Efficacy and Safety Study of Mepolizumab Adjunctive Therapy in Participants With Severe Eosinophilic Asthma on Markers of Asthma Control
A Randomised, Double-blind, Placebo-controlled, Parallel-group, Multi-centre 24-week Study to Evaluate the Efficacy and Safety of Mepolizumab Adjunctive Therapy in Subjects With Severe Eosinophilic Asthma on Markers of Asthma Control
1 other identifier
interventional
556
18 countries
136
Brief Summary
This is a multi-centre, placebo-controlled, double-blind, parallel-group study to evaluate the efficacy and safety of mepolizumab adjunctive therapy in participants with severe eosinophilic asthma on markers of asthma control. The overall intent of the current study is to more fully explore the impact of mepolizumab on health-related quality of life (HR-QoL) and other measures of asthma control, including lung function. Participants who meet the predefined criteria will be randomised to receive either mepolizumab or placebo in addition to standard of care asthma treatment. Approximately 780 participants with severe eosinophilic asthma will be screened to ensure the randomisation of 544 participants (272 participants per treatment group) into the study.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3 asthma
Started Dec 2014
136 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
October 30, 2014
CompletedFirst Posted
Study publicly available on registry
November 3, 2014
CompletedStudy Start
First participant enrolled
December 11, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 10, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
June 10, 2016
CompletedResults Posted
Study results publicly available
May 4, 2017
CompletedAugust 6, 2018
August 1, 2018
1.5 years
October 30, 2014
December 5, 2016
August 2, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Mean Change From Baseline (BL) in St. George's Respiratory Questionnaire (SGRQ) Score at Week 24
SGRQ consisted of 50 questions (scored from 0 to 100 where 0 indicates best and 100 indicates worst health) designed to measure Quality of Life in par. with diseases of airway obstruction, measuring symptoms, impact, and activity. Questions were completed by the par. with a recall over the past 4 weeks. SGRQ Total Score was calculated by summing the pre-assigned weights of answers, dividing by the sum of the maximum weights for items in SGRQ and multiplying by 100 to get a %. Change from BL in SGRQ was calculated as value at Week 24 minus value at BL for each par. and was analyzed using mixed model repeated measures allowing for covariates of BL value, region, BL maintenance oral corticosteroid (OCS) therapy, exacerbations in the year prior to the study (as an ordinal variable), BL % predicted FEV1 and visit, plus interaction terms for visit by BL and visit by treatment group. Modified Intent-to-Treat (mITT) Population consisted of all randomized par. who received \>= 1 dose of drug.
Baseline and Week 24
Secondary Outcomes (3)
Mean Change From Baseline in Clinic Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Week 24
Baseline and Week 24
Percentage of Participants Achieving a 4 Point or Greater Reduction From Baseline in SGRQ Score at Week 24
Baseline (Visit 2-latest pre-dose assessment) and Week 24
Mean Change From Baseline in Asthma Control Questionnaire (ACQ-5) Score at Week 24
Baseline and Week 24
Study Arms (2)
Mepolizumab SC
EXPERIMENTALParticipants will receive Mepolizumab 100 mg subcutaneously (SC) into the upper arm or thigh every 4 weeks for a period of 24 weeks (total of 6 doses) along with their respective standard care of treatment
Placebo SC
PLACEBO COMPARATORParticipants will receive placebo (0.9% sodium chloride) subcutaneously into the upper arm or thigh every 4 weeks for a period of 24 weeks (total of 6 doses) along with their respective standard care of treatment
Interventions
Humanised Immunoglobulin G (IgG) antibody (IgG1, kappa) with human heavy and light chain frameworks, provided as a lyophilised cake in sterile vial. Vial to be reconstituted with sterile water for injection, just prior to use
Standard of Care (SOC) will differ by participants, however it will include high dose ICS with at least one other controller, e.g. LABA, with or without maintenance OCS
Eligibility Criteria
You may qualify if:
- Age: At least 12 years of age at the time of signing the informed consent/assent (For those countries where local regulations permit enrolment of adults only, participant recruitment will be restricted to those who are \>=18 years of age)
- Inhaled Corticosteroid: A well-documented requirement for regular treatment with high dose inhaled corticosteroid (ICS) in the 12 months prior to Visit 1 with or without maintenance oral corticosteroids (OCS). For participants \>=18 years old: ICS dose must be \>=880 micrograms (mcg)/day fluticasone propionate (FP) (exactuator) or equivalent daily. For ICS/long-acting beta-2-agonist (LABA) combination preparations, the highest approved maintenance dose in the local country will meet this ICS criterion. For participants \>=12 to \<=17 years old: ICS dose must be \>=440 mcg/day FP (ex-actuator) or equivalent daily. For ICS/LABA combination preparations, the mid-strength approved maintenance dose in the local country will meet this ICS criterion
- Controller Medication: Current treatment with an additional controller medication, besides ICS, for at least 3 months or a documented failure in the past 12 months of an additional controller medication for at least 3 successive months (e.g. LABA, leukotriene receptor antagonist \[LTRA\], or theophylline)
- Eosinophilic asthma: Prior documentation of eosinophilic asthma or high likelihood of eosinophilic asthma as per Randomisation Criteria 1 and 2
- FEV1: Persistent airflow obstruction as indicated by : For participants \>=18 years of age at visit 1, a pre-bronchodilator FEV1 \<80% predicted (National Health and Nutrition Examination Survey \[NHANES III\]) recorded at Visit 1. For participants 12-17 years of age at Visit 1: A pre-bronchodilator FEV1 \<90% predicted (NHANES III) recorded at Visit 1 OR FEV1:FVC ratio \<0.8 recorded at Visit 1
- Exacerbation history: Previously confirmed history of two or more exacerbations requiring treatment with systemic Corticosteroid (CS) (intramuscular, intravenous, or oral), in the 12 months prior to visit 1, despite the use of high-dose inhaled corticosteroids (ICS). For participants receiving maintenance CS, the CS treatment for the exacerbations must have been a two-fold dose increase or greater.
- Gender: Male or Eligible Female. To be eligible for entry into the study, females of childbearing potential must commit to consistent and correct use of an acceptable method of birth control listed in the protocol for the duration of the trial and for 4 months after the last study drug administration.
- Informed Consent/Assent: Able to give written informed consent/assent prior to participation in the core study, which will include the ability to comply with the requirements and restrictions listed in the consent/assent form and in this protocol. Participants must be able to read, comprehend, and write at a level sufficient to complete study related materials. Written informed consent must be obtained from ALL patients/legally authorized representative(s); for patients 12-17 years old, written informed assent must be obtained in addition to the legally authorized representative(s)' consent.
You may not qualify if:
- Smoking history: Current smokers or former smokers with a smoking history of \>=10 pack years (number of pack years = (number of cigarettes per day/20) x number of years smoked). A former smoker is defined as a participant who quit smoking at least 6 months prior to Visit 1.
- Concurrent Respiratory Disease: Presence of a known pre-existing, clinically important lung condition other than asthma. This includes current infection, bronchiectasis, pulmonary fibrosis, bronchopulmonary aspergillosis, or diagnoses of emphysema or chronic bronchitis (chronic obstructive pulmonary disease other than asthma) or a history of lung cancer.
- Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior to screening (Participants that had localized carcinoma of the skin which was resected for cure will not be excluded).
- Liver Disease: Known, pre-existing, unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices or persistent jaundice), cirrhosis, and known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
- Cardiovascular: Participants who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment. Including but not limited to: (a) known ejection fraction of \<30% OR (b) severe heart failure meeting New York Heart Association Class IV classification OR (c) hospitalised in the 12 months prior to Visit 1 for severe heart failure meeting New York Heart Association Class III OR (d) angina diagnosed less than 3 months prior to Visit 1 or at Visit 1.
- Other Concurrent Medical Conditions: Participants 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: Participants with other conditions that could lead to elevated eosinophils such as Hypereosinophilic Syndromes, including Churg-Strauss Syndrome (Eosinophilic Granulomatosis with Polyangiitis \[EGPA\]), or Eosinophilic Esophagitis. Participants with a known, pre-existing parasitic infestation within 6 months prior to Visit 1 are also to be excluded.
- Electrocardiogram (ECG) Assessment: QT interval corrected for heart rate by Fridericia's formula (QTc(F)) \>=450 milliseconds (msec) or QTc(F) \>=480 msec for participants with Bundle Branch Block at Visit 1.
- Alcohol/Substance Abuse: A history (or suspected history) of alcohol misuse or substance abuse within 2 years prior to Visit 1.
- Immunodeficiency: A known immunodeficiency (e.g. human immunodeficiency virus \[HIV\]), other than that explained by the use of corticosteroids taken as therapy for asthma.
