Efficacy and Safety Study of Mepolizumab Adjunctive Therapy in Participants With Severe Eosinophilic Asthma on Markers of Asthma Control

NCT ID: NCT02281318

Last Updated: 2018-08-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 556 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-11
• Study Completion Date: 2016-06-10

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.

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Mepolizumab SC

Participants 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

Group Type: EXPERIMENTAL

Mepolizumab

Intervention Type: BIOLOGICAL

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

SOC

Intervention Type: DRUG

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

Placebo SC

Participants 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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Sterile 0.9% sodium chloride solution

SOC

Intervention Type: DRUG

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

Interventions

Mepolizumab

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

Intervention Type: BIOLOGICAL

Placebo

Sterile 0.9% sodium chloride solution

Intervention Type: DRUG

SOC

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

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.
• French participants: In France, a participant will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

Exclusion Criteria

• 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.
• Adherence: Participants who have known evidence of lack of adherence to controller medications and/or ability to follow physician's recommendations.
• Previous participation: Previously participated in any study with mepolizumab and received investigational product (including placebo)

• Minimum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Birmingham, Alabama, United States

GSK Investigational Site

Birmingham, Alabama, United States

GSK Investigational Site

Fresno, California, United States

GSK Investigational Site

Long Beach, California, United States

GSK Investigational Site

Newport Beach, California, United States

GSK Investigational Site

Riverside, California, United States

GSK Investigational Site

Rolling Hills Estates, California, United States

GSK Investigational Site

Upland, California, United States

GSK Investigational Site

Denver, Colorado, United States

GSK Investigational Site

New Haven, Connecticut, United States

GSK Investigational Site

Aventura, Florida, United States

GSK Investigational Site

Orlando, Florida, United States

GSK Investigational Site

Baltimore, Maryland, United States

GSK Investigational Site

Rochester, Minnesota, United States

GSK Investigational Site

Rochester, New York, United States

GSK Investigational Site

Durham, North Carolina, United States

GSK Investigational Site

Gastonia, North Carolina, United States

GSK Investigational Site

Cincinnati, Ohio, United States

GSK Investigational Site

Upland, Pennsylvania, United States

GSK Investigational Site

Orangeburg, South Carolina, United States

GSK Investigational Site

Rapid City, South Dakota, United States

GSK Investigational Site

Salt Lake City, Utah, United States

GSK Investigational Site

Richmond, Virginia, United States

GSK Investigational Site

Williamsburg, Virginia, United States

GSK Investigational Site

La Plata, Buenos Aires, Argentina

GSK Investigational Site

Mar del Plata, Buenos Aires, Argentina

GSK Investigational Site

Concepción del Uruguay, Entre Ríos Province, Argentina

GSK Investigational Site

San Rafael, Mendoza Province, Argentina

GSK Investigational Site

Rosario, Santa Fe Province, Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Buenos Aires, , Argentina

GSK Investigational Site

Mendoza, , Argentina

GSK Investigational Site

Brussels, , Belgium

GSK Investigational Site

Erpent, , Belgium

GSK Investigational Site

Ghent, , Belgium

GSK Investigational Site

Leuven, , Belgium

GSK Investigational Site

Liège, , Belgium

GSK Investigational Site

Pleven, , Bulgaria

GSK Investigational Site

Sofia, , Bulgaria

GSK Investigational Site

Calgary, Alberta, Canada

GSK Investigational Site

Vancouver, British Columbia, Canada

GSK Investigational Site

Winnipeg, Manitoba, Canada

GSK Investigational Site

Burlington, Ontario, Canada

GSK Investigational Site

St-Charles-Borromée, Ontario, Canada

GSK Investigational Site

Toronto, Ontario, Canada

GSK Investigational Site

Windsor, Ontario, Canada

GSK Investigational Site

Montreal, Quebec, Canada

GSK Investigational Site

Sainte-Foy, Quebec, Canada

GSK Investigational Site

Trois-Rivières, Quebec, Canada

GSK Investigational Site

Brno, , Czechia

GSK Investigational Site

Hlučín, , Czechia

GSK Investigational Site

Hradec Králové, , Czechia

GSK Investigational Site

Kralupy nad Vltavou, , Czechia

GSK Investigational Site

Olomouc, , Czechia

GSK Investigational Site

Pilsen, , Czechia

GSK Investigational Site

Prague, , Czechia

GSK Investigational Site

Tallinn, , Estonia

GSK Investigational Site

Tallinn, , Estonia

GSK Investigational Site

Tartu, , Estonia

GSK Investigational Site

Brest, , France

GSK Investigational Site

Dijon, , France

GSK Investigational Site

Lille, , France

GSK Investigational Site

Lyon, , France

GSK Investigational Site

Marseille, , France

GSK Investigational Site

Montpellier, , France

GSK Investigational Site

Nantes, , France

GSK Investigational Site

Paris, , France

GSK Investigational Site

Pessac, , France

GSK Investigational Site

Reims, , France

GSK Investigational Site

Bamberg, Bavaria, Germany

GSK Investigational Site

Munich, Bavaria, Germany

GSK Investigational Site

Witten, North Rhine-Westphalia, Germany

GSK Investigational Site

Koblenz, Rhineland-Palatinate, Germany

GSK Investigational Site

Leipzig, Saxony, Germany

GSK Investigational Site

Leipzig, Saxony, Germany

GSK Investigational Site

Schleswig, Schleswig-Holstein, Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Berlin, , Germany

GSK Investigational Site

Hamburg, , Germany

GSK Investigational Site

Hamburg, , Germany

GSK Investigational Site

Athens, , Greece

GSK Investigational Site

Athens, , Greece

GSK Investigational Site

Haidari / Athens, , Greece

GSK Investigational Site

Rethymnon, Crete, , Greece

GSK Investigational Site

Thessaloniki, , Greece

GSK Investigational Site

Thessaloniki, , Greece

GSK Investigational Site

Thessaloniki, , Greece

GSK Investigational Site

Chieti, Abruzzo, Italy

GSK Investigational Site

Bari, Apulia, Italy

GSK Investigational Site

Foggia, Apulia, Italy

GSK Investigational Site

Parma, Emilia-Romagna, Italy

GSK Investigational Site

Reggio Emilia, Emilia-Romagna, Italy

GSK Investigational Site

Florence, Tuscany, Italy

GSK Investigational Site

Pisa, Tuscany, Italy

GSK Investigational Site

Amsterdam, , Netherlands

GSK Investigational Site

Breda, , Netherlands

GSK Investigational Site

Leeuwarden, , Netherlands

GSK Investigational Site

Leiden, , Netherlands

GSK Investigational Site

Rotterdam, , Netherlands

GSK Investigational Site

Bergen, , Norway

GSK Investigational Site

Oslo, , Norway

GSK Investigational Site

Stavanger, , Norway

GSK Investigational Site

Trondheim, , Norway

GSK Investigational Site

Lima, Lima Province, Peru

GSK Investigational Site

San Martín de Porres, Lima region, Peru

GSK Investigational Site

San Miguel, Lima region, Peru

GSK Investigational Site

Lima, , Peru

GSK Investigational Site

Lima, , Peru

GSK Investigational Site

Irkutsk, , Russia

GSK Investigational Site

Moscow, , Russia

GSK Investigational Site

Novosibirsk, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

GSK Investigational Site

Saint Petesburg, , Russia

GSK Investigational Site

Sestroretsk, , Russia

GSK Investigational Site

Stavropol, , Russia

GSK Investigational Site

Voronezh, , Russia

GSK Investigational Site

Yekaterinburg, , Russia

GSK Investigational Site

Bojnice, , Slovakia

GSK Investigational Site

Spišská Nová Ves, , Slovakia

GSK Investigational Site

Šaľa, , Slovakia

GSK Investigational Site

Vráble, , Slovakia

GSK Investigational Site

Alcorcón (Madrid), , Spain

GSK Investigational Site

Alicante, , Spain

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Madrid, , Spain

GSK Investigational Site

Pozuelo de Alarcón/Madrid, , Spain

GSK Investigational Site

Santander, , Spain

GSK Investigational Site

Santiago de Compostela, , Spain

GSK Investigational Site

Valencia, , Spain

GSK Investigational Site

Dnipro, , Ukraine

GSK Investigational Site

Kharkiv, , Ukraine

GSK Investigational Site

Kharkiv, , Ukraine

GSK Investigational Site

Kyiv, , Ukraine

GSK Investigational Site

Kyiv, , Ukraine

GSK Investigational Site

Kyiv, , Ukraine

GSK Investigational Site

Odesa, , Ukraine

GSK Investigational Site

Vinnytsia, , Ukraine

GSK Investigational Site

Vinnytsia, , Ukraine

GSK Investigational Site

Zaporizhia, , Ukraine

GSK Investigational Site

Bradford, , United Kingdom

GSK Investigational Site

Oxford, , United Kingdom

GSK Investigational Site

Plymouth, , United Kingdom

GSK Investigational Site

Swansea, , United Kingdom

Countries

United States; Argentina; Belgium; Bulgaria; Canada; Czechia; Estonia; France; Germany; Greece; Italy; Netherlands; Norway; Peru; Russia; Slovakia; Spain; Ukraine; United Kingdom

References

Gibson 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.

Reference Type: DERIVED

PMID: 34098955 (View on PubMed)

Yancey 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.

Reference Type: DERIVED

PMID: 31507641 (View on PubMed)

Nelsen 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.

Reference Type: DERIVED

PMID: 31251094 (View on PubMed)

Yancey 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.

Reference Type: DERIVED

PMID: 31047111 (View on PubMed)

Ortega 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.

Reference Type: DERIVED

PMID: 29949045 (View on PubMed)

Chupp 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.

Reference Type: DERIVED

PMID: 28395936 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34158028 (View on PubMed)

Study Documents

Document Type: Dataset Specification

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Clinical Study Report

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Annotated Case Report Form

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Individual Participant Data Set

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Study Protocol

For additional information about this study please refer to the GSK Clinical Study Register

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Document Type: Informed Consent Form

For additional information about this study please refer to the GSK Clinical Study Register

View Document

Document Type: Statistical Analysis Plan

For additional information about this study please refer to the GSK Clinical Study Register

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Related Links

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Other Identifiers

200862

Identifier Type: -

Identifier Source: org_study_id