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CHINOOK: Benralizumab Airway Remodeling Study in Severe Eosinophilic Asthmatics

Sponsor
AstraZeneca (Industry)
Overall Status
Recruiting
CT.gov ID
NCT03953300
Collaborator
(none)
81
Enrollment
36
Locations
2
Arms
71.5
Anticipated Duration (Months)
2.3
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Biological: Benralizumab
  • Biological: Placebo
 Phase 4

Study Design

Study Type:
Interventional
Anticipated Enrollment :
81 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Care Provider, Investigator)
Primary Purpose:
Treatment
Official 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
Actual Study Start Date :
Oct 17, 2019
Anticipated Primary Completion Date :
Sep 30, 2025
Anticipated Study Completion Date :
Sep 30, 2025

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

  1. 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 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 [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 Outcome Measures

  1. 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 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 [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 [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 [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) [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 [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 [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 [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 [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) [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) [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) [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) [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) [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) [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 [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) [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) [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) [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) [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) [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 [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) [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) [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) [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) [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) [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 [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) [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) [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 [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 [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 [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) [From baseline to Week 48 (Visit 10)]

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

Other Outcome Measures

  1. The number of Adverse events (AEs)/serious adverse events (SAEs). [From baseline to Week 52 (Visit 11)]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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 of: ≥300 cells/µL during screening 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 or sputum eosinophil count of ≥2% 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

  1. Use of chronic immunosuppressive medication or receipt of immunoglobulin (or blood products) within 30 days prior to the date informed consent is obtained.

  2. 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 22 days (or 5 half-lives) prior to the date informed consent is obtained, whichever is longer.

  • any marketed or investigational biologic within 4 months (or 5 half-lives) prior to the date informed consent is obtained, whichever is longer.

  1. Currently pregnant, breastfeeding or lactating women.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Research Site Los Angeles California United States 90033
2 Research Site New Haven Connecticut United States 06510
3 Research Site Decatur Georgia United States 30033
4 Research Site Iowa City Iowa United States 52242
5 Research Site Kansas City Kansas United States 66160
6 Research Site Baltimore Maryland United States 21224
7 Research Site Ann Arbor Michigan United States 48109
8 Research Site Rochester Minnesota United States 55905
9 Research Site Saint Louis Missouri United States 63156
10 Research Site Port Jefferson Station New York United States 11776
11 Research Site Durham North Carolina United States 27705
12 Research Site New Bern North Carolina United States 28562
13 Research Site Winston-Salem North Carolina United States 27104
14 Research Site Philadelphia Pennsylvania United States 19107
15 Research Site Philadelphia Pennsylvania United States 19140
16 Research Site Pittsburgh Pennsylvania United States 15213
17 Research Site Sayre Pennsylvania United States 18840
18 Research Site Galveston Texas United States 77555
19 Research Site Williamsburg Virginia United States 23188
20 Research Site Calgary Alberta Canada T2N 4Z6
21 Research Site Edmonton Alberta Canada T6G 2G3
22 Research Site Hamilton Ontario Canada L8N 4A6
23 Research Site Aarhus N Denmark 8200
24 Research Site Hvidovre Denmark 2650
25 Research Site København NV Denmark 2400
26 Research Site Naestved Denmark 4700
27 Research Site Odense C Denmark 5000
28 Research Site Vejle Denmark 7100
29 Research Site Ålborg Denmark 9000
30 Research Site Göteborg Sweden 413 45
31 Research Site Lund Sweden 221 85
32 Research Site Cambridge United Kingdom CB2 2QQ
33 Research Site Headington United Kingdom OX3 9DU
34 Research Site Liverpool United Kingdom L7 8XP
35 Research Site London United Kingdom W1G 8HU
36 Research Site Wythenshawe United Kingdom M23 9LT

Sponsors and Collaborators

  • AstraZeneca

Investigators

  • Principal Investigator: Mario Castro, MD, University of Kansas School of Medicine 3901 Rainbow Blvd. Kansas City, KS 66160, United States of America (USA)

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
AstraZeneca
ClinicalTrials.gov Identifier:
NCT03953300
Other Study ID Numbers:
  • D3250C00059
  • 2018-003391-13
First Posted:
May 16, 2019
Last Update Posted:
Aug 24, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by AstraZeneca
Asthma
Eosinophilic Asthma
Lung Diseases
Inhaled Corticosteroids
ICS
LABA
benralizumab
Fasenra
mechanism of action
remodeling
Additional relevant MeSH terms:
Asthma
Benralizumab

Study Results

No Results Posted as of Aug 24, 2022