- Xolair: Participants who have received omalizumab (Xolair) within 130 days of Visit 1.
- Other Monoclonal Antibodies: Participants who have received any monoclonal antibody (other than Xolair) to treat inflammatory disease within 5 half-lives of Visit 1.
- Investigational Medications: Participants 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: Participants with allergy/intolerance to a monoclonal antibody or biologic.
- Pregnancy: Participants who are pregnant or breastfeeding. Patients should not be enrolled if they plan to become pregnant during the time of study participation. A urine pregnancy test is required of all women of child bearing potential. This test will be performed at the time points specified in the Time and Events Schedule in protocol.
- +2 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- GlaxoSmithKlinelead
Study Sites (144)
GSK Investigational Site
Birmingham, Alabama, 35243, United States
GSK Investigational Site
Birmingham, Alabama, 35294, United States
GSK Investigational Site
Fresno, California, 93720, United States
GSK Investigational Site
Long Beach, California, 90808, United States
GSK Investigational Site
Newport Beach, California, 92663, United States
GSK Investigational Site
Riverside, California, 92506, United States
GSK Investigational Site
Rolling Hills Estates, California, 90274, United States
GSK Investigational Site
Upland, California, 91786, United States
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Denver, Colorado, 80206, United States
GSK Investigational Site
New Haven, Connecticut, 06520, United States
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Aventura, Florida, 33180, United States
GSK Investigational Site
Orlando, Florida, 32825, United States
GSK Investigational Site
Baltimore, Maryland, 21236, United States
GSK Investigational Site
Rochester, Minnesota, 55905, United States
GSK Investigational Site
Rochester, New York, 14642, United States
GSK Investigational Site
Durham, North Carolina, 27705, United States
GSK Investigational Site
Gastonia, North Carolina, 28054, United States
GSK Investigational Site
Cincinnati, Ohio, 45231, United States
GSK Investigational Site
Upland, Pennsylvania, 19013, United States
GSK Investigational Site
Orangeburg, South Carolina, 29118, United States
GSK Investigational Site
Rapid City, South Dakota, 57702, United States
GSK Investigational Site
Salt Lake City, Utah, 84132, United States
GSK Investigational Site
Richmond, Virginia, 23229, United States
GSK Investigational Site
Williamsburg, Virginia, 23188, United States
GSK Investigational Site
La Plata, Buenos Aires, 1900, Argentina
GSK Investigational Site
Mar del Plata, Buenos Aires, 7600, Argentina
GSK Investigational Site
Concepción del Uruguay, Entre Ríos Province, 3260, Argentina
GSK Investigational Site
San Rafael, Mendoza Province, 5600, Argentina
GSK Investigational Site
Rosario, Santa Fe Province, 2000, Argentina
GSK Investigational Site
Buenos Aires, C1121ABE, Argentina
GSK Investigational Site
Buenos Aires, C1425BEN, Argentina
GSK Investigational Site
Mendoza, 5500, Argentina
GSK Investigational Site
Brussels, 1000, Belgium
GSK Investigational Site
Erpent, 5101, Belgium
GSK Investigational Site
Ghent, 9000, Belgium
GSK Investigational Site
Leuven, 3000, Belgium
GSK Investigational Site
Liège, 4000, Belgium
GSK Investigational Site
Pleven, 5800, Bulgaria
GSK Investigational Site
Sofia, 1431, Bulgaria
GSK Investigational Site
Calgary, Alberta, T2N 4Z6, Canada
GSK Investigational Site
Vancouver, British Columbia, V5Z 1M9, Canada
GSK Investigational Site
Winnipeg, Manitoba, R2H 2A6, Canada
GSK Investigational Site
Burlington, Ontario, L7N 3V2, Canada
GSK Investigational Site
St-Charles-Borromée, Ontario, J6E 2B4, Canada
GSK Investigational Site
Toronto, Ontario, M5T 3A9, Canada
GSK Investigational Site
Windsor, Ontario, N8X 5A6, Canada
GSK Investigational Site
