search
Back to results

Mepolizumab for the Treatment of Chronic Cough With Eosinophilic Airways Diseases (MUCOSA)

Primary Purpose

Chronic Cough, Eosinophilic Bronchitis, Asthma

Status
Recruiting
Phase
Phase 4
Locations
Canada
Study Type
Interventional
Intervention
Mepolizumab
Normal Saline
Sponsored by
McMaster University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Cough focused on measuring Mepolizumab, Treatment, Anti-interleukin-5, Proof-of-concept study, Randomized, Double-blind, Placebo controlled

Eligibility Criteria

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

Inclusion Criteria:

  1. Aged ≥18
  2. Subjects with a history of chronic cough (cough lasting for >8 weeks)
  3. Evidence of airway eosinophilia (sputum eosinophilia>2%)
  4. Forced expiratory volume-1 ≥ 70% of predicted
  5. Normal chest x-ray (within the last 6 months)
  6. At least one dose of a COVID-19 vaccine a minimum of 2 weeks prior to enrollment

Exclusion Criteria:

  1. Symptoms of upper respiratory tract infection in the last 1 month which have not resolved.
  2. Lower respiratory tract infection or pneumonia in the last 1 month.
  3. Subjects with a positive covid-19 test within 2 weeks of screening
  4. Subjects with seasonal allergic rhinitis that affects their asthma control
  5. Current smoker or ex-smoker with ≥10 pack year smoking history and abstinence of ≤6 months
  6. Symptoms of uncontrolled asthma at screening defined as: Asthma Control Questionnaire-5 >1.5, or use of 3 or more puffs of a short acting beta-2 agonist per week, or an exacerbation in the previous month requiring oral prednisone or antibiotics.
  7. Use of regular maintenance oral corticosteroids or long-acting muscarinic antagonist within 4 weeks prior to enrolment into the study.
  8. A previous asthma exacerbation requiring Intensive Care Unit admission.
  9. Significant other primary pulmonary disorders in particular; pulmonary embolism, pulmonary hypertension, interstitial lung disease, lung cancer, cystic fibrosis, emphysema or bronchiectasis.
  10. Any history or symptoms of cardiovascular disease, particularly coronary artery disease, arrhythmias, hypertension, or congestive heart failure.
  11. Any history or symptoms of significant neurologic disease, including transient ischemic attack, stroke, seizure disorder, or behavioural disturbances
  12. Uncontrolled diabetes
  13. End-stage kidney or liver disease
  14. Clinically significant abnormalities in laboratory test results during the screening period (including complete blood count, coagulation, electrolytes, liver function tests) unless deemed not significant by the investigator.
  15. Any history or symptoms of clinically significant autoimmune disease
  16. History of anaphylaxis to any biologic therapy or vaccine
  17. History of Guillain-Barre Syndrome
  18. A helminth parasitic infection diagnosed within 24 weeks prior to the date of informed consent is obtained that has not been treated with or has failed to respond to standard of care therapy.
  19. 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 can enroll.
  20. A history of immunodeficiency disorders including a positive human immunodeficiency virus test
  21. Pregnancy or breast-feeding.
  22. Women of childbearing potential must not be actively seeking pregnancy, and 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/ intrauterine system levonorgestrel Intrauterine system, Depo-Provera™ injections, oral contraceptive, and Evra Patch™ or Nuvaring™. Women of childbearing potential must agree to use an effective method of birth control, as defined above, from enrolment, throughout the study duration and within the 8 treatment weeks. They must demonstrate a negative serum pregnancy test at screening and demonstrate a negative urine pregnancy test immediately before each dose of study drug or placebo. 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:

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

    ii. 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.

  23. Male patients not using an acceptable method of contraception. All male patients who are sexually active must agree to use an acceptable method of contraception (condom with or without spermicide, vasectomy) from the first dose of study drug until their last dose.
  24. Use of angiotensin-converting-enzyme inhibitors
  25. Use of immunosuppressive medication (including but not limited to: methotrexate, 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
  26. Use of any other biological within 4 months or 5 half-lives prior to randomization, whichever is longer.
  27. Any centrally acting medication within the last 2 weeks which in the view of the investigator could influence the coughing (Any participant who is taking amitriptyline, dextromethorphan, pregabalin, gabapentin or opioids will not be eligible to take part in this study unless they are willing and medically able to withdraw from such medication for the duration of the study. The reason for this is that centrally acting medications may influence coughing rates.)
  28. History of psychiatric illness, drug or alcohol abuse which may interfere in the participation of the trial.

Sites / Locations

  • McMaster UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Mepolizumab arm

Placebo arm

Arm Description

Mepolizumab Dosage form: 1ml pre-filled syringe Dosage: 100mg Frequency: 3 doses at days 0, 28, 56 and 84 Duration: 12 weeks

Normal Saline (0.09% normal saline) Dosage form: 1ml pre-filled syringe Dosage: n/a Frequency: 3 doses at days 0, 28, 56 and 84 Duration: 12 weeks

Outcomes

Primary Outcome Measures

Cough frequency
Change in 24 hour cough frequency (coughs/hour) from baseline to visit 8 of treatment with Mepolizumab compared with placebo.

Secondary Outcome Measures

Awake cough frequency at 8 weeks
Change in awake cough frequency (coughs/hour) from baseline to visit 5 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis).
Awake cough frequency at 14 weeks
Change in awake cough frequency (coughs/hour) from baseline to visit 8 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis).
Night-time cough frequency at 8 weeks
Change in night-time cough frequency (coughs/hour) from baseline to visit 5 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis).
Night-time cough frequency at 14 weeks
Change in night-time cough frequency (coughs/hour) from baseline to visit 8 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis).
Percent reduction in 24 hour cough frequency at 8 weeks
Percentage of participants with a reduction in 24-hour cough frequency of ≥30% from baseline to visit 5 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis).
Percent reduction in 24 hour cough frequency at 14 weeks
Percentage of participants with a reduction in 24-hour cough frequency of ≥30% from baseline to visit 8 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis).
Cough severity and intensity of sensations at 8 weeks
Change in the cough severity and intensity of sensations (itch, tickle, irritation, urge to cough on a modified Borg Scale (mBorg Scale)) from baseline to visit 5 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis). The mBorg scale minimum value is 0 for no cough sensations and the maximum value is 10 for most severe cough sensations.
Cough severity and intensity of sensations at 14 weeks
Change in the cough severity and intensity of sensations (itch, tickle, irritation, urge to cough on a modified Borg Scale (mBorg Scale)) from baseline to visit 8 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis). The mBorg scale minimum value is 0 for no cough sensations and the maximum value is 10 for most severe cough sensations.
Cough severity at 8 weeks
Change in the cough severity measured using the Cough Severity Visual Analogue Scale (0-100mm) from baseline to visit 5 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis). Participants will rate their severity of cough on the scale which has a minimum value of 0 equalling "no cough" and a maximum value of 100 equalling "worst cough". A higher score indicates greater cough severity.
Cough severity at 14 weeks
Change in the cough severity measured using the Cough Severity Visual Analogue Scale (0-100mm) from baseline to visit 8 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis). Participants will rate their severity of cough on the scale which has a minimum value of 0 equalling "no cough" and a maximum value of 100 equalling "worst cough". A higher score indicates greater cough severity.
Leicester Cough Questionnaire at 8 weeks
Change in Leicester Cough Questionnaire (LCQ) score from baseline to visit 5 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis). The LCQ is a 7 point Likert scale where the minimum value is 1 indicating chronic cough impacts the participants all the time and a maximum value of 7 indicating chronic cough impacts the participants none of the time.
Leicester Cough Questionnaire at 14 weeks
Change in Leicester Cough Questionnaire (LCQ) score from baseline to visit 8 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis). The LCQ is a 7 point Likert scale where the minimum value is 1 indicating chronic cough impacts the participants all the time and a maximum value of 7 indicating chronic cough impacts the participants none of the time.
Blood eosinophils at 8 weeks
Change in blood eosinophils from baseline to visit 5 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis).
Blood eosinophils at 14 weeks
Change in blood eosinophils from baseline to visit 8 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis).
Sputum eosinophils at 8 weeks
Change in sputum eosinophils from baseline to visit 5 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis).
Sputum eosinophils at 14 weeks
Change in sputum eosinophils from baseline to visit 8 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis).

Full Information

First Posted
February 5, 2021
Last Updated
March 13, 2023
Sponsor
McMaster University
Collaborators
GlaxoSmithKline, University of Manchester
search

1. Study Identification

Unique Protocol Identification Number
NCT04765722
Brief Title
Mepolizumab for the Treatment of Chronic Cough With Eosinophilic Airways Diseases
Acronym
MUCOSA
Official Title
Mepolizumab for the Treatment of Chronic Cough With Eosinophilic Airways Diseases
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 14, 2021 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
April 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
McMaster University
Collaborators
GlaxoSmithKline, University of Manchester

4. Oversight

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

5. Study Description

Brief Summary
Cough is the most common presenting symptom to family physician. Chronic Cough affects approximately 10-12% of the general population and is one of the commonest reasons for referral to secondary care. Unfortunately, there are no licensed treatments for this debilitating condition, which is associated with a poor quality of life, affecting the social, physical and psychological well-being of patients. The aim of this single-centre proof-of-concept study is to investigate whether mepolizumab reduces objective cough frequency in patients with eosinophilic asthma and non-asthmatic eosinophilic bronchitis presenting with chronic cough. Secondary outcomes including the effects on quality of life, the intensity of irritant sensations, airway hyper-reactivity and inflammatory cells and their progenitors will also be evaluated. The investigators hypothesize that in patients with asthma and non-asthmatic eosinophilic bronchitis, eosinophils are involved in sensitizing airway nerves and thereby increasing spontaneous objective coughs. The investigators predict that treatment with mepolizumab will reduce airway eosinophilia in patients with chronic cough due to eosinophilic asthma and non-asthmatic eosinophilic bronchitis, thereby causing a reduction in objective cough frequency.
Detailed Description
This is a 9-visit randomized, double-blind, placebo-controlled, parallel-group Phase IV study. The purpose of this study is to evaluate the effectiveness of mepolizumab for the treatment of refractory chronic cough in patients with eosinophilic airway disease. Patients will be recruited from secondary care clinics. Patient eligibility will be assessed against the study inclusion/exclusion criteria and patients will undergo informed consent in the research centre. Subjects who provide informed consent and are enrolled in the study will undergo screening procedures. The study will consist of a Mepolizumab treatment arm and placebo arm (normal saline). Fifteen subjects will be randomly assigned to the treatment arm and fifteen subjects will be randomly assigned to the placebo arm in a 1:1 ratio. Following screening and randomization, subjects will under an 12-week treatment period during which they will receive 4 doses of the study drug at days 0, 28, 56, and 84. The primary study outcomes will be measured at week 14 week, 2 weeks following the treatment period. At Visit 1 (screening), subjects will undergo screening procedures: complete medical history, physical examination, methacholine challenge, spirometry, sputum induction, and blood sampling. Subjects will complete the Leicester Cough Questionnaire and modified Borg Scale. At Visit 2, subjects will be fitted with a 24-hour cough monitor. At Visit 3, 24-hour cough monitors will be removed and subjects will undergo spirometry, blood sampling and sputum induction. Subjects will complete the Leicester Cough Questionnaire, modified Borg Scale, and Cough Severity Visual Analogue Scale. The first dose of the study drug will be administered in the clinical research facility by a study physician. At Visit 4, subjects will undergo spirometry and blood sampling and complete the Leicester Cough Questionnaire, modified Borg Scale, and Cough Severity Visual Analogue Scale. The second dose of the study drug will be administered in the clinical research facility by a study physician. At Visit 5, the third dose of the study drug will be administered in the clinical research facility by a study physician. Subjects will be fitted with a 24-hour cough monitor. At Visit 6, 24-hour cough monitors will be removed and subjects will undergo spirometry, sputum induction and blood sampling and complete the Leicester Cough Questionnaire, modified Borg Scale, and Cough Severity Visual Analogue Scale. At Visit 7, subjects will undergo spirometry and blood sampling and complete the Leicester Cough Questionnaire, modified Borg Scale, and Cough Severity Visual Analogue Scale. The fourth dose of the study drug will be administered in the clinical research facility by a study physician. At Visit 8, subjects will be fitted with a 24-hour cough monitor. At Visit 9, the 24-hour cough monitors will be removed and subjects will undergo spirometry, methacholine challenge, sputum induction, and blood sampling. Subjects will complete the Leicester Cough Questionnaire, modified Borg Scale, and Cough Severity Visual Analogue Scale. All study procedures will be performed according to local standard operating procedures and be conducted by trained and experienced staff with supervision by medical doctors. Study physicians will administer all study drug injections. Safety will be assessed throughout the study by monitoring for adverse events and serious adverse events.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Cough, Eosinophilic Bronchitis, Asthma
Keywords
Mepolizumab, Treatment, Anti-interleukin-5, Proof-of-concept study, Randomized, Double-blind, Placebo controlled

