A Study to Determine Long-term Safety of Mepolizumab in Asthmatic Subjects

NCT01842607 | Completed Phase 3 Results DMC

• 1 other identifier: 115661
• Study Type: interventional
• Target: 651
• Locations: 19 countries
• Sites: 137

Brief Summary

This is a multi-centre, open-label long-term safety study of 100 milligram (mg) mepolizumab administered subcutaneously (SC) every 4 weeks for 12 months in addition to standard of care in subjects who have severe, refractory asthma and a history of eosinophilic inflammation. Subjects who completed either MEA115588 or MEA115575 will be offered the opportunity to consent for this study.

Conditions

Asthma

Keywords

eosinophils; mepolizumab; SB-240563; safety; extension study; Severe refractory asthma

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events (AEs) Including Both Systemic (i.e. Allergic/Immunoglobulin (Ig)E-mediated and Non-allergic) and Local Site Reactions

  AEs were collected from the Baseline visit until the follow-up visit (approx. 12 weeks post-last dose). Participants were monitored to evaluate the AEs of systemic and local site reaction. AE is defined as any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. On treatment AEs were defined as events occurring from the first dose until 28 days after the last dose of mepolizumab.

  From Baseline visit until the follow-up visit (approximately [approx.] week 60 [12 weeks post-last dose])

Secondary Outcomes (15)

• Number of Participants With Positive Anti-mepolizumab Binding Antibodies and Neutralizing Antibodies (NAb) at the Indicated Time Points

  From Baseline visit until the follow-up visit (approx. week 60 [12 weeks post-last dose])

• Annualized Rate of Exacerbations Per Year

  Baseline up to Exit Visit (approx. 52 weeks) or if Early Withdrawal 4 weeks post last dose

• Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score

  From Baseline visit until the follow-up visit (approx. week 60 [12 weeks post-last dose])

• Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period

  From Baseline and up to Week 52

• Number of Participants Withdrawn Due to Lack of Efficacy and Adverse Events From the Study

  From Baseline visit until the follow-up visit (approx. week 60 [12 weeks post-last dose])

Study Arms (1)

Mepolizumab Arm

EXPERIMENTAL

Subjects will receive 100 mg of Mepolizumab (in polypropylene syringe) injected subcutaneously (SC) once every 4 weeks for 12 months

Biological: Mepolizumab

Interventions

Mepolizumab BIOLOGICAL

Mepolizumab (a fully humanised IgG antibody) 100 mg injected SC once every 4 weeks for 12 months. Mepolizumab will be provided as a lyophilised cake in sterile vials

Mepolizumab Arm

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.
• MEA115588 or MEA115575 study completion: Completion of the double-blind investigational product treatment during MEA115588 or MEA115575.
• Current Anti-Asthma Therapy: Asthma is currently being treated with a controller medication (i.e., inhaled corticosteroids \[ICS\] or other asthma controlled medication) and the subject has been on a controller medication for the past 12 weeks. Subjects will be expected to continue controller therapy for the duration of the study.
• Male or eligible female subjects:
• 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 for the duration of the trial and for 4 months after the last study drug administration.
• A serum pregnancy test is required of all females at the initial Baseline Visit (Visit 1). In addition, a urine pregnancy test will be performed for all females prior to enrollment, during each scheduled study visit prior to the injection of investigational product, and during the Follow-up Visit.

You may not qualify if:

• Hypersensitivity: Hypersensitivity reaction related to study medication during the MEA115588 or MEA115575 that led to patient withdrawal. Subjects who experienced a localized injection site reaction do not need to be excluded.
• Health Status: Clinically significant change in health status during MEA115588 or MEA115575 which in the opinion of the investigator would make the subject unsuitable for participation in this long-term study.
• Malignancy: A current malignancy or malignancy that developed during MEA115588 or MEA115575 (subjects that had localized carcinoma of the skin which was resected for cure will not be excluded). \[Note for South Korea: Korean subjects with a diagnosis of malignancy within 5 years are excluded\]
• Prior SAE: A study related SAE in MEA115588 or MEA115575 that was assessed as possibly related to study medication by the investigator.
• Pregnancy: Subjects who are pregnant or breastfeeding. Subjects should not be enrolled if they plan to become pregnant during the time of study participation.
• ECG: Baseline ECG which has a clinically significant abnormality or which shows corrected QT interval with Fridericia (QTcF) \>=450 millisecond (msec) or QTcF \>=480 msec for subjects with Bundle Branch Block.
• Smoking status: Current smokers
• Liver Function: Liver function tests that meet any of the following during one of the last treatment visits in MEA115588 or MEA115575 : alanine transaminase (ALT) \>=2 x upper limit of normal (ULN); aspartate transaminase (AST) \>=2 x ULN; alkaline phosphatase \>=2 x ULN; Bilirubin \>1.5 x ULN (isolated bilirubin \>1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin is \<35%
• Hepatitis Status: Positive Hepatitis B Surface Antigen (HBsAg) screen at Visit 1
• ECG Over-read: Clinically significant abnormality identified during the central over-read during one of the last treatment visits in MEA115588 or MEA115575

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (137)

GSK Investigational Site

Long Beach, California, 90808, United States

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Newport Beach, California, 92663, United States

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Riverside, California, 92506, United States

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Rolling Hills Estates, California, 90274, United States

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Denver, Colorado, 80206, United States

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New Haven, Connecticut, 06520, United States

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Albany, Georgia, 31707, United States

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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, 27704, United States

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Winston-Salem, North Carolina, 27103, United States

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Cincinnati, Ohio, 45229, United States

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Cincinnati, Ohio, 45231, 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, PA 15213, United States

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Nashville, Tennessee, 37203, United States

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Salt Lake City, Utah, 84132, United States

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Mar del Plata, Buenos Aires, 7600, Argentina

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Mar del Plata, Buenos Aires, B7600FZN, Argentina

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San Rafael, Mendoza Province, 5600, Argentina

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Rosario, Santa Fe Province, S2000DBS, Argentina

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Buenos Aires, C1424BSF, Argentina

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Buenos Aires, C1426ABP, Argentina

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Mendoza, 5500, Argentina

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New Lambton, New South Wales, 2310, 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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Hamilton, Ontario, L8N 4A6, Canada

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Montreal, Quebec, H2W 1T8, Canada

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Montreal, Quebec, H2X 2P4, Canada

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Montreal, Quebec, H4J 1C5, Canada

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Québec, Quebec, G1V 4G5, Canada

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Saint-Charles-Borromée, Quebec, J6E 2B4, Canada

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Trois-Rivières, Quebec, G8T 7A1, Canada

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Rancagua, Reg Del Libert Bern Ohiggins, 2841959, Chile

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Santiago, 8380453, Chile

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Talcahuano, 4270918, Chile

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Brno, 625 00, Czechia

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Olomouc, 775 20, Czechia

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Olomouc, 775 25, Czechia

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Prague, 140 00, Czechia

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Prague, 180 01, Czechia

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Gières, 38610, France

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Le Kremlin-Bicêtre, 94275, 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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Montpellier, 34295, France

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Nantes, 44093, France

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Paris, 75877, France

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Perpignan, 66000, France

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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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Magdeburg, Saxony-Anhalt, 39112, 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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Foggia, Apulia, 71100, Italy

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Napoli, Campania, 80131, Italy

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Parma, Emilia-Romagna, 43100, Italy

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Genoa, Liguria, 16132, Italy

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Pietra Ligure (SV), Liguria, 17027, Italy

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Pisa, Tuscany, 56124, 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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Hiroshima, 732-0052, Japan

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Hokkaido, 070-8644, Japan

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Hyōgo, 672-8064, Japan

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Ibaraki, 319-1113, Japan

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Kanagawa, 252-0392, Japan

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Mie, 515-8544, Japan

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Okinawa, 901-2132, 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, 171-0014, Japan

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Tokyo, 187-0024, Japan

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Guadalajara, Jalisco, 44100, Mexico

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Monterrey, Nuevo León, 64020, Mexico

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Amsterdam, 1105 AZ, Netherlands

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Leeuwarden, 8934 AD, Netherlands

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Bialystok, 15-044, Poland

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Krakow, 31-024, Poland

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Chelyabinsk, 454021, Russia

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Moscow, 123 182, Russia

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Saint Petersburg, 194354, Russia

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Saint Petersburg, 194356, Russia

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Anyang-si, 431-070, South Korea

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Bucheon-si, 420-767, South Korea

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

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Daegu, 705-717, South Korea

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Donggu Gwangju, 501757, South Korea

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Incheon, 405-760, South Korea

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Kangwon-do, 220-701, South Korea

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Seoul, 120-752, South Korea

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Seoul, South Korea

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Suwon, Kyonggi-do, 443-721, South Korea

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Alicante, 03004, Spain

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Barcelona, 08025, Spain

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Barcelona, 08036, Spain

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Barcelona, 08208, Spain

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Pozuelo de Alarcón/Madrid, 28223, Spain

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Kharkiv, 61124, Ukraine

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Kyiv, 03680, Ukraine

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Mykolayiv, 54003, Ukraine

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Vinnytsia, 21018, Ukraine

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Leicester, Leicestershire, LE3 9QP, United Kingdom

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Bradford, BD9 6RJ, United Kingdom

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Liverpool, L9 7AL, United Kingdom

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London, EC1M 6BQ, United Kingdom

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Newcastle upon Tyne, NE1 4LP, United Kingdom

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Plymouth, PL6 8DH, United Kingdom

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Southampton, SO16 6YD, United Kingdom

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Related Publications (5)

• 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.

  PMID: 34098955 DERIVED

• 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.

  PMID: 31507641 DERIVED

• 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 DERIVED

• Ortega 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: 30954640 DERIVED

• Lugogo N, Domingo C, Chanez P, Leigh R, Gilson MJ, Price RG, Yancey SW, Ortega HG. Long-term Efficacy and Safety of Mepolizumab in Patients With Severe Eosinophilic Asthma: A Multi-center, Open-label, Phase IIIb Study. Clin Ther. 2016 Sep;38(9):2058-2070.e1. doi: 10.1016/j.clinthera.2016.07.010. Epub 2016 Aug 21.

  PMID: 27553751 DERIVED

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Asthma

Interventions

mepolizumab

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

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

Study Record Dates

• First Submitted: April 25, 2013
• First Posted: April 29, 2013
• Study Start: May 27, 2013
• Primary Completion: March 13, 2015
• Study Completion: March 13, 2015
• Last Updated: August 6, 2018
• Results First Posted: March 3, 2016

Record last verified: 2018-08

Data Sharing

• IPD Sharing: Will share

Locations

NL (2); CL (3); UA (4); PL (2); CA (11); ES (5); AU (4); ME (2); CZ (5); KR (10); JP (17); RU (4); US (20); DE (12); IT (8); GB (7); AR (7); FR (10); BE (4)