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

NCT02135692 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: 2013122014-000314-54
• Study Type: interventional
• Target: 339
• Locations: 18 countries
• Sites: 114

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

Keywords

Severe eosinophilic asthma; Extension study; Expanded access; Safety; Mepolizumab; Eosinophils

Outcome Measures

Primary Outcomes (2)

• Annualized Rate of On-treatment Exacerbations Per Year

  Exacerbations are defined as the worsening of asthma which requires use of systemic corticosteroids intravenous (IV) or oral steroid like prednisone, for at least 3 days or a single intramuscular (IM) corticosteroid (CS) dose is required. For maintenance systemic corticosteroids, at least double the existing maintenance dose for at least 3 days was required) and/or hospitalization and/or emergency department (ED) visit. On-Treatment data between first dose date and earliest of Withdrawal date/last dose + 28 days was considered for analysis. Analysis of the number of exacerbations was performed using a negative binomial generalized linear model.

  Baseline (Week 0) to Week 172

• Number of Participants With Any On-treatment Adverse Event (AE) or On-treatment Serious AE (SAE)

  An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention or event associated with liver injury and impaired liver function were categorized as SAE. On-treatment AEs and on-treatment SAEs are the events occurring on/after the first dose of open-label mepolizumab date and before/on last dose+28 days.

  Baseline (Week 0) to Week 172

Secondary Outcomes (12)

• Mean Change From Baseline in Asthma Control Questionnaire (ACQ)-5 On-treatment Score

  Baseline (Week 0) to Week 168

• Mean Change From Baseline in On-treatment Clinic Pre-bronchodilator FEV1

  Baseline (Week 0) to Week 168

• Number of Participants Withdrawn From the Study Due to Lack of Efficacy and Adverse Events

  Baseline (Week 0) to Week 172

• Number of Participants Hospitalized Due to Adverse Events Including Asthma Exacerbations

  Baseline (Week 0) to Week 172

• Number of Participants With AEs Including Both Systemic (Allergic and Non-allergic) and Local Site Reactions

  Baseline (Week 0) to Week 172

Study Arms (1)

Mepolizumab 100 mg

EXPERIMENTAL

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

Biological: Mepolizumab; Drug: SOC

Interventions

Mepolizumab 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.

Mepolizumab 100 mg

SOC 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

Mepolizumab 100 mg

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (114)

GSK Investigational Site

Newport Beach, California, 92663, United States

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Riverside, California, 92506-0174, United States

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Rolling Hills Estates, California, 90274, United States

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GSK Investigational Site

Denver, Colorado, 80206, United States

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GSK Investigational Site

New Haven, Connecticut, 06510, United States

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GSK Investigational Site

Albany, Georgia, 31707, United States

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GSK Investigational Site

Baltimore, Maryland, 21224, United States

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Rochester, Minnesota, 55905, United States

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New York, New York, 10029, United States

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Rochester, New York, 14642, United States

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Durham, North Carolina, 27705, United States

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Winston-Salem, North Carolina, 27103, United States

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Cleveland, Ohio, 44195, United States

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Hershey, Pennsylvania, 17033, United States

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Pittsburgh, Pennsylvania, 15213, United States

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Salt Lake City, Utah, 84112, United States

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Mar del Plata, Buenos Aires, 7600, Argentina

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San Rafael, Mendoza Province, Argentina

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Rosario, Santa Fe Province, S2000DBS, Argentina

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Buenos Aires, C1424BSF, Argentina

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Mendoza, 5500, Argentina

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New Lambton, New South Wales, 2305, Australia

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Bedford Park, South Australia, 5042, Australia

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Clayton, Victoria, 3168, Australia

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Nedlands, Western Australia, 6009, Australia

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Brussels, 1020, Belgium

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Ghent, 9000, Belgium

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Leuven, 3000, Belgium

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Liège, 4000, Belgium

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Calgary, Alberta, T2N 4Z6, Canada

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Edmonton, Alberta, T6G 2G3, Canada

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Vancouver, British Columbia, V5Z 1M9, Canada

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Winnipeg, Manitoba, R2H 2A6, Canada

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St-Charles-Borromée, Ontario, J6E 2B4, Canada

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Montreal, Quebec, H2W 1T8, Canada

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Montreal, Quebec, H2X 2P2, Canada

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Montreal, Quebec, H4J 1C5, Canada

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Sainte-Foy, Quebec, G1V 4G5, Canada

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Rancagua, Reg Del Libert Bern Ohiggins, 2843099, Chile

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Santiago, 8380453, Chile

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Talcahuano, 4270918, Chile

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GSK Investigational Site

Brno, 625 00, Czechia

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Olomouc, 775 20, Czechia

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Prague, 140 59, Czechia

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GSK Investigational Site

Prague, 180 01, Czechia

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Gières, 38610, France

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Le Kremlin-Bicêtre, 94270, France

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Lille, 59037, France

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Lyon, 69317, France

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Marseille, 13915, France

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GSK Investigational Site

Montpellier, 34295, France

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GSK Investigational Site

Nantes, 44093, France

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Paris, 75877, France

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Perpignan, 66000, France

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GSK Investigational Site

Strasbourg, 67091, France

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Aschaffenburg, Bavaria, 63739, Germany

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Rüdersdorf, Brandenburg, 15562, Germany

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Frankfurt am Main, Hesse, 60389, Germany

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Frankfurt am Main, Hesse, 60596, Germany

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Gelnhausen, Hesse, 63571, Germany

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Neu-Isenburg, Hesse, 63263, Germany

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Hanover, Lower Saxony, 30173, Germany

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Mainz, Rhineland-Palatinate, 55131, Germany

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Lübeck, Schleswig-Holstein, 23552, Germany

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Berlin, 10367, Germany

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Hamburg, 22299, Germany

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Magdeburg, 39120, Germany

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Foggia, Apulia, 71100, Italy

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Napoli, Campania, 80131, Italy

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Parma, Emilia-Romagna, 43125, Italy

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Genoa, Liguria, 16132, Italy

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Pietra Ligure (SV), Liguria, 17027, Italy

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Perugia, Umbria, 06156, Italy

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Cittadella PD, Veneto, 35013, Italy

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Chiba, 296-8602, Japan

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Fukuoka, 802-0052, Japan

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Fukuoka, 811-1394, Japan

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Gunma, 370-0615, Japan

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Hokkaido, 070-8644, Japan

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Ibaraki, 319-1113, Japan

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Kanagawa, 252-0392, Japan

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Okinawa, 904-2293, Japan

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Osaka, 596-8501, Japan

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Tokyo, 102-0083, Japan

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Tokyo, 103-0027, Japan

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Tokyo, 187-0024, Japan

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GSK Investigational Site

Amsterdam, 1105 AZ, Netherlands

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GSK Investigational Site

Leeuwarden, 8934 AD, Netherlands

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GSK Investigational Site

Bialystok, 15-044, Poland

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Krakow, 31-024, Poland

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GSK Investigational Site

Chelyabinsk, 454106, Russia

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Moscow, 123182, Russia

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Saint Petersburg, 194354, Russia

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GSK Investigational Site

Saint Petersburg, 194356, Russia

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GSK Investigational Site

Anyang-Si Gyeonggi-do, 431-070, South Korea

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GSK Investigational Site

Bucheon City, Gyenggi-do, 420-767, South Korea

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Cheongju, Chungcheongbuk-do, 361-711, South Korea

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GSK Investigational Site

Donggu Gwangju, 501757, South Korea

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Seoul, 120-752, South Korea

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Seoul, 156-755, South Korea

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GSK Investigational Site

Suwon-si, Gyeonggi-do, 443-380, South Korea

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GSK Investigational Site

Alicante, 03004, Spain

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GSK Investigational Site

Barcelona, 08036, Spain

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GSK Investigational Site

Barcelona, 08041, Spain

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GSK Investigational Site

Barcelona, 08208, Spain

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GSK Investigational Site

Pozuelo de Alarcón/Madrid, 28223, Spain

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GSK Investigational Site

Kharkiv, 61124, Ukraine

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GSK Investigational Site

Kiev, 03680, Ukraine

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GSK Investigational Site

Mykolaiv, 54003, Ukraine

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GSK Investigational Site

Vinnytsia, 21018, Ukraine

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GSK Investigational Site

Leicester, Leicestershire, LE3 9QP, United Kingdom

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GSK Investigational Site

Bradford, BD9 6RJ, United Kingdom

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Plymouth, PL6 8DH, United Kingdom

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GSK Investigational Site

Southampton, SO16 6YD, United Kingdom

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Related Publications (1)

• 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.

  PMID: 31447130 BACKGROUND

MeSH Terms

Conditions

Asthma; Pulmonary Eosinophilia

Interventions

mepolizumab

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Hypereosinophilic Syndrome; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: May 8, 2014
• First Posted: May 12, 2014
• Study Start: May 29, 2014
• Primary Completion: October 5, 2017
• Study Completion: October 5, 2017
• Last Updated: December 3, 2019
• Results First Posted: May 2, 2018

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD is available via the Clinical Study Data Request site (click on the link provided below)
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.

Locations

RU (4); FR (10); UA (4); GB (4); BE (4); CZ (4); CL (3); PL (2); JP (12); ES (5); US (16); IT (7); KR (7); AR (5); CA (9); NL (2); AU (4); DE (12)