Benralizumab Airway Remodeling Study in Severe Eosinophilic Asthmatics

NCT03953300 | Active Not Recruiting Phase 4 FDA Drug

• 2 other identifiers: D3250C000592018-003391-13
• Study Type: interventional
• Target: 75
• Locations: 5 countries
• Sites: 35

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.

Conditions

Asthma

Keywords

Asthma; Eosinophilic Asthma; Lung Diseases; Inhaled Corticosteroids; ICS; LABA; benralizumab; Fasenra; mechanism of action; remodeling

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (35)

• 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

  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

  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

  From baseline to Week 48 (Visit 10)

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

  From baseline to Week 48 (Visit 10)

Other Outcomes (1)

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

  From baseline to Week 52 (Visit 11)

Study Arms (2)

Benralizumab

EXPERIMENTAL

Administrated subcutaneously (SC) every 4 weeks for the first 3 doses, then every 8 weeks

Biological: Benralizumab

Placebo

PLACEBO COMPARATOR

Administrated subcutaneously every 4 weeks for the first 3 doses, then every 8 weeks

Biological: Placebo

Interventions

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.

Benralizumab

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.

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (35)

Research Site

Birmingham, Alabama, 35209, United States

Location

Research Site

Los Angeles, California, 90033, United States

Location

Research Site

Jacksonville, Florida, 32204, United States

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Miami, Florida, 33166, United States

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Snellville, Georgia, 30078, United States

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Indianapolis, Indiana, 46268, United States

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Iowa City, Iowa, 52242, United States

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Kansas City, Kansas, 66160, United States

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Ann Arbor, Michigan, 48109, United States

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Bloomfield Hills, Michigan, 48301, United States

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Rochester, Minnesota, 55905, United States

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St Louis, Missouri, 63156, United States

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Maspeth, New York, 11378, United States

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New Bern, North Carolina, 28562, United States

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Winston-Salem, North Carolina, 27104, United States

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Pittsburgh, Pennsylvania, 15213, United States

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Galveston, Texas, 77555, United States

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Lewisville, Texas, 75067, United States

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Mansfield, Texas, 76063, United States

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Calgary, Alberta, T2N 4Z6, Canada

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Aalborg, 9000, Denmark

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Aarhus N, 8200, Denmark

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Copenhagen, 2400, Denmark

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Hvidovre, 2650, Denmark

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Næstved, 4700, Denmark

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Odense C, 5000, Denmark

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Vejle, 7100, Denmark

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Gothenburg, 413 45, Sweden

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Lund, 22185, Sweden

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Cambridge, CB2 2QQ, United Kingdom

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Headington, OX3 9DU, United Kingdom

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Leicester, LE3 9QP, United Kingdom

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Liverpool, L7 8XP, United Kingdom

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London, W1G 8HU, United Kingdom

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Wythenshawe, M23 9LT, United Kingdom

Location

MeSH Terms

Conditions

Asthma; Pulmonary Eosinophilia; Lung Diseases

Interventions

benralizumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Mario Castro, MD

  University of Kansas School of Medicine 3901 Rainbow Blvd. Kansas City, KS 66160, USA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2019
• First Posted: May 16, 2019
• Study Start: October 8, 2019
• Primary Completion (Estimated): October 19, 2026
• Study Completion (Estimated): October 19, 2026
• Last Updated: May 5, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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.
• 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.

Locations

US (19); SE (2); CA (1); GB (6); DK (7)