Asthma, Chronic Cough, Eosinophilic Bronchitis
Conditions
Keywords
Mepolizumab, Treatment, Anti-interleukin-5, Proof-of-concept study, Randomized, Double-blind, Placebo controlled
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.
Interventions
DRUGMepolizumab
Mepolizumab subcutaneous injection administered 4 times days 0, 28, 56 and 84 during 12 week treatment period.
DRUGNormal Saline
Placebo subcutaneous injection administered 4 times days 0, 28, 56 and 84 during 12 week treatment period.
Sponsors
University of Manchester
McMaster University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes 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.
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in 24-hour Cough Frequency at 14 Weeks | 14 weeks | Change from baseline in 24-hour cough frequency (coughs/hour) measured by the VitaloJAK cough monitor at 14 weeks. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Awake Cough Frequency at 8 Weeks | 8 weeks | Change from baseline in awake cough frequency (coughs/hour) measured by the VitaloJAK cough monitor at 8 weeks. |
| Change From Baseline in Awake Cough Frequency at 14 Weeks | 14 weeks | Change from baseline in awake cough frequency (coughs/hour) at 14 weeks. |
| Change From Baseline in Sleep Cough Frequency at 8 Weeks | 8 weeks | Change from baseline in sleep cough frequency (coughs/hour) measured by the VitaloJAK cough monitor at 8 weeks. |
| Change From Baseline in Sleep Cough Frequency at 14 Weeks | 14 weeks | Change from baseline in sleep cough frequency (coughs/hour) measured by the VitaloJAK cough monitor at 14 weeks. |
| Change From Baseline in Cough Severity at 8 Weeks | 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. |
| Change From Baseline in Cough Severity at 14 Weeks | 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. |
| Change From Baseline on the Leicester Cough Questionnaire at 14 Weeks | 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. |
| Change From Baseline in Blood Eosinophils at 8 Weeks | 8 weeks | Change from baseline in blood eosinophils at 8 weeks. |
| Change From Baseline in Blood Eosinophils at 14 Weeks | 14 weeks | Change from baseline in blood eosinophils at 14 weeks. |
| Change From Baseline in Sputum Eosinophils at 8 Weeks | 8 weeks | Change from baseline in sputum eosinophils (%) at 8 weeks. |
| Change From Baseline in Sputum Eosinophils at 14 Weeks | 14 weeks | Change from baseline in sputum eosinophils (%) at 14 weeks. |
| Change From Baseline on the Leicester Cough Questionnaire at 8 Weeks | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Methacholine Provocative Concentration Eliciting a 20% Fall in FEV1 (PC20) at 14 Weeks | 14 weeks | Change from baseline in methacholine provocative concentration eliciting a 20% fall in FEV1 (PC20) at 14 weeks. |
Countries
Canada
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Mepolizumab Arm Mepolizumab Dosage form: 1 ml pre-filled syringe Dosage: 100 mg Frequency: 4 doses at days 0, 28, 56 and 84 Duration: 12 weeks
Mepolizumab: Mepolizumab subcutaneous injection administered 4 times days 0, 28, 56 and 84 during 12 week treatment period. | 15 |
| Placebo Arm 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
Normal Saline: Placebo subcutaneous injection administered 4 times days 0, 28, 56 and 84 during 12 week treatment period. | 15 |
| Total | 30 |
Baseline characteristics
| Characteristic | Total | Placebo Arm | Mepolizumab Arm |
|---|---|---|---|
| Age, Continuous | 65.83 Years STANDARD_DEVIATION 11.8 | 65.80 Years STANDARD_DEVIATION 13.93 | 65.87 Years STANDARD_DEVIATION 9.72 |
| Cough Duration (months) | 115.5 Months | 61 Months | 120 Months |
| Diagnosis Asthma | 19 Participants | 11 Participants | 8 Participants |
| Diagnosis Non-asthmatic eosinophilic bronchitis | 11 Participants | 4 Participants | 7 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Caucasian | 27 Participants | 14 Participants | 13 Participants |
| Race/Ethnicity, Customized Race/Ethnicity Other | 3 Participants | 1 Participants | 2 Participants |
| Region of Enrollment Canada | 30 Participants | 15 Participants | 15 Participants |
| Sex: Female, Male Female | 17 Participants | 8 Participants | 9 Participants |
| Sex: Female, Male Male | 13 Participants | 7 Participants | 6 Participants |
| % Sputum Eosinophils | 2.6 Percentage | 2.6 Percentage | 2.6 Percentage |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 4 / 15 | 6 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
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.