Montreal, Quebec, H4J 1C5, Canada
GSK Investigational Site
Sainte-Foy, Quebec, G1V 4G5, Canada
GSK Investigational Site
Trois-Rivières, Quebec, G8T 7A1, Canada
GSK Investigational Site
Brno, 625 00, Czechia
GSK Investigational Site
Hlučín, 748 01, Czechia
GSK Investigational Site
Hradec Králové, 500 05, Czechia
GSK Investigational Site
Kralupy nad Vltavou, 278 01, Czechia
GSK Investigational Site
Olomouc, 775 20, Czechia
GSK Investigational Site
Pilsen, 305 99, Czechia
GSK Investigational Site
Prague, 140 59, Czechia
GSK Investigational Site
Tallinn, 13419, Estonia
GSK Investigational Site
Tallinn, 13619, Estonia
GSK Investigational Site
Tartu, 51014, Estonia
GSK Investigational Site
Brest, 29609, France
GSK Investigational Site
Dijon, 21079, France
GSK Investigational Site
Lille, 59037, France
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Lyon, 69317, France
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Marseille, 13915, France
GSK Investigational Site
Montpellier, 34295, France
GSK Investigational Site
Nantes, 44093, France
GSK Investigational Site
Paris, 75877, France
GSK Investigational Site
Pessac, 33604, France
GSK Investigational Site
Reims, 51092, France
GSK Investigational Site
Bamberg, Bavaria, 96049, Germany
GSK Investigational Site
Munich, Bavaria, 80539, Germany
GSK Investigational Site
Witten, North Rhine-Westphalia, 58452, Germany
GSK Investigational Site
Koblenz, Rhineland-Palatinate, 56068, Germany
GSK Investigational Site
Leipzig, Saxony, 04103, Germany
GSK Investigational Site
Leipzig, Saxony, 04357, Germany
GSK Investigational Site
Schleswig, Schleswig-Holstein, 24837, Germany
GSK Investigational Site
Berlin, 10717, Germany
GSK Investigational Site
Berlin, 12157, Germany
GSK Investigational Site
Berlin, 12203, Germany
GSK Investigational Site
Hamburg, 20354, Germany
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Hamburg, 22299, Germany
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Athens, 106 76, Greece
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Athens, 11527, Greece
GSK Investigational Site
Haidari / Athens, 124 62, Greece
GSK Investigational Site
Rethymnon, Crete, 74100, Greece
GSK Investigational Site
Thessaloniki, 56403, Greece
GSK Investigational Site
Thessaloniki, 56429, Greece
GSK Investigational Site
Thessaloniki, 57010, Greece
GSK Investigational Site
Chieti, Abruzzo, 66100, Italy
GSK Investigational Site
Bari, Apulia, 70124, Italy
GSK Investigational Site
Foggia, Apulia, 71100, Italy
GSK Investigational Site
Parma, Emilia-Romagna, 43100, Italy
GSK Investigational Site
Reggio Emilia, Emilia-Romagna, 42100, Italy
GSK Investigational Site
Florence, Tuscany, 50134, Italy
GSK Investigational Site
Pisa, Tuscany, 56124, Italy
GSK Investigational Site
Amsterdam, 1105 AZ, Netherlands
GSK Investigational Site
Breda, 4818 CK, Netherlands
GSK Investigational Site
Leeuwarden, 8934 AD, Netherlands
GSK Investigational Site
Leiden, 2333 ZA, Netherlands
GSK Investigational Site
Rotterdam, 3045 PM, Netherlands
GSK Investigational Site
Bergen, 5021, Norway
GSK Investigational Site
Oslo, 0405, Norway
GSK Investigational Site
Stavanger, 4011, Norway
GSK Investigational Site
Trondheim, 7006, Norway
GSK Investigational Site
Lima, Lima Province, Lima 27, Peru
GSK Investigational Site
San Martín de Porres, Lima region, Lima 31, Peru
GSK Investigational Site
San Miguel, Lima region, Lima 32, Peru
GSK Investigational Site
Lima, Lima 1, Peru
GSK Investigational Site
Lima, Lima 32, Peru
GSK Investigational Site
Irkutsk, 664043, Russia
GSK Investigational Site
Moscow, 115211, Russia
GSK Investigational Site
Novosibirsk, 630102, Russia
GSK Investigational Site
Saint Petersburg, 198216, Russia
GSK Investigational Site
Saint Petesburg, 195030, Russia
GSK Investigational Site
Sestroretsk, 197706, Russia
GSK Investigational Site
Stavropol, 355030, Russia
GSK Investigational Site
Voronezh, 394066, Russia
GSK Investigational Site
Yekaterinburg, 620109, Russia
GSK Investigational Site
Bojnice, 972 01, Slovakia
GSK Investigational Site
Spišská Nová Ves, 052 01, Slovakia
GSK Investigational Site
Šaľa, 927 01, Slovakia
GSK Investigational Site
Vráble, 952 01, Slovakia
GSK Investigational Site
Alcorcón (Madrid), 28922, Spain
GSK Investigational Site
Alicante, 03004, Spain
GSK Investigational Site
Barcelona, 08041, Spain
GSK Investigational Site
Madrid, 28041, Spain
GSK Investigational Site
Pozuelo de Alarcón/Madrid, 28223, Spain
GSK Investigational Site
Santander, 39008, Spain
GSK Investigational Site
Santiago de Compostela, 15706, Spain
GSK Investigational Site
Valencia, 46026, Spain
GSK Investigational Site
Dnipro, 49074, Ukraine
GSK Investigational Site
Kharkiv, 61093, Ukraine
GSK Investigational Site
Kharkiv, 61124, Ukraine
GSK Investigational Site
Kyiv, 03038, Ukraine
GSK Investigational Site
Kyiv, 03049, Ukraine
GSK Investigational Site
Kyiv, 03680, Ukraine
GSK Investigational Site
Odesa, 65025, Ukraine
GSK Investigational Site
Vinnytsia, 21018, Ukraine
GSK Investigational Site
Vinnytsia, 21029, Ukraine
GSK Investigational Site
Zaporizhia, 69076, Ukraine
GSK Investigational Site
Bradford, BD9 6RJ, United Kingdom
GSK Investigational Site
Oxford, OX3 7LE, United Kingdom
GSK Investigational Site
Plymouth, PL6 8DH, United Kingdom
GSK Investigational Site
Swansea, SA2 8PP, United Kingdom
Related Publications (7)
Lemiere C, Taille C, Lee JK, Smith SG, Mallett S, Albers FC, Bradford ES, Yancey SW, Liu MC. Impact of baseline clinical asthma characteristics on the response to mepolizumab: a post hoc meta-analysis of two Phase III trials. Respir Res. 2021 Jun 22;22(1):184. doi: 10.1186/s12931-021-01767-z.
PMID: 34158028DERIVEDGibson PG, Prazma CM, Chupp GL, Bradford ES, Forshag M, Mallett SA, Yancey SW, Smith SG, Bel EH. Mepolizumab improves clinical outcomes in patients with severe asthma and comorbid conditions. Respir Res. 2021 Jun 7;22(1):171. doi: 10.1186/s12931-021-01746-4.
PMID: 34098955DERIVEDYancey SW, Ortega HG, Keene ON, Bradford ES. Efficacy of add-on mepolizumab in adolescents with severe eosinophilic asthma. Allergy Asthma Clin Immunol. 2019 Sep 3;15:53. doi: 10.1186/s13223-019-0366-x. eCollection 2019.
PMID: 31507641DERIVEDNelsen LM, Cockle SM, Gunsoy NB, Jones P, Albers FC, Bradford ES, Mullerova H. Impact of exacerbations on St George's Respiratory Questionnaire score in patients with severe asthma: post hoc analyses of two clinical trials and an observational study. J Asthma. 2020 Sep;57(9):1006-1016. doi: 10.1080/02770903.2019.1630640. Epub 2019 Jun 28.
PMID: 31251094DERIVEDYancey 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 H, Menzies-Gow A, Llanos JP, Forshag M, Albers F, Gunsoy N, Bradford ES, Yancey SW, Kraft M. Rapid and Consistent Improvements in Morning PEF in Patients with Severe Eosinophilic Asthma Treated with Mepolizumab. Adv Ther. 2018 Jul;35(7):1059-1068. doi: 10.1007/s12325-018-0727-8. Epub 2018 Jun 15.
PMID: 29949045DERIVEDChupp GL, Bradford ES, Albers FC, Bratton DJ, Wang-Jairaj J, Nelsen LM, Trevor JL, Magnan A, Ten Brinke A. Efficacy of mepolizumab add-on therapy on health-related quality of life and markers of asthma control in severe eosinophilic asthma (MUSCA): a randomised, double-blind, placebo-controlled, parallel-group, multicentre, phase 3b trial. Lancet Respir Med. 2017 May;5(5):390-400. doi: 10.1016/S2213-2600(17)30125-X. Epub 2017 Apr 5.
PMID: 28395936DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition 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
October 30, 2014
First Posted
November 3, 2014
Study Start
December 11, 2014
Primary Completion
June 10, 2016
Study Completion
June 10, 2016
Last Updated
August 6, 2018
Results First Posted
May 4, 2017
Record last verified: 2018-08
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.