Clinical trial NCT02135692: A Phase 3a, Repeat Dose, Open-label, Long-term Safety Study of Mepolizumab in Asthmatic Subjects
Official title: A Multi-Centre, Open-Label, Study of Mepolizumab in a Subset of Subjects With a History of Life Threatening/Seriously Debilitating Asthma Who Participated in the MEA115661 Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Asthma
Keywords: Severe eosinophilic asthma
Extension study
Expanded access
Safety
Mepolizumab
Eosinophils
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2014-05-12
Enrollment: 339
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-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.


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.

Primary outcomes:
measure: Annualized Rate of On-treatment Exacerbations Per Year
timeFrame: Baseline (Week 0) to Week 172
measure: Number of Participants With Any On-treatment Adverse Event (AE) or On-treatment Serious AE (SAE)
timeFrame: Baseline (Week 0) to Week 172
Secondary outcomes:
measure: Mean Change From Baseline in Asthma Control Questionnaire (ACQ)-5 On-treatment Score
timeFrame: Baseline (Week 0) to Week 168
measure: Mean Change From Baseline in On-treatment Clinic Pre-bronchodilator FEV1
timeFrame: Baseline (Week 0) to Week 168
measure: Number of Participants Withdrawn From the Study Due to Lack of Efficacy and Adverse Events
timeFrame: Baseline (Week 0) to Week 172
measure: Number of Participants Hospitalized Due to Adverse Events Including Asthma Exacerbations
timeFrame: Baseline (Week 0) to Week 172
measure: Number of Participants With AEs Including Both Systemic (Allergic and Non-allergic) and Local Site Reactions
timeFrame: Baseline (Week 0) to Week 172
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 12-lead Electrocardiogram (ECG)
timeFrame: Baseline (Week 0) to Week 172
measure: Number of Participants With Maximum Change From Baseline in QTcB and QTcF Interval for ECG Assessed at Any Time Post Baseline
timeFrame: Baseline (Week 0) to Week 172
measure: Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure
timeFrame: Baseline (Week 0) to Week 168
measure: Change From Baseline in Pulse Rate
timeFrame: Baseline (Week 0) to Week 168
measure: Number of Participants With Positive Anti-mepolizumab Binding Antibodies (ADA) and Neutralizing Antibodies (NAb)
timeFrame: Baseline (Week 0) to Week 172
measure: Number of Participants With Potential Clinical Importance Values for Change From Baseline Relative to the Reference Range for Clinical Chemistry Parameters at Any Time Post-Baseline
timeFrame: Baseline (Week 0) to Week 172
measure: Number of Participants With Potential Clinical Importance Values for Change From Baseline Relative to the Reference Range for Hematology Parameters at Any Time Post-Baseline
timeFrame: Baseline (Week 0) to Week 172
Other outcomes:
Locations:
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: 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: 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: 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: 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: St-Charles-Borromée
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: Sainte-Foy
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: 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: Kremlin-Bicêtre
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: 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: Magdeburg
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: 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: Hokkaido
country: Japan
facility: GSK Investigational Site
city: Ibaraki
country: Japan
facility: GSK Investigational Site
city: Kanagawa
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: Anyang-Si Gyeonggi-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Bucheon city, Gyenggi-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Cheongju, Chungcheongbuk-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Donggu Gwangju
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-si, Gyeonggi-do
country: Korea, Republic of
facility: GSK Investigational Site
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: Kiev
country: Ukraine
facility: GSK Investigational Site
city: Mykolaiv
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: 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: 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.