Mepolizumab for the Treatment of Chronic Cough With Eosinophilic Airways Diseases

NCT04765722 | Completed Phase 4 Results FDA Drug

• 1 other identifier: ISS-21-4463
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Cough; Eosinophilic Bronchitis; Asthma

Keywords

Mepolizumab; Treatment; Anti-interleukin-5; Proof-of-concept study; Randomized; Double-blind; Placebo controlled

Outcome Measures

Primary Outcomes (1)

• 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.

  14 weeks

Secondary Outcomes (12)

• Change From Baseline in Awake Cough Frequency at 8 Weeks

  8 weeks

• Change From Baseline in Awake Cough Frequency at 14 Weeks

  14 weeks

• Change From Baseline in Sleep Cough Frequency at 8 Weeks

  8 weeks

• Change From Baseline in Sleep Cough Frequency at 14 Weeks

  14 weeks

• Change From Baseline in Cough Severity at 8 Weeks

  8 weeks

Other Outcomes (1)

• Change From Baseline in Methacholine Provocative Concentration Eliciting a 20% Fall in FEV1 (PC20) at 14 Weeks

  14 weeks

Study Arms (2)

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

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

Drug: Normal Saline

Interventions

Mepolizumab DRUG

Mepolizumab subcutaneous injection administered 4 times days 0, 28, 56 and 84 during 12 week treatment period.

Also known as: Nucala

Mepolizumab arm

Normal Saline DRUG

Placebo subcutaneous injection administered 4 times days 0, 28, 56 and 84 during 12 week treatment period.

Also known as: 0.09% normal saline

Placebo arm

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• McMaster University: lead
• University of Manchester: collaborator

Study Sites (1)

McMaster University

Hamilton, Ontario, L8S 4L8, Canada

Location

Related Publications (10)

• 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.

  PMID: 16471269 BACKGROUND

• 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.

  PMID: 25657027 BACKGROUND

• 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.

  PMID: 16428686 BACKGROUND

• 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.

  PMID: 9701100 BACKGROUND

• 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.

  PMID: 10430705 BACKGROUND

• 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.

  PMID: 2567371 BACKGROUND

• 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.

  PMID: 9230750 BACKGROUND

• 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.

  PMID: 30660644 BACKGROUND

• 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.

  PMID: 30185653 BACKGROUND

• Diab N, Brister D, Kum E, Wahab M, Hassan W, Beaudin S, Obminski C, Wattie J, Wiltshire L, Howie K, Killian K, Holt K, Sehmi R, Gauvreau GM, Smith JA, O'Byrne PM, Satia I. Mepolizumab for the treatment of refractory chronic cough in patients with eosinophilic airways disease (MUCOSA): a randomized, double-blind, parallel-group, placebo-controlled trial. Eur Respir J. 2025 Nov 6:2501573. doi: 10.1183/13993003.01573-2025. Online ahead of print.

  PMID: 41198391 DERIVED

MeSH Terms

Conditions

Chronic Cough; Asthma

Interventions

mepolizumab; Saline Solution

Condition Hierarchy (Ancestors)

Cough; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Bronchial Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Results Point of Contact

• Title: Dr. Imran Satia
• Organization: McMaster University

satiai@mcmaster.ca

905 5212100

Study Officials

• Imran Satia, MD, PhD

  McMaster University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: February 5, 2021
• First Posted: February 21, 2021
• Study Start: December 14, 2021
• Primary Completion: November 12, 2024
• Study Completion: November 12, 2024
• Last Updated: September 16, 2025
• Results First Posted: September 16, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)