Chronic CoughPhase 4MUCOSANCT04765722
Mepolizumab for the Treatment of Chronic Cough With Eosinophilic Airways Diseases
A Phase 4 study testing Mepolizumab and Normal Saline in people with Chronic Cough and Eosinophilic Bronchitis, run by McMaster University at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Cough, Eosinophilic Bronchitis, Asthma
- What is being tested?
- Mepolizumab and Normal Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 46 participants
- Where
- 1 siteCanada
- Study dates
- 14 Dec 2021to 12 Nov 2024
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 30Show fewer
- 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:
- 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.
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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.
- Conditions
- Chronic Cough, Eosinophilic Bronchitis, Asthma
- Being tested
- Mepolizumab, Normal Saline
- Keywords
- Mepolizumab, Treatment, Anti-interleukin-5, Proof-of-concept study, Randomized, Double-blind, Placebo controlled
- Medical subject headings
- Chronic Cough, Asthma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MepolizumabDrug
Also called Nucala
Mepolizumab subcutaneous injection administered 4 times days 0, 28, 56 and 84 during 12 week treatment period.
Normal SalineDrug
Also called 0.09% normal saline
Placebo subcutaneous injection administered 4 times days 0, 28, 56 and 84 during 12 week treatment period.
| Study group | Role | What they receive |
|---|---|---|
| Mepolizumab arm | Experimental | Mepolizumab Dosage form: 1ml pre-filled syringe Dosage: 100mg Frequency: 4 doses at days 0, 28, 56 and 84 Duration: 12 weeks Receives: Drug: Mepolizumab |
| Placebo arm | Placebo comparator | Normal Saline (0.09% normal saline) Dosage form: 1ml pre-filled syringe Dosage: n/a Frequency: 4 doses at days 0, 28, 56 and 84 Duration: 12 weeks Receives: Drug: Normal Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in 24-hour Cough Frequency at 14 Weeks
Change from baseline in 24-hour cough frequency (coughs/hour) measured by the VitaloJAK cough monitor at 14 weeks.
Measured: 14 weeks
Secondary outcomes (12)
Change From Baseline in Awake Cough Frequency at 8 Weeks
Change from baseline in awake cough frequency (coughs/hour) measured by the VitaloJAK cough monitor at 8 weeks.
Measured: 8 weeks
Change From Baseline in Awake Cough Frequency at 14 Weeks
Change from baseline in awake cough frequency (coughs/hour) at 14 weeks.
Measured: 14 weeks
Change From Baseline in Sleep Cough Frequency at 8 Weeks
Change from baseline in sleep cough frequency (coughs/hour) measured by the VitaloJAK cough monitor at 8 weeks.
Measured: 8 weeks
Change From Baseline in Sleep Cough Frequency at 14 Weeks
Change from baseline in sleep cough frequency (coughs/hour) measured by the VitaloJAK cough monitor at 14 weeks.
Measured: 14 weeks
Change From Baseline in Cough Severity at 8 Weeks
Change from baseline in cough severity measured on the 100-mm visual analogue scale at 8 weeks. Scale ranges from 0 mm (no cough) to 100 mm (worst possible cough). Higher scores reflect worse cough severity.
Measured: 8 weeks
Change From Baseline in Cough Severity at 14 Weeks
Change from baseline in cough severity measured on the 100-mm visual analogue scale at 14 weeks. Scale ranges from 0 mm (no cough) to 100 mm (worst possible cough). Higher scores reflect worse cough severity.
Measured: 14 weeks
Change From Baseline on the Leicester Cough Questionnaire at 8 Weeks
Change from baseline in cough quality of life measured by the Leicester Cough Questionnaire at 8 weeks. Total score ranges from 3 to 21, with higher scores indicating better cough quality of life.
Measured: 8 weeks
Change From Baseline on the Leicester Cough Questionnaire at 14 Weeks
Change from baseline in cough quality of life measured by the Leicester Cough Questionnaire at 14 weeks. Total score ranges from 3 to 21, with higher scores indicating better cough quality of life.
Measured: 14 weeks
Change From Baseline in Blood Eosinophils at 8 Weeks
Change from baseline in blood eosinophils at 8 weeks.
Measured: 8 weeks
Change From Baseline in Blood Eosinophils at 14 Weeks
Change from baseline in blood eosinophils at 14 weeks.
Measured: 14 weeks
Change From Baseline in Sputum Eosinophils at 8 Weeks
Change from baseline in sputum eosinophils (%) at 8 weeks.
Measured: 8 weeks
Change From Baseline in Sputum Eosinophils at 14 Weeks
Change from baseline in sputum eosinophils (%) at 14 weeks.
Measured: 14 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2021
- Study start14 Dec 2021
- Primary completion12 Nov 2024
- Study completion12 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Chronic CoughStudies of the same condition, open and under way.
- More trials run by McMaster UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Collaborators
- University of Manchester
- Responsible party
- Sponsor
- Investigators
- Imran Satia, MD, PhD, Principal investigator, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04765722
- Sponsor's protocol ID
- ISS-21-4463
- Acronym
- MUCOSA
- Status last verified
- Jan 2025
- First submitted
- 5 Feb 2021
- Last updated
- 16 Sep 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 16471269Song 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.
PubMed 25657027Irwin 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.
PubMed 16428686French 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.
PubMed 9701100Brightling 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.
PubMed 10430705Gibson 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.
PubMed 2567371Carney 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.
PubMed 9230750Satia 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.
PubMed 30660644Drake 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.
PubMed 30185653
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mepolizumab for the Treatment of Chronic Cough With Eosinophilic Airways Diseases
- ClinicalTrials.gov ID
- NCT04765722
- Acronym / sponsor ID
- MUCOSA / ISS-21-4463
- Conditions
- Chronic Cough, Eosinophilic Bronchitis, Asthma
- Keywords
- Mepolizumab, Treatment, Anti-interleukin-5, Proof-of-concept study, Randomized, Double-blind, Placebo controlled
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Collaborators
- University of Manchester
- Study start
- 14 Dec 2021 (actual)
- Primary completion
- 12 Nov 2024 (actual)
- Study completion
- 12 Nov 2024 (actual)
- First posted
- 21 Feb 2021 (actual)
- Results
- Posted 16 Sep 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Mepolizumab arm | Experimental | Drug: MepolizumabMepolizumab Dosage form: 1ml pre-filled syringe Dosage: 100mg Frequency: 4 doses at days 0, 28, 56 and 84 Duration: 12 weeks |
| Placebo arm | Placebo comparator | Drug: Normal SalineNormal Saline (0.09% normal saline) Dosage form: 1ml pre-filled syringe Dosage: n/a Frequency: 4 doses at days 0, 28, 56 and 84 Duration: 12 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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)
Key exclusion criteria (30 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MepolizumabAlso: NucalaMepolizumab subcutaneous injection administered 4 times days 0, 28, 56 and 84 during 12 week treatment period. | Drug | Mepolizumab arm |
| Normal SalineAlso: 0.09% normal salinePlacebo subcutaneous injection administered 4 times days 0, 28, 56 and 84 during 12 week treatment period. | Drug | Placebo arm |
Primary outcome
Change From Baseline in 24-hour Cough Frequency at 14 Weeks
Time frame: 14 weeks
Change from baseline in 24-hour cough frequency (coughs/hour) measured by the VitaloJAK cough monitor at 14 weeks.
12 secondary outcomes
Change From Baseline in Awake Cough Frequency at 8 Weeks
Time frame: 8 weeks
Change From Baseline in Awake Cough Frequency at 14 Weeks
Time frame: 14 weeks
Change From Baseline in Sleep Cough Frequency at 8 Weeks
Time frame: 8 weeks
Change From Baseline in Sleep Cough Frequency at 14 Weeks
Time frame: 14 weeks
Change From Baseline in Cough Severity at 8 Weeks
Time frame: 8 weeks
Change From Baseline in Cough Severity at 14 Weeks
Time frame: 14 weeks
Change From Baseline on the Leicester Cough Questionnaire at 8 Weeks
Time frame: 8 weeks
Change From Baseline on the Leicester Cough Questionnaire at 14 Weeks
Time frame: 14 weeks
Change From Baseline in Blood Eosinophils at 8 Weeks
Time frame: 8 weeks
Change From Baseline in Blood Eosinophils at 14 Weeks
Time frame: 14 weeks
Change From Baseline in Sputum Eosinophils at 8 Weeks
Time frame: 8 weeks
Change From Baseline in Sputum Eosinophils at 14 Weeks
Time frame: 14 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Sep 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 16471269Schappert 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.
- Background: PubMed 25657027Song 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.
- Background: PubMed 16428686Irwin 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.
- Background: PubMed 9701100French 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.
- Background: PubMed 10430705Brightling 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.
- Background: PubMed 2567371Gibson 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.
- Background: PubMed 9230750Carney 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.
- Background: PubMed 30660644Satia 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.
- Background: PubMed 30185653Drake 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Imran Satia, MD, PhD principal investigator
McMaster University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Mepolizumab and Normal Saline in people with Chronic Cough and Eosinophilic Bronchitis, run by McMaster University at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 16 Sep 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change From Baseline in 24-hour Cough Frequency at 14 Weeks (time frame: 14 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04765722, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Sep 2025; AzTrials last refreshed its copy on 8 Nov 2026.