Clinical trial NCT03953300: Benralizumab Airway Remodeling Study in Severe Eosinophilic Asthmatics
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Asthma
Keywords: Asthma
Eosinophilic Asthma
Lung Diseases
Inhaled Corticosteroids
ICS
LABA
benralizumab
Fasenra
mechanism of action
remodeling
Lead sponsor: AstraZeneca
Sponsor class: INDUSTRY
First posted: 2019-05-16
Enrollment: 81
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: The change in eosinophil numbers expressed as number/mm2 in submucosa as measured by major basic protein (MBP) staining in endobronchial biopsies
timeFrame: From baseline to Week 48 (Visit 10)
measure: 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
timeFrame: From baseline to Week 48 (Visit 10)
Secondary outcomes:
measure: The change in eosinophil numbers, expressed as number/mm2 in epithelium as measured by major basic protein (MBP) staining in endobronchial biopsies
timeFrame: From baseline to Week 48 (Visit 10)
measure: The change in eosinophil numbers, expressed as number/mm2 in epithelium and submucosa as measured by major basic protein (MBP) staining in endobronchial biopsies
timeFrame: From baseline to Week 48 (Visit 10)
measure: 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
timeFrame: From baseline to Week 48 (Visit 10)
measure: Absolute change in air trapping/small airway obstruction derived from regional matching of the inspiratory/expiratory computed tomography (CT) scans
timeFrame: From baseline to Week 48 (Visit 10)
measure: Change in airway lumen volume and airway resistance as measured by quantitative computed tomography (QCT)
timeFrame: From baseline to Week 48 (Visit 10)
measure: Change in endobronchial biopsies on airway epithelial cell integrity
timeFrame: From baseline to Week 48 (Visit 10)
measure: Change in endobronchial biopsies on reticular basement membrane (RBM) thickening
timeFrame: From baseline to Week 48 (Visit 10)
measure: Change in endobronchial biopsies on vascularization of the sub-mucosa
timeFrame: From baseline to Week 48 (Visit 10)
measure: Assessments of peripheral airway resistance measured by AO
timeFrame: From baseline to Week 48 (Visit 10)
measure: Change in endobronchial biopsies on mucin 5AC, oligomeric mucus/gel-forming (MUC5AC)
timeFrame: From baseline to Week 48 (Visit 10)
measure: 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)
timeFrame: From baseline to Week 48 (Visit 10)
measure: Absolute change in area under the reactance curve (AX) as measured by airwave oscillometry (AO)
timeFrame: From baseline to Week 48 (Visit 10)
measure: Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) residual volume (RV)
timeFrame: From baseline to Week 48 (Visit 10)
measure: Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) total lung capacity (TLC)
timeFrame: From baseline to Week 48 (Visit 10)
measure: Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) inspiratory capacity (IC)
timeFrame: From baseline to Week 48 (Visit 10)
measure: Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) RV/TLC ratio
timeFrame: From baseline to Week 48 (Visit 10)
measure: Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP)functional residual capacity (FRC)
timeFrame: From baseline to Week 48 (Visit 10)
measure: Absolute change in pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) vital capacity (VC)
timeFrame: From baseline to Week 48 (Visit 10)
measure: Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP) residual volume (RV)
timeFrame: From baseline to Week 48 (Visit 10)
measure: Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP) total lung capacity (TLC)
timeFrame: From baseline to Week 48 (Visit 10)
measure: Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP) inspiratory capacity (IC)
timeFrame: From baseline to Week 48 (Visit 10)
measure: Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP) RV/TLC ratio
timeFrame: From baseline to Week 48 (Visit 10)
measure: Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP)functional residual capacity (FRC)
timeFrame: From baseline to Week 48 (Visit 10)
measure: Absolute change in post-bronchodilator (BD) whole body plethysmogrpahy (WBP) vital capacity (VC)
timeFrame: From baseline to Week 48 (Visit 10)
measure: Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP residual volume (RV)
timeFrame: From baseline to Week 48 (Visit 10)
measure: Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP total lung capacity (TLC)
timeFrame: From baseline to Week 48 (Visit 10)
measure: Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP inspiratory capacity (IC)
timeFrame: From baseline to Week 48 (Visit 10)
measure: Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP RV/TLC ratio
timeFrame: From baseline to Week 48 (Visit 10)
measure: Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP functional residual capacity (FRC)
timeFrame: From baseline to Week 48 (Visit 10)
measure: Change from pre-bronchodilator (BD) whole body plethysmogrpahy (WBP) to post-BD WBP vital capacity (VC)
timeFrame: From baseline to Week 48 (Visit 10)
measure: Change in post-bronchodilator (BD) forced expiratory volume in 1 second (FEV1) as measured by spirometry
timeFrame: From baseline to Week 48 (Visit 10)
measure: Change in post-bronchodilator (BD) forced vital capacity (FVC) as measured by spirometry
timeFrame: From baseline to Week 48 (Visit 10)
measure: Change in post-bronchodilator (BD) FEV1/FVC as measured by spirometry
timeFrame: From baseline to Week 48 (Visit 10)
measure: Change in basophil number (number/mm2) in endobronchial biopsies as measured by immunohistochemistry (IHC)
timeFrame: From baseline to Week 48 (Visit 10)
measure: Absolute change from baseline to End of Treatment in mucus score assessed using computed tomography (CT) scans
timeFrame: From baseline to Week 48 (Visit 10)
Other outcomes:
measure: The number of Adverse events (AEs)/serious adverse events (SAEs).
timeFrame: From baseline to Week 52 (Visit 11)
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Jacksonville
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Decatur
country: United States
facility: Research Site
state: Georgia
city: Snellville
country: United States
facility: Research Site
state: Georgia
city: Indianapolis
country: United States
facility: Research Site
state: Indiana
city: Iowa City
country: United States
facility: Research Site
state: Iowa
city: Hutchinson
country: United States
facility: Research Site
state: Kansas
city: Kansas City
country: United States
facility: Research Site
state: Kansas
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Ann Arbor
country: United States
facility: Research Site
state: Michigan
city: Bloomfield Hills
country: United States
facility: Research Site
state: Michigan
city: Rochester
country: United States
facility: Research Site
state: Minnesota
city: Saint Louis
country: United States
facility: Research Site
state: Missouri
city: Maspeth
country: United States
facility: Research Site
state: New York
city: Port Jefferson Station
country: United States
facility: Research Site
state: New York
city: Durham
country: United States
facility: Research Site
state: North Carolina
city: New Bern
country: United States
facility: Research Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Research Site
state: North Carolina
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Sayre
country: United States
facility: Research Site
state: Pennsylvania
city: Charleston
country: United States
facility: Research Site
state: South Carolina
city: Galveston
country: United States
facility: Research Site
state: Texas
city: Lewisville
country: United States
facility: Research Site
state: Texas
city: Mansfield
country: United States
facility: Research Site
state: Texas
city: McAllen
country: United States
facility: Research Site
state: Texas
city: McKinney
country: United States
facility: Research Site
state: Texas
city: Williamsburg
country: United States
facility: Research Site
state: Virginia
city: Calgary
country: Canada
facility: Research Site
state: Alberta
city: Edmonton
country: Canada
facility: Research Site
state: Alberta
city: Hamilton
country: Canada
facility: Research Site
state: Ontario
city: Aarhus N
country: Denmark
facility: Research Site
city: Hvidovre
country: Denmark
facility: Research Site
city: København
country: Denmark
facility: Research Site
city: Naestved
country: Denmark
facility: Research Site
city: Odense C
country: Denmark
facility: Research Site
city: Vejle
country: Denmark
facility: Research Site
city: Ålborg
country: Denmark
facility: Research Site
city: Göteborg
country: Sweden
facility: Research Site
city: Lund
country: Sweden
facility: Research Site
city: Cambridge
country: United Kingdom
facility: Research Site
city: Headington
country: United Kingdom
facility: Research Site
city: Leicester
country: United Kingdom
facility: Research Site
city: Liverpool
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Wythenshawe
country: United Kingdom
facility: Research Site
Study officials:
affiliation: University of Kansas School of Medicine 3901 Rainbow Blvd. Kansas City, KS 66160, USA
name: Mario Castro, MD
role: PRINCIPAL_INVESTIGATOR
References: