search
Back to results

The Effect of Benralizumab on Exercise-induced Bronchoconstriction

Primary Purpose

Asthma, Exercise-Induced

Status
Unknown status
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Benralizumab
Sponsored by
Louis-Philippe Boulet
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Asthma, Exercise-Induced focused on measuring Exercise-induced bronchoconstriction, Benralizumab, Antiinterleukin 5 receptor α monoclonal antibody

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Written informed consent for study participants must be obtained prior to any study related procedures being performed and according to local guidelines;
  2. Asthma diagnosis according to current guidelines;
  3. General good health as declared by the investigator;
  4. Respiratory symptoms such as wheeze, shortness of breath, chest tightness or cough during physical activity;
  5. Moderate to severe eosinophilic asthma (Inhaled corticosteroids, 250 mcg/day fluticasone equivalent or more and long acting beta2-agonists, stable for at least one month);
  6. Sufficient adherence to maintenance therapy (from questionnaire and pharmacy reports: adherence to at least 80% of medication prescribed on both);
  7. Baseline blood eosinophil counts of at least 300 cells/ul and/or sputum eosinophil of at least 3%;
  8. Exercise less than 4 hours per week and remain stable through the study;
  9. Presence of EIB: A post-exercise fall in FEV1 of at least 10% from baseline;
  10. Pre-bronchodilator FEV1 at screening of at least 70% of the predicted value;
  11. Women of childbearing potential (WOCBP) must use an effective form of birth control (confirmed by the investigator). Effective forms of birth control include: true sexual abstinence, a vasectomized sexual partner, Implanon, female sterilization by tubal occlusion, any effective intrauterine device/levonorgestrel Intrauterine system, Depo-Provera™ injections, oral contraceptive, and Evra Patch™ or Nuvaring™. WOCBP must agree to use effective method of birth control, as defined above, from enrolment, throughout the study duration and 20 weeks after last dose of study product, and have negative serum pregnancy test result on Visit 1;

    a. Women not of childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrheic for 12 months prior to the planned date of randomization without an alternative medical cause. The following age-specific requirements apply:

  12. Women <50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatment. They also need follicle stimulating hormone (FSH) levels in the postmenopausal range.
  13. Women ≥50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatment.

Exclusion Criteria:

  1. Respiratory tract infection within 6 weeks preceding enrolment;
  2. Asthma exacerbation in the last month;
  3. Use of prednisone in the last 30 days;
  4. Current lung disease other than moderate to severe eosinophilic asthma;
  5. History of clinically significant hypotensive episodes or symptoms of fainting, dizziness, or light headedness, as judged by the investigator;
  6. Any history or symptoms of uncontrolled cardiovascular disease, particularly coronary artery disease, arrhythmias, hypertension, or congestive heart failure;
  7. Any history or symptoms of significant neurologic disease, including transient ischemic attack (TIA), stroke, seizure disorder, or behavioural disturbances;
  8. Any history or symptoms of clinically significant autoimmune disease;
  9. Any history of clinically significant haematologic abnormality, including coagulopathy or any history of chronic treatment with anti-coagulants (e.g. warfarin, etc.) or anti-platelet agent (e.g. aspirin, etc.);
  10. Clinically significant abnormalities in laboratory test results at enrolment and during the screening period (including complete blood count, coagulation, chemistry panel and urinalysis) unless judged not significant by the investigator;
  11. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥2.5 times the upper limit of normal (ULN) confirmed during screening period;
  12. Being pregnant or lactating or have positive serum pregnancy test at enrolment or positive urine pregnancy test during the study;
  13. Use of nonsteroidal anti-inflammatory drugs (NSAIDs) 72 hours before or aspirin prn within 7 days of enrolment (Visit 1), as judged by the investigator;
  14. Current smokers. Ex-smokers must not have smoked for a minimum of 12 months, and should not have a smoking history ≥10 pack years. Subjects who administer nicotine in other forms (patches, chew tobacco, etc.) will also be excluded from the study;
  15. Concomitant disease or condition which could interfere with the conduct of the study, or for which the treatment might interfere with the conduct of the study, or which would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study, including, but not limited to, cancer, alcoholism, drug dependency or abuse, or psychiatric disease;
  16. History of cancer in last 5 years:
  17. Alcohol or drug abuse (past or present);
  18. Subject who is scheduled to be admitted to hospital or undergo in-subject surgery during the study;
  19. History of anaphylaxis to any biologic therapy or vaccine;
  20. History of Guillain-Barré syndrome;
  21. A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent is obtained that has not been treated with, or has failed to respond to standard of care therapy;
  22. Positive hepatitis B surface antigen, or hepatitis C virus antibody serology, or a positive medical history for hepatitis B or C. Subjects with a history of hepatitis B vaccination without history of hepatitis B are allowed to enrol;
  23. A history of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test;
  24. Use of immunosuppressive medication (including but not limited to: methotrexate, troleandomycin, cyclosporine, azathioprine, intramuscular long-acting depot corticosteroid, oral corticosteroid, or any experimental anti-inflammatory therapy) within 3 months prior to the date informed consent is obtained;
  25. Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained;
  26. Receipt of any marketed (e.g. omalizumab) or investigational biologic within 4 months or 5 half-lives prior to randomization is obtained, whichever is longer;
  27. Receipt of live attenuated vaccines 30 days prior to the date of randomization

    - Receipt of inactive/killed vaccinations (e.g., inactive influenza) are allowed provided they are not administered within 1 week before/after any IP administration.

  28. Previously received benralizumab (MEDI-563);
  29. AstraZeneca staff involved in planning and/or conducting the study;

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Placebo Comparator

    Arm Label

    Experimental

    Placebo

    Arm Description

    Subjects will receive benralizumab 30 mg (subcutaneous) every 4 weeks for three doses followed by a fourth dose 8 weeks later.

    Subjects will receive placebo 30 mg (subcutaneous) every 4 weeks for three doses followed by a fourth dose 8 weeks later.

    Outcomes

    Primary Outcome Measures

    Change in post-exercise fall in expiratory flows
    Maximal fall in forced expiratory volume in one second (FEV1) post-exercise challenge

    Secondary Outcome Measures

    Change in exercise tolerance
    Endurance time on a steady-state exercise

    Full Information

    First Posted
    October 19, 2017
    Last Updated
    October 26, 2017
    Sponsor
    Louis-Philippe Boulet
    Collaborators
    AstraZeneca
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT03327701
    Brief Title
    The Effect of Benralizumab on Exercise-induced Bronchoconstriction
    Official Title
    The Effect of Benralizumab on Lung Physiology, Exercise-induced Bronchoconstriction and General Health Status: an Exploratory Mechanistic Study
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2017
    Overall Recruitment Status
    Unknown status
    Study Start Date
    December 2017 (Anticipated)
    Primary Completion Date
    December 2019 (Anticipated)
    Study Completion Date
    April 2020 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor-Investigator
    Name of the Sponsor
    Louis-Philippe Boulet
    Collaborators
    AstraZeneca

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No

    5. Study Description

    Brief Summary
    Severe asthma affects 5-10% of more than 300 million asthmatics. Ten to twenty percent of individuals suffering from asthma do not respond well to current treatment due to the complexity of the different mechanisms underlying asthma pathogenesis, and sometimes due to an insufficient effect of treatment on underlying airway inflammation. Consequently, some asthmatics have poorer quality of life due to: frequent asthma symptoms, regular medical or emergency visits, limitation in their activities of daily living, including exercise. It is believed that the benralizumab can help to reduce airway inflammation and thus improve exercise tolerance in individuals with asthma. The main objective of this study is to determine the effect of benralizumab on exercise-induced bronchoconstriction (EIB) and exercise tolerance in moderate to severe eosinophilic asthmatics, in comparison with baseline values and a placebo treatment.
    Detailed Description
    Subjects will receive benralizumab every 4 weeks for three doses followed by a fourth dose 8 weeks later. On baseline and after 4, 16 and 20 weeks, subjects will be assess for airway responsiveness to exercise and exercise tolerance.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Asthma, Exercise-Induced
    Keywords
    Exercise-induced bronchoconstriction, Benralizumab, Antiinterleukin 5 receptor α monoclonal antibody

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Model Description
    This study is a parallel study, double-blind, placebo controlled randomized trial, with a ratio placebo-active drug 1:2.
    Masking
    ParticipantCare ProviderInvestigator
    Masking Description
    The study will be conducted under double-blind conditions. Neither the subject nor the investigator and clinical site personnel will know which medication is administered. The medication given will be determined according to a randomization table handled by a collaborating IUCPQ-UL pharmacist. Only the pharmacist responsible for preparing the medication for the randomized patients will have access to information on treatment allocations (unblended). Benralizumab and placebo solutions for injection in an accessorized pre-filled syringe (PFS) will have the same packaging.
    Allocation
    Randomized
    Enrollment
    40 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Experimental
    Arm Type
    Active Comparator
    Arm Description
    Subjects will receive benralizumab 30 mg (subcutaneous) every 4 weeks for three doses followed by a fourth dose 8 weeks later.
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Subjects will receive placebo 30 mg (subcutaneous) every 4 weeks for three doses followed by a fourth dose 8 weeks later.
    Intervention Type
    Drug
    Intervention Name(s)
    Benralizumab
    Intervention Description
    Subjects will receive benralizumab 30 mg (subcutaneous) every 4 weeks for three doses followed by a fourth dose 8 weeks later.
    Primary Outcome Measure Information:
    Title
    Change in post-exercise fall in expiratory flows
    Description
    Maximal fall in forced expiratory volume in one second (FEV1) post-exercise challenge
    Time Frame
    Baseline and after 4, 16 and 20 weeks
    Secondary Outcome Measure Information:
    Title
    Change in exercise tolerance
    Description
    Endurance time on a steady-state exercise
    Time Frame
    Baseline and after 4, 16 and 20 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    65 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Written informed consent for study participants must be obtained prior to any study related procedures being performed and according to local guidelines; Asthma diagnosis according to current guidelines; General good health as declared by the investigator; Respiratory symptoms such as wheeze, shortness of breath, chest tightness or cough during physical activity; Moderate to severe eosinophilic asthma (Inhaled corticosteroids, 250 mcg/day fluticasone equivalent or more and long acting beta2-agonists, stable for at least one month); Sufficient adherence to maintenance therapy (from questionnaire and pharmacy reports: adherence to at least 80% of medication prescribed on both); Baseline blood eosinophil counts of at least 300 cells/ul and/or sputum eosinophil of at least 3%; Exercise less than 4 hours per week and remain stable through the study; Presence of EIB: A post-exercise fall in FEV1 of at least 10% from baseline; Pre-bronchodilator FEV1 at screening of at least 70% of the predicted value; Women of childbearing potential (WOCBP) must use an effective form of birth control (confirmed by the investigator). Effective forms of birth control include: true sexual abstinence, a vasectomized sexual partner, Implanon, female sterilization by tubal occlusion, any effective intrauterine device/levonorgestrel Intrauterine system, Depo-Provera™ injections, oral contraceptive, and Evra Patch™ or Nuvaring™. WOCBP must agree to use effective method of birth control, as defined above, from enrolment, throughout the study duration and 20 weeks after last dose of study product, and have negative serum pregnancy test result on Visit 1; a. Women not of childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal. Women will be considered postmenopausal if they have been amenorrheic for 12 months prior to the planned date of randomization without an alternative medical cause. The following age-specific requirements apply: Women <50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatment. They also need follicle stimulating hormone (FSH) levels in the postmenopausal range. Women ≥50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatment. Exclusion Criteria: Respiratory tract infection within 6 weeks preceding enrolment; Asthma exacerbation in the last month; Use of prednisone in the last 30 days; Current lung disease other than moderate to severe eosinophilic asthma; History of clinically significant hypotensive episodes or symptoms of fainting, dizziness, or light headedness, as judged by the investigator; Any history or symptoms of uncontrolled cardiovascular disease, particularly coronary artery disease, arrhythmias, hypertension, or congestive heart failure; Any history or symptoms of significant neurologic disease, including transient ischemic attack (TIA), stroke, seizure disorder, or behavioural disturbances; Any history or symptoms of clinically significant autoimmune disease; Any history of clinically significant haematologic abnormality, including coagulopathy or any history of chronic treatment with anti-coagulants (e.g. warfarin, etc.) or anti-platelet agent (e.g. aspirin, etc.); Clinically significant abnormalities in laboratory test results at enrolment and during the screening period (including complete blood count, coagulation, chemistry panel and urinalysis) unless judged not significant by the investigator; Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) level ≥2.5 times the upper limit of normal (ULN) confirmed during screening period; Being pregnant or lactating or have positive serum pregnancy test at enrolment or positive urine pregnancy test during the study; Use of nonsteroidal anti-inflammatory drugs (NSAIDs) 72 hours before or aspirin prn within 7 days of enrolment (Visit 1), as judged by the investigator; Current smokers. Ex-smokers must not have smoked for a minimum of 12 months, and should not have a smoking history ≥10 pack years. Subjects who administer nicotine in other forms (patches, chew tobacco, etc.) will also be excluded from the study; Concomitant disease or condition which could interfere with the conduct of the study, or for which the treatment might interfere with the conduct of the study, or which would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study, including, but not limited to, cancer, alcoholism, drug dependency or abuse, or psychiatric disease; History of cancer in last 5 years: Alcohol or drug abuse (past or present); Subject who is scheduled to be admitted to hospital or undergo in-subject surgery during the study; History of anaphylaxis to any biologic therapy or vaccine; History of Guillain-Barré syndrome; A helminth parasitic infection diagnosed within 24 weeks prior to the date informed consent is obtained that has not been treated with, or has failed to respond to standard of care therapy; Positive hepatitis B surface antigen, or hepatitis C virus antibody serology, or a positive medical history for hepatitis B or C. Subjects with a history of hepatitis B vaccination without history of hepatitis B are allowed to enrol; A history of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test; Use of immunosuppressive medication (including but not limited to: methotrexate, troleandomycin, cyclosporine, azathioprine, intramuscular long-acting depot corticosteroid, oral corticosteroid, or any experimental anti-inflammatory therapy) within 3 months prior to the date informed consent is obtained; Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained; Receipt of any marketed (e.g. omalizumab) or investigational biologic within 4 months or 5 half-lives prior to randomization is obtained, whichever is longer; Receipt of live attenuated vaccines 30 days prior to the date of randomization - Receipt of inactive/killed vaccinations (e.g., inactive influenza) are allowed provided they are not administered within 1 week before/after any IP administration. Previously received benralizumab (MEDI-563); AstraZeneca staff involved in planning and/or conducting the study;
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Louis-Philippe Boulet, MD
    Phone
    418-656-4747
    Email
    lpboulet@med.ulaval.ca
    First Name & Middle Initial & Last Name or Official Title & Degree
    Julie Turmel, PhD
    Phone
    418-656-8711
    Ext
    2814
    Email
    julie.turmel@criucpq.ulaval.ca
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Louis-Philippe Boulet, MD
    Organizational Affiliation
    Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No

    Learn more about this trial

    The Effect of Benralizumab on Exercise-induced Bronchoconstriction

    We'll reach out to this number within 24 hrs