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

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

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.

Study Overview

• Status: Completed
• Conditions: Eosinophilic Chronic Rhinosinusitis
• Intervention / Treatment: Drug: Placebo; Drug: benralizumab

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 2

Contacts and Locations

Study Locations

• Japan
  • Tokyo, Japan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: benralizumab A; Subcutaneous (SC) administration	Drug: benralizumab; SC administration
EXPERIMENTAL: benralizumab B; SC administration	Drug: benralizumab; SC administration
PLACEBO_COMPARATOR: Placebo; Placebo SC administration	Drug: Placebo; SC administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Other Outcome Measures

Outcome Measure	Time Frame
Serum concentration of benralizumab	Pre-dose and 4, 8, 12, 16, 20, 24 days post-dose

Collaborators and Investigators

• Sponsor: Kyowa Kirin Co., Ltd.

Publications and helpful links

General Publications

• Tokunaga T, Sakashita M, Haruna T, Asaka D, Takeno S, Ikeda H, Nakayama T, Seki N, Ito S, Murata J, Sakuma Y, Yoshida N, Terada T, Morikura I, Sakaida H, Kondo K, Teraguchi K, Okano M, Otori N, Yoshikawa M, Hirakawa K, Haruna S, Himi T, Ikeda K, Ishitoya J, Iino Y, Kawata R, Kawauchi H, Kobayashi M, Yamasoba T, Miwa T, Urashima M, Tamari M, Noguchi E, Ninomiya T, Imoto Y, Morikawa T, Tomita K, Takabayashi T, Fujieda S. Novel scoring system and algorithm for classifying chronic rhinosinusitis: the JESREC Study. Allergy. 2015 Aug;70(8):995-1003. doi: 10.1111/all.12644. Epub 2015 May 26.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 1, 2016
• Primary Completion (ACTUAL): March 27, 2017
• Study Completion (ACTUAL): March 27, 2017

Study Registration Dates

• First Submitted: April 25, 2016
• First Submitted That Met QC Criteria: May 11, 2016
• First Posted (ESTIMATE): May 13, 2016

Study Record Updates

• Last Update Posted (ACTUAL): April 23, 2018
• Last Update Submitted That Met QC Criteria: April 20, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Otorhinolaryngologic Diseases; Paranasal Sinus Diseases; Nose Diseases; Sinusitis; Anti-Asthmatic Agents; Respiratory System Agents; Benralizumab
• Other Study ID Numbers: 4563-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO