Clinical trial NCT01842607: A Study to Determine Long-term Safety of Mepolizumab in Asthmatic Subjects
Official title: A Multi-centre, Open-label, Long-term Safety Study of Mepolizumab in Asthmatic Subjects Who Participated in theMEA115588 or MEA115575 Trials
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Keywords: eosinophils
mepolizumab
SB-240563
safety
extension study
Severe refractory asthma
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2013-04-29
Enrollment: 651
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* French subjects: 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.
* 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.

Exclusion Criteria:

* 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

Primary outcomes:
measure: Number of Participants With Adverse Events (AEs) Including Both Systemic (i.e. Allergic/Immunoglobulin (Ig)E-mediated and Non-allergic) and Local Site Reactions
timeFrame: From Baseline visit until the follow-up visit (approximately [approx.] week 60 [12 weeks post-last dose])
Secondary outcomes:
measure: Number of Participants With Positive Anti-mepolizumab Binding Antibodies and Neutralizing Antibodies (NAb) at the Indicated Time Points
timeFrame: From Baseline visit until the follow-up visit (approx. week 60 [12 weeks post-last dose])
measure: Annualized Rate of Exacerbations Per Year
timeFrame: Baseline up to Exit Visit (approx. 52 weeks) or if Early Withdrawal 4 weeks post last dose
measure: Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score
timeFrame: From Baseline visit until the follow-up visit (approx. week 60 [12 weeks post-last dose])
measure: Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period
timeFrame: From Baseline and up to Week 52
measure: Number of Participants Withdrawn Due to Lack of Efficacy and Adverse Events From the Study
timeFrame: From Baseline visit until the follow-up visit (approx. week 60 [12 weeks post-last dose])
measure: Number of Participants Hospitalized Due to Exacerbations and Adverse Events
timeFrame: From Baseline visit until the follow-up visit (approx. week 60 [12 weeks post-last dose])
measure: Number of Participants With Systemic (i.e., Allergic/IgE-mediated and Non-allergic) and Local Site Reactions
timeFrame: From Baseline visit until the follow-up visit (approx. week 60 [12 weeks post-last dose])
measure: Number of Participants With Electrocardiogram (ECG) Findings at Any Time Post Baseline
timeFrame: From Baseline visit until the follow-up visit (approx. week 60 [12 weeks post-last dose])
measure: Mean Change From Baseline in QT Interval Corrected by Bazett's Method (QTcB) and QT Interval Corrected by Fridericia's Method (QTcF) Values for ECG Assessed at Baseline, Week 28, Week 52 and at Follow-up Visit (Approx. 12 Weeks Post-last Dose)
timeFrame: From Baseline visit until the follow-up visit (approx. week 60 [12 weeks post-last dose])
measure: Number of Participants With Maximum Change From Baseline in QTcF Interval for ECG Assessed at Any Time Post Baseline
timeFrame: From Baseline visit until the follow-up visit (approx. week 60 [12 weeks post-last dose])
measure: Number of Participants With Maximum Change From Baseline in QTcB Interval for ECG Assessed at Any Time Post Baseline
timeFrame: From Baseline visit until the follow-up visit (approx. week 60 [12 weeks post-last dose])
measure: Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure Assessed at Week 52
timeFrame: Baseline and Week 52
measure: Change From Baseline in Pulse Rate Assessed at Week 52
timeFrame: Baseline and Week 52
measure: Number of Participants With Clinical Chemistry Parameters Outside the Normal Range at Any Time Post-baseline
timeFrame: From Baseline visit until the follow-up visit (approx. week 60 [12 weeks post-last dose])
measure: Number of Participants With Haematology Laboratory Parameters Outside the Normal Range at Any Time Post-baseline
timeFrame: From Baseline visit until the follow-up visit (approx. week 60 [12 weeks post-last dose])
Other outcomes:
Locations:
city: Long Beach
country: United States
facility: GSK Investigational Site
state: California
city: Newport Beach
country: United States
facility: GSK Investigational Site
state: California
city: Riverside
country: United States
facility: GSK Investigational Site
state: California
city: Rolling Hills Estates
country: United States
facility: GSK Investigational Site
state: California
city: Denver
country: United States
facility: GSK Investigational Site
state: Colorado
city: New Haven
country: United States
facility: GSK Investigational Site
state: Connecticut
city: Albany
country: United States
facility: GSK Investigational Site
state: Georgia
city: Baltimore
country: United States
facility: GSK Investigational Site
state: Maryland
city: Rochester
country: United States
facility: GSK Investigational Site
state: Minnesota
city: New York
country: United States
facility: GSK Investigational Site
state: New York
city: Rochester
country: United States
facility: GSK Investigational Site
state: New York
city: Durham
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Winston-Salem
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Cincinnati
country: United States
facility: GSK Investigational Site
state: Ohio
city: Cleveland
country: United States
facility: GSK Investigational Site
state: Ohio
city: Hershey
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: Nashville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Salt Lake City
country: United States
facility: GSK Investigational Site
state: Utah
city: Mar del Plata
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: Mar del Plata
country: Argentina
facility: GSK Investigational Site
state: Buenos Aires
city: San Rafael
country: Argentina
facility: GSK Investigational Site
state: Mendoza
city: Rosario
country: Argentina
facility: GSK Investigational Site
state: Santa Fe
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autónoma de Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Mendoza
country: Argentina
facility: GSK Investigational Site
city: New Lambton
country: Australia
facility: GSK Investigational Site
state: New South Wales
city: Bedford Park
country: Australia
facility: GSK Investigational Site
state: South Australia
city: Clayton
country: Australia
facility: GSK Investigational Site
state: Victoria
city: Nedlands
country: Australia
facility: GSK Investigational Site
state: Western Australia
city: Bruxelles
country: Belgium
facility: GSK Investigational Site
city: Gent
country: Belgium
facility: GSK Investigational Site
city: Leuven
country: Belgium
facility: GSK Investigational Site
city: Liège
country: Belgium
facility: GSK Investigational Site
city: Calgary
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Edmonton
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Vancouver
country: Canada
facility: GSK Investigational Site
state: British Columbia
city: Winnipeg
country: Canada
facility: GSK Investigational Site
state: Manitoba
city: Hamilton
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Montreal
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Quebec City
country: Canada
facility: GSK Investigational Site
state: Quebec
city: St-Charles-Borromée
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Trois Rivieres
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Rancagua
country: Chile
facility: GSK Investigational Site
state: Reg Del Libert Bern Ohiggins
city: Santiago
country: Chile
facility: GSK Investigational Site
city: Talcahuano
country: Chile
facility: GSK Investigational Site
city: Brno
country: Czechia
facility: GSK Investigational Site
city: Olomouc
country: Czechia
facility: GSK Investigational Site
city: Olomouc
country: Czechia
facility: GSK Investigational Site
city: Praha 4
country: Czechia
facility: GSK Investigational Site
city: Praha 8
country: Czechia
facility: GSK Investigational Site
city: Gières
country: France
facility: GSK Investigational Site
city: Le Kremlin-Bicêtre Cedex
country: France
facility: GSK Investigational Site
city: Lille cedex
country: France
facility: GSK Investigational Site
city: Lyon cedex 04
country: France
facility: GSK Investigational Site
city: Marseille cedex 20
country: France
facility: GSK Investigational Site
city: Montpellier cedex 5
country: France
facility: GSK Investigational Site
city: Nantes cedex 1
country: France
facility: GSK Investigational Site
city: Paris Cedex 18
country: France
facility: GSK Investigational Site
city: Perpignan
country: France
facility: GSK Investigational Site
city: Strasbourg
country: France
facility: GSK Investigational Site
city: Aschaffenburg
country: Germany