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Single-centre, randomized, double-blind, placebo-controlled, parallel-group proof-of-concept study to evaluate the effectiveness of 4 doses of mepolizumab for the treatment of refractory chronic cough in patients with asthma and non-asthmatic eosinophilic bronchitis. The study will have 2 arms, each with 15 participants, and a total of 9 visits per subject. Subjects will be screened and within 2 weeks randomized to the intervention (mepolizumab) or placebo arm. Subjects will receive the intervention over a 12 week period at visits 3, 4, 5, and 7. The primary outcome will be measured at visit 14 which will occur 2 weeks after the final intervention dose.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Subjects will be assigned to one of the two possible treatment arms generated by a computer-generated randomization schedule prepared by McMaster University, with a ratio of 1:1, mepolizumab or placebo. As there is a known imbalance in the prevalence and cough rates, the study will include sex as a randomization factor. This will mitigate the possibility of the intervention being confounded by sex differences in the 2 arms of the study. Blinded study drug supplies will be provided in sequentially numbered identical syringes in accordance with the randomization schedule and dispensed by a pharmacist who shall not be delegated any other role in the study. Subjects, investigators, research staff (with the exception of the pharmacist) and the sponsor will be masked to the treatment sequence assignment. A sealed code-break envelope for each subject containing details of the treatment allocated will be kept in a locked safe at the study site.
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Mepolizumab arm
Arm Type
Experimental
Arm Description
Mepolizumab Dosage form: 1ml pre-filled syringe Dosage: 100mg Frequency: 3 doses at days 0, 28, 56 and 84 Duration: 12 weeks
Arm Title
Placebo arm
Arm Type
Placebo Comparator
Arm Description
Normal Saline (0.09% normal saline) Dosage form: 1ml pre-filled syringe Dosage: n/a Frequency: 3 doses at days 0, 28, 56 and 84 Duration: 12 weeks
Intervention Type
Drug
Intervention Name(s)
Mepolizumab
Other Intervention Name(s)
Nucala
Intervention Description
Mepolizumab subcutaneous injection administered 3 times days 0, 28, 56 and 84 during 12 week treatment period.
Intervention Type
Drug
Intervention Name(s)
Normal Saline
Other Intervention Name(s)
0.09% normal saline
Intervention Description
Placebo subcutaneous injection administered 3 times days 0, 28, 56 and 84 during 12 week treatment period.
Primary Outcome Measure Information:
Title
Cough frequency
Description
Change in 24 hour cough frequency (coughs/hour) from baseline to visit 8 of treatment with Mepolizumab compared with placebo.
Time Frame
14 weeks
Secondary Outcome Measure Information:
Title
Awake cough frequency at 8 weeks
Description
Change in awake cough frequency (coughs/hour) from baseline to visit 5 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis).
Time Frame
8 weeks
Title
Awake cough frequency at 14 weeks
Description
Change in awake cough frequency (coughs/hour) from baseline to visit 8 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis).
Time Frame
14 weeks
Title
Night-time cough frequency at 8 weeks
Description
Change in night-time cough frequency (coughs/hour) from baseline to visit 5 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis).
Time Frame
8 weeks
Title
Night-time cough frequency at 14 weeks
Description
Change in night-time cough frequency (coughs/hour) from baseline to visit 8 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis).
Time Frame
14 weeks
Title
Percent reduction in 24 hour cough frequency at 8 weeks
Description
Percentage of participants with a reduction in 24-hour cough frequency of ≥30% from baseline to visit 5 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis).
Time Frame
8 weeks
Title
Percent reduction in 24 hour cough frequency at 14 weeks
Description
Percentage of participants with a reduction in 24-hour cough frequency of ≥30% from baseline to visit 8 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis).
Time Frame
14 weeks
Title
Cough severity and intensity of sensations at 8 weeks
Description
