Asthma
Conditions
Keywords
urban setting, children and adolescents, double-masked, placebo-controlled randomized trial, asthma exacerbations (attacks), mepolizumab adjunctive therapy, asthma exacerbations prevention, difficult-to-control exacerbation-prone asthma
Brief summary
The purpose of this study is to see if treatment with a medication called Nucala® (mepolizumab), given along with standard asthma care, makes children less likely to have asthma attacks.
Detailed description
Asthma is a growing problem, especially in children. It causes frequent wheezing, shortness of breath, chest tightness, and cough. Asthma attacks, or exacerbations, are problems for children with asthma. The purpose of this study is to see if treatment with a medication called mepolizumab (Nucala®), given along with standard asthma care, makes children less likely to have asthma attacks. Mepolizumab is a new drug that is approved by the Food and Drug Administration (FDA) for use in children with asthma who are aged 12 years and older. Mepolizumab is given by injection. It is being studied by other researchers in children aged 6-11 years. All participants will be prescribed standard asthma medications by a clinician who is trained in asthma care. Medications will include controller medications, a rescue medication, and a medication for severe asthma attacks (prednisone). The amount of medication that participants receive may be increased or decreased during the study based on their symptoms and breathing test results. Study clinicians will treat all participants according to the same guidelines. These treatment guidelines are based on recommendations from a group of national experts in asthma. This study has been designed this way so that all participants will have safe and effective standard asthma care. In order to enroll in this study, participants must be willing to have their asthma managed by the study clinician during the entire study period. Participants must also be willing to bring study medications to all study visits. This study will include up to 20 study visits. Participant involvement in the study will endure for approximately 1 year. During the treatment period, participants will be placed in one of two treatment groups: * Mepolizumab injection and guidelines-based asthma care or * Placebo injection and guidelines-based asthma care. Participants will not be able to choose which group they are assigned. This assignment is random and by chance, much like flipping a coin. Participants will not know if they are receiving mepolizumab or placebo. Investigators will compare the study results between the participants of each group.
Interventions
BIOLOGICALMepolizumab
Mepolizumab administered every 4 weeks by subcutaneous injection at a dose of: * 100 mg for participants ≥12 years of age and * 40 mg for participants ages 6 to 11 years and weighing ≥40 kg. Note: Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in the study under previous versions of the protocol and were initially assigned a 100 mg dose will have their dose reduced to 40 mg. Participants 11 years of age will increase to the 100 mg dose if they become age 12 years during the study.
DRUGPlacebo
Placebo administered every 4 weeks by subcutaneous injection at a dose of: * 100 mg for participants ≥12 years of age and * 40 mg for participants ages 6 to 11 years and weighing ≥40 kg. Note: Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in the study under previous versions of the protocol and were initially assigned a 100 mg dose will have their dose reduced to 40 mg. Participants 11 years of age will increase to the 100 mg dose if they become age 12 years during the study.
Sponsors
Inner-City Asthma Consortium
GlaxoSmithKline
Rho Federal Systems Division, Inc.
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
Study applicant(s) that fulfill all of the inclusion criteria and none of the
Exclusion criteria
are eligible for the study- * Participant and/or parent guardian must be able to understand and provide informed consent and age-appropriate assent; * Must have a primary place of residence in one of the pre-selected recruitment census tracts as outlined in the study's Manual of Procedures (MOP); * Has had a diagnosis of asthma made \>1 year prior to recruitment; --Those who received an asthma diagnosis by a clinician ≤1 year prior to recruitment must report that their respiratory symptoms were present for more than 1 year prior to recruitment. * Has had ≥2 asthma exacerbations in the prior year (defined as a requirement for systemic corticosteroids and/or hospitalization); * At Visit 0 (Screening), has the following requirement for asthma controller medication: * For those ages 6 to 11 years, treatments with at least fluticasone 250 mcg dry powder inhaler (DPI) one puff twice daily or its equivalent and, * For those ≥12 years of age, treatment with at least Advair 250/50 mcg dry powder inhaler (DPI), one puff twice daily or its equivalent. * Has peripheral blood eosinophils ≥150 cells/µl obtained at Visit 0 (Screening) or in another Inner-City Asthma Consortium (ICAC) clinical research study within 6 months; * Is able to perform spirometry at randomization (Visit for treatment assignment); * Has documentation of current medical insurance with prescription coverage at randomization; and * Has had varicella or the varicella vaccination.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Asthma Exacerbations During the Treatment Period | Up to 12 months | Exacerbations were defined as a prescription of a course of systemic corticosteroids by a clinician, initiation of a course of systemic corticosteroids by a participant, or as a hospitalization for asthma. If a participant initiated and completed a course of systemic corticosteroids without clinician involvement, this course was counted only if the study clinician agreed the treatment was warranted, and it met the following dosage: the course for prednisone, prednisolone, or methylprednisolone was at least 20 mg daily dose for 3 of 5 consecutive days. The course for dexamethasone was at least a 10 mg single daily dose. If a corticosteroid burst for the treatment of an asthma exacerbation was prescribed by a non-ICAC clinician, it was counted regardless of dose. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Participant Quality of Life Measured Using the Patient Global Assessment, at Visit 14 | Week 56 | The Patient Global Assessment Tool was used to assess the quality of life of the subjects during treatment. The questionnaire is one question that asks the participant to evaluate how their quality of life changed over the course of treatment. There are seven possible options ranging from significantly worse to significantly improved. |
| Lung Function as Assessed by Spirometry | Weeks 12, 24, 36, 48, 52 after randomization | A generalized mixed model was used to analyze spirometry parameter at each visit where the lung function was collected. The ratio of the forced expiratory volume to the forced vital capacity of the lungs (FEV1/FVC) is the outcome that measured lung function. |
| Lung Function as Assessed by Impulse Oscillometry | Weeks 12, 24, 36, 48, 52 after randomization | A generalized mixed model was used to analyze impulse oscillometry parameter at each visit where the lung function was collected. The Percent Predicted FEV1 (%) is the outcome that measured lung function. |
| Rate of Exacerbations (Mepolizumab vs. Placebo) During the Treatment Period for Participants Who Did Not Fit the FDA-approved Dosing Table for Omalizumab Therapy. | Up to 12 months | Looking at the rate of exacerbations similarly to the primary endpoint. This outcome measure also took into consideration FDA- approved dosing of omalizumab. The FDA-approved dosing table is based off of age, weight and pre-treatment Serum IGE |
| Rate of Exacerbations (Mepolizumab vs. Placebo) During the Treatment Period for Participants Who Fit the FDA-approved Dosing Table. | Up to 12 months | Looking at the rate of exacerbations similarly to the primary endpoint. This outcome measure also took into consideration FDA- approved dosing of omalizumab. The FDA-approved dosing table is based off of age, weight and pre-treatment Serum IGE |
| Time to First Asthma Exacerbation | Up to 12 months | A Cox PH model was also used to model the time to first asthma exacerbation during the treatment period. The Cox PH model included treatment arm as the primary exposure but was also adjusted for study site, number of exacerbations in year prior to study (2 or 3+), peripheral blood eosinophils (above or below 400 cells/μl), BMI (above or below 95th percentile for age) and total serum IgE (above or below 540 kUA/L). |
| Number of Reported Adverse Events (AEs), Including Their Severity | Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment) | The number of AEs by severity was used to assess safety. Please refer to the Adverse Event tables for specifics. |
| Number of Reported Adverse Events (AEs), Including Their Treatment Relatedness | Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment) | The number of AEs by relationship to study drug was used to assess safety. Please refer to the Adverse Event tables for specifics. |
| Number of Reported Serious Adverse Events (SAEs) Inclusive of Severity. Please Refer to the Adverse Event Tables for Specifics. | Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment) | The number of SAEs by severity and relationship to study drug was used to assess safety. |
| Number of Reported Serious Adverse Events (SAEs) Inclusive of Treatment Relatedness. Please Refer to the Adverse Event Tables for Specifics. | Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment) | The number of SAEs by relationship to study drug was used to assess safety. |
| Composite Asthma Severity Index (CASI) | Week 12, 24, 36, 48, 52 after randomization | Composite Asthma Severity Index (CASI) scores included 5 domains: day symptoms and albuterol use, night symptoms and albuterol use, controller treatment, lung function measures, and exacerbations. The minimum composite score was 0 while the maximum was 20. The higher the score the more allergy symptoms a subject has. |
| Participant Quality of Life Measured Using the Physician Global Assessment Tool | Week 56 | The Physician Global Assessment Tool was used to assess the quality of life of the subjects during treatment. The questionnaire is one question that asks the physician to evaluate how the participant's quality of life changed over the course of treatment. There are seven possible options ranging from significantly worse to significantly improved. |
Other
| Measure | Time frame | Description |
|---|---|---|
| EXPLORATORY:Childhood Asthma Control Test (ACT)/c-ACT | Visits (V) 4 (Week 4 Treatment Initiation) , V4 (Week 16), V7 (Week 28), V10 (Week 40), V13 (Week 52) and V14 (Week 56, Completion of Treatment) | A validated tool to assess overall asthma control (over the last 4 weeks) in participants. |
| EXPLORATORY:Maximum Number of Asthma Symptom Days | Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment) | Defined as the highest value among the following variables over a two-week period: * number of days with wheezing, tightness in the chest, or cough; * number of nights with disturbed sleep as a result of asthma; and * number of days on which the participant had to slow down or discontinue play/physical activities. |
| EXPLORATORY:Bronchodilator Responsiveness | Baseline (prior to treatment initiation), Week 56 (Completion of Treatment) | A measure to determine whether mepolizumab improves pulmonary outcomes. |
| EXPLORATORY: Gene Expression in Nasal Lavage Samples | Visits (V) 1 (Week 4 Treatment Initiation) , V3(Week 12), and V14 (Week 56, Completion of Treatment) | Whole genome transcriptomics of nasal lavage samples to identify inflammatory pathways affected by mepolizumab. |
| EXPLORATORY: Gene Expression in Whole Blood RNA Samples | Visits (V) 1 (Week 4 Treatment Initiation) , V3(Week 12), and V14 (Week 56, Completion of Treatment) | Whole genome transcriptomics of whole blood RNA samples to identify inflammatory pathways affected by mepolizumab.. |
| EXPLORATORY:Levels of Antibody to Mepolizumab | Visit (V) 1 (Week 4, prior to treatment initiation), V3 (Week 12), and Visit 14 (Week 56, Completion of Treatment) | An assay for detection/measurement of levels of antibody to mepolizumab. Analysis will include participants randomized to mepolizumab. |
| EXPLORATORY:Other Potential Biomarkers Not Specified to Date | Visit (V) 1 (Week 4, prior to treatment initiation), V3 (Week 12), and Visit 14 (Week 56, Completion of Treatment) | Plasma, nasal samples, RNA and DNA will be banked for possible future study of potential biomarkers associated with asthma and asthma exacerbations. |
| EXPLORATORY: Time to First Respiratory Virus-Induced Exacerbation | Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment) | As measured by an exacerbation associated with a respiratory virus detected using nasal mucus samples obtained at the time of an exacerbation. |
| EXPLORATORY:Number of Respiratory Virus-Induced Exacerbations | Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment) | Measured by an exacerbation associated with a respiratory virus detected using nasal mucus samples obtained at the time of an exacerbation. |
Countries
United States
Participant flow
Pre-assignment details
335 people were enrolled in the study (signed a consent and were assigned a unique participant number). However, 45 participants dropped out before receiving treatment bringing the total to 290 participants who started treatment.
Participants by arm
| Arm | Count |
|---|---|
| Mepolizumab Intervention: Mepolizumab plus guidelines-based standard of care asthma treatment.
Mepolizumab: Mepolizumab administered every 4 weeks by subcutaneous injection at a dose of:
* 100 mg for participants ≥12 years of age and
* 40 mg for participants ages 6 to 11 years and weighing ≥40 kg.
Note: Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in the study under previous versions of the protocol and were initially assigned a 100 mg dose will have their dose reduced to 40 mg.
Participants 11 years of age will increase to the 100 mg dose if they become age 12 years during the study. | 146 |
| Placebo Intervention: Placebo for mepolizumab plus guidelines-based standard of care asthma treatment.
Placebo: Placebo administered every 4 weeks by subcutaneous injection at a dose of:
* 100 mg for participants ≥12 years of age and
* 40 mg for participants ages 6 to 11 years and weighing ≥40 kg.
Note: Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in the study under previous versions of the protocol and were initially assigned a 100 mg dose will have their dose reduced to 40 mg.
Participants 11 years of age will increase to the 100 mg dose if they become age 12 years during the study. | 144 |
| Total | 290 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | >3 bursts of systemic corticosteroids for asthma during treatment period (Starting Nov 2020) | 2 | 1 |
| Overall Study | Death | 1 | 0 |
| Overall Study | Lost to Follow-up | 12 | 16 |
| Overall Study | Move out of town | 1 | 0 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 4 |
Baseline characteristics
| Characteristic | Mepolizumab | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 146 Participants | 144 Participants | 290 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 10.8 years STANDARD_DEVIATION 2.87 | 10.8 years STANDARD_DEVIATION 2.88 | 10.8 years STANDARD_DEVIATION 2.87 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 35 Participants | 37 Participants | 72 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 111 Participants | 107 Participants | 218 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 146 participants | 144 participants | 290 participants |
| Sex: Female, Male Female | 71 Participants | 55 Participants | 126 Participants |
| Sex: Female, Male Male | 75 Participants | 89 Participants | 164 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 146 | 0 / 144 |
| other Total, other adverse events | 53 / 146 | 42 / 144 |
| serious Total, serious adverse events | 4 / 146 | 2 / 144 |
Outcome results
Primary
Number of Asthma Exacerbations During the Treatment Period
Exacerbations were defined as a prescription of a course of systemic corticosteroids by a clinician, initiation of a course of systemic corticosteroids by a participant, or as a hospitalization for asthma. If a participant initiated and completed a course of systemic corticosteroids without clinician involvement, this course was counted only if the study clinician agreed the treatment was warranted, and it met the following dosage: the course for prednisone, prednisolone, or methylprednisolone was at least 20 mg daily dose for 3 of 5 consecutive days. The course for dexamethasone was at least a 10 mg single daily dose. If a corticosteroid burst for the treatment of an asthma exacerbation was prescribed by a non-ICAC clinician, it was counted regardless of dose.
Time frame: Up to 12 months
Population: All participants who were randomized and received at least one dose of study treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mepolizumab | Number of Asthma Exacerbations During the Treatment Period | 0.96 Exacerbations during treatment | Standard Error 0.1 |
| Placebo | Number of Asthma Exacerbations During the Treatment Period | 1.30 Exacerbations during treatment | Standard Error 0.13 |
p-value: 0.02795% CI: [0.56, 0.96]Regression, Negative Binomial
Secondary
Composite Asthma Severity Index (CASI)
Composite Asthma Severity Index (CASI) scores included 5 domains: day symptoms and albuterol use, night symptoms and albuterol use, controller treatment, lung function measures, and exacerbations. The minimum composite score was 0 while the maximum was 20. The higher the score the more allergy symptoms a subject has.
