Study of Benralizumab (KHK4563) in Patients With Eosinophilic Chronic Rhinosinusitis

Study Overview
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Brief Summary
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The objective of this study is to evaluate the efficacy and safety of SC administrations of Benralizumab or Placebo in the subjects with Eosinophilic Chronic Rhinosinusitis in a multicenter, randomized, double-blind, placebo-controlled study. The pharmacokinetics and immunogenicity will be assessed secondarily.

Detailed Description
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Screening Period (maximum 4 weeks) , Randomized Treatment Period (24 weeks)

Official Title
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A Phase 2, Double-Blind, Placebo-Controlled Study of Benralizumab (KHK4563) in Patients With Eosinophilic Chronic Rhinosinusitis

Conditions
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Eosinophilic Chronic Rhinosinusitis

Intervention / Treatment
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* Drug: benralizumab
* Drug: benralizumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients 20 years to 75 years of age Eosinophilic chronic rhinosinusitis with a total score of ≥ 11 according to the diagnosis of eosinophilic chronic rhinosinusitis at enrollment A minimum bilateral nasal polyp score of 3 out of the maximum score of 8 (with a score of at least 1 out of the maximum score of 4 for each nostril) at screening and at enrollment Weight of ≥ 40 kg at screening Exclusion Criteria: A Sino-Nasal Outcome Test-22 (SNOT-22) score of < 7 at enrollment Any nasal surgery (including polypectomy) within 1 year prior to the date of consent Hospitalization for ≥ 24 hours for treatment of asthma exacerbation, within 12 weeks prior to the date of consent Exposure to any commercially available (e.g., omalizumab) or investigational biologic agent within 16 weeks or 5 half-lives prior to enrollment, whichever is longer Use of systemic corticosteroids (including oral corticosteroids) or corticosteroid nasal solution (except spraying) within 4 weeks prior to enrollment or planned use of such medications during the double-blind period Prior treatment with benralizumab

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: benralizumab A<br>Subcutaneous (SC) administration | Drug: benralizumab<br>* SC administration<br>|
| Experimental: benralizumab B<br>SC administration | Drug: benralizumab<br>* SC administration<br>|
| Placebo Comparator: Placebo<br>Placebo SC administration | Drug: Placebo<br>* SC administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change from baseline in nasal polyp score at Week 12 |  | baseline and 12 weeks post-dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The change from baseline in nasal polyp score |  | Pre-dose and 4,8,12,16,20,24 weeks post-dose | 
| The change from baseline in Computed tomography (CT) score |  | baseline and 12 weeks post-dose | 
| Number of subjects discontinued from the study due to aggravation of eosinophilic chronic rhinosinusitis |  | Up to 24 weeks after dosing | 
| Time to discontinuation (days) from the study due to aggravation of eosinophilic chronic rhinosinusitis |  | Up to 24 weeks after dosing | 
| The change from baseline in Blood eosinophil count |  | Pre-dose and 4,8,12,16,20,24 weeks post-dose | 
| The change from baseline in Nasal Airway Resistance | Nasal airway resistance (Pa/cm^3/s) | Pre-dose and 4,8,12,24 weeks post-dose | 
| The change from baseline in the averaged values of the Olfactory thresholds | Olfactory thresholds are assessed by T&T Olfactometer Test Score (Five kinds of smell with eight (5 to -2) phases). | Pre-dose and 4,8,12,24 weeks post-dose | 
| The change from baseline in the improvement of olfactory dysfunction | Olfactory dysfunction (1 to 5) is calculated by the Olfactory thresholds. | Pre-dose and 4,8,12,24 weeks post-dose | 
| The change from baseline in Sino-Nasal Outcome Test-2 (SNOT-22) | Symptom score are assessed by VAS (nasal congestion, anterior and posterior nasal drip, loss of the sense of smell, headache, and impairment in activity of daily living) | Pre-dose and 4,8,12, 16, 20, 24 weeks post-dose | 
| The change from baseline in Symptom score by Visual Analog Scale (VAS) | Symptom score are assessed by VAS (nasal congestion, anterior and posterior nasal drip, loss of the sense of smell, headache, and impairment in activity of daily living) | Pre-dose and 4,8,12, 16, 20, 24 weeks post-dose | 
| Incidence of treatment-emergent adverse events (TEAEs) or drug-related TEAEs and their nature |  | Up to 24 weeks after dosing |