Skip to main content
OpenTrials
Active, Not Recruiting

NCT Number: NCT03953300

Benralizumab Airway Remodeling Study 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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Asthma Bronchial Diseases Eosinophilia Hematologic Diseases Hemic and Lymphatic Diseases Hypereosinophilic Syndrome Hypersensitivity Hypersensitivity, Immediate Immune System Diseases Leukocyte Disorders Lung Diseases Lung Diseases, Obstructive Pulmonary Eosinophilia Respiratory Hypersensitivity Respiratory Tract Diseases

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Research Site, Calgary, Alberta, Canada

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Male or female aged 18 through 70 years.
  • 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.
  • 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.
  • 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
  • Negative pregnancy test.
  • Asthma control questionnaire (ACQ-6) >1.5.
  • Fewer than 12 exacerbations within the 6 months prior to Visit 3.

Exclusion criteria

  • 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
  • Use of chronic immunosuppressive medication or receipt of immunoglobulin (or blood products) within 30 days prior to the date informed consent is obtained.
  • 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.
  • Currently pregnant, breastfeeding or lactating women.

Treatment and study plan

Benralizumab

Biological

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

Biological

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.

Primary outcomes

  1. The change in eosinophil numbers expressed as number/mm2 in submucosa as measured by major basic protein (MBP) staining in endobronchial biopsies

    Time frame: From baseline to Week 48 (Visit 10)

    The change in eosinophil numbers expressed as number/mm2 in submucosa as measured by major basic protein (MBP) staining in endobronchial biopsies

  2. 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

    Time frame: 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

Secondary outcomes

  1. The change in eosinophil numbers, expressed as number/mm2 in epithelium as measured by major basic protein (MBP) staining in endobronchial biopsies

    Time frame: From baseline to Week 48 (Visit 10)

    The change in eosinophil numbers, expressed as number/mm2 in epithelium as measured by major basic protein (MBP) staining in endobronchial biopsies

  2. The change in eosinophil numbers, expressed as number/mm2 in epithelium and submucosa as measured by major basic protein (MBP) staining in endobronchial biopsies

    Time frame: 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

  3. 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

    Time frame: 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

  4. Absolute change in air trapping/small airway obstruction derived from regional matching of the inspiratory/expiratory computed tomography (CT) scans

    Time frame: 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

  5. Change in airway lumen volume and airway resistance as measured by quantitative computed tomography (QCT)

    Time frame: From baseline to Week 48 (Visit 10)

    Change in airway lumen volume and airway resistance as measured by quantitative computed tomography (QCT)

  6. Change in endobronchial biopsies on airway epithelial cell integrity

    Time frame: From baseline to Week 48 (Visit 10)

    Change in endobronchial biopsies on airway epithelial cell integrity

  7. Change in endobronchial biopsies on reticular basement membrane (RBM) thickening

    Time frame: From baseline to Week 48 (Visit 10)

    Change in endobronchial biopsies on reticular basement membrane (RBM) thickening

  8. Change in endobronchial biopsies on vascularization of the sub-mucosa

    Time frame: From baseline to Week 48 (Visit 10)

    Change in endobronchial biopsies on vascularization of the sub-mucosa

  9. Assessments of peripheral airway resistance measured by AO

    Time frame: From baseline to Week 48 (Visit 10)

    Assessments of peripheral airway resistance measured by AO

  10. Change in endobronchial biopsies on mucin 5AC, oligomeric mucus/gel-forming (MUC5AC)

    Time frame: From baseline to Week 48 (Visit 10)

    Change in endobronchial biopsies on mucin 5AC, oligomeric mucus/gel-forming (MUC5AC)

  11. 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)

    Time frame: 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)

  12. Absolute change in area under the reactance curve (AX) as measured by airwave oscillometry (AO)

    Time frame: From baseline to Week 48 (Visit 10)

    Absolute change in area under the reactance curve (AX) as measured by airwave oscillometry (AO)

  13. Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) residual volume (RV)

    Time frame: From baseline to Week 48 (Visit 10)

    Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) residual volume (RV)

  14. Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) total lung capacity (TLC)

    Time frame: From baseline to Week 48 (Visit 10)

    Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) total lung capacity (TLC)

  15. Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) inspiratory capacity (IC)

    Time frame: From baseline to Week 48 (Visit 10)

    Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) inspiratory capacity (IC)

  16. Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) RV/TLC ratio

    Time frame: From baseline to Week 48 (Visit 10)

    Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) residual volume / total lung capacity (RV/TLC) ratio

  17. Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP)functional residual capacity (FRC)

    Time frame: From baseline to Week 48 (Visit 10)

    Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP)functional residual capacity (FRC)

  18. Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) vital capacity (VC)

    Time frame: From baseline to Week 48 (Visit 10)

    Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) vital capacity (VC)

  19. Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP) residual volume (RV)

    Time frame: From baseline to Week 48 (Visit 10)

    Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP) residual volume (RV)

  20. Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP) total lung capacity (TLC)

    Time frame: From baseline to Week 48 (Visit 10)

    Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP) total lung capacity (TLC)

  21. Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP) inspiratory capacity (IC)

    Time frame: From baseline to Week 48 (Visit 10)

    Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP) inspiratory capacity (IC)

  22. Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP) RV/TLC ratio

    Time frame: From baseline to Week 48 (Visit 10)

    Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP) residual volume / total lung capacity(RV/TLC) ratio

  23. Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP)functional residual capacity (FRC)

    Time frame: From baseline to Week 48 (Visit 10)

    Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP)functional residual capacity (FRC)

  24. Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP) vital capacity (VC)

    Time frame: From baseline to Week 48 (Visit 10)

    Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP) vital capacity (VC)

  25. Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP residual volume (RV)

    Time frame: From baseline to Week 48 (Visit 10)

    Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP residual volume (RV)

  26. Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP total lung capacity (TLC)

    Time frame: From baseline to Week 48 (Visit 10)

    Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP total lung capacity (TLC)

  27. Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP inspiratory capacity (IC)

    Time frame: From baseline to Week 48 (Visit 10)

    Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP inspiratory capacity (IC)

  28. Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP RV/TLC ratio

    Time frame: From baseline to Week 48 (Visit 10)

    Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP residual volume / total lung capacity (RV/TLC) ratio

  29. Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP functional residual capacity (FRC)

    Time frame: From baseline to Week 48 (Visit 10)

    Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP functional residual capacity (FRC)

  30. Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP vital capacity (VC)

    Time frame: From baseline to Week 48 (Visit 10)

    Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP vital capacity (VC)

  31. Change in post-bronchodilator (BD) forced expiratory volume in 1 second (FEV1) as measured by spirometry

    Time frame: From baseline to Week 48 (Visit 10)

    Change in post-bronchodilator (BD) forced expiratory volume in 1 second (FEV1) as measured by spirometry

  32. Change in post-bronchodilator (BD) forced vital capacity (FVC) as measured by spirometry

    Time frame: From baseline to Week 48 (Visit 10)

    Change in post-bronchodilator (BD) forced vital capacity (FVC) as measured by spirometry

  33. Change in post-bronchodilator (BD) FEV1/FVC as measured by spirometry

    Time frame: From baseline to Week 48 (Visit 10)

    Change in post-bronchodilator (BD) FEV1/FVC as measured by spirometry

  34. Change in basophil number (number/mm2) in endobronchial biopsies as measured by immunohistochemistry (IHC)

    Time frame: From baseline to Week 48 (Visit 10)

    Change in basophil number (number/mm2) in endobronchial biopsies as measured by immunohistochemistry (IHC)

  35. Absolute change from baseline to End of Treatment in mucus score assessed using computed tomography (CT) scans

    Time frame: From baseline to Week 48 (Visit 10)

    Absolute change from baseline to End of Treatment in mucus score assessed using computed tomography (CT) scans

Other outcomes

  1. The number of Adverse events (AEs)/serious adverse events (SAEs).

    Time frame: From baseline to Week 52 (Visit 11)

    To evaluate the safety and tolerability of benralizumab. The number of Adverse events (AEs)/serious adverse events (SAEs).

Sponsors and collaborators

Lead sponsor

AstraZeneca

Industry

Registry information

Official study title

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

Acronym: CHINOOK

Important dates

Study start
2019
Primary completion
2026
Study completion
2026
First posted
May 16, 2019
Registry last updated
Jul 28, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.