Time frame: Week 12, 24, 36, 48, 52 after randomization
Population: All participants who were randomized and received at least one dose of study treatment
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Mepolizumab | Composite Asthma Severity Index (CASI) | Week 24 | 5.94 Composite Asthma Severity Index | Standard Error 0.23 |
| Mepolizumab | Composite Asthma Severity Index (CASI) | Week 48 | 5.16 Composite Asthma Severity Index | Standard Error 0.22 |
| Mepolizumab | Composite Asthma Severity Index (CASI) | Week 36 | 5.48 Composite Asthma Severity Index | Standard Error 0.22 |
| Mepolizumab | Composite Asthma Severity Index (CASI) | Week 52 | 5.03 Composite Asthma Severity Index | Standard Error 0.23 |
| Mepolizumab | Composite Asthma Severity Index (CASI) | Week 12 | 6.17 Composite Asthma Severity Index | Standard Error 0.2 |
| Placebo | Composite Asthma Severity Index (CASI) | Week 52 | 5.00 Composite Asthma Severity Index | Standard Error 0.23 |
| Placebo | Composite Asthma Severity Index (CASI) | Week 12 | 6.45 Composite Asthma Severity Index | Standard Error 0.2 |
| Placebo | Composite Asthma Severity Index (CASI) | Week 24 | 6.01 Composite Asthma Severity Index | Standard Error 0.23 |
| Placebo | Composite Asthma Severity Index (CASI) | Week 36 | 5.99 Composite Asthma Severity Index | Standard Error 0.23 |
| Placebo | Composite Asthma Severity Index (CASI) | Week 48 | 5.23 Composite Asthma Severity Index | Standard Error 0.22 |
Comparison: Week 12p-value: 0.2995% CI: [-0.81, 0.24]Mixed Models Analysis
Comparison: Week 24p-value: 0.8295% CI: [-0.69, 0.55]Mixed Models Analysis
Comparison: Week 36p-value: 0.09695% CI: [-1.11, 0.09]Mixed Models Analysis
Comparison: Week 48p-value: 0.83195% CI: [-0.65, 0.52]Mixed Models Analysis
Comparison: Week 52p-value: 0.94795% CI: [-0.6, 0.64]Mixed Models Analysis
Secondary
Lung Function as Assessed by Impulse Oscillometry
A generalized mixed model was used to analyze impulse oscillometry parameter at each visit where the lung function was collected. The Percent Predicted FEV1 (%) is the outcome that measured lung function.
Time frame: Weeks 12, 24, 36, 48, 52 after randomization
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Mepolizumab | Lung Function as Assessed by Impulse Oscillometry | FEV1PP - Week 52 | 90.9 Percent Predicted FEV1 (%) | Standard Error 1.45 |
| Mepolizumab | Lung Function as Assessed by Impulse Oscillometry | FEV1PP - Week 12 | 91.9 Percent Predicted FEV1 (%) | Standard Error 1.27 |
| Mepolizumab | Lung Function as Assessed by Impulse Oscillometry | FEV1PP - Week 24 | 90.8 Percent Predicted FEV1 (%) | Standard Error 1.46 |
| Mepolizumab | Lung Function as Assessed by Impulse Oscillometry | FEV1PP - Week 36 | 91.5 Percent Predicted FEV1 (%) | Standard Error 1.45 |
| Mepolizumab | Lung Function as Assessed by Impulse Oscillometry | FEV1PP - Week 48 | 90.4 Percent Predicted FEV1 (%) | Standard Error 1.46 |
| Placebo | Lung Function as Assessed by Impulse Oscillometry | FEV1PP - Week 48 | 89.8 Percent Predicted FEV1 (%) | Standard Error 1.48 |
| Placebo | Lung Function as Assessed by Impulse Oscillometry | FEV1PP - Week 36 | 89.9 Percent Predicted FEV1 (%) | Standard Error 1.46 |
| Placebo | Lung Function as Assessed by Impulse Oscillometry | FEV1PP - Week 12 | 92.3 Percent Predicted FEV1 (%) | Standard Error 1.27 |
| Placebo | Lung Function as Assessed by Impulse Oscillometry | FEV1PP - Week 52 | 93.5 Percent Predicted FEV1 (%) | Standard Error 1.43 |
| Placebo | Lung Function as Assessed by Impulse Oscillometry | FEV1PP - Week 24 | 94.2 Percent Predicted FEV1 (%) | Standard Error 1.49 |
Comparison: FEV1PP Week 12p-value: 0.81695% CI: [-3.8, 3]Mixed Models Analysis
Comparison: FEV1PP Week 24p-value: 0.09595% CI: [-7.4, 0.6]Mixed Models Analysis
Comparison: FEV1PP Week 36p-value: 0.44495% CI: [-2.4, 5.5]Mixed Models Analysis
Comparison: FEV1PP Week 48p-value: 0.75195% CI: [-3.3, 4.6]Mixed Models Analysis
Comparison: FEV1PP Week 52p-value: 0.18495% CI: [-6.5, 1.3]Mixed Models Analysis
Secondary
Lung Function as Assessed by Spirometry
A generalized mixed model was used to analyze spirometry parameter at each visit where the lung function was collected. The ratio of the forced expiratory volume to the forced vital capacity of the lungs (FEV1/FVC) is the outcome that measured lung function.
Time frame: Weeks 12, 24, 36, 48, 52 after randomization
Population: All participants who were randomized and received at least one dose of study treatment
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Mepolizumab | Lung Function as Assessed by Spirometry | FEV1/FVC - Week 24 | 0.755 FEV1/FVC | Standard Error 0.007 |
| Mepolizumab | Lung Function as Assessed by Spirometry | FEV1/FVC - Week 48 | 0.755 FEV1/FVC | Standard Error 0.008 |
| Mepolizumab | Lung Function as Assessed by Spirometry | FEV1/FVC - Week 36 | 0.758 FEV1/FVC | Standard Error 0.008 |
| Mepolizumab | Lung Function as Assessed by Spirometry | FEV1/FVC - Week 52 | 0.761 FEV1/FVC | Standard Error 0.008 |
| Mepolizumab | Lung Function as Assessed by Spirometry | FEV1/FVC - Week 12 | 0.747 FEV1/FVC | Standard Error 0.007 |
| Placebo | Lung Function as Assessed by Spirometry | FEV1/FVC - Week 52 | 0.763 FEV1/FVC | Standard Error 0.008 |
| Placebo | Lung Function as Assessed by Spirometry | FEV1/FVC - Week 12 | 0.752 FEV1/FVC | Standard Error 0.007 |
| Placebo | Lung Function as Assessed by Spirometry | FEV1/FVC - Week 24 | 0.766 FEV1/FVC | Standard Error 0.007 |
| Placebo | Lung Function as Assessed by Spirometry | FEV1/FVC - Week 36 | 0.747 FEV1/FVC | Standard Error 0.008 |
| Placebo | Lung Function as Assessed by Spirometry | FEV1/FVC - Week 48 | 0.742 FEV1/FVC | Standard Error 0.008 |
Comparison: FEV1/FVC Week 12p-value: 0.59195% CI: [-0.023, 0.013]Mixed Models Analysis
Comparison: FEV1/FVC Week 24p-value: 0.26595% CI: [-0.031, 0.008]Mixed Models Analysis
Comparison: FEV1/FVC Week 36p-value: 0.34595% CI: [-0.012, 0.033]Mixed Models Analysis
Comparison: FEV1/FVC Week 48p-value: 0.24895% CI: [-0.009, 0.036]Mixed Models Analysis
Comparison: FEV1/FVC Week 52p-value: 0.86495% CI: [-0.023, 0.02]Mixed Models Analysis
Secondary
Number of Reported Adverse Events (AEs), Including Their Severity
The number of AEs by severity was used to assess safety. Please refer to the Adverse Event tables for specifics.
Time frame: Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)
Population: Number of Subjects with at Least One AE by severity
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mepolizumab | Number of Reported Adverse Events (AEs), Including Their Severity | Severity: Grade 2 - Moderate | 58 Participants |
| Mepolizumab | Number of Reported Adverse Events (AEs), Including Their Severity | Severity: Grade 4 - Life-threatening or disabling | 0 Participants |
| Mepolizumab | Number of Reported Adverse Events (AEs), Including Their Severity | Severity: Grade 3 - Severe and undesirable | 8 Participants |
| Mepolizumab | Number of Reported Adverse Events (AEs), Including Their Severity | Severity: Grade 5 - Death | 0 Participants |
| Mepolizumab | Number of Reported Adverse Events (AEs), Including Their Severity | Severity: Grade 1 - Mild | 47 Participants |
| Placebo | Number of Reported Adverse Events (AEs), Including Their Severity | Severity: Grade 5 - Death | 0 Participants |
| Placebo | Number of Reported Adverse Events (AEs), Including Their Severity | Severity: Grade 1 - Mild | 39 Participants |
| Placebo | Number of Reported Adverse Events (AEs), Including Their Severity | Severity: Grade 2 - Moderate | 51 Participants |
| Placebo | Number of Reported Adverse Events (AEs), Including Their Severity | Severity: Grade 3 - Severe and undesirable | 3 Participants |
| Placebo | Number of Reported Adverse Events (AEs), Including Their Severity | Severity: Grade 4 - Life-threatening or disabling | 1 Participants |
Secondary
Number of Reported Adverse Events (AEs), Including Their Treatment Relatedness
The number of AEs by relationship to study drug was used to assess safety. Please refer to the Adverse Event tables for specifics.
Time frame: Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)
Population: Number of Subjects with any study procedures related AEs
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mepolizumab | Number of Reported Adverse Events (AEs), Including Their Treatment Relatedness | 46 Participants |
| Placebo | Number of Reported Adverse Events (AEs), Including Their Treatment Relatedness | 26 Participants |
Secondary
Number of Reported Serious Adverse Events (SAEs) Inclusive of Severity. Please Refer to the Adverse Event Tables for Specifics.
The number of SAEs by severity and relationship to study drug was used to assess safety.
Time frame: Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)
Population: Number of subjects with Serious Adverse Events
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mepolizumab | Number of Reported Serious Adverse Events (SAEs) Inclusive of Severity. Please Refer to the Adverse Event Tables for Specifics. | Severity: Grade 5 - Death | 1 Participants |
| Mepolizumab | Number of Reported Serious Adverse Events (SAEs) Inclusive of Severity. Please Refer to the Adverse Event Tables for Specifics. | Severity: Grade 3 - Severe and undesirable | 3 Participants |
| Mepolizumab | Number of Reported Serious Adverse Events (SAEs) Inclusive of Severity. Please Refer to the Adverse Event Tables for Specifics. | Severity: Grade 4 - Life threatening | 0 Participants |
| Mepolizumab | Number of Reported Serious Adverse Events (SAEs) Inclusive of Severity. Please Refer to the Adverse Event Tables for Specifics. | Severity: Grade 2 - Moderate | 0 Participants |
| Placebo | Number of Reported Serious Adverse Events (SAEs) Inclusive of Severity. Please Refer to the Adverse Event Tables for Specifics. | Severity: Grade 5 - Death | 0 Participants |
| Placebo | Number of Reported Serious Adverse Events (SAEs) Inclusive of Severity. Please Refer to the Adverse Event Tables for Specifics. | Severity: Grade 2 - Moderate | 1 Participants |
| Placebo | Number of Reported Serious Adverse Events (SAEs) Inclusive of Severity. Please Refer to the Adverse Event Tables for Specifics. | Severity: Grade 4 - Life threatening | 0 Participants |
| Placebo | Number of Reported Serious Adverse Events (SAEs) Inclusive of Severity. Please Refer to the Adverse Event Tables for Specifics. | Severity: Grade 3 - Severe and undesirable | 1 Participants |
Secondary
Number of Reported Serious Adverse Events (SAEs) Inclusive of Treatment Relatedness. Please Refer to the Adverse Event Tables for Specifics.
The number of SAEs by relationship to study drug was used to assess safety.
Time frame: Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)
Population: Number of subjects with any study procedures related Serious Adverse Events
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Mepolizumab | Number of Reported Serious Adverse Events (SAEs) Inclusive of Treatment Relatedness. Please Refer to the Adverse Event Tables for Specifics. | 0 Participants |
| Placebo | Number of Reported Serious Adverse Events (SAEs) Inclusive of Treatment Relatedness. Please Refer to the Adverse Event Tables for Specifics. | 1 Participants |
Secondary
Participant Quality of Life Measured Using the Patient Global Assessment, at Visit 14
The Patient Global Assessment Tool was used to assess the quality of life of the subjects during treatment. The questionnaire is one question that asks the participant to evaluate how their quality of life changed over the course of treatment. There are seven possible options ranging from significantly worse to significantly improved.
Time frame: Week 56
Population: All participants who were randomized and received at least one dose of study treatment and completed the quality of life questionnaire at visit 14.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mepolizumab | Participant Quality of Life Measured Using the Patient Global Assessment, at Visit 14 | Patient Global Assessment Tool - Mildly Worse | 2 Participants |
| Mepolizumab | Participant Quality of Life Measured Using the Patient Global Assessment, at Visit 14 | Patient Global Assessment Tool - Significantly Worse | 0 Participants |
| Mepolizumab | Participant Quality of Life Measured Using the Patient Global Assessment, at Visit 14 | Patient Global Assessment Tool - No Change | 7 Participants |
| Mepolizumab | Participant Quality of Life Measured Using the Patient Global Assessment, at Visit 14 | Patient Global Assessment Tool - Significantly Improved | 82 Participants |
| Mepolizumab | Participant Quality of Life Measured Using the Patient Global Assessment, at Visit 14 | Patient Global Assessment Tool - Moderately Worse | 0 Participants |
| Mepolizumab | Participant Quality of Life Measured Using the Patient Global Assessment, at Visit 14 | Patient Global Assessment Tool - Moderately Improved | 27 Participants |
| Mepolizumab | Participant Quality of Life Measured Using the Patient Global Assessment, at Visit 14 | Patient Global Assessment Tool - Mildly Improved | 11 Participants |
| Placebo | Participant Quality of Life Measured Using the Patient Global Assessment, at Visit 14 | Patient Global Assessment Tool - Moderately Improved | 23 Participants |
| Placebo | Participant Quality of Life Measured Using the Patient Global Assessment, at Visit 14 | Patient Global Assessment Tool - Mildly Improved | 12 Participants |
| Placebo | Participant Quality of Life Measured Using the Patient Global Assessment, at Visit 14 | Patient Global Assessment Tool - No Change | 2 Participants |
| Placebo | Participant Quality of Life Measured Using the Patient Global Assessment, at Visit 14 | Patient Global Assessment Tool - Mildly Worse | 0 Participants |
| Placebo | Participant Quality of Life Measured Using the Patient Global Assessment, at Visit 14 | Patient Global Assessment Tool - Moderately Worse | 0 Participants |
| Placebo | Participant Quality of Life Measured Using the Patient Global Assessment, at Visit 14 | Patient Global Assessment Tool - Significantly Worse | 0 Participants |
| Placebo | Participant Quality of Life Measured Using the Patient Global Assessment, at Visit 14 | Patient Global Assessment Tool - Significantly Improved | 87 Participants |
Comparison: Patient Global Assessment Toolp-value: 0.23895% CI: [0.42, 1.24]Regression, Logistic
Secondary
Participant Quality of Life Measured Using the Physician Global Assessment Tool
The Physician Global Assessment Tool was used to assess the quality of life of the subjects during treatment. The questionnaire is one question that asks the physician to evaluate how the participant's quality of life changed over the course of treatment. There are seven possible options ranging from significantly worse to significantly improved.
Time frame: Week 56
Population: All participants who were randomized and received at least one dose of study treatment and completed the quality of life questionnaire at visit 14.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Mepolizumab | Participant Quality of Life Measured Using the Physician Global Assessment Tool | Physician Global Assessment Tool - Mildly Improved | 22 Participants |
| Mepolizumab | Participant Quality of Life Measured Using the Physician Global Assessment Tool | Physician Global Assessment Tool - Mildly Worse | 1 Participants |
| Mepolizumab | Participant Quality of Life Measured Using the Physician Global Assessment Tool | Physician Global Assessment Tool - Moderately Improved | 27 Participants |
| Mepolizumab | Participant Quality of Life Measured Using the Physician Global Assessment Tool | Physician Global Assessment Tool - Moderately Worse | 0 Participants |
| Mepolizumab | Participant Quality of Life Measured Using the Physician Global Assessment Tool | Physician Global Assessment Tool - No Change | 20 