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

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ClinicalTrials.gov Identifier: NCT03470311
Recruitment Status : Recruiting
First Posted : March 19, 2018
Last Update Posted : March 20, 2019
Sponsor:
Collaborators:
St. Joseph's Healthcare Hamilton
AstraZeneca
Information provided by (Responsible Party):
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

Condition or disease Intervention/treatment Phase
Severe Prednisone Dependent Eosinophilic Asthma Biological: Benralizumab Biological: Placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: Benralizumab in Patients With Inadequate Response to Anti-IL5 Monoclonal Antibody Therapies
Actual Study Start Date : April 26, 2018
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : January 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma Steroids

Arm Intervention/treatment
Active Comparator: Benralizumab
Benralizumab 30mg in 1mL subcutaneously
Biological: Benralizumab
30mg in 1mL pre-filled syringe
Other Name: MEDI-563

Placebo Comparator: Placebo
Matched placebo (1mL) to active Benralizumab subcutaneously
Biological: Placebo
Matched placebo (1mL) in pre-filled syringe




Primary Outcome Measures :
  1. Sputum eosinophil percentage [ Time Frame: Visit 1 (Week 2) and Visit 10 (Week 38) ]
    Change in Percentage of sputum eosinophils (%)


Secondary Outcome Measures :
  1. Blood eosinophils [ Time Frame: Visit 1 (Week 2) and Visit 10 (Week 38) ]
    Blood eosinophil level (x10^9/L)

  2. Forced Expired Volume in 1 second (FEV1)(pre and post bronchodilator) [ Time Frame: Visit 1 (Week 2) and Visit 10 (Week 38) ]
    FEV1 in litres both pre and post bronchodilator

  3. ACQ-5 (Asthma Control Questionnaire) [ Time Frame: 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).

  4. Fraction of exhaled nitric oxide (FeNO) [ Time Frame: Visit 1 (Week 2) and Visit 10 (Week 38) ]
    Exhaled nitric oxide measurement in ppb

  5. Number of Exacerbations (defined as: ER visit/hospitalization requiring prednisone burst) [ Time Frame: Visit 1 (Week 2) and Visit 10 (Week 38) ]
    Worsening requiring increase in oral steroids/prednisone (30mg x 5 days)

  6. Sputum and blood ILC2 biology [ Time Frame: Visit 1 (Week 2) and Visit 10 (Week 38) ]
    Measurement of ILC2 biological cells in both blood and sputum

  7. Sputum autoimmune responses [ Time Frame: 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)



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03470311


Contacts
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Contact: Melanie Kjarsgaard 9055221155 ext 33024 mkjarsga@stjoes.ca
Contact: Manali Mukherjee 9055221155 ext 37313 mukherj@mcmaster.ca

Locations
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Canada, Ontario
Firestone Institute for Respiratory Health, Research - St. Joseph's Healthcare Recruiting
Hamilton, Ontario, Canada, L8N 4A6
Contact: Melanie Kjarsgaard, RRT    9055221155 ext 33024    mkjarsga@stjoes.ca   
Contact: Manali Mukherjee, PhD    9055221155 ext 37313    mukherj@mcmaster.ca   
Principal Investigator: Parameswaran Nair, MD, PhD         
Sub-Investigator: Paul O'Byrne, MB         
Sponsors and Collaborators
McMaster University
St. Joseph's Healthcare Hamilton
AstraZeneca
Investigators
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Principal Investigator: Parameswaran Nair, MD, PhD McMaster University and St. Joseph's Healthcare Hamilton

Publications:

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Responsible Party: McMaster University
ClinicalTrials.gov Identifier: NCT03470311     History of Changes
Other Study ID Numbers: 17-12992
First Posted: March 19, 2018    Key Record Dates
Last Update Posted: March 20, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by McMaster University:
Eosinophils
asthma
inflammation
prednisone

Additional relevant MeSH terms:
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Benralizumab
Pulmonary Eosinophilia
Lung Diseases
Respiratory Tract Diseases
Hypereosinophilic Syndrome
Eosinophilia
Leukocyte Disorders
Hematologic Diseases
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents