E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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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] - Ear, nose and throat diseases [C09] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028756 |
E.1.2 | Term | Nasal polyps |
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 define the effect of mepolizumab in reducing the need for surgery, defined as reduced endoscopic polyp score and symptom score after six months of dosing. |
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E.2.2 | Secondary objectives of the trial |
• To investigate the effects of 750 mg doses of mepolizumab on nasal polyp size in subjects with severe bilateral nasal polyposis.
• To investigate actual requirement for polyp surgery during the study between the treatment groups.
• To further assess the safety and tolerability of mepolizumab in subjects with severe bilateral nasal polyposis.
• To assess effects of mepolizumab on associated lower respiratory tract symptoms, inflammation and function.
• To assess effects of mepolizumab on clinical PD assessments.
• To characterise the population PK and PK-PD of mepolizumab.
• Investigation of immunogenicity.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subjects have a diagnosis of severe bilateral nasal polyposis at the screening visit and Visit 1 (i.e. at end of run-in period) which meets the definition of the situation indicative of the need for surgery.
2. Subjects must have had at least one previous surgery for the removal of nasal polyps.
3. Subjects must have an history of refractory response to steroid therapy as shown by being deemed potentially eligible for surgery.
4. Male or female between 18 and 70 years of age, inclusive.
5. BMI within the range 19.0 to 31.0 kg/m2 (inclusive).
6. Subjects must be free of any clinically significant disease that would interfere with the study schedule or procedures or compromise his/her safety.
7. Subjects with concurrent asthma must be maintained on no more than 10mg/day of Prednisolone or the equivalent.
8. Female subjects of childbearing potential must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from 1 month prior to first dose of study medication until four months after last dose of study medication.
9. Male subjects must agree to use one of the contraception methods listed in the protocol. This criterion must be followed from the time of the first dose of study medication until four months after last dose of study medication. |
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E.4 | Principal exclusion criteria |
1. As a result of medical interview, physical examination, or screening investigation the physician responsible considers the subject unfit for the study.
2. Subjects requiring oral corticosteroids at a dose greater than 10mg Prednisolone or equivalent during the study will be terminated from the study.
3. Subjects who have had an asthma exacerbation requiring admission to hospital within 4 weeks of Screening.
4. Subjects who have received immunotherapy within the previous 12 months.
5. Subjects with a positive pre-study drug/alcohol screen.
6. Subjects who are currently receiving, or have received within 3 months prior to first mepolizumab dose, chemotherapy, radiotherapy or investigational medications/therapies.
7. Subjects with one or more of the following abnormal laboratory values:
• Serum creatinine > 3 times institutional ULN
• AST or/ALT > 5 times institutional ULN
• Platelet count < 50,000/µL
8. Subjects with a history of allergic reaction to anti-IL-5 or other antibody therapy.
9. Pregnant females.
10. Breastfeeding/Lactating females.
11. Subjects who currently smoke or have smoked in the last 6 months. |
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E.5 End points |
E.5.1 | Primary end point(s) |
• Number of subjects with reduced need for surgery at the end of Part A (based on the assessment of nasal polyposis at Visit 8).
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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) |
1. Endoscopic nasal polyp score dynamics for 750 mg dose levels and placebo subjects.
2. The number of subjects requiring polyp surgery per treatment group.
3. Vital signs, ECGs, and safety laboratory parameters and incidence of treatment
4. FEV1, FVC, and PEFR parameters.
5. Clinical PD assessments: Symptoms, PnIF, Olfaction testing, Questionnaires
6. Population PK, PK-PD parameters: Systemic clearance, volume of distribution,covariate effects on systemic levels, between- and within-subject variability in PK parameters.
7. Anti-mepolizumab antibody testing.
8. Population PK, PK-PD parameters (continued) : systemic and tissue (nasal secretion) potency for eosinophil inhibition and Emax if data permit. Systemic exposure- clinical outcome relationship.
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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 | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 6 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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 | 4 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 4 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |