Asthma
Conditions
Keywords
Dose-ranging, Safety, Pharmacodynamics, eosinophils, SB-240563, Efficacy, Severe refractory asthma, mepolizumab, Placebo
Brief summary
The purpose of this study is to show whether mepolizumab given every 4 weeks intravenously (i.v.) can reduce the frequency of asthma exacerbations in subjects with severe asthma despite receiving high doses of standard asthma medications. The study will look at different doses of mepolizumab in comparison to a placebo.
Detailed description
A double-blind, placebo-controlled study to evaluate the efficacy, safety and pharmacodynamics of three doses (75 mg, 250 mg and 750 mg) of mepolizumab intravenous (i.v.) administered every 4 weeks compared with placebo over a 52-week treatment period in subjects with severe uncontrolled refractory asthma. Efficacy will be measured by the frequency of asthma exacerbations. In addition lung function, rescue medication usage, daily symptoms, asthma control score, asthma quality of life score and withdrawals due to asthma exacerbations will be assessed. Safety will be assessed by adverse events, clinical laboratory evaluations, ECGs, immunogenicity and vital signs. Pharmacodynamics will be assessed by eosinophil levels in blood, serum IL-5 and eosinophil levels in induced sputum.
Interventions
BIOLOGICALMepolizumab 750
Mepolizumab 750mg every four weeks by i.v.
BIOLOGICALMepolizumab 250
Mepolizumab 250mg every four weeks by i.v.
BIOLOGICALMepolizumab 75
Mepolizumab 75mg every four weeks by i.v.
DRUGPlacebo saline
Placebo saline every four weeks by i.v.
Sponsors
GlaxoSmithKline
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Male or female * Aged 12 to 65 years inclusive * Minimum weight 45kg * Clinical features of severe refractory asthma * Well documented requirement for high dose inhaled corticosteroids (ICS) \[i.e. \>= 880mcg/day fluticasone propionate or equivalent daily\] for at least 12 months * Using additional controller medication in addition to high dose ICS for at least 12 months * Persistent airflow obstruction indicated by a pre-bronchodilator FEV1\<80% predicted at visit 1 or 2 or peak flow diurnal variability of \>20% on 3 or more days during the run-in * Airway inflammation which is likely to be eosinophilic in nature demonstrated by either raised peripheral blood eosinophils (\>=300/microL), sputum eosinophils (\>=3%), exhaled nitric oxide (\>=50ppb) or prompt deterioration of asthma control following a \<=25% reduction in regular maintenance dose of inhaled or oral corticosteroids (OCS) * History of 2 or more exacerbations requiring systemic corticosteroids in the previous 12 months * Evidence of asthma documented by airway reversibility, airway hyperresponsiveness or airflow variability * ECG assessment demonstrating QTc\<450msec or QTc\<480msec for patients with bundle branch block * Liver function tests demonstrating ALT\<2xUpper Limit of Normal (ULN), AST\<2xULN, Alk Phos \<=1.5xULN, bilirubin \<=1.5xULN * Female of non-child-bearing potential or child-bearing potential with a negative pregnancy test at screening and prepared to agree to an acceptable method of contraception * Able to give written informed consent * Able to read, comprehend and write at a sufficient level to complete study materials
Exclusion criteria
* Current smokers or smoking history of \>=10 pack years * Clinically important lung condition other than asthma * Diagnosis of malignancy or in the process of investigation * Unstable liver disease * Churg-Strauss syndrome * Using methotrexate, troleandomycin, oral gold, cyclosporine, azathioprine or any experimental anti-inflammatory therapy within 3 months of screening * Omalizumab (Xolair) or any other biological for the treatment of inflammatory disease within 6 months of Visit 1 * Regular use of oral or systemic corticosteroids for diseases other than asthma within 12 months or any intra-articular, short-acting intramuscular corticosteroid within 1 month or intramuscular, long-acting depot corticosteroid within 3 months * Allergy/intolerance to the excipients in the mepolizumab formulation * Any investigational drug within 30 days or 5 terminal half-lives, whichever is longer * Pregnant or breastfeeding or planning to become pregnant * Clinically significant disease which is uncontrolled with standard treatment * History of alcohol misuse or substance abuse * Parasitic infestation within previous 6 months * Known immunodeficiency * Unable to follow instructions, use the electronic diary or peak flow meter * Known evidence of lack of adherence to controller medications and/or follow physician's recommendations * Previous participation in a study of mepolizumab and received study medication within 90 days
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Clinically Significant Exacerbations of Asthma Per Year | From randomization (Week 0) to Week 52 or early withdrawal (EW) | Clinically significant exacerbations of asthma are defined as worsening of asthma which required use of oral/systemic corticosteroids (for participants on maintenance oral corticosteroids \[OCS\], an exacerbation requiring OCS is defined as the use of oral/systemic corticosteroids at least double the existing maintenance dose for at least 3 days) and/or hospitalization and/or emergency department (ED) visit. The frequency of clinically significant exacerbations of asthma over the 52-week treatment period is expressed as exacerbation rate per year. Analysis of the number of exacerbations was performed using a negative binomial regression model with covariates of treatment group, Baseline (BL) maintenance OCS therapy (OCS vs. no OCS), region, exacerbations in the year prior to the study (as an ordinal variable) and BL percent (%) predicted forced expiratory volume in 1 second (FEV1), and with logarithm of time on treatment as an offset variable |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Exacerbations Requiring Hospitalization (Including Intubation and Admittance to an Intensive Care Unit [ICU]) or ED Visit Per Year | From randomization (Week 0) to Week 52 or EW | The frequency of exacerbations of asthma requiring hospitalization (including intubation and admittance to an intensive care unit \[ICU\]) or ED visit over the 52-week treatment period is expressed as exacerbation rate per year. Analysis of the number of exacerbations was performed using a negative binomial regression model with covariates of treatment group, Baseline (BL) maintenance OCS therapy (OCS vs. no OCS), region, exacerbations in the year prior to the study (as an ordinal variable) and BL percent (%) predicted forced expiratory volume in 1 second (FEV1), and with logarithm of time on treatment as an offset variable. |
| Time to First Exacerbation Requiring Hospitalization or ED Visit | From randomization (Week 0) to Week 52 or EW | Exacerbations of asthma requiring hospitalization or ED visit were assessed. Kaplan-Meier estimates of the probability of an exacerbation is expressed as percentage of participants with an exacerbation over time (by Week 16, Week 32 and Week 52). |
| Number of All Recorded Exacerbations Per Year | From randomization (Week 0) to Week 52 or EW | Clinically significant exacerbations (ex) of asthma are defined as worsening of asthma which required use of oral/systemic corticosteroids (for par. on maintenance OCS, an ex requiring OCS is defined as the use of oral/systemic corticosteroids at least double the existing maintenance dose for at least 3 days) and/or hospitalization and/or ED visit. In the case, an event described as an ex was not associated with a deterioration in \>=1 of the objectives of eDiary parameters, the investigator (inv) provided an explanation to support the decision for defining the event as an ex. All recorded ex were defined as those recorded by inv, regardless of the outcome of the ex review process. Analysis was performed using Negative Binomial regression model with covariates of treatment group, BL maintenance OCS therapy (OCS vs. no OCS), region, ex in the year prior to the study (as an ordinal variable) and BL % predicted FEV1, and with logarithm of time on treatment as an offset variable. |
| Time to First Clinically Significant Exacerbation Requiring Oral or Systemic Corticosteroid, Hospitalization and/ or ED Visit | From randomization (Week 0) to Week 52 or EW | Clinically significant exacerbations of asthma are defined as worsening of asthma which required use of oral/systemic corticosteroids (for participants on maintenance OCS, an exacerbation requiring OCS is defined as the use of oral/systemic corticosteroids at least double the existing maintenance dose for at least 3 days) and/or hospitalization and/or ED visit. Kaplan-Meier estimates of the probability of an exacerbation is expressed as percentage of participants with an exacerbation over time (by Week 16, Week 32 and Week 52). |
| Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | From Baseline up to Week 52 or EW | FEV1 is defined as the volume of air forcefully expelled from the lungs in 1 second. Pre-bronchodilator FEV1 measurements were taken by spirometry at each clinic visit. The change from Baseline is defined as the difference between the value of the endpoint at the time point of interest and the Baseline value. Analysis was performed using mixed model repeated measures with covariates of Baseline, region, Baseline maintenance OCS therapy (OCS vs. no OCS), exacerbations in the year prior to the study (as an ordinal variable), treatment and visit, plus interaction terms for visit by Baseline and visit by treatment group. |
| Mean Change From Baseline in Clinic Post-bronchodilator FEV1 Over the 52-week Treatment Period | From Baseline up to Week 52 or EW | FEV1 is defined as the volume of air forcefully expelled from the lungs in 1 second. Post-bronchodilator FEV1 measurements were taken by spirometry at Baseline, Week 16, Week 32 and Week 52. Post bronchodilator values were recorded following reversibility testing, using the maximum post bronchodilator method. Participants unable to achieve \>=12% reversibility and 200 mL change at Visit 1, reversibility test was repeated at Visit 2. These procedures to achieve the maximum post-bronchodilator are generated by the Asthma Clinical Research Network. The change from Baseline is defined as the difference between the value of the endpoint at the time point of interest and the Baseline value. Analysis was performed using mixed model repeated measures with covariates of Baseline, region, Baseline maintenance OCS therapy (OCS vs. no OCS), exacerbations in the year prior to the study (as an ordinal variable), treatment and visit, plus interaction terms for visit by Baseline and visit by treatment |
| Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | From Baseline up to Week 52 or EW | The ACQ-6 is a six-item questionnaire. The six questions enquire about the frequency and/or severity of symptoms (nocturnal awakening on waking in the morning, activity limitation, shortness of breath, wheeze) and use of short-acting bronchodilator over the previous week. The response options for all these questions consist of a 0 (no impairment/limitation) to 6 (total impairment/ limitation) scale. The overall ACQ score is calculated as the mean of the 6 questions and therefore ranges between 0 (totally controlled) and 6 (severely uncontrolled). Change from BL is defined as the difference between the value of the endpoint at the time point of interest and BL value. Analysis was performed using mixed model repeated measures with covariates of BL, region, BL maintenance OCS therapy (OCS vs. no OCS), exacerbations in the year prior to the study (as an ordinal variable), BL % predicted FEV1, treatment and visit, plus interaction terms for visit by BL and visit by treatment group. |
| Time to First All Recorded Exacerbation | From randomization (Week 0) to Week 52 or EW | All recorded exacerbations are defined as those recorded by investigators, regardless of the outcome of the exacerbation review process. In the case, an event described as an exacerbation was not associated with a deterioration in at least one of the objectives of eDiary parameters, the investigator provided an explanation to support the decision for defining the event as an exacerbation. Kaplan-Meier estimates of the probability of an exacerbation is expressed as percentage of participants with an exacerbation over time (by week 16, week 32 and week 52). |
Countries
Argentina, Australia, Canada, Chile, France, Germany, Poland, Romania, Russia, South Korea, Ukraine, United Kingdom, United States
Participant flow
Recruitment details
Participants (par.) who met the eligibility criteria at screening, entered the two week Run-in phase and par. who met the randomization eligibility criteria at the end of the Run-in phase entered into the 52-week Double-blind treatment period followed by a 4-week Follow-up phase. The total duration of participation in the study was 58 Weeks.
Pre-assignment details
A total of 888 par. were enrolled, of these, 168 were screen failures and 720 entered the run-in phase. 99 participants were run-in failures and 621 completed the run-in phase and were randomized. Of these, 616 participants were randomized and received treatment and were included within the Intent-to-Treat (ITT) Population.
Participants by arm
| Arm | Count |
|---|---|
| Placebo IV Participants received placebo intravenous (IV) infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). | 155 |
| Mepolizumab 75 mg IV Participants received mepolizumab 75 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). | 153 |
| Mepolizumab 250 mg IV Participants received mepolizumab 250 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). | 152 |
| Mepolizumab 750 mg IV Participants received mepolizumab 750 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). | 156 |
| Total | 616 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 6 | 5 | 8 | 9 |
| Overall Study | Lack of Efficacy | 8 | 6 | 4 | 4 |
| Overall Study | Lost to Follow-up | 1 | 1 | 4 | 0 |
| Overall Study | Physician Decision | 1 | 3 | 3 | 3 |
| Overall Study | Protocol Violation | 1 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 11 | 8 | 2 | 7 |
Baseline characteristics
| Characteristic | Total | Mepolizumab 750 mg IV | Mepolizumab 250 mg IV | Mepolizumab 75 mg IV | Placebo IV |
|---|---|---|---|---|---|
| Age, Continuous | 48.6 Years STANDARD_DEVIATION 11.28 | 48.6 Years STANDARD_DEVIATION 11.06 | 49.4 Years STANDARD_DEVIATION 11.63 | 50.2 Years STANDARD_DEVIATION 10.84 | 46.4 Years STANDARD_DEVIATION 11.33 |
| Race/Ethnicity, Customized African American/African Heritage | 24 Participants | 5 Participants | 8 Participants | 5 Participants | 6 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian - Central/South Asian Heritage | 5 Participants | 2 Participants | 0 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian - East Asian Heritage | 26 Participants | 6 Participants | 7 Participants | 6 Participants | 7 Participants |
| Race/Ethnicity, Customized Asian - South East Asian Heritage | 3 Participants | 2 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized Mixed Race | 2 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized White - Arabic/North African Heritage | 7 Participants | 1 Participants | 2 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized White - White/Caucasian/European Heritage | 547 Participants | 139 Participants | 133 Participants | 138 Participants | 137 Participants |
| Sex: Female, Male Female | 387 Participants | 93 Participants | 93 Participants | 104 Participants | 97 Participants |
| Sex: Female, Male Male | 229 Participants | 63 Participants | 59 Participants | 49 Participants | 58 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 106 / 155 | 113 / 153 | 113 / 152 | 112 / 156 |
| serious Total, serious adverse events | 25 / 155 | 20 / 153 | 24 / 152 | 19 / 156 |
Outcome results
Primary
Number of Clinically Significant Exacerbations of Asthma Per Year
Clinically significant exacerbations of asthma are defined as worsening of asthma which required use of oral/systemic corticosteroids (for participants on maintenance oral corticosteroids \[OCS\], an exacerbation requiring OCS is defined as the use of oral/systemic corticosteroids at least double the existing maintenance dose for at least 3 days) and/or hospitalization and/or emergency department (ED) visit. The frequency of clinically significant exacerbations of asthma over the 52-week treatment period is expressed as exacerbation rate per year. Analysis of the number of exacerbations was performed using a negative binomial regression model with covariates of treatment group, Baseline (BL) maintenance OCS therapy (OCS vs. no OCS), region, exacerbations in the year prior to the study (as an ordinal variable) and BL percent (%) predicted forced expiratory volume in 1 second (FEV1), and with logarithm of time on treatment as an offset variable
Time frame: From randomization (Week 0) to Week 52 or early withdrawal (EW)
Population: Intent-to-Treat (ITT) Population: all participants who were randomized and who received at least one dose of study medication.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo IV | Number of Clinically Significant Exacerbations of Asthma Per Year | 2.40 Exacerbations per year |
| Mepolizumab 75 mg IV | Number of Clinically Significant Exacerbations of Asthma Per Year | 1.24 Exacerbations per year |
| Mepolizumab 250 mg IV | Number of Clinically Significant Exacerbations of Asthma Per Year | 1.46 Exacerbations per year |
| Mepolizumab 750 mg IV | Number of Clinically Significant Exacerbations of Asthma Per Year | 1.15 Exacerbations per year |
p-value: <0.00195% CI: [0.39, 0.69]Negative Binomial regression model
p-value: <0.00195% CI: [0.46, 0.81]Negative Binomial regression model
p-value: <0.00195% CI: [0.36, 0.64]Negative Binomial regression model
Secondary
Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period
The ACQ-6 is a six-item questionnaire. The six questions enquire about the frequency and/or severity of symptoms (nocturnal awakening on waking in the morning, activity limitation, shortness of breath, wheeze) and use of short-acting bronchodilator over the previous week. The response options for all these questions consist of a 0 (no impairment/limitation) to 6 (total impairment/ limitation) scale. The overall ACQ score is calculated as the mean of the 6 questions and therefore ranges between 0 (totally controlled) and 6 (severely uncontrolled). Change from BL is defined as the difference between the value of the endpoint at the time point of interest and BL value. Analysis was performed using mixed model repeated measures with covariates of BL, region, BL maintenance OCS therapy (OCS vs. no OCS), exacerbations in the year prior to the study (as an ordinal variable), BL % predicted FEV1, treatment and visit, plus interaction terms for visit by BL and visit by treatment group.
Time frame: From Baseline up to Week 52 or EW
Population: ITT Population. Only those participants available at the specified time points were analyzed for each treatment and represented as n=X, X, X, X respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 40, n=126, 128, 129, 131 | -0.64 Scores on a scale | Standard Error 0.09 |
| Placebo IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 16, n=138, 143, 143, 146 | -0.59 Scores on a scale | Standard Error 0.085 |
| Placebo IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 20, n=138, 140, 137, 139 | -0.59 Scores on a scale | Standard Error 0.081 |
| Placebo IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 48, n=122, 130, 130, 129 | -0.63 Scores on a scale | Standard Error 0.085 |
| Placebo IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 4, n=146, 139, 148, 150 | -0.45 Scores on a scale | Standard Error 0.076 |
| Placebo IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 52, n=121, 127, 126, 129 | -0.59 Scores on a scale | Standard Error 0.087 |
| Placebo IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 8, n=147, 140, 142, 145 | -0.50 Scores on a scale | Standard Error 0.08 |
| Placebo IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 12, n=148, 142, 144, 147 | -0.63 Scores on a scale | Standard Error 0.08 |
| Placebo IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 28, n=131, 135, 135, 136 | -0.70 Scores on a scale | Standard Error 0.082 |
| Placebo IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 44, n=123, 125, 129, 129 | -0.62 Scores on a scale | Standard Error 0.089 |
| Placebo IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 32, n=130, 133, 136, 136 | -0.62 Scores on a scale | Standard Error 0.084 |
| Placebo IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 36, n=129, 133, 133, 134 | -0.60 Scores on a scale | Standard Error 0.082 |
| Placebo IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 24, n=135, 133, 138, 137 | -0.66 Scores on a scale | Standard Error 0.08 |
| Mepolizumab 75 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 24, n=135, 133, 138, 137 | -0.85 Scores on a scale | Standard Error 0.08 |
| Mepolizumab 75 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 44, n=123, 125, 129, 129 | -0.75 Scores on a scale | Standard Error 0.089 |
| Mepolizumab 75 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 12, n=148, 142, 144, 147 | -0.79 Scores on a scale | Standard Error 0.081 |
| Mepolizumab 75 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 40, n=126, 128, 129, 131 | -0.76 Scores on a scale | Standard Error 0.09 |
| Mepolizumab 75 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 28, n=131, 135, 135, 136 | -0.81 Scores on a scale | Standard Error 0.081 |
| Mepolizumab 75 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 48, n=122, 130, 130, 129 | -0.72 Scores on a scale | Standard Error 0.084 |
| Mepolizumab 75 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 8, n=147, 140, 142, 145 | -0.73 Scores on a scale | Standard Error 0.081 |
| Mepolizumab 75 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 16, n=138, 143, 143, 146 | -0.80 Scores on a scale | Standard Error 0.085 |
| Mepolizumab 75 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 36, n=129, 133, 133, 134 | -0.78 Scores on a scale | Standard Error 0.082 |
| Mepolizumab 75 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 4, n=146, 139, 148, 150 | -0.61 Scores on a scale | Standard Error 0.077 |
| Mepolizumab 75 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 32, n=130, 133, 136, 136 | -0.74 Scores on a scale | Standard Error 0.084 |
| Mepolizumab 75 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 20, n=138, 140, 137, 139 | -0.82 Scores on a scale | Standard Error 0.081 |
| Mepolizumab 75 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 52, n=121, 127, 126, 129 | -0.75 Scores on a scale | Standard Error 0.087 |
| Mepolizumab 250 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 48, n=122, 130, 130, 129 | -0.74 Scores on a scale | Standard Error 0.083 |
| Mepolizumab 250 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 4, n=146, 139, 148, 150 | -0.50 Scores on a scale | Standard Error 0.075 |
| Mepolizumab 250 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 8, n=147, 140, 142, 145 | -0.60 Scores on a scale | Standard Error 0.08 |
| Mepolizumab 250 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 12, n=148, 142, 144, 147 | -0.65 Scores on a scale | Standard Error 0.08 |
| Mepolizumab 250 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 16, n=138, 143, 143, 146 | -0.52 Scores on a scale | Standard Error 0.084 |
| Mepolizumab 250 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 20, n=138, 140, 137, 139 | -0.61 Scores on a scale | Standard Error 0.08 |
| Mepolizumab 250 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 24, n=135, 133, 138, 137 | -0.70 Scores on a scale | Standard Error 0.079 |
| Mepolizumab 250 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 32, n=130, 133, 136, 136 | -0.76 Scores on a scale | Standard Error 0.083 |
| Mepolizumab 250 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 36, n=129, 133, 133, 134 | -0.75 Scores on a scale | Standard Error 0.081 |
| Mepolizumab 250 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 44, n=123, 125, 129, 129 | -0.77 Scores on a scale | Standard Error 0.087 |
| Mepolizumab 250 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 52, n=121, 127, 126, 129 | -0.87 Scores on a scale | Standard Error 0.086 |
| Mepolizumab 250 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 28, n=131, 135, 135, 136 | -0.66 Scores on a scale | Standard Error 0.08 |
| Mepolizumab 250 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 40, n=126, 128, 129, 131 | -0.73 Scores on a scale | Standard Error 0.089 |
| Mepolizumab 750 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 12, n=148, 142, 144, 147 | -0.72 Scores on a scale | Standard Error 0.079 |
| Mepolizumab 750 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 48, n=122, 130, 130, 129 | -0.68 Scores on a scale | Standard Error 0.084 |
| Mepolizumab 750 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 16, n=138, 143, 143, 146 | -0.76 Scores on a scale | Standard Error 0.083 |
| Mepolizumab 750 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 44, n=123, 125, 129, 129 | -0.69 Scores on a scale | Standard Error 0.087 |
| Mepolizumab 750 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 20, n=138, 140, 137, 139 | -0.72 Scores on a scale | Standard Error 0.08 |
| Mepolizumab 750 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 36, n=129, 133, 133, 134 | -0.76 Scores on a scale | Standard Error 0.081 |
| Mepolizumab 750 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 24, n=135, 133, 138, 137 | -0.79 Scores on a scale | Standard Error 0.079 |
| Mepolizumab 750 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 28, n=131, 135, 135, 136 | -0.73 Scores on a scale | Standard Error 0.08 |
| Mepolizumab 750 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 32, n=130, 133, 136, 136 | -0.74 Scores on a scale | Standard Error 0.083 |
| Mepolizumab 750 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 8, n=147, 140, 142, 145 | -0.65 Scores on a scale | Standard Error 0.079 |
| Mepolizumab 750 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 40, n=126, 128, 129, 131 | -0.67 Scores on a scale | Standard Error 0.089 |
| Mepolizumab 750 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 4, n=146, 139, 148, 150 | -0.56 Scores on a scale | Standard Error 0.075 |
| Mepolizumab 750 mg IV | Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period | Week 52, n=121, 127, 126, 129 | -0.80 Scores on a scale | Standard Error 0.086 |
Secondary
Mean Change From Baseline in Clinic Post-bronchodilator FEV1 Over the 52-week Treatment Period
FEV1 is defined as the volume of air forcefully expelled from the lungs in 1 second. Post-bronchodilator FEV1 measurements were taken by spirometry at Baseline, Week 16, Week 32 and Week 52. Post bronchodilator values were recorded following reversibility testing, using the maximum post bronchodilator method. Participants unable to achieve \>=12% reversibility and 200 mL change at Visit 1, reversibility test was repeated at Visit 2. These procedures to achieve the maximum post-bronchodilator are generated by the Asthma Clinical Research Network. The change from Baseline is defined as the difference between the value of the endpoint at the time point of interest and the Baseline value. Analysis was performed using mixed model repeated measures with covariates of Baseline, region, Baseline maintenance OCS therapy (OCS vs. no OCS), exacerbations in the year prior to the study (as an ordinal variable), treatment and visit, plus interaction terms for visit by Baseline and visit by treatment
Time frame: From Baseline up to Week 52 or EW
Population: ITT Population. Only those participants available at the specified time points were analyzed for each treatment and represented as n=X, X, X, X respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo IV | Mean Change From Baseline in Clinic Post-bronchodilator FEV1 Over the 52-week Treatment Period | Week 32, n=130, 132, 133, 132 | 40 mL | Standard Error 37.8 |
| Placebo IV | Mean Change From Baseline in Clinic Post-bronchodilator FEV1 Over the 52-week Treatment Period | Week 16, n=142, 140, 141, 147 | 59 mL | Standard Error 37.6 |
| Placebo IV | Mean Change From Baseline in Clinic Post-bronchodilator FEV1 Over the 52-week Treatment Period | Week 52, n=126, 128, 129, 130 | -9 mL | Standard Error 36.7 |
| Mepolizumab 75 mg IV | Mean Change From Baseline in Clinic Post-bronchodilator FEV1 Over the 52-week Treatment Period | Week 52, n=126, 128, 129, 130 | 36 mL | Standard Error 36.4 |
| Mepolizumab 75 mg IV | Mean Change From Baseline in Clinic Post-bronchodilator FEV1 Over the 52-week Treatment Period | Week 32, n=130, 132, 133, 132 | 49 mL | Standard Error 37.5 |
| Mepolizumab 75 mg IV | Mean Change From Baseline in Clinic Post-bronchodilator FEV1 Over the 52-week Treatment Period | Week 16, n=142, 140, 141, 147 | 77 mL | Standard Error 37.5 |
| Mepolizumab 250 mg IV | Mean Change From Baseline in Clinic Post-bronchodilator FEV1 Over the 52-week Treatment Period | Week 52, n=126, 128, 129, 130 | 80 mL | Standard Error 36.1 |
| Mepolizumab 250 mg IV | Mean Change From Baseline in Clinic Post-bronchodilator FEV1 Over the 52-week Treatment Period | Week 16, n=142, 140, 141, 147 | 50 mL | Standard Error 37.3 |
| Mepolizumab 250 mg IV | Mean Change From Baseline in Clinic Post-bronchodilator FEV1 Over the 52-week Treatment Period | Week 32, n=130, 132, 133, 132 | 72 mL | Standard Error 37.2 |
| Mepolizumab 750 mg IV | Mean Change From Baseline in Clinic Post-bronchodilator FEV1 Over the 52-week Treatment Period | Week 32, n=130, 132, 133, 132 | 17 mL | Standard Error 36.8 |
| Mepolizumab 750 mg IV | Mean Change From Baseline in Clinic Post-bronchodilator FEV1 Over the 52-week Treatment Period | Week 16, n=142, 140, 141, 147 | 87 mL | Standard Error 36.3 |
| Mepolizumab 750 mg IV | Mean Change From Baseline in Clinic Post-bronchodilator FEV1 Over the 52-week Treatment Period | Week 52, n=126, 128, 129, 130 | 69 mL | Standard Error 35.6 |
Secondary
Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period
FEV1 is defined as the volume of air forcefully expelled from the lungs in 1 second. Pre-bronchodilator FEV1 measurements were taken by spirometry at each clinic visit. The change from Baseline is defined as the difference between the value of the endpoint at the time point of interest and the Baseline value. Analysis was performed using mixed model repeated measures with covariates of Baseline, region, Baseline maintenance OCS therapy (OCS vs. no OCS), exacerbations in the year prior to the study (as an ordinal variable), treatment and visit, plus interaction terms for visit by Baseline and visit by treatment group.
Time frame: From Baseline up to Week 52 or EW
Population: ITT Population. Only those participants available at the specified time points were analyzed for each treatment and represented as n=X, X, X, X respectively.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 48, n=128, 132, 133, 133 | 91 Milliliters (mL) | Standard Error 36.7 |
| Placebo IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 44, n=127, 133, 134, 134 | 125 Milliliters (mL) | Standard Error 37.4 |
| Placebo IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 32, n=134, 136, 139, 137 | 139 Milliliters (mL) | Standard Error 37.6 |
| Placebo IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 40, n=129, 133, 135, 135 | 125 Milliliters (mL) | Standard Error 38.9 |
| Placebo IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 36, n=132, 136, 137, 135 | 88 Milliliters (mL) | Standard Error 36.7 |
| Placebo IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 12, n=150, 147, 148, 151 | 118 Milliliters (mL) | Standard Error 36.5 |
| Placebo IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 8, n=152, 149, 149, 154 | 154 Milliliters (mL) | Standard Error 36 |
| Placebo IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 28, n=135, 136, 139, 141 | 125 Milliliters (mL) | Standard Error 37.9 |
| Placebo IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 24, n=136, 138, 141, 141 | 148 Milliliters (mL) | Standard Error 38.7 |
| Placebo IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 16, n=143, 147, 144, 150 | 135 Milliliters (mL) | Standard Error 37.4 |
| Placebo IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 4, n=154, 151, 151, 155 | 149 Milliliters (mL) | Standard Error 35.3 |
| Placebo IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 20, n=141, 144, 142, 147 | 131 Milliliters (mL) | Standard Error 37.3 |
| Placebo IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 52, n=127, 129, 129, 132 | 60 Milliliters (mL) | Standard Error 37.7 |
| Mepolizumab 75 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 32, n=134, 136, 139, 137 | 142 Milliliters (mL) | Standard Error 37.6 |
| Mepolizumab 75 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 8, n=152, 149, 149, 154 | 165 Milliliters (mL) | Standard Error 36.3 |
| Mepolizumab 75 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 12, n=150, 147, 148, 151 | 129 Milliliters (mL) | Standard Error 36.9 |
| Mepolizumab 75 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 20, n=141, 144, 142, 147 | 155 Milliliters (mL) | Standard Error 37.3 |
| Mepolizumab 75 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 28, n=135, 136, 139, 141 | 176 Milliliters (mL) | Standard Error 37.9 |
| Mepolizumab 75 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 40, n=129, 133, 135, 135 | 180 Milliliters (mL) | Standard Error 38.8 |
| Mepolizumab 75 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 48, n=128, 132, 133, 133 | 140 Milliliters (mL) | Standard Error 36.5 |
| Mepolizumab 75 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 52, n=127, 129, 129, 132 | 121 Milliliters (mL) | Standard Error 37.6 |
| Mepolizumab 75 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 16, n=143, 147, 144, 150 | 137 Milliliters (mL) | Standard Error 37.4 |
| Mepolizumab 75 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 24, n=136, 138, 141, 141 | 153 Milliliters (mL) | Standard Error 38.7 |
| Mepolizumab 75 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 4, n=154, 151, 151, 155 | 163 Milliliters (mL) | Standard Error 35.6 |
| Mepolizumab 75 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 36, n=132, 136, 137, 135 | 138 Milliliters (mL) | Standard Error 36.6 |
| Mepolizumab 75 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 44, n=127, 133, 134, 134 | 153 Milliliters (mL) | Standard Error 37.1 |
| Mepolizumab 250 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 20, n=141, 144, 142, 147 | 89 Milliliters (mL) | Standard Error 37.1 |
| Mepolizumab 250 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 4, n=154, 151, 151, 155 | 137 Milliliters (mL) | Standard Error 35.3 |
| Mepolizumab 250 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 48, n=128, 132, 133, 133 | 123 Milliliters (mL) | Standard Error 36.2 |
| Mepolizumab 250 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 52, n=127, 129, 129, 132 | 140 Milliliters (mL) | Standard Error 37.3 |
| Mepolizumab 250 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 36, n=132, 136, 137, 135 | 133 Milliliters (mL) | Standard Error 36.3 |
| Mepolizumab 250 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 16, n=143, 147, 144, 150 | 97 Milliliters (mL) | Standard Error 37.3 |
| Mepolizumab 250 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 8, n=152, 149, 149, 154 | 133 Milliliters (mL) | Standard Error 36.1 |
| Mepolizumab 250 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 24, n=136, 138, 141, 141 | 148 Milliliters (mL) | Standard Error 38.3 |
| Mepolizumab 250 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 12, n=150, 147, 148, 151 | 115 Milliliters (mL) | Standard Error 36.5 |
| Mepolizumab 250 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 28, n=135, 136, 139, 141 | 89 Milliliters (mL) | Standard Error 37.5 |
| Mepolizumab 250 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 32, n=134, 136, 139, 137 | 134 Milliliters (mL) | Standard Error 37.2 |
| Mepolizumab 250 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 40, n=129, 133, 135, 135 | 140 Milliliters (mL) | Standard Error 38.4 |
| Mepolizumab 250 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 44, n=127, 133, 134, 134 | 93 Milliliters (mL) | Standard Error 36.8 |
| Mepolizumab 750 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 36, n=132, 136, 137, 135 | 119 Milliliters (mL) | Standard Error 36.1 |
| Mepolizumab 750 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 40, n=129, 133, 135, 135 | 87 Milliliters (mL) | Standard Error 38.1 |
| Mepolizumab 750 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 24, n=136, 138, 141, 141 | 123 Milliliters (mL) | Standard Error 38 |
| Mepolizumab 750 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 48, n=128, 132, 133, 133 | 112 Milliliters (mL) | Standard Error 36 |
| Mepolizumab 750 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 28, n=135, 136, 139, 141 | 95 Milliliters (mL) | Standard Error 37.1 |
| Mepolizumab 750 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 52, n=127, 129, 129, 132 | 115 Milliliters (mL) | Standard Error 36.9 |
| Mepolizumab 750 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 16, n=143, 147, 144, 150 | 94 Milliliters (mL) | Standard Error 36.7 |
| Mepolizumab 750 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 4, n=154, 151, 151, 155 | 112 Milliliters (mL) | Standard Error 34.9 |
| Mepolizumab 750 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 8, n=152, 149, 149, 154 | 142 Milliliters (mL) | Standard Error 35.6 |
| Mepolizumab 750 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 44, n=127, 133, 134, 134 | 111 Milliliters (mL) | Standard Error 36.6 |
| Mepolizumab 750 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 32, n=134, 136, 139, 137 | 43 Milliliters (mL) | Standard Error 37 |
| Mepolizumab 750 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 20, n=141, 144, 142, 147 | 124 Milliliters (mL) | Standard Error 36.6 |
| Mepolizumab 750 mg IV | Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period | Week 12, n=150, 147, 148, 151 | 136 Milliliters (mL) | Standard Error 36.1 |
Secondary
Number of All Recorded Exacerbations Per Year
Clinically significant exacerbations (ex) of asthma are defined as worsening of asthma which required use of oral/systemic corticosteroids (for par. on maintenance OCS, an ex requiring OCS is defined as the use of oral/systemic corticosteroids at least double the existing maintenance dose for at least 3 days) and/or hospitalization and/or ED visit. In the case, an event described as an ex was not associated with a deterioration in \>=1 of the objectives of eDiary parameters, the investigator (inv) provided an explanation to support the decision for defining the event as an ex. All recorded ex were defined as those recorded by inv, regardless of the outcome of the ex review process. Analysis was performed using Negative Binomial regression model with covariates of treatment group, BL maintenance OCS therapy (OCS vs. no OCS), region, ex in the year prior to the study (as an ordinal variable) and BL % predicted FEV1, and with logarithm of time on treatment as an offset variable.
Time frame: From randomization (Week 0) to Week 52 or EW
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo IV | Number of All Recorded Exacerbations Per Year | 2.46 Exacerbations per year |
| Mepolizumab 75 mg IV | Number of All Recorded Exacerbations Per Year | 1.34 Exacerbations per year |
| Mepolizumab 250 mg IV | Number of All Recorded Exacerbations Per Year | 1.49 Exacerbations per year |
| Mepolizumab 750 mg IV | Number of All Recorded Exacerbations Per Year | 1.20 Exacerbations per year |
Secondary
Number of Exacerbations Requiring Hospitalization (Including Intubation and Admittance to an Intensive Care Unit [ICU]) or ED Visit Per Year
The frequency of exacerbations of asthma requiring hospitalization (including intubation and admittance to an intensive care unit \[ICU\]) or ED visit over the 52-week treatment period is expressed as exacerbation rate per year. Analysis of the number of exacerbations was performed using a negative binomial regression model with covariates of treatment group, Baseline (BL) maintenance OCS therapy (OCS vs. no OCS), region, exacerbations in the year prior to the study (as an ordinal variable) and BL percent (%) predicted forced expiratory volume in 1 second (FEV1), and with logarithm of time on treatment as an offset variable.
Time frame: From randomization (Week 0) to Week 52 or EW
Population: ITT Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo IV | Number of Exacerbations Requiring Hospitalization (Including Intubation and Admittance to an Intensive Care Unit [ICU]) or ED Visit Per Year | 0.43 Exacerbations per year |
| Mepolizumab 75 mg IV | Number of Exacerbations Requiring Hospitalization (Including Intubation and Admittance to an Intensive Care Unit [ICU]) or ED Visit Per Year | 0.17 Exacerbations per year |
| Mepolizumab 250 mg IV | Number of Exacerbations Requiring Hospitalization (Including Intubation and Admittance to an Intensive Care Unit [ICU]) or ED Visit Per Year | 0.25 Exacerbations per year |
| Mepolizumab 750 mg IV | Number of Exacerbations Requiring Hospitalization (Including Intubation and Admittance to an Intensive Care Unit [ICU]) or ED Visit Per Year | 0.22 Exacerbations per year |
Secondary
Time to First All Recorded Exacerbation
All recorded exacerbations are defined as those recorded by investigators, regardless of the outcome of the exacerbation review process. In the case, an event described as an exacerbation was not associated with a deterioration in at least one of the objectives of eDiary parameters, the investigator provided an explanation to support the decision for defining the event as an exacerbation. Kaplan-Meier estimates of the probability of an exacerbation is expressed as percentage of participants with an exacerbation over time (by week 16, week 32 and week 52).
Time frame: From randomization (Week 0) to Week 52 or EW
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo IV | Time to First All Recorded Exacerbation | Week 32 | 60.9 Percentage of participants |
| Placebo IV | Time to First All Recorded Exacerbation | Week 52 | 70.1 Percentage of participants |
| Placebo IV | Time to First All Recorded Exacerbation | Week 16 | 45.9 Percentage of participants |
| Mepolizumab 75 mg IV | Time to First All Recorded Exacerbation | Week 32 | 41.5 Percentage of participants |
| Mepolizumab 75 mg IV | Time to First All Recorded Exacerbation | Week 52 | 52.2 Percentage of participants |
| Mepolizumab 75 mg IV | Time to First All Recorded Exacerbation | Week 16 | 26.1 Percentage of participants |
| Mepolizumab 250 mg IV | Time to First All Recorded Exacerbation | Week 16 | 27.5 Percentage of participants |
| Mepolizumab 250 mg IV | Time to First All Recorded Exacerbation | Week 52 | 58.3 Percentage of participants |
| Mepolizumab 250 mg IV | Time to First All Recorded Exacerbation | Week 32 | 45.5 Percentage of participants |
| Mepolizumab 750 mg IV | Time to First All Recorded Exacerbation | Week 52 | 50.8 Percentage of participants |
| Mepolizumab 750 mg IV | Time to First All Recorded Exacerbation | Week 32 | 40.5 Percentage of participants |
| Mepolizumab 750 mg IV | Time to First All Recorded Exacerbation | Week 16 | 19.6 Percentage of participants |
Secondary
Time to First Clinically Significant Exacerbation Requiring Oral or Systemic Corticosteroid, Hospitalization and/ or ED Visit
Clinically significant exacerbations of asthma are defined as worsening of asthma which required use of oral/systemic corticosteroids (for participants on maintenance OCS, an exacerbation requiring OCS is defined as the use of oral/systemic corticosteroids at least double the existing maintenance dose for at least 3 days) and/or hospitalization and/or ED visit. Kaplan-Meier estimates of the probability of an exacerbation is expressed as percentage of participants with an exacerbation over time (by Week 16, Week 32 and Week 52).
Time frame: From randomization (Week 0) to Week 52 or EW
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo IV | Time to First Clinically Significant Exacerbation Requiring Oral or Systemic Corticosteroid, Hospitalization and/ or ED Visit | Week 16 | 45.2 Percentage of participants |
| Placebo IV | Time to First Clinically Significant Exacerbation Requiring Oral or Systemic Corticosteroid, Hospitalization and/ or ED Visit | Week 32 | 60.4 Percentage of participants |
| Placebo IV | Time to First Clinically Significant Exacerbation Requiring Oral or Systemic Corticosteroid, Hospitalization and/ or ED Visit | Week 52 | 69.7 Percentage of participants |
| Mepolizumab 75 mg IV | Time to First Clinically Significant Exacerbation Requiring Oral or Systemic Corticosteroid, Hospitalization and/ or ED Visit | Week 52 | 48.5 Percentage of participants |
| Mepolizumab 75 mg IV | Time to First Clinically Significant Exacerbation Requiring Oral or Systemic Corticosteroid, Hospitalization and/ or ED Visit | Week 32 | 38.2 Percentage of participants |
| Mepolizumab 75 mg IV | Time to First Clinically Significant Exacerbation Requiring Oral or Systemic Corticosteroid, Hospitalization and/ or ED Visit | Week 16 | 22.8 Percentage of participants |
| Mepolizumab 250 mg IV | Time to First Clinically Significant Exacerbation Requiring Oral or Systemic Corticosteroid, Hospitalization and/ or ED Visit | Week 52 | 58.3 Percentage of participants |
| Mepolizumab 250 mg IV | Time to First Clinically Significant Exacerbation Requiring Oral or Systemic Corticosteroid, Hospitalization and/ or ED Visit | Week 16 | 26.8 Percentage of participants |
| Mepolizumab 250 mg IV | Time to First Clinically Significant Exacerbation Requiring Oral or Systemic Corticosteroid, Hospitalization and/ or ED Visit | Week 32 | 45.5 Percentage of participants |
| Mepolizumab 750 mg IV | Time to First Clinically Significant Exacerbation Requiring Oral or Systemic Corticosteroid, Hospitalization and/ or ED Visit | Week 52 | 50.1 Percentage of participants |
| Mepolizumab 750 mg IV | Time to First Clinically Significant Exacerbation Requiring Oral or Systemic Corticosteroid, Hospitalization and/ or ED Visit | Week 16 | 18.9 Percentage of participants |
| Mepolizumab 750 mg IV | Time to First Clinically Significant Exacerbation Requiring Oral or Systemic Corticosteroid, Hospitalization and/ or ED Visit | Week 32 | 39.9 Percentage of participants |
Secondary
Time to First Exacerbation Requiring Hospitalization or ED Visit
Exacerbations of asthma requiring hospitalization or ED visit were assessed. Kaplan-Meier estimates of the probability of an exacerbation is expressed as percentage of participants with an exacerbation over time (by Week 16, Week 32 and Week 52).
Time frame: From randomization (Week 0) to Week 52 or EW
Population: ITT Population
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo IV | Time to First Exacerbation Requiring Hospitalization or ED Visit | Week 32 | 14.8 Percentage of participants |
| Placebo IV | Time to First Exacerbation Requiring Hospitalization or ED Visit | Week 52 | 18.5 Percentage of participants |
| Placebo IV | Time to First Exacerbation Requiring Hospitalization or ED Visit | Week 16 | 8.6 Percentage of participants |
| Mepolizumab 75 mg IV | Time to First Exacerbation Requiring Hospitalization or ED Visit | Week 16 | 3.4 Percentage of participants |
| Mepolizumab 75 mg IV | Time to First Exacerbation Requiring Hospitalization or ED Visit | Week 52 | 10.4 Percentage of participants |
| Mepolizumab 75 mg IV | Time to First Exacerbation Requiring Hospitalization or ED Visit | Week 32 | 8.3 Percentage of participants |
| Mepolizumab 250 mg IV | Time to First Exacerbation Requiring Hospitalization or ED Visit | Week 16 | 6.7 Percentage of participants |
| Mepolizumab 250 mg IV | Time to First Exacerbation Requiring Hospitalization or ED Visit | Week 52 | 15.9 Percentage of participants |
| Mepolizumab 250 mg IV | Time to First Exacerbation Requiring Hospitalization or ED Visit | Week 32 | 15.1 Percentage of participants |
| Mepolizumab 750 mg IV | Time to First Exacerbation Requiring Hospitalization or ED Visit | Week 32 | 8.0 Percentage of participants |
| Mepolizumab 750 mg IV | Time to First Exacerbation Requiring Hospitalization or ED Visit | Week 52 | 12.4 Percentage of participants |
| Mepolizumab 750 mg IV | Time to First Exacerbation Requiring Hospitalization or ED Visit | Week 16 | 3.9 Percentage of participants |