E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hypereosinophilic syndrome (HES) |
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E.1.1.1 | Medical condition in easily understood language |
Hypereosinophilic syndrome (HES) |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10048643 |
E.1.2 | Term | Hypereosinophilic syndrome |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Safety: To assess the long-term AE profile associated with mepolizumab therapy.
Efficacy: To characterize individual dosing requirements for control of disease. |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. In accordance with local procedures, written informed consent/assent can be obtained from the subject or legally authorized representative 2. ≥ 12 years of age at the time of signing the informed consent/assent 3. Meets the diagnostic criteria for HES as defined by: - Eosinophilia >1500 cells/μl for at least 6 months with evidence of symptoms and signs of organ system involvement or dysfunction that can be directly related to eosinophilia (with no evidence of parasitic, allergic or other recognised causes of eosinophilia such as connective tissues disease, malignancy) or - Eosinophilia of >1500 cells/μl for less than 6 months and meet the other criteria for HES accompanied by clear evidence of eosinophil tissue infiltration and with exclusion of secondary causes of eosinophilia as above.
4. Subjects meeting all three of the following criteria will be eligible: - The indication, HES, is a seriously debilitating or life-threatening disease; - There is no satisfactory alternative treatment: documented failure (lack of efficacy or a contra-indication) to at least 3 standard therapies (corticosteroids, cytotoxic agents, immunomodulatory therapy, and Imatinib mesylate) at the appropriate duration and dose or demonstrated clinical benefit from prior treatment with mepolizumab; and - There is reason to believe that the benefit:risk ratio for mepolizumab in the indication is positive. |
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E.4 | Principal exclusion criteria |
1. Subjects without HES but with other conditions associated with eosinophilic pathological processes such as Eosinophilic Granulomatosis with Polyangiitis [EGPA], Wegener’s Granulomatosis, atopic disorders, parasitic infections, eosinophilic gastroenteropathies. 2. Female subjects of childbearing potential who are not using a highly effective method of contraception: Consistent and correct use of an acceptable method of birth control for one month prior to the start of the investigational product and until 16 weeks after the last dose (see Section 12.2 of the protocol for a list of acceptable methods of contraception). 3. Pregnant or lactating females 4. Subjects with severe/life-threatening underlying disease unrelated to HES where life expectancy is estimated to be less than 3 months 5. Subjects with a history of or current malignancy: - Subjects with a history of or current lymphoma - Subjects with current malignancy or previous history of cancer in remission for less than 12 months prior to the first dose. Subjects that had localized carcinoma (i.e., basal or squamous cell) of the skin which was resected for cure will not be excluded. 6. Subjects with history of serious allergic reaction (hypersensitivity/anaphylaxis) to anti-IL5 or other antibody therapy or known or suspected hypersensitivity to any component of mepolizumab, leading to treatment discontinuation 7. Subjects with current drug or alcohol abuse where uncertain compliance with the protocol and/or with the medical management instruction of the investigator may cause safety risk.
8. Subjects who have received treatment with an investigational agent (biologic or nonbiologic, excluding mepolizumab) within the past 30 days or 5 drug half-lives whichever is longer, prior to the administration of mepolizumab under this protocol.The term “investigational” applies to any drug not approved for sale in the country in which it is being used or investigational formulations of marketed products.
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E.5 End points |
E.5.1 | Primary end point(s) |
Serious AEs (SAEs). Non-serious AEs related to mepolizumab as assessed by the investigator |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
-Mean 28-day SC dose (mg) for the last 3 administrations |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | Yes |
E.7.1.3.1 | Other trial type description |
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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.8.3 |
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 | 1 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 10 |
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 |
Australia |
Canada |
United States |
France |
Poland |
Romania |
Spain |
Germany |
Belgium |
Norway |
Russian Federation |
United Kingdom |
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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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As this is an open label extension study, there is no defined end of trial other than until the product becomes commercially available. |
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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 | 5 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 28 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 28 |