Benralizumab in Patients With Inadequate Response to Anti-IL5 Monoclonal Antibody Therapies

Phase 3

Completed

• Conditions: Severe Prednisone Dependent Eosinophilic Asthma
• Interventions: Biological: Benralizumab; Biological: Placebo

• Registration Number: NCT03470311
• Lead Sponsor: McMaster University

Brief Summary

In severe prednisone-dependent eosinophilic asthma, Benralizumab would suppress airway eosinophilia that is not suppressed by either Mepolizumab or Reslizumab and this would be associated with greater asthma control

Detailed Description

Benralizumab thus targets 'eosinophil biology', by inhibiting the interleukin (IL-5) receptor signalling, and inducing apoptosis in cells with an IL-5receptor. Hence, for patients who remain 'uncontrolled' on anti-IL-5 therapy (with detectable eosinophil activity and IL5-Rα+ cells in the airways), the investigators believe would benefit from a strategy that not only reduces eosinophil proliferation/recruitment/maturation, but also depletes cells capable of inducing downstream IL-5 signalling.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2018-03-01
• Study First Submitted QC: 2018-03-16
• Study First Posted: 2018-03-19
• Study Start: 2018-04-26
• Primary Completion: 2022-06-14
• Study Completion: 2022-11-30
• Status Verified: 2023-01
• Last Update Submitted: 2023-01-18
• Last Update Posted: 2023-01-20

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Informed consent Prior to the beginning of the study, patients must be willing and fully capable to provide written informed consent.

2. Diagnosed prednisone-dependent eosinophilic asthma

3. Previous treatment with 100 mg mepolizumab administered subcutaneously Q4W or reslizumab 3 mg/kg IV Q4W for at least 6 months

4. Sputum eosinophils >3%

5. ACQ ≥1.5

6. Age >18

7. Male or eligible female subjects:

   To be eligible for entry into the study, females of childbearing potential (premenopausal women who are not permanently sterilized by means of hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) must commit to consistent and correct use of a highly effective method of birth control (true sexual abstinence, a vasectomized sexual partner, Implanon, female tubal occlusion, Intrauterine device (IUD), Depo provera injections, oral contraceptive pills or Nuvaring) for the duration of the trial and for 3 months after the last study drug administration. A serum pregnancy test is required of all females at the initial Baseline Visit (Visit 1). In addition, a urine pregnancy test will be performed for all females prior to enrollment, during each scheduled study visit prior to the injection of investigational product, and during the Follow-up Visit.

8. Male subjects who are sexually active must agree to use a double barrier method of contraception (condom with spermicide) from the first dose of study drug and for 3 months after the last dose of study drug.

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Exclusion Criteria

1. Currently receiving another monoclonal antibody
2. Intolerance, hypersensitivity, insensitivity or neutralizing antibody to Mepolizumab and/or Reslizumab
3. Malignancy within the last 5 years
4. Any co-morbidity that the investigator believes is a contraindication. This includes but is not limited to any respiratory, cardiovascular, gastrointestinal, hematological, neurological, immunological, musculoskeletal, renal, infectious, neoplastic or inflammatory condition that may place the safety of the subject at risk during the duration of the study, influence the results of the study or their interpretation, or prevent the patient from completing the entire duration of the study.
5. Current pregnancy or lactation
6. Current smoker or ex-smoker with a smoking history greater than 20 pack years.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Benralizumab	Benralizumab	Benralizumab 30mg in 1mL subcutaneously
Placebo	Placebo	Matched placebo (1mL) to active Benralizumab subcutaneously

Primary Outcome Measures

Name	Time	Method
Sputum eosinophil percentage	Visit 1 (Week 2) and Visit 10 (Week 38)	Change in Percentage of sputum eosinophils (%)

Secondary Outcome Measures

Name	Time	Method
Fraction of exhaled nitric oxide (FeNO)	Visit 1 (Week 2) and Visit 10 (Week 38)	Exhaled nitric oxide measurement in ppb
Sputum and blood ILC2 biology	Visit 1 (Week 2) and Visit 10 (Week 38)	Measurement of ILC2 biological cells in both blood and sputum
Blood eosinophils	Visit 1 (Week 2) and Visit 10 (Week 38)	Blood eosinophil level (x10\^9/L)
Forced Expired Volume in 1 second (FEV1)(pre and post bronchodilator)	Visit 1 (Week 2) and Visit 10 (Week 38)	FEV1 in litres both pre and post bronchodilator
ACQ-5 (Asthma Control Questionnaire)	Visit 1 (Week 2) and Visit 10 (Week 38)	Asthma Control Questionnaire score (mean answer of 5 questions on a 7-point scale (0=no impairment, 6= maximum impairment).
Number of Exacerbations (defined as: ER visit/hospitalization requiring prednisone burst)	Visit 1 (Week 2) and Visit 10 (Week 38)	Worsening requiring increase in oral steroids/prednisone (30mg x 5 days)
Sputum autoimmune responses	Visit 1 (Week 2) and Visit 10 (Week 38)	Measurement of autoimmune markers in sputum: anti-eosinophil peroxidase (EPX) and anti-nuclear antibodies (ANA) - (See last reference PubMed ID: 28751233)

Trial Locations

Locations (1)

Firestone Institute for Respiratory Health, Research - St. Joseph's Healthcare; 🇨🇦 Hamilton, Ontario, Canada