E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with Severe Asthma |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 18.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003553 |
E.1.2 | Term | Asthma |
E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
● 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 |
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E.2.2 | Secondary objectives of the trial |
● To further describe the long-term clinical experience of mepolizumab in a subset of subjects who demonstrated significant clinical benefit since receiving mepolizumab
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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
Those subjects that do not meet the definition of potentially life threatening asthma must be assessed as having serious debilitating asthma.
Subjects enrolled in MEA115588 or MEA115575 must meet the following criteria:
At randomisation of MEA115588 or MEA115575 must have:
g) A % predicted FEV1 of ≤50% and either
h) ACQ5 score of ≥3 or
i) SGRQ score of ≥60
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 confirms that the subject demonstrated improvement during MEA115588.
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 confirms that the subject demonstrated improvement during MEA115575.
8. 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.
8. Subjects at Significant Safety Risk: If either criteria 6 or 7 are not met, subjects who are considered to be at risk of experiencing a lifethreatening event, or whose functional health status will become significantly worse if returned to standard of care, as judged by the investigator and agreed by GSK. |
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E.4 | Principal 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 a significant protocol deviation in either study MEA115575 or MEA115588 which is deemed by the GSK Medical Monitor to put the subject at risk from further participation.
7. ECG Assessment: A clinically significant ECG abnormality as determined by the investigator. |
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E.5 End points |
E.5.1 | Primary end point(s) |
● Annualized rate of exacerbations
● Frequency of adverse events |
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E.5.1.1 | 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
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E.5.2 | 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 |
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E.5.2.1 | 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
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 11 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 54 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Argentina |
Australia |
Belgium |
Canada |
Chile |
Czech Republic |
France |
Germany |
Italy |
Japan |
Korea, Republic of |
Netherlands |
Poland |
Russian Federation |
Spain |
Ukraine |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |