Subjects with Severe Asthma MedDRA version: 16.1 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects eligible for enrolment in the study must additionally meet all of the following criteria: 1. Informed Consent: Prior to commencing any study related activities, subjects must be able and willing to provide written informed consent. 2. 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. Methods of acceptable birth control and the definitions for child-bearing and non-child bearing potential are provided in Appendix 1 of study protocol. A urine pregnancy test is required of all females of childbearing potential at the initial Baseline Visit (Visit 1). 3. 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. 4. MEA115661 Participation: Subjects must have completed Visit 14 of MEA115661. 5. 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). 6. 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 7. 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 OCS dose at randomization in MEA115575 f) The investigator response on the “Clinician-Rated Response to Therapy” questionnaire at Visit
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. 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. 2. Pregnancy: Subjects who are pregnant or breastfeeding. Subjects should not be enrolled if they plan to become pregnant during the time of study participation. 3. Exacerbation History: Subjects who received placebo in MEA115588 and had NO exacerbations during the study. 4. Oral Corticosteroid Use: Subjects who received placebo in MEA115575 and were able to discontinue oral corticosteroid therapy by the end of the study. 5. Smoking Status: Current smokers 6. Previous Significant Protocol Deviation: Subjects who were excluded from the per protocol analysis due to significant protocol deviations in either study MEA115575 or MEA115588. 7. ECG Assessment: A clinically significant ECG abnormality at the exit visit of MEA115661, as determined by the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: ? To provide extended treatment with mepolizumab to subjects with a history of lifethreatening or seriously debilitating asthma and a history of improved disease control while receiving mepolizumab as defined by this protocol;Secondary Objective: ? To further describe the long-term clinical experience of mepolizumab in a subset of subjects who demonstrated significant clinical benefit since receiving mepolizumab ;Primary end point(s): ? Annualized rate of exacerbations ? Frequency of adverse events;Timepoint(s) of evaluation of this end point: Interim analysis will be performed as needed in order to provide open-label safety data to inform the risk-benefit assessment of mepolizumab in severe asthma | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? Asthma Control Questionnaire-5 score ? Forced expiratory volume in 1 second (FEV1) ? Number of withdrawals due to lack of efficacy ? Number of withdrawals due to adverse events ? Number of hospitalizations due to adverse events including asthma exacerbations ? Frequency of both systemic (i.e., allergic and non-allergic) and local site reactions ? 12-lead ECG parameters ? Vital signs ? Frequency of positive anti-mepolizumab binding antibodies/neutralizing antibodies ? Clinical Laboratory Parameters;Timepoint(s) of evaluation of this end point: Interim analysis will be performed as needed in order to provide open-label safety data to inform the risk-benefit assessment of mepolizumab in severe asthma | — |
Countries
Argentina, Australia, Belgium, Canada, Chile, Czech Republic, France, Germany, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Russian Federation, Spain, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Trials Helpdesk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed