Benralizumab Airway Remodeling Study in Severe Eosinophilic Asthmatics

Asthma Clinical Trial

— CHINOOK  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03953300
• Other study ID #: D3250C00059
• Secondary ID: 2018-003391-13
• Status: Recruiting
• Phase: Phase 4
• Start date: October 17, 2019
• Est. completion date: September 9, 2026

Study information

• Verified date: June 2024
• Source: AstraZeneca
• Contact: AstraZeneca Clinical Study Information Center
• Phone: 1-877-240-9479
• Email: information.center[@]astrazeneca.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 81
• Est. completion date: September 9, 2026
• Est. primary completion date: September 9, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Asthma

Intervention

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
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.

Locations

Country	Name	City	State
Canada	Research Site	Calgary	Alberta
Canada	Research Site	Edmonton	Alberta
Canada	Research Site	Hamilton	Ontario
Denmark	Research Site	Aarhus N
Denmark	Research Site	Ålborg
Denmark	Research Site	Hvidovre
Denmark	Research Site	København NV
Denmark	Research Site	Naestved
Denmark	Research Site	Odense C
Denmark	Research Site	Vejle
Sweden	Research Site	Göteborg
Sweden	Research Site	Lund
United Kingdom	Research Site	Cambridge
United Kingdom	Research Site	Headington
United Kingdom	Research Site	Leicester
United Kingdom	Research Site	Liverpool
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Wythenshawe
United States	Research Site	Ann Arbor	Michigan
United States	Research Site	Baltimore	Maryland
United States	Research Site	Bloomfield Hills	Michigan
United States	Research Site	Charleston	South Carolina
United States	Research Site	Decatur	Georgia
United States	Research Site	Durham	North Carolina
United States	Research Site	Galveston	Texas
United States	Research Site	Indianapolis	Indiana
United States	Research Site	Iowa City	Iowa
United States	Research Site	Jacksonville	Florida
United States	Research Site	Jacksonville	Florida
United States	Research Site	Kansas City	Kansas
United States	Research Site	Los Angeles	California
United States	Research Site	Maspeth	New York
United States	Research Site	McAllen	Texas
United States	Research Site	McKinney	Texas
United States	Research Site	New Bern	North Carolina
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Philadelphia	Pennsylvania
United States	Research Site	Pittsburgh	Pennsylvania
United States	Research Site	Port Jefferson Station	New York
United States	Research Site	Rochester	Minnesota
United States	Research Site	Saint Louis	Missouri
United States	Research Site	Sayre	Pennsylvania
United States	Research Site	Williamsburg	Virginia
United States	Research Site	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
AstraZeneca

Countries where clinical trial is conducted

United States,  Canada,  Denmark,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)
Primary	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)
Primary	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	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Assessments of peripheral airway resistance measured by AO	Assessments of peripheral airway resistance measured by AO	From baseline to Week 48 (Visit 10)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)