Benralizumab Airway Remodeling Study in Severe Eosinophilic Asthmatics

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

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.

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.