1.
- Investigational Medications: Subjects who have received treatment with an investigational drug within the past 30 days or five terminal phase half-lives of the drug whichever is longer, prior to Visit 1 (this also includes investigational formulations of marketed products).
- Hypersensitivity: Subjects with a known allergy or intolerance to a monoclonal antibody or biologic.
- Pregnancy: Subjects who are pregnant or breastfeeding. Patients should not be enrolled if they plan to become pregnant during the time of study participation.
- Alcohol/Substance Abuse: A history (or suspected history) of alcohol misuse or substance abuse within 2 years prior to Visit 1.
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- GlaxoSmithKlinelead
Study Sites (47)
GSK Investigational Site
Long Beach, California, 90808, United States
GSK Investigational Site
Denver, Colorado, 80206, United States
GSK Investigational Site
New Haven, Connecticut, 06520, United States
GSK Investigational Site
Rochester, Minnesota, 55905, United States
GSK Investigational Site
St Louis, Missouri, 63110, United States
GSK Investigational Site
Cincinnati, Ohio, 45229, United States
GSK Investigational Site
Pittsburgh, Pennsylvania, PA 15213, United States
GSK Investigational Site
Spartanburg, South Carolina, 29303, United States
GSK Investigational Site
New Lambton, New South Wales, 2305, Australia
GSK Investigational Site
Bedford Park, South Australia, 5042, Australia
GSK Investigational Site
Parkville, Victoria, 3050, Australia
GSK Investigational Site
Nedlands, Western Australia, 6009, Australia
GSK Investigational Site
Hamilton, Ontario, L8N 4A6, Canada
GSK Investigational Site
Montreal, Quebec, H2X 2P4, Canada
GSK Investigational Site
Montreal, Quebec, H4J 1C5, Canada
GSK Investigational Site
Québec, Quebec, G1V 4G5, Canada
GSK Investigational Site
Brno, 625 00, Czechia
GSK Investigational Site
Olomouc, 775 20, Czechia
GSK Investigational Site
Prague, 140 59, Czechia
GSK Investigational Site
Prague, 180 01, Czechia
GSK Investigational Site
Gières, 38610, France
GSK Investigational Site
Montpellier, 34295, France
GSK Investigational Site
Nantes, 44093, France
GSK Investigational Site
Paris, 75877, France
GSK Investigational Site
Strasbourg, 67091, France
GSK Investigational Site
Aschaffenburg, Bavaria, 63739, Germany
GSK Investigational Site
Potsdam, Brandenburg, 14478, Germany
GSK Investigational Site
Rüdersdorf, Brandenburg, 15562, Germany
GSK Investigational Site
Frankfurt am Main, Hesse, 60596, Germany
GSK Investigational Site
Gelnhausen, Hesse, 63571, Germany
GSK Investigational Site
Neu-Isenburg, Hesse, 63263, Germany
GSK Investigational Site
Hanover, Lower Saxony, 30173, Germany
GSK Investigational Site
Mainz, Rhineland-Palatinate, 55131, Germany
GSK Investigational Site
Lübeck, Schleswig-Holstein, 23552, Germany
GSK Investigational Site
Guadalajara, Jalisco, 44100, Mexico
GSK Investigational Site
Zapopan, Jalisco, 45040, Mexico
GSK Investigational Site
Amsterdam, 1105 AZ, Netherlands
GSK Investigational Site
Leeuwarden, 8934 AD, Netherlands
GSK Investigational Site
Rotterdam, 3045 PM, Netherlands
GSK Investigational Site
Bialystok, 15-010, Poland
GSK Investigational Site
Bialystok, 15-044, Poland
GSK Investigational Site
Krakow, 31-024, Poland
GSK Investigational Site
Lodz, 90-153, Poland
GSK Investigational Site
Leicester, Leicestershire, LE3 9QP, United Kingdom
GSK Investigational Site
Liverpool, L9 7AL, United Kingdom
GSK Investigational Site
Newcastle upon Tyne, NE1 4LP, United Kingdom
GSK Investigational Site
Southampton, SO16 6YD, United Kingdom
Related Publications (7)
Casale TB, Burnette A, Bourdin A, Howarth P, Hahn B, Stach-Klysh A, Khurana S. Oral corticosteroid-sparing effects of mepolizumab in severe eosinophilic asthma: evidence from randomized controlled trials and real-world studies. Ther Adv Respir Dis. 2022 Jan-Dec;16:17534666221107313. doi: 10.1177/17534666221107313.
PMID: 35972211DERIVEDKhurana S, Brusselle GG, Bel EH, FitzGerald JM, Masoli M, Korn S, Kato M, Albers FC, Bradford ES, Gilson MJ, Price RG, Humbert M. Long-term Safety and Clinical Benefit of Mepolizumab in Patients With the Most Severe Eosinophilic Asthma: The COSMEX Study. Clin Ther. 2019 Oct;41(10):2041-2056.e5. doi: 10.1016/j.clinthera.2019.07.007. Epub 2019 Aug 22.
PMID: 31447130DERIVEDYancey SW, Bradford ES, Keene ON. Disease burden and efficacy of mepolizumab in patients with severe asthma and blood eosinophil counts of >/=150-300 cells/muL. Respir Med. 2019 May;151:139-141. doi: 10.1016/j.rmed.2019.04.008. Epub 2019 Apr 8.
PMID: 31047111DERIVEDOrtega HG, Meyer E, Brusselle G, Asano K, Prazma CM, Albers FC, Mallett SA, Yancey SW, Gleich GJ. Update on immunogenicity in severe asthma: Experience with mepolizumab. J Allergy Clin Immunol Pract. 2019 Sep-Oct;7(7):2469-2475.e1. doi: 10.1016/j.jaip.2019.03.042. Epub 2019 Apr 5. No abstract available.
PMID: 30954640DERIVEDKeene ON. Strategies for composite estimands in confirmatory clinical trials: Examples from trials in nasal polyps and steroid reduction. Pharm Stat. 2019 Jan;18(1):78-84. doi: 10.1002/pst.1909. Epub 2018 Oct 29.
PMID: 30370691DERIVEDMagnan A, Bourdin A, Prazma CM, Albers FC, Price RG, Yancey SW, Ortega H. Treatment response with mepolizumab in severe eosinophilic asthma patients with previous omalizumab treatment. Allergy. 2016 Sep;71(9):1335-44. doi: 10.1111/all.12914. Epub 2016 May 24.
PMID: 27087007DERIVEDBel EH, Wenzel SE, Thompson PJ, Prazma CM, Keene ON, Yancey SW, Ortega HG, Pavord ID; SIRIUS Investigators. Oral glucocorticoid-sparing effect of mepolizumab in eosinophilic asthma. N Engl J Med. 2014 Sep 25;371(13):1189-97. doi: 10.1056/NEJMoa1403291. Epub 2014 Sep 8.
PMID: 25199060DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- GSK Response Center
- Organization
- GlaxoSmithKline
Study Officials
- STUDY DIRECTOR
GSK Clinical Trials
GlaxoSmithKline
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 20, 2012
First Posted
September 24, 2012
Study Start
October 1, 2012
Primary Completion
December 1, 2013
Study Completion
December 1, 2013
Last Updated
March 23, 2017
Results First Posted
January 26, 2016
Record last verified: 2017-03
Data Sharing
- IPD Sharing
- Will share
Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.