A Phase IIa Study of KHK4563

Study Overview
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Brief Summary
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This is a double-blind, placebo-controlled dose-ranging study of KHK4563 to evaluate the effect of multiple-dose subcutaneous administration of KHK4563 on the annual asthma exacerbation rate in adult subjects with uncontrolled, suspected eosinophilic asthma.

Official Title
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A Phase IIa , Double-blind, Placebo-controlled Dose-ranging Study to Evaluate the Efficacy and Safety of KHK4563 in Adults With Uncontrolled, Suspected Eosinophilic Asthma

Conditions
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Uncontrolled and Suspected Eosinophilic Asthma

Intervention / Treatment
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* Drug: KHK4563
* Drug: KHK4563
* Drug: KHK4563
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 20 through 75 years at the time of Week -3 visit. Written informed consent obtained from the subject prior to performing any protocol-related procedures, including screening evaluations. Physician prescribed daily use of medium-dose or high-dose ICS plus LABA or any combination of sequential dosing of either medium-dose or high-dose ICS/LABA for at least 12 months prior to Week -3 visit. Dose must be stable for at least 30 days prior to Week -3 visit. At least 2, but not more than 6, documented asthma exacerbations in the 12 months prior to Week -3 visit that required use of a systemic corticosteroid burst. Exclusion Criteria Any condition (eg, any eosinophilic lower respiratory disease other than asthma, Churg-Strauss syndrome, hypereosinophilic syndrome, eosinophilic bronchitis, eosinophilic pneumonia, chronic obstructive pulmonary disease (COPD), bronchiectasis or cystic fibrosis (CF)) that, in the opinion of the investigator or Medical Expert, would interfere with evaluation of the investigational product or interpretation of subject safety or study results. Any clinically relevant abnormal findings in physical examination, vital signs, hematology, clinical chemistry, or urinalysis during screening period, which in the opinion of the investigator, may put the subject at risk because of his/her participation in the study, or may influence the results of the study, or the subject's ability to participate in the study. Acute upper or lower respiratory infections requiring antibiotics or antiviral medications within 30 days prior to Week -3 visit or during the screening period.

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: 2mg<br>sterile lyophilized formulation, 2mg | Drug: KHK4563<br>* every 4 weeks for the first 3 doses on Weeks 0 (Day 1), 4, and 8 and then every 8 weeks thereafter for the last 4 doses on Weeks 16, 24, 32, and 40.<br>|
| Experimental: 20mg<br>sterile lyophilized formulation, 20mg | Drug: KHK4563<br>* every 4 weeks for the first 3 doses on Weeks 0 (Day 1), 4, and 8 and then every 8 weeks thereafter for the last 4 doses on Weeks 16, 24, 32, and 40.<br>|
| Experimental: 100mg<br>sterile lyophilized formulation, 100mg | Drug: KHK4563<br>* every 4 weeks for the first 3 doses on Weeks 0 (Day 1), 4, and 8 and then every 8 weeks thereafter for the last 4 doses on Weeks 16, 24, 32, and 40.<br>|
| Placebo Comparator: Placebo<br>two SC administration on day 1 | Drug: Placebo<br>* every 4 weeks for the first 3 doses on Weeks 0 (Day 1), 4, and 8 and then every 8 weeks thereafter for the last 4 doses on Weeks 16, 24, 32, and 40.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| evaluation of the effect of multiple-dose subcutaneous(SC) administration of benralizumab on the annual asthma exacerbation rate in adult subjects with uncontrolled, suspected eosinophilic asthma. | annual asthma exacerbation rate | Immediately following the first administration of study drug through Study Week 52. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary function as assessed by Forced Expiratory Volume in 1 Second (FEV1) and Peak Expiratory flow (PEF) | Pre-dose/pre-bronchodilator Forced Expiratory Volume in 1 Second ( FEV1 ) at the study centre, morning and evening peak expiratory flow (PEF) | From first administration of study drug through Study Week 52. | 
| Asthma control as assessed by ASTHMA CONTROL QUESTIONNAIRE6(ACQ6) | ASTHMA CONTROL QUESTIONNAIRE6(ACQ6) | From first administration of study drug through Study Week 52. | 
| Number of participants with Adverse Events as a Measure of Safety and Tolerability | Adverse Events/Serious Adverse Events (AE/SAE) - Laboratory variables - ECG (Electrocardiogram) - Physical Examination | From first administration of study drug through Study Week 68. | 
| Time Profiles of Serum Concentration | Serum benralizumab concentration | From first administration of study drug through Study Week 68 | 
| Immunogenicity by serum incidence rate of positive anti-drug antibody | Anti-drug antibodies (ADA) | From first administration of study drug through Study Week 68 |