E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with severe, refractory asthma and a history of eosinophilic inflammation. |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Body processes [G] - Circulatory and Respiratory Physiological Phenomena [G09] |
MedDRA Classification |
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 |
The primary objective of this study is to describe the long-term safety profile of mepolizumab. |
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E.2.2 | Secondary objectives of the trial |
To provide long-term treatment with mepolizumab to subjects who participated in MEA112997.
To evaluate the effects of mepolizumab on a range of clinical markers of asthma control. |
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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 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. MEA112997 Study Participation: Received at least 2 doses of double-blind investigational product during the MEA112997 trial.
3. MEA112997 Treatment Assignment: If the subject received mepolizumab, they must have had a positive risk: benefit ratio in the opinion of the investigator.
4. Current Anti-Asthma Therapy: Asthma is currently being treated with a controller 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.
5. 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 (see appendix 2 of the protocol) 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 Screening Visit (Visit 1). In addition, a urine pregnancy test will be performed for all females prior to Visit 2, during each scheduled study visit prior to the injection of investigational product, and during the Follow-up Visit.
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. |
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E.4 | Principal exclusion criteria |
Subjects meeting any of the following criteria must not be enrolled in the study:
1. Immunogenicity: Positive neutralizing antibody status based on the last sample obtained during the MEA112997 study.
2. Hypersensitivity: Report of a hypersensitivity reaction assessed as related to mepolizumab that led to patient withdrawal. Subjects who experienced a localized injection-site reaction do not need to be excluded.
3. Health Status: Clinically significant change in health status since completing participation in the MEA112997 trial which in the opinion of the investigator would make the subject unsuitable for participation in this long term study.
4. Cardiovascular: Subjects who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment. Including but not limited to:
• known ejection fraction of <30% OR
• severe heart failure meeting New York Heart Association Class IV (see Protocol Appendix 6) classification OR
• hospitalised in the 12 months prior to Visit 1 for severe heart failure meeting New York Heart Association Class III (see Appendix 6) OR
• angina diagnosed less than 3 months prior to Visit 1 or at Visit 1
5. Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior to screening (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]
6. Prior SAE: For those subjects who had a SAE in MEA112997 that was assessed as possibly related to mepolizumab by the investigator
7. Pregnancy: Subjects who are pregnant or breastfeeding. Subjects should not be enrolled if they plan to become pregnant during the time of study participation.
8. ECG: Screening ECG which has a clinically significant abnormality or which shows QTcF > 450msec or QTcF >480msec for subjects with Bundle Branch Block.
9. Xolair: Received Xolair (omalizumab) within the past 130 days
10. Clinical trial: Participated in a clinical trial within the past 30 days or have received investigational medication within five terminal half-lives of Screen Visit, whichever is longer.
11. Smoking status: Current smokers
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E.5 End points |
E.5.1 | Primary end point(s) |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Interim data analysis will occur at least yearly. |
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E.5.2 | Secondary end point(s) |
• Frequency of positive anti-mepolizumab binding antibodies and neutralizing
antibodies
• Annualized rate of exacerbations
• Asthma Control Questionnaire score
• FEV1 measured by clinic spirometry
• 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/IgE-mediated and non-allergic) and local site reactions
• 12 Lead ECG parameters
• Vital signs
• Clinical Laboratory Parameters |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Interim data analysis will occur at least yearly. |
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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 | 8 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 21 |
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 |
Canada |
Chile |
France |
Germany |
Korea, Republic of |
Poland |
Romania |
Russian Federation |
Ukraine |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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 | 3 |
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 | 3 |
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 |