Change in the cough severity and intensity of sensations (itch, tickle, irritation, urge to cough on a modified Borg Scale (mBorg Scale)) from baseline to visit 5 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis). The mBorg scale minimum value is 0 for no cough sensations and the maximum value is 10 for most severe cough sensations.
Time Frame
8 weeks
Title
Cough severity and intensity of sensations at 14 weeks
Description
Change in the cough severity and intensity of sensations (itch, tickle, irritation, urge to cough on a modified Borg Scale (mBorg Scale)) from baseline to visit 8 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis). The mBorg scale minimum value is 0 for no cough sensations and the maximum value is 10 for most severe cough sensations.
Time Frame
14 weeks
Title
Cough severity at 8 weeks
Description
Change in the cough severity measured using the Cough Severity Visual Analogue Scale (0-100mm) from baseline to visit 5 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis). Participants will rate their severity of cough on the scale which has a minimum value of 0 equalling "no cough" and a maximum value of 100 equalling "worst cough". A higher score indicates greater cough severity.
Time Frame
8 weeks
Title
Cough severity at 14 weeks
Description
Change in the cough severity measured using the Cough Severity Visual Analogue Scale (0-100mm) from baseline to visit 8 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis). Participants will rate their severity of cough on the scale which has a minimum value of 0 equalling "no cough" and a maximum value of 100 equalling "worst cough". A higher score indicates greater cough severity.
Time Frame
14 weeks
Title
Leicester Cough Questionnaire at 8 weeks
Description
Change in Leicester Cough Questionnaire (LCQ) score from baseline to visit 5 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis). The LCQ is a 7 point Likert scale where the minimum value is 1 indicating chronic cough impacts the participants all the time and a maximum value of 7 indicating chronic cough impacts the participants none of the time.
Time Frame
8 weeks
Title
Leicester Cough Questionnaire at 14 weeks
Description
Change in Leicester Cough Questionnaire (LCQ) score from baseline to visit 8 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis). The LCQ is a 7 point Likert scale where the minimum value is 1 indicating chronic cough impacts the participants all the time and a maximum value of 7 indicating chronic cough impacts the participants none of the time.
Time Frame
14 weeks
Title
Blood eosinophils at 8 weeks
Description
Change in blood eosinophils from baseline to visit 5 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis).
Time Frame
8 weeks
Title
Blood eosinophils at 14 weeks
Description
Change in blood eosinophils from baseline to visit 8 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis).
Time Frame
14 weeks
Title
Sputum eosinophils at 8 weeks
Description
Change in sputum eosinophils from baseline to visit 5 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis).
Time Frame
8 weeks
Title
Sputum eosinophils at 14 weeks
Description
Change in sputum eosinophils from baseline to visit 8 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis).
Time Frame
14 weeks
Other Pre-specified Outcome Measures:
Title
Methacholine provocative concentration20 at 14 weeks
Description
Change in methacholine provocative concentration20 from baseline to visit 8 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis).
Time Frame
14 weeks
Title
Total and activated mature eosinophils at 14 weeks
Description
Change in total and activated mature eosinophils in blood and sputum from baseline to visit 8 of treatment with Mepolizumab compared with placebo among all participants and by disease group (participants with asthma and participants with non-asthmatic eosinophilic bronchitis).
Time Frame
14 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Aged ≥18 Subjects with a history of chronic cough (cough lasting for >8 weeks) Evidence of airway eosinophilia (sputum eosinophilia>2%) Forced expiratory volume-1 ≥ 70% of predicted Normal chest x-ray (within the last 6 months) At least one dose of a COVID-19 vaccine a minimum of 2 weeks prior to enrollment Exclusion Criteria: Symptoms of upper respiratory tract infection in the last 1 month which have not resolved. Lower respiratory tract infection or pneumonia in the last 1 month. Subjects with a positive covid-19 test within 2 weeks of screening Subjects with seasonal allergic rhinitis that affects their asthma control Current smoker or ex-smoker with ≥10 pack year smoking history and abstinence of ≤6 months Symptoms of uncontrolled asthma at screening defined as: Asthma Control Questionnaire-5 >1.5, or use of 3 or more puffs of a short acting beta-2 agonist per week, or an exacerbation in the previous month requiring oral prednisone or antibiotics. Use of regular maintenance oral corticosteroids or long-acting muscarinic antagonist within 4 weeks prior to enrolment into the study. A previous asthma exacerbation requiring Intensive Care Unit admission. Significant other primary pulmonary disorders in particular; pulmonary embolism, pulmonary hypertension, interstitial lung disease, lung cancer, cystic fibrosis, emphysema or bronchiectasis. Any history or symptoms of cardiovascular disease, particularly coronary artery disease, arrhythmias, hypertension, or congestive heart failure. Any history or symptoms of significant neurologic disease, including transient ischemic attack, stroke, seizure disorder, or behavioural disturbances Uncontrolled diabetes End-stage kidney or liver disease Clinically significant abnormalities in laboratory test results during the screening period (including complete blood count, coagulation, electrolytes, liver function tests) unless deemed not significant by the investigator. Any history or symptoms of clinically significant autoimmune disease History of anaphylaxis to any biologic therapy or vaccine History of Guillain-Barre Syndrome A helminth parasitic infection diagnosed within 24 weeks prior to the date of 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 can enroll. A history of immunodeficiency disorders including a positive human immunodeficiency virus test Pregnancy or breast-feeding. Women of childbearing potential must not be actively seeking pregnancy, and 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/ intrauterine system levonorgestrel Intrauterine system, Depo-Provera™ injections, oral contraceptive, and Evra Patch™ or Nuvaring™. Women of childbearing potential must agree to use an effective method of birth control, as defined above, from enrolment, throughout the study duration and within the 8 treatment weeks. They must demonstrate a negative serum pregnancy test at screening and demonstrate a negative urine pregnancy test immediately before each dose of study drug or placebo. 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: i. Women <50 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatment and follicle stimulating hormone (FSH) levels in the postmenopausal range. ii. 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. Male patients not using an acceptable method of contraception. All male patients who are sexually active must agree to use an acceptable method of contraception (condom with or without spermicide, vasectomy) from the first dose of study drug until their last dose. Use of angiotensin-converting-enzyme inhibitors Use of immunosuppressive medication (including but not limited to: methotrexate, 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 Use of any other biological within 4 months or 5 half-lives prior to randomization, whichever is longer. Any centrally acting medication within the last 2 weeks which in the view of the investigator could influence the coughing (Any participant who is taking amitriptyline, dextromethorphan, pregabalin, gabapentin or opioids will not be eligible to take part in this study unless they are willing and medically able to withdraw from such medication for the duration of the study. The reason for this is that centrally acting medications may influence coughing rates.) History of psychiatric illness, drug or alcohol abuse which may interfere in the participation of the trial.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Imran Satia, MD, PhD
Phone
905-521-2100
Ext
76228
Email
satiai@mcmaster.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Paul O'Byrne, MD
Phone
905-521-2100
Ext
76373
Email
obyrnep@mcmaster.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Imran Satia, MD, PhD
Organizational Affiliation
McMaster University
Official's Role
Principal Investigator
Facility Information:
Facility Name
McMaster University
City
Hamilton
State/Province
Ontario
ZIP/Postal Code
L8S 4L8
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Imran Satia, MD PhD
Email
satiai@mcmaster.ca

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
16471269
Citation
Schappert SM, Burt CW. Ambulatory care visits to physician offices, hospital outpatient departments, and emergency departments: United States, 2001-02. Vital Health Stat 13. 2006 Feb;(159):1-66.
Results Reference
background
PubMed Identifier
25657027
Citation
Song WJ, Chang YS, Faruqi S, Kim JY, Kang MG, Kim S, Jo EJ, Kim MH, Plevkova J, Park HW, Cho SH, Morice AH. The global epidemiology of chronic cough in adults: a systematic review and meta-analysis. Eur Respir J. 2015 May;45(5):1479-81. doi: 10.1183/09031936.00218714. Epub 2015 Feb 5. No abstract available.
Results Reference
background
PubMed Identifier
16428686
Citation
Irwin RS, Baumann MH, Bolser DC, Boulet LP, Braman SS, Brightling CE, Brown KK, Canning BJ, Chang AB, Dicpinigaitis PV, Eccles R, Glomb WB, Goldstein LB, Graham LM, Hargreave FE, Kvale PA, Lewis SZ, McCool FD, McCrory DC, Prakash UBS, Pratter MR, Rosen MJ, Schulman E, Shannon JJ, Hammond CS, Tarlo SM. Diagnosis and management of cough executive summary: ACCP evidence-based clinical practice guidelines. Chest. 2006 Jan;129(1 Suppl):1S-23S. doi: 10.1378/chest.129.1_suppl.1S. No abstract available.
Results Reference
background
PubMed Identifier
9701100
Citation
French CL, Irwin RS, Curley FJ, Krikorian CJ. Impact of chronic cough on quality of life. Arch Intern Med. 1998 Aug 10-24;158(15):1657-61. doi: 10.1001/archinte.158.15.1657.
Results Reference
background
PubMed Identifier
10430705
Citation
Brightling CE, Ward R, Goh KL, Wardlaw AJ, Pavord ID. Eosinophilic bronchitis is an important cause of chronic cough. Am J Respir Crit Care Med. 1999 Aug;160(2):406-10. doi: 10.1164/ajrccm.160.2.9810100.
Results Reference
background
PubMed Identifier
2567371
Citation
Gibson PG, Dolovich J, Denburg J, Ramsdale EH, Hargreave FE. Chronic cough: eosinophilic bronchitis without asthma. Lancet. 1989 Jun 17;1(8651):1346-8. doi: 10.1016/s0140-6736(89)92801-8.
Results Reference
background
PubMed Identifier
9230750
Citation
Carney IK, Gibson PG, Murree-Allen K, Saltos N, Olson LG, Hensley MJ. A systematic evaluation of mechanisms in chronic cough. Am J Respir Crit Care Med. 1997 Jul;156(1):211-6. doi: 10.1164/ajrccm.156.1.9605044.
Results Reference
background
PubMed Identifier
30660644
Citation
Satia I, Watson R, Scime T, Dockry RJ, Sen S, Ford JW, Mitchell PD, Fowler SJ, Gauvreau GM, O'Byrne PM, Smith JA. Allergen challenge increases capsaicin-evoked cough responses in patients with allergic asthma. J Allergy Clin Immunol. 2019 Sep;144(3):788-795.e1. doi: 10.1016/j.jaci.2018.11.050. Epub 2019 Jan 17.
Results Reference
background
PubMed Identifier
30185653
Citation
Drake MG, Scott GD, Blum ED, Lebold KM, Nie Z, Lee JJ, Fryer AD, Costello RW, Jacoby DB. Eosinophils increase airway sensory nerve density in mice and in human asthma. Sci Transl Med. 2018 Sep 5;10(457):eaar8477. doi: 10.1126/scitranslmed.aar8477.
Results Reference
background

Learn more about this trial

Mepolizumab for the Treatment of Chronic Cough With Eosinophilic Airways Diseases

We'll reach out to this number within 24 hrs