A Phase 3a, Repeat Dose, Open-label, Long-term Safety Study of Mepolizumab in Asthmatic Subjects

NCT ID: NCT02135692

Last Updated: 2019-12-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 339 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-29
• Study Completion Date: 2017-10-05

Brief Summary

This is a multi-center, open-label, long-term study of subcutaneously (SC) administered mepolizumab 100mg in addition to standard of care (SOC), in subjects with severe eosinophilic asthma. This study will enroll a subset of subjects from Study MEA115661 who have demonstrated clear benefit from therapy and who without continuation of mepolizumab therapy are individuals at greatest risk of serious deterioration of their health status. In order to target individuals at greatest risk for serious deterioration of their health status, only subjects from the MEA115661 study with a history of life-threatening or seriously debilitating asthma, will be allowed to participate. Subjects meeting all of the eligibility criteria for the study will be offered the opportunity to consent for this study of up to 128 weeks in length (including the Follow-Up Visit). This study will give opportunity to extend the collection of clinical data for long-term use and further assess the sustainability of efficacy in a population likely to experience significant loss of asthma control and the need for higher doses of systemic steroids if returned to SOC only.

Conditions

Asthma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Mepolizumab 100 mg

All subjects will receive mepolizumab 100mg administered SC into the upper arm or thigh approximately every 4 weeks.

Group Type: EXPERIMENTAL

Mepolizumab

Intervention Type: BIOLOGICAL

Mepolizumab is a fully humanised IgG antibody (IgG1, kappa) with human heavy and light chain frameworks. Mepolizumab will be supplied as a lyophilised cake in sterile vials for individual use.

SOC

Intervention Type: DRUG

Standard of Care (SOC) will differ by participant, however it will generally include oral corticosteroids and an inhaled controller medicine (an inhaled corticosteroid plus a long acting beta agonist) and/or short acting beta agonists

Interventions

Mepolizumab

Mepolizumab is a fully humanised IgG antibody (IgG1, kappa) with human heavy and light chain frameworks. Mepolizumab will be supplied as a lyophilised cake in sterile vials for individual use.

Intervention Type: BIOLOGICAL

SOC

Standard of Care (SOC) will differ by participant, however it will generally include oral corticosteroids and an inhaled controller medicine (an inhaled corticosteroid plus a long acting beta agonist) and/or short acting beta agonists

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Informed Consent: Prior to commencing any study related activities, subjects must be able and willing to provide written informed consent.
• Male or Eligible Female Subjects: To be eligible for the study, females of child-bearing potential must commit to consistent and correct use of an acceptable method of birth control and for 4 months after the last study drug administration. A urine pregnancy test is required of all females of childbearing potential at the initial Baseline Visit (Visit 1).
• French Subjects Only: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
• MEA115661 Participation: Subjects must have completed Visit 14 of MEA115661.
• Current Anti-Asthma Therapy: The subject's asthma has been treated with an ICS controller medication for the last 8 months with fluticasone propionate (FP) >=500 mcg/day (or equivalent).
• Disease Severity: Subjects must be assessed as having life-threatening /serious debilitating asthma in order to enroll, as defined by the following: Subjects enrolled in MEA115588 must meet one of the following criteria: a) Subject has a history of at least one intubation during their lifetime; b) >=3 asthma exacerbations in the 12 months prior to screening for MEA115588; c) >=1 or more hospitalization for asthma exacerbation in the 12 months prior to screening for MEA115588. Subjects enrolled in MEA115575 must meet one of the following criteria: d) Subject has a history of at least one intubation during their lifetime; e) Their optimized dose at randomization in MEA115575 was >=10mg of prednisone; f) >=1 or more hospitalization for asthma exacerbation in the 12 months prior to screening for MEA115575.
• Clinical Benefit: Subjects must have experienced documented clinical benefit to enroll. Subjects must meet the following criteria demonstrating clinical benefit: Subjects enrolled in MEA115588 who received mepolizumab must meet all of the following criteria: a) Subject must have had a reduction in their exacerbation frequency by >=50% during MEA115588. The baseline for comparison is the total number of exacerbations reported in the 12 months prior to screening for MEA115588. b) The investigator response on the "Clinician-Rated Response to Therapy" questionnaire at Visit 10 was either: mildly improved, moderately improved or significantly improved. Subjects enrolled in MEA115588 who received placebo must meet all of the following criteria: c) Subject must have had a reduction in their exacerbation frequency by >=50% during the first 8 months of MEA115661. The baseline for comparison is the total number of exacerbations reported in the 12 months prior to screening for MEA115588; d) The investigator confirms that the subject demonstrated improvement during MEA115661. Subjects enrolled in MEA115575 who received mepolizumab must meet all of the following criteria: e) Subject must have reduced their oral corticosteroid dose by >=50% during MEA115575. The baseline for comparison is the subject's optimized oral corticosteroid (OCS) dose at randomization in MEA115575; f) The investigator response on the "Clinician-Rated Response to Therapy" questionnaire at Visit 9 was either: mildly improved, moderately improved or significantly improved. Subjects enrolled in MEA115575 who received placebo must meet all of the following criteria: g) Subject must have reduced their oral corticosteroid dose at randomization by >=50% in the first 6 months of MEA115661. The baseline for comparison is the subject's optimized OCS dose at randomization in MEA115575; h) The investigator confirms that the subject demonstrated improvement during MEA115661.

Exclusion Criteria

• Health Status: Clinically significant change in health status during MEA115661 which in the opinion of the investigator would make the subject unsuitable for participation in this long-term study.
• Pregnancy: Subjects who are pregnant or breastfeeding. Subjects should not be enrolled if they plan to become pregnanDeart during the time of study participation.
• Exacerbation History: Subjects who received placebo in MEA115588 and had NO exacerbations during the study.
• Oral Corticosteroid Use: Subjects who received placebo in MEA115575 and were able to discontinue oral corticosteroid therapy by the end of the study.
• Smoking Status: Current smokers
• Previous Significant Protocol Deviation: Subjects who were excluded from the per protocol analysis due to significant protocol deviations in either study MEA115575 or MEA115588.
• Electrocardiogram (ECG) Assessment: A clinically significant ECG abnormality at the exit visit of MEA115661, as determined by the investigator.

• 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

Newport Beach, California, United States

GSK Investigational Site

Riverside, California, United States

GSK Investigational Site

Rolling Hills Estates, California, United States

GSK Investigational Site

Denver, Colorado, United States

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New Haven, Connecticut, United States

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Albany, Georgia, United States

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Baltimore, Maryland, United States

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Rochester, Minnesota, United States

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New York, New York, United States

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Rochester, New York, United States

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Durham, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Cleveland, Ohio, United States

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Hershey, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Salt Lake City, Utah, United States

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Mar del Plata, Buenos Aires, Argentina

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San Rafael, Mendoza Province, Argentina

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Rosario, Santa Fe Province, Argentina

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Buenos Aires, , Argentina

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Mendoza, , Argentina

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New Lambton, New South Wales, Australia

GSK Investigational Site

Bedford Park, South Australia, Australia

GSK Investigational Site

Clayton, Victoria, Australia

GSK Investigational Site

Nedlands, Western Australia, Australia

GSK Investigational Site

Brussels, , Belgium

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Ghent, , Belgium

GSK Investigational Site

Leuven, , Belgium

GSK Investigational Site

Liège, , Belgium

GSK Investigational Site

Calgary, Alberta, Canada

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Edmonton, Alberta, Canada

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Vancouver, British Columbia, Canada

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Winnipeg, Manitoba, Canada

GSK Investigational Site

St-Charles-Borromée, Ontario, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