Time frame: 14 weeks
Population: All patients who received at least one dose of a study drug were included in a modified intention-to-treat analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Mepolizumab Arm | Change From Baseline in 24-hour Cough Frequency at 14 Weeks | Week 0 | 17.0 Coughs/hour |
| Mepolizumab Arm | Change From Baseline in 24-hour Cough Frequency at 14 Weeks | Week 14 | 12.6 Coughs/hour |
| Placebo Arm | Change From Baseline in 24-hour Cough Frequency at 14 Weeks | Week 0 | 17.0 Coughs/hour |
| Placebo Arm | Change From Baseline in 24-hour Cough Frequency at 14 Weeks | Week 14 | 10.6 Coughs/hour |
Comparison: The primary outcome was the change from baseline in log-transformed 24-hour cough frequency (coughs/hour) at week 14.p-value: 0.9995% CI: [-46.4, 160.1]Generalized estimating equations
Secondary
Change From Baseline in Awake Cough Frequency at 14 Weeks
Change from baseline in awake cough frequency (coughs/hour) at 14 weeks.
Time frame: 14 weeks
Population: All patients who received at least one dose of a study drug were included in a modified intention-to-treat analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Mepolizumab Arm | Change From Baseline in Awake Cough Frequency at 14 Weeks | Week 0 | 22.5 Coughs/hour |
| Mepolizumab Arm | Change From Baseline in Awake Cough Frequency at 14 Weeks | Week 14 | 16.3 Coughs/hour |
| Placebo Arm | Change From Baseline in Awake Cough Frequency at 14 Weeks | Week 0 | 22.5 Coughs/hour |
| Placebo Arm | Change From Baseline in Awake Cough Frequency at 14 Weeks | Week 14 | 14.1 Coughs/hour |
Secondary
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.
Time frame: 8 weeks
Population: All patients who received at least one dose of a study drug were included in a modified intention-to-treat analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Mepolizumab Arm | Change From Baseline in Awake Cough Frequency at 8 Weeks | Week 0 | 22.5 Coughs/hour |
| Mepolizumab Arm | Change From Baseline in Awake Cough Frequency at 8 Weeks | Week 8 | 17.8 Coughs/hour |
| Placebo Arm | Change From Baseline in Awake Cough Frequency at 8 Weeks | Week 0 | 22.5 Coughs/hour |
| Placebo Arm | Change From Baseline in Awake Cough Frequency at 8 Weeks | Week 8 | 12.5 Coughs/hour |
Secondary
Change From Baseline in Blood Eosinophils at 14 Weeks
Change from baseline in blood eosinophils at 14 weeks.
Time frame: 14 weeks
Population: All patients who received at least one dose of a study drug were included in a modified intention-to-treat analysis.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mepolizumab Arm | Change From Baseline in Blood Eosinophils at 14 Weeks | Week 0 | 284.2 cells/µL |
| Mepolizumab Arm | Change From Baseline in Blood Eosinophils at 14 Weeks | Week 14 | 44.2 cells/µL |
| Placebo Arm | Change From Baseline in Blood Eosinophils at 14 Weeks | Week 0 | 288.9 cells/µL |
| Placebo Arm | Change From Baseline in Blood Eosinophils at 14 Weeks | Week 14 | 281.9 cells/µL |
Secondary
Change From Baseline in Blood Eosinophils at 8 Weeks
Change from baseline in blood eosinophils at 8 weeks.
Time frame: 8 weeks
Population: All patients who received at least one dose of a study drug were included in a modified intention-to-treat analysis.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mepolizumab Arm | Change From Baseline in Blood Eosinophils at 8 Weeks | Week 0 | 284.2 cells/µL |
| Mepolizumab Arm | Change From Baseline in Blood Eosinophils at 8 Weeks | Week 8 | 57.5 cells/µL |
| Placebo Arm | Change From Baseline in Blood Eosinophils at 8 Weeks | Week 0 | 288.9 cells/µL |
| Placebo Arm | Change From Baseline in Blood Eosinophils at 8 Weeks | Week 8 | 282.2 cells/µL |
Secondary
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.
Time frame: 14 weeks
Population: All patients who received at least one dose of a study drug were included in a modified intention-to-treat analysis.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mepolizumab Arm | Change From Baseline in Cough Severity at 14 Weeks | Week 0 | 65.3 mm |
| Mepolizumab Arm | Change From Baseline in Cough Severity at 14 Weeks | Week 14 | 49.5 mm |
| Placebo Arm | Change From Baseline in Cough Severity at 14 Weeks | Week 0 | 63.9 mm |
| Placebo Arm | Change From Baseline in Cough Severity at 14 Weeks | Week 14 | 51.4 mm |
Secondary
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.
Time frame: 8 weeks
Population: All patients who received at least one dose of a study drug were included in a modified intention-to-treat analysis.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mepolizumab Arm | Change From Baseline in Cough Severity at 8 Weeks | Week 0 | 65.3 mm |
| Mepolizumab Arm | Change From Baseline in Cough Severity at 8 Weeks | Week 8 | 55.7 mm |
| Placebo Arm | Change From Baseline in Cough Severity at 8 Weeks | Week 0 | 63.9 mm |
| Placebo Arm | Change From Baseline in Cough Severity at 8 Weeks | Week 8 | 49.3 mm |
Secondary
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.
Time frame: 14 weeks
Population: All patients who received at least one dose of a study drug were included in a modified intention-to-treat analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Mepolizumab Arm | Change From Baseline in Sleep Cough Frequency at 14 Weeks | Week 0 | 1.8 Coughs/hour |
| Mepolizumab Arm | Change From Baseline in Sleep Cough Frequency at 14 Weeks | Week 14 | 1.9 Coughs/hour |
| Placebo Arm | Change From Baseline in Sleep Cough Frequency at 14 Weeks | Week 0 | 1.7 Coughs/hour |
| Placebo Arm | Change From Baseline in Sleep Cough Frequency at 14 Weeks | Week 14 | 1.5 Coughs/hour |
Secondary
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.
Time frame: 8 weeks
Population: All patients who received at least one dose of a study drug were included in a modified intention-to-treat analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Mepolizumab Arm | Change From Baseline in Sleep Cough Frequency at 8 Weeks | Week 0 | 1.8 Coughs/hour |
| Mepolizumab Arm | Change From Baseline in Sleep Cough Frequency at 8 Weeks | Week 8 | 1.0 Coughs/hour |
| Placebo Arm | Change From Baseline in Sleep Cough Frequency at 8 Weeks | Week 0 | 1.7 Coughs/hour |
| Placebo Arm | Change From Baseline in Sleep Cough Frequency at 8 Weeks | Week 8 | 1.4 Coughs/hour |
Secondary
Change From Baseline in Sputum Eosinophils at 14 Weeks
Change from baseline in sputum eosinophils (%) at 14 weeks.
Time frame: 14 weeks
Population: All patients who received at least one dose of a study drug were included in a modified intention-to-treat analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Mepolizumab Arm | Change From Baseline in Sputum Eosinophils at 14 Weeks | Week 0 | 2.9 % sputum eosinophils |
| Mepolizumab Arm | Change From Baseline in Sputum Eosinophils at 14 Weeks | Week 14 | 1.6 % sputum eosinophils |
| Placebo Arm | Change From Baseline in Sputum Eosinophils at 14 Weeks | Week 0 | 2.8 % sputum eosinophils |
| Placebo Arm | Change From Baseline in Sputum Eosinophils at 14 Weeks | Week 14 | 2.6 % sputum eosinophils |
Secondary
Change From Baseline in Sputum Eosinophils at 8 Weeks
Change from baseline in sputum eosinophils (%) at 8 weeks.
Time frame: 8 weeks
Population: All patients who received at least one dose of a study drug were included in a modified intention-to-treat analysis.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| Mepolizumab Arm | Change From Baseline in Sputum Eosinophils at 8 Weeks | Week 0 | 2.9 % sputum eosinophils |
| Mepolizumab Arm | Change From Baseline in Sputum Eosinophils at 8 Weeks | Week 8 | 1.8 % sputum eosinophils |
| Placebo Arm | Change From Baseline in Sputum Eosinophils at 8 Weeks | Week 0 | 2.8 % sputum eosinophils |
| Placebo Arm | Change From Baseline in Sputum Eosinophils at 8 Weeks | Week 8 | 2.8 % sputum eosinophils |
Secondary
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.
Time frame: 14 weeks
Population: All patients who received at least one dose of a study drug were included in a modified intention-to-treat analysis.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mepolizumab Arm | Change From Baseline on the Leicester Cough Questionnaire at 14 Weeks | Week 0 | 11.3 points |
| Mepolizumab Arm | Change From Baseline on the Leicester Cough Questionnaire at 14 Weeks | Week 14 | 12.8 points |
| Placebo Arm | Change From Baseline on the Leicester Cough Questionnaire at 14 Weeks | Week 0 | 11.1 points |
| Placebo Arm | Change From Baseline on the Leicester Cough Questionnaire at 14 Weeks | Week 14 | 13.7 points |
Secondary
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.
Time frame: 8 weeks
Population: All patients who received at least one dose of a study drug were included in a modified intention-to-treat analysis.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mepolizumab Arm | Change From Baseline on the Leicester Cough Questionnaire at 8 Weeks | Week 0 | 11.3 points |
| Mepolizumab Arm | Change From Baseline on the Leicester Cough Questionnaire at 8 Weeks | Week 8 | 11.6 points |
| Placebo Arm | Change From Baseline on the Leicester Cough Questionnaire at 8 Weeks | Week 0 | 11.1 points |
| Placebo Arm | Change From Baseline on the Leicester Cough Questionnaire at 8 Weeks | Week 8 | 13.7 points |
Other Pre-specified
Change From Baseline in Methacholine Provocative Concentration Eliciting a 20% Fall in FEV1 (PC20) at 14 Weeks
Change from baseline in methacholine provocative concentration eliciting a 20% fall in FEV1 (PC20) at 14 weeks.
Time frame: 14 weeks
Population: All patients who received at least one dose of a study drug were included in a modified intention-to-treat analysis.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Mepolizumab Arm | Change From Baseline in Methacholine Provocative Concentration Eliciting a 20% Fall in FEV1 (PC20) at 14 Weeks | Week -2 | 14.4 mg/mL |
| Mepolizumab Arm | Change From Baseline in Methacholine Provocative Concentration Eliciting a 20% Fall in FEV1 (PC20) at 14 Weeks | Week 14 | 15.8 mg/mL |
| Placebo Arm | Change From Baseline in Methacholine Provocative Concentration Eliciting a 20% Fall in FEV1 (PC20) at 14 Weeks | Week -2 | 13.1 mg/mL |
| Placebo Arm | Change From Baseline in Methacholine Provocative Concentration Eliciting a 20% Fall in FEV1 (PC20) at 14 Weeks | Week 14 | 24.3 mg/mL |