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

NCT03470311 | Completed Phase 3 DMC

• 1 other identifier: 17-12992
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Conditions

Severe Prednisone Dependent Eosinophilic Asthma

Keywords

Eosinophils; asthma; inflammation; prednisone

Outcome Measures

Primary Outcomes (1)

• Sputum eosinophil percentage

  Change in Percentage of sputum eosinophils (%)

  Visit 1 (Week 2) and Visit 10 (Week 38)

Secondary Outcomes (7)

• Blood eosinophils

  Visit 1 (Week 2) and Visit 10 (Week 38)

• Forced Expired Volume in 1 second (FEV1)(pre and post bronchodilator)

  Visit 1 (Week 2) and Visit 10 (Week 38)

• ACQ-5 (Asthma Control Questionnaire)

  Visit 1 (Week 2) and Visit 10 (Week 38)

• Fraction of exhaled nitric oxide (FeNO)

  Visit 1 (Week 2) and Visit 10 (Week 38)

• Number of Exacerbations (defined as: ER visit/hospitalization requiring prednisone burst)

  Visit 1 (Week 2) and Visit 10 (Week 38)

Study Arms (2)

Benralizumab

ACTIVE COMPARATOR

Benralizumab 30mg in 1mL subcutaneously

Biological: Benralizumab

Placebo

PLACEBO COMPARATOR

Matched placebo (1mL) to active Benralizumab subcutaneously

Biological: Placebo

Interventions

Benralizumab BIOLOGICAL

30mg in 1mL pre-filled syringe

Also known as: MEDI-563

Benralizumab

Placebo BIOLOGICAL

Matched placebo (1mL) in pre-filled syringe

Placebo

Eligibility Criteria

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

You may qualify if:

• Informed consent Prior to the beginning of the study, patients must be willing and fully capable to provide written informed consent.
• Diagnosed prednisone-dependent eosinophilic asthma
• Previous treatment with 100 mg mepolizumab administered subcutaneously Q4W or reslizumab 3 mg/kg IV Q4W for at least 6 months
• Sputum eosinophils \>3%
• ACQ ≥1.5
• Age \>18
• 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.
• 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.

You may not qualify if:

• Currently receiving another monoclonal antibody
• Intolerance, hypersensitivity, insensitivity or neutralizing antibody to Mepolizumab and/or Reslizumab
• Malignancy within the last 5 years
• 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.
• Current pregnancy or lactation
• Current smoker or ex-smoker with a smoking history greater than 20 pack years.

Sponsors & Collaborators

• McMaster University: lead
• St. Joseph's Healthcare Hamilton: collaborator
• AstraZeneca: collaborator

Study Sites (1)

Firestone Institute for Respiratory Health, Research - St. Joseph's Healthcare

Hamilton, Ontario, L8N 4A6, Canada

Location

Related Publications (7)

• Mukherjee M, Lim HF, Thomas S, Miller D, Kjarsgaard M, Tan B, Sehmi R, Khalidi N, Nair P. Airway autoimmune responses in severe eosinophilic asthma following low-dose Mepolizumab therapy. Allergy Asthma Clin Immunol. 2017 Jan 6;13:2. doi: 10.1186/s13223-016-0174-5. eCollection 2017.

  PMID: 28070196 BACKGROUND

• Smith SG, Chen R, Kjarsgaard M, Huang C, Oliveria JP, O'Byrne PM, Gauvreau GM, Boulet LP, Lemiere C, Martin J, Nair P, Sehmi R. Increased numbers of activated group 2 innate lymphoid cells in the airways of patients with severe asthma and persistent airway eosinophilia. J Allergy Clin Immunol. 2016 Jan;137(1):75-86.e8. doi: 10.1016/j.jaci.2015.05.037. Epub 2015 Jul 17.

  PMID: 26194544 BACKGROUND

• Sehmi R, Smith SG, Kjarsgaard M, Radford K, Boulet LP, Lemiere C, Prazma CM, Ortega H, Martin JG, Nair P. Role of local eosinophilopoietic processes in the development of airway eosinophilia in prednisone-dependent severe asthma. Clin Exp Allergy. 2016 Jun;46(6):793-802. doi: 10.1111/cea.12695.

  PMID: 26685004 BACKGROUND

• Kolbeck R, Kozhich A, Koike M, Peng L, Andersson CK, Damschroder MM, Reed JL, Woods R, Dall'acqua WW, Stephens GL, Erjefalt JS, Bjermer L, Humbles AA, Gossage D, Wu H, Kiener PA, Spitalny GL, Mackay CR, Molfino NA, Coyle AJ. MEDI-563, a humanized anti-IL-5 receptor alpha mAb with enhanced antibody-dependent cell-mediated cytotoxicity function. J Allergy Clin Immunol. 2010 Jun;125(6):1344-1353.e2. doi: 10.1016/j.jaci.2010.04.004.

  PMID: 20513525 BACKGROUND

• Mukherjee M, Aleman Paramo F, Kjarsgaard M, Salter B, Nair G, LaVigne N, Radford K, Sehmi R, Nair P. Weight-adjusted Intravenous Reslizumab in Severe Asthma with Inadequate Response to Fixed-Dose Subcutaneous Mepolizumab. Am J Respir Crit Care Med. 2018 Jan 1;197(1):38-46. doi: 10.1164/rccm.201707-1323OC.

  PMID: 28915080 BACKGROUND

• Nair P, Wenzel S, Rabe KF, Bourdin A, Lugogo NL, Kuna P, Barker P, Sproule S, Ponnarambil S, Goldman M; ZONDA Trial Investigators. Oral Glucocorticoid-Sparing Effect of Benralizumab in Severe Asthma. N Engl J Med. 2017 Jun 22;376(25):2448-2458. doi: 10.1056/NEJMoa1703501. Epub 2017 May 22.

  PMID: 28530840 BACKGROUND

• Mukherjee M, Bulir DC, Radford K, Kjarsgaard M, Huang CM, Jacobsen EA, Ochkur SI, Catuneanu A, Lamothe-Kipnes H, Mahony J, Lee JJ, Lacy P, Nair PK. Sputum autoantibodies in patients with severe eosinophilic asthma. J Allergy Clin Immunol. 2018 Apr;141(4):1269-1279. doi: 10.1016/j.jaci.2017.06.033. Epub 2017 Jul 24.

  PMID: 28751233 BACKGROUND

MeSH Terms

Conditions

Asthma; Inflammation

Interventions

benralizumab

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Parameswaran Nair, MD, PhD

  McMaster University and St. Joseph's Healthcare Hamilton

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2018
• First Posted: March 19, 2018
• Study Start: April 26, 2018
• Primary Completion: June 14, 2022
• Study Completion: November 30, 2022
• Last Updated: January 20, 2023

Record last verified: 2023-01

Locations

CA (1)