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Montreal, Quebec, Canada

GSK Investigational Site

Sainte-Foy, Quebec, Canada

GSK Investigational Site

Rancagua, Reg Del Libert Bern Ohiggins, Chile

GSK Investigational Site

Santiago, , Chile

GSK Investigational Site

Talcahuano, , Chile

GSK Investigational Site

Brno, , Czechia

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Olomouc, , Czechia

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Prague, , Czechia

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Prague, , Czechia

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Gières, , France

GSK Investigational Site

Le Kremlin-Bicêtre, , France

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Lille, , France

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Lyon, , France

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Marseille, , France

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Montpellier, , France

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Nantes, , France

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Paris, , France

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Perpignan, , France

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Strasbourg, , France

GSK Investigational Site

Aschaffenburg, Bavaria, Germany

GSK Investigational Site

Rüdersdorf, Brandenburg, Germany

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Frankfurt am Main, Hesse, Germany

GSK Investigational Site

Frankfurt am Main, Hesse, Germany

GSK Investigational Site

Gelnhausen, Hesse, Germany

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Neu-Isenburg, Hesse, Germany

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Hanover, Lower Saxony, Germany

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Mainz, Rhineland-Palatinate, Germany

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Lübeck, Schleswig-Holstein, Germany

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Berlin, , Germany

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Hamburg, , Germany

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Magdeburg, , Germany

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Foggia, Apulia, Italy

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Napoli, Campania, Italy

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Parma, Emilia-Romagna, Italy

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Genoa, Liguria, Italy

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Pietra Ligure (SV), Liguria, Italy

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Perugia, Umbria, Italy

GSK Investigational Site

Cittadella PD, Veneto, Italy

GSK Investigational Site

Chiba, , Japan

GSK Investigational Site

Fukuoka, , Japan

GSK Investigational Site

Fukuoka, , Japan

GSK Investigational Site

Gunma, , Japan

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Hokkaido, , Japan

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Ibaraki, , Japan

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Kanagawa, , Japan

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Okinawa, , Japan

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Osaka, , Japan

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Tokyo, , Japan

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Tokyo, , Japan

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Tokyo, , Japan

GSK Investigational Site

Amsterdam, , Netherlands

GSK Investigational Site

Leeuwarden, , Netherlands

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Bialystok, , Poland

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Krakow, , Poland

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Chelyabinsk, , Russia

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Moscow, , Russia

GSK Investigational Site

Saint Petersburg, , Russia

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Saint Petersburg, , Russia

GSK Investigational Site

Anyang-Si Gyeonggi-do, , South Korea

GSK Investigational Site

Bucheon City, Gyenggi-do, , South Korea

GSK Investigational Site

Cheongju, Chungcheongbuk-do, , South Korea

GSK Investigational Site

Donggu Gwangju, , South Korea

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Seoul, , South Korea

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Seoul, , South Korea

GSK Investigational Site

Suwon-si, Gyeonggi-do, , South Korea

GSK Investigational Site

Alicante, , Spain

GSK Investigational Site

Barcelona, , Spain

GSK Investigational Site

Barcelona, , Spain

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Barcelona, , Spain

GSK Investigational Site

Pozuelo de Alarcón/Madrid, , Spain

GSK Investigational Site

Kharkiv, , Ukraine

GSK Investigational Site

Kiev, , Ukraine

GSK Investigational Site

Mykolaiv, , Ukraine

GSK Investigational Site

Vinnytsia, , Ukraine

GSK Investigational Site

Leicester, Leicestershire, United Kingdom

GSK Investigational Site

Bradford, , United Kingdom

GSK Investigational Site

Plymouth, , United Kingdom

GSK Investigational Site

Southampton, , United Kingdom

Countries

United States; Argentina; Australia; Belgium; Canada; Chile; Czechia; France; Germany; Italy; Japan; Netherlands; Poland; Russia; South Korea; Spain; Ukraine; United Kingdom

References

Khurana 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.

Reference Type: BACKGROUND

PMID: 31447130 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2014-000314-54

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

201312

Identifier Type: -

Identifier Source: org_study_id