Benralizumab Airway Remodeling Study in Severe Eosinophilic Asthmatics (CHINOOK)

A Phase 4, Multicenter, Randomized, Double-blind, Parallel Group, Placebo Controlled Study to Evaluate the Effect of Benralizumab on Structural and Lung Function Changes in Severe Eosinophilic Asthmatics

The purpose of the study is to evaluate effect of benralizumab on structural and lung function changes in severe eosinophilic asthmatics.

Changes will be assessed over 48 week treatment period in patients with persistent symptoms despite standard therapy of inhaled corticosteroids (ICS) plus long acting B2-agonist (LABA) with or without additional controller medication.

Patients who complete treatment will enter 4 weeks follow-up period.

Study Overview

• Status: Recruiting
• Conditions: Asthma
• Intervention / Treatment: Biological: Benralizumab; Biological: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 81
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • Recruiting
      • Research Site
    • Edmonton, Alberta, Canada, T6G 2G3
      • Withdrawn
      • Research Site
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • Withdrawn
      • Research Site
• Denmark
  • Aarhus N, Denmark, 8200
    • Recruiting
    • Research Site
  • Hvidovre, Denmark, 2650
    • Recruiting
    • Research Site
  • København NV, Denmark, 2400
    • Recruiting
    • Research Site
  • Naestved, Denmark, 4700
    • Recruiting
    • Research Site
  • Odense C, Denmark, 5000
    • Recruiting
    • Research Site
  • Vejle, Denmark, 7100
    • Recruiting
    • Research Site
  • Ålborg, Denmark, 9000
    • Recruiting
    • Research Site
• Sweden
  • Göteborg, Sweden, 413 45
    • Recruiting
    • Research Site
  • Lund, Sweden, 221 85
    • Recruiting
    • Research Site
• United Kingdom
  • Cambridge, United Kingdom, CB2 2QQ
    • Recruiting
    • Research Site
  • Headington, United Kingdom, OX3 9DU
    • Recruiting
    • Research Site
  • Leicester, United Kingdom, LE3 9QP
    • Not yet recruiting
    • Research Site
  • Liverpool, United Kingdom, L7 8XP
    • Recruiting
    • Research Site
  • London, United Kingdom, W1G 8HU
    • Recruiting
    • Research Site
  • London, United Kingdom, SW3 6HP
    • Not yet recruiting
    • Research Site
  • Wythenshawe, United Kingdom, M23 9LT
    • Recruiting
    • Research Site
• United States
  • California
    • Los Angeles, California, United States, 90033
      • Recruiting
      • Research Site
  • Florida
    • Jacksonville, Florida, United States, 32204
      • Not yet recruiting
      • Research Site
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Withdrawn
      • Research Site
  • Indiana
    • Indianapolis, Indiana, United States, 46268
      • Not yet recruiting
      • Research Site
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Recruiting
      • Research Site
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Recruiting
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Withdrawn
      • Research Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • Research Site
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Research Site
  • Missouri
    • Saint Louis, Missouri, United States, 63156
      • Recruiting
      • Research Site
  • New York
    • Port Jefferson Station, New York, United States, 11776
      • Withdrawn
      • Research Site
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Withdrawn
      • Research Site
    • New Bern, North Carolina, United States, 28562
      • Active, not recruiting
      • Research Site
    • Winston-Salem, North Carolina, United States, 27104
      • Active, not recruiting
      • Research Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Withdrawn
      • Research Site
    • Philadelphia, Pennsylvania, United States, 19107
      • Withdrawn
      • Research Site
    • Pittsburgh, Pennsylvania, United States, 15213
      • Active, not recruiting
      • Research Site
    • Sayre, Pennsylvania, United States, 18840
      • Withdrawn
      • Research Site
  • South Carolina
    • Spartanburg, South Carolina, United States, 29303
      • Not yet recruiting
      • Research Site
  • Texas
    • Galveston, Texas, United States, 77555
      • Recruiting
      • Research Site
    • McKinney, Texas, United States, 75069
      • Not yet recruiting
      • Research Site
  • Virginia
    • Williamsburg, Virginia, United States, 23188
      • Withdrawn
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female aged 18 through 70 years.
2. Physician-diagnosed asthma requiring continuous treatment with medium- or high-dose ICS plus LABA with or without additional controller medication for at least 12 months prior to Visit 1, and current treatment with high-dose ICS plus LABA for at least 3 months prior to Visit 1 with or without additional asthma maintenance medication.
3. Morning pre-BD FEV1 ≥50 to <80% of predicted normal value (PNV) and ≥1 liter (L) or morning pre-BD FEV1 ≥ 50 to < 90% of PNV, if historical pre-BD FEV1 value (within 12 months prior to screening visit) was < 80% of PNV.
4. A blood eosinophil count meeting any of 3 criteria: ≥300 cells/µL during screening or ≥ 220 to < 300 cells/μL during screening and documented eosinophil count of ≥ 300 cells/μL in the past 12 months, or ≥150 to <300 cells/µL during screening plus one of the following: presence of nasal polyps or pre-BD FVC <65% predicted at Visit 2
5. Negative pregnancy test.
6. Asthma control questionnaire (ACQ-6) >1.5.
7. Fewer than 12 exacerbations within the 6 months prior to Visit 3.

