E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patient with Eosinophilic Chronic Rhinosinusitis with Nasal Polyps |
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E.1.1.1 | Medical condition in easily understood language |
Chronic Rhinosinusitis with Nasal polyposis (CRSwNP) is a chronic inflammatory disease of the nasal mucosa characterized by the presence of polyps in the upper nasal cavity. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
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 |
To evaluate the effect of benralizumab on nasal polyp burden (assessed by nasal endoscopy) and patient-reported nasal blockage (NB). |
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of benralizumab on: • Sense of Smell • Sinus Opacification by computed tomography (CT) scan • Disease specific health-related quality of life (HRQoL) • Nasal polyp surgery • Systemic corticosteroid (SCS) use • Symptoms associated with CRSwNP |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Female or male patients aged 18 to 75 years inclusive 2. Stable Intranasal corticosteroids (INCS) use for at least 4 weeks prior to enrolment and throughout screening 3. History of treatment with systemic corticosteroids (SCS) or prior surgery for CRSwNP 4. Bilateral sinonasal polyposis with a nasal polyp score (NPS) of 5 at enrolment and randomization (unilateral score of at least 2 for each nostril) 5. Ongoing symptoms for at least 12 weeks prior to enrolment 6. Patient-reported moderate to severe nasal blockage score (NBS) ≥2 at enrolment 7. Bi-weekly mean NBS ≥ 1.5 at randomization 8. SNOT-22 total score ≥ 20 at enrolment and randomization 9. Documented physician-diagnosed asthma 10. Blood eosinophil count of >2% or ≥150/μL at enrolment |
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E.4 | Principal exclusion criteria |
1. Any nasal and/or sinus surgery within 3 months prior to enrolment 2. Patients with conditions that makes them non evaluable for the co-primary efficacy endpoint including but not limited to: • Unilateral antrochoanal polyps • Nasal septal deviation that occludes at least one nostril • Current rhinitis medicamentosa • Allergic fungal rhinosinusitis or allergic fungal sinusitis;
3. Clinically important comorbidities that may put the patient at risk, or may confound interpretation of clinical efficacy and/or safety results 4. Receipt of SCS for within 4 weeks prior to screening, or a scheduled SCS treatment during the study period. 5. Receipt of any marketed or investigational biologic product within 6 months of enrolment 6. Currently pregnant or breastfeeding |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change form baseline in endoscopic total nasal polyp score (NPS) Change form baseline in mean nasal blockage score(NBS) |
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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) |
• Change from baseline in difficulty with sense of smell (DSS) score • Change from baseline in Lund Mackay score • Change from baseline in SinoNasal Outcome Test (SNOT-22) score. • Time to first nasal polyp surgery • Time to first SCS course for NP • Change from baseline in nasal symptom score(s) |
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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 | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
open label extension after double blind parallel group duration |
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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 | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 40 |
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 |
China |
Japan |
Russian Federation |
Taiwan |
Thailand |
Turkey |
United States |
Vietnam |
Belgium |
France |
Hungary |
Italy |
Poland |
Sweden |
Argentina |
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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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The end of study is planned to be when the last randomized patient completes one year in the open label extension. |
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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 | 8 |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 7 |