facility: GSK Investigational Site
state: Bayern
city: Ruedersdorf
country: Germany
facility: GSK Investigational Site
state: Brandenburg
city: Frankfurt
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Frankfurt
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Gelnhausen
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Neu-Isenburg
country: Germany
facility: GSK Investigational Site
state: Hessen
city: Hannover
country: Germany
facility: GSK Investigational Site
state: Niedersachsen
city: Mainz
country: Germany
facility: GSK Investigational Site
state: Rheinland-Pfalz
city: Magdeburg
country: Germany
facility: GSK Investigational Site
state: Sachsen-Anhalt
city: Luebeck
country: Germany
facility: GSK Investigational Site
state: Schleswig-Holstein
city: Berlin
country: Germany
facility: GSK Investigational Site
city: Hamburg
country: Germany
facility: GSK Investigational Site
city: Napoli
country: Italy
facility: GSK Investigational Site
state: Campania
city: Parma
country: Italy
facility: GSK Investigational Site
state: Emilia-Romagna
city: Genova
country: Italy
facility: GSK Investigational Site
state: Liguria
city: Pietra Ligure (SV)
country: Italy
facility: GSK Investigational Site
state: Liguria
city: Foggia
country: Italy
facility: GSK Investigational Site
state: Puglia
city: Pisa
country: Italy
facility: GSK Investigational Site
state: Toscana
city: Perugia
country: Italy
facility: GSK Investigational Site
state: Umbria
city: Cittadella (PD)
country: Italy
facility: GSK Investigational Site
state: Veneto
city: Chiba
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Gunma
country: Japan
facility: GSK Investigational Site
city: Hiroshima
country: Japan
facility: GSK Investigational Site
city: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Hyogo
country: Japan
facility: GSK Investigational Site
city: Ibaraki
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Mie
country: Japan
facility: GSK Investigational Site
city: Okinawa
country: Japan
facility: GSK Investigational Site
city: Okinawa
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Tokyo
country: Japan
facility: GSK Investigational Site
city: Anyang-Si
country: Korea, Republic of
facility: GSK Investigational Site
city: Bucheon-si,
country: Korea, Republic of
facility: GSK Investigational Site
city: Cheongju, Chungcheongbuk-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Daegu
country: Korea, Republic of
facility: GSK Investigational Site
city: Donggu Gwangju
country: Korea, Republic of
facility: GSK Investigational Site
city: Incheon
country: Korea, Republic of
facility: GSK Investigational Site
city: Kangwon-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Suwon, Kyonggi-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Guadalajara
country: Mexico
facility: GSK Investigational Site
state: Jalisco
city: Monterrey
country: Mexico
facility: GSK Investigational Site
state: Nuevo León
city: Amsterdam
country: Netherlands
facility: GSK Investigational Site
city: Leeuwarden
country: Netherlands
facility: GSK Investigational Site
city: Bialystok
country: Poland
facility: GSK Investigational Site
city: Krakow
country: Poland
facility: GSK Investigational Site
city: Chelyabinsk
country: Russian Federation
facility: GSK Investigational Site
city: Moscow
country: Russian Federation
facility: GSK Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: St. Petersburg
country: Russian Federation
facility: GSK Investigational Site
city: Alicante
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Pozuelo De Alarcón/Madrid
country: Spain
facility: GSK Investigational Site
city: Kharkiv
country: Ukraine
facility: GSK Investigational Site
city: Kyiv
country: Ukraine
facility: GSK Investigational Site
city: Mykolayiv
country: Ukraine
facility: GSK Investigational Site
city: Vinnytsia
country: Ukraine
facility: GSK Investigational Site
city: Leicester
country: United Kingdom
facility: GSK Investigational Site
state: Leicestershire
city: Bradford
country: United Kingdom
facility: GSK Investigational Site
city: Liverpool
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: Newcastle Upon Tyne
country: United Kingdom
facility: GSK Investigational Site
city: Plymouth
country: United Kingdom
facility: GSK Investigational Site
city: Southampton
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.