Exclusion Criteria:

1. Any disease or concomitant medication which could affect study results or safety of study participants, including:

   • current smokers
   • history of cancer
   • life-threatening asthma
   • clinically important pulmonary disease other than asthma
2. Use of chronic immunosuppressive medication or receipt of immunoglobulin (or blood products) within 30 days prior to the date informed consent is obtained.

3. Previously received:

   • benralizumab
   • live attenuated vaccines 30 days prior to the date of randomization.
   • bronchial thermoplasty in the last 24 months prior to Visit 1
   • any investigational non-biologic within 30 days (or 5 half-lives) prior to the date informed consent is obtained, whichever is longer.
   • any marketed or investigational biologic for the treatment of asthma within 4 months (or 5 half-lives) prior to the date informed consent is obtained, whichever is longer.
4. Currently pregnant, breastfeeding or lactating women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Benralizumab; Administrated subcutaneously (SC) every 4 weeks for the first 3 doses, then every 8 weeks	Biological: Benralizumab; Benralizumab: 30 mg/mL solution for injection in accessorized prefilled syringe (APFS) will be administered subcutaneously (SC) every 4 weeks for the first 3 doses - Weeks 0, 4 and 8, and then every 8 weeks - Weeks 16, 24, 32, 40.
Placebo Comparator: Placebo; Administrated subcutaneously every 4 weeks for the first 3 doses, then every 8 weeks	Biological: Placebo; Matching placebo will be administered subcutaneously with accessorized prefilled syringe (APFS) every 4 weeks for the first 3 doses - Weeks 0, 4 and 8, and then every 8 weeks - Weeks 16, 24, 32, 40.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in eosinophil numbers expressed as number/mm2 in submucosa as measured by major basic protein (MBP) staining in endobronchial biopsies	The change in eosinophil numbers expressed as number/mm2 in submucosa as measured by major basic protein (MBP) staining in endobronchial biopsies	From baseline to Week 48 (Visit 10)
The change in airway wall area percentage as the overall median for airway generations 3 and 4 combined as measured by quantitative computed tomography (QCT) imaging	The change in airway wall area percentage as the overall median for airway generations 3 and 4 combined as measured by quantitative computed tomography (QCT) imaging	From baseline to Week 48 (Visit 10)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in eosinophil numbers, expressed as number/mm2 in epithelium as measured by major basic protein (MBP) staining in endobronchial biopsies	The change in eosinophil numbers, expressed as number/mm2 in epithelium as measured by major basic protein (MBP) staining in endobronchial biopsies	From baseline to Week 48 (Visit 10)
The change in eosinophil numbers, expressed as number/mm2 in epithelium and submucosa as measured by major basic protein (MBP) staining in endobronchial biopsies	The change in eosinophil numbers, expressed as number/mm2 in epithelium and submucosa as measured by major basic protein (MBP) staining in endobronchial biopsies	From baseline to Week 48 (Visit 10)
Absolute change in air trapping of the lung with expiratory density less than -856 Hounsfield Units (HU), and as expiratory-to-inspiratory ratio of mean lung density on computed tomography (CT) scans	Absolute change in air trapping of the lung with expiratory density less than -856 Hounsfield Units (HU), and as expiratory-to-inspiratory ratio of mean lung density on computed tomography (CT) scans	From baseline to Week 48 (Visit 10)
Absolute change in air trapping/small airway obstruction derived from regional matching of the inspiratory/expiratory computed tomography (CT) scans	Absolute change in air trapping/small airway obstruction derived from regional matching of the inspiratory/expiratory computed tomography (CT) scans	From baseline to Week 48 (Visit 10)
Change in airway lumen volume and airway resistance as measured by quantitative computed tomography (QCT)	Change in airway lumen volume and airway resistance as measured by quantitative computed tomography (QCT)	From baseline to Week 48 (Visit 10)
Change in endobronchial biopsies on airway epithelial cell integrity	Change in endobronchial biopsies on airway epithelial cell integrity	From baseline to Week 48 (Visit 10)
Change in endobronchial biopsies on reticular basement membrane (RBM) thickening	Change in endobronchial biopsies on reticular basement membrane (RBM) thickening	From baseline to Week 48 (Visit 10)
Change in endobronchial biopsies on vascularization of the sub-mucosa	Change in endobronchial biopsies on vascularization of the sub-mucosa	From baseline to Week 48 (Visit 10)
Assessments of peripheral airway resistance measured by AO	Assessments of peripheral airway resistance measured by AO	From baseline to Week 48 (Visit 10)
Change in endobronchial biopsies on mucin 5AC, oligomeric mucus/gel-forming (MUC5AC)	Change in endobronchial biopsies on mucin 5AC, oligomeric mucus/gel-forming (MUC5AC)	From baseline to Week 48 (Visit 10)
Absolute change in R5-R20 (peripheral airway resistance defined as the difference in resistance between 5 Hz [R5, total respiratory system resistance] and 20 Hz [R20, central resistance]) as measured by airwave oscillometry (AO)	Absolute change in R5-R20 (peripheral airway resistance defined as the difference in resistance between 5 Hz [R5, total respiratory system resistance] and 20 Hz [R20, central resistance]) as measured by airwave oscillometry (AO)	From baseline to Week 48 (Visit 10)
Absolute change in area under the reactance curve (AX) as measured by airwave oscillometry (AO)	Absolute change in area under the reactance curve (AX) as measured by airwave oscillometry (AO)	From baseline to Week 48 (Visit 10)
Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) residual volume (RV)	Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) residual volume (RV)	From baseline to Week 48 (Visit 10)
Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) total lung capacity (TLC)	Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) total lung capacity (TLC)	From baseline to Week 48 (Visit 10)
Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) inspiratory capacity (IC)	Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) inspiratory capacity (IC)	From baseline to Week 48 (Visit 10)
Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) RV/TLC ratio	Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) residual volume / total lung capacity (RV/TLC) ratio	From baseline to Week 48 (Visit 10)
Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP)functional residual capacity (FRC)	Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP)functional residual capacity (FRC)	From baseline to Week 48 (Visit 10)
Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) vital capacity (VC)	Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) vital capacity (VC)	From baseline to Week 48 (Visit 10)
Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP) residual volume (RV)	Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP) residual volume (RV)	From baseline to Week 48 (Visit 10)
Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP) total lung capacity (TLC)	Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP) total lung capacity (TLC)	From baseline to Week 48 (Visit 10)
Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP) inspiratory capacity (IC)	Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP) inspiratory capacity (IC)	From baseline to Week 48 (Visit 10)
Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP) RV/TLC ratio	Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP) residual volume / total lung capacity(RV/TLC) ratio	From baseline to Week 48 (Visit 10)
Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP)functional residual capacity (FRC)	Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP)functional residual capacity (FRC)	From baseline to Week 48 (Visit 10)
Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP) vital capacity (VC)	Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP) vital capacity (VC)	From baseline to Week 48 (Visit 10)
Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP residual volume (RV)	Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP residual volume (RV)	From baseline to Week 48 (Visit 10)
Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP total lung capacity (TLC)	Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP total lung capacity (TLC)	From baseline to Week 48 (Visit 10)
Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP inspiratory capacity (IC)	Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP inspiratory capacity (IC)	From baseline to Week 48 (Visit 10)
Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP RV/TLC ratio	Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP residual volume / total lung capacity (RV/TLC) ratio	From baseline to Week 48 (Visit 10)
Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP functional residual capacity (FRC)	Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP functional residual capacity (FRC)	From baseline to Week 48 (Visit 10)
Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP vital capacity (VC)	Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP vital capacity (VC)	From baseline to Week 48 (Visit 10)
Change in post-bronchodilator (BD) forced expiratory volume in 1 second (FEV1) as measured by spirometry	Change in post-bronchodilator (BD) forced expiratory volume in 1 second (FEV1) as measured by spirometry	From baseline to Week 48 (Visit 10)
Change in post-bronchodilator (BD) forced vital capacity (FVC) as measured by spirometry	Change in post-bronchodilator (BD) forced vital capacity (FVC) as measured by spirometry	From baseline to Week 48 (Visit 10)
Change in post-bronchodilator (BD) FEV1/FVC as measured by spirometry	Change in post-bronchodilator (BD) FEV1/FVC as measured by spirometry	From baseline to Week 48 (Visit 10)
Change in basophil number (number/mm2) in endobronchial biopsies as measured by immunohistochemistry (IHC)	Change in basophil number (number/mm2) in endobronchial biopsies as measured by immunohistochemistry (IHC)	From baseline to Week 48 (Visit 10)
Absolute change from baseline to End of Treatment in mucus score assessed using computed tomography (CT) scans	Absolute change from baseline to End of Treatment in mucus score assessed using computed tomography (CT) scans	From baseline to Week 48 (Visit 10)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of Adverse events (AEs)/serious adverse events (SAEs).	To evaluate the safety and tolerability of benralizumab. The number of Adverse events (AEs)/serious adverse events (SAEs).	From baseline to Week 52 (Visit 11)

Collaborators and Investigators

• Sponsor: AstraZeneca
• Investigators: Principal Investigator: Mario Castro, MD, University of Kansas School of Medicine 3901 Rainbow Blvd. Kansas City, KS 66160, USA

Study record dates

Study Major Dates

• Study Start (Actual): October 17, 2019
• Primary Completion (Estimated): September 9, 2026
• Study Completion (Estimated): September 9, 2026

Study Registration Dates

• First Submitted: April 10, 2019
• First Submitted That Met QC Criteria: May 14, 2019
• First Posted (Actual): May 16, 2019

Study Record Updates

• Last Update Posted (Estimated): February 15, 2024
• Last Update Submitted That Met QC Criteria: February 14, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Asthma; Lung Diseases; Eosinophilic Asthma; ICS; remodeling; Inhaled Corticosteroids; LABA; benralizumab; Fasenra; mechanism of action
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Anti-Asthmatic Agents; Respiratory System Agents; Benralizumab
• Other Study ID Numbers: D3250C00059; 2018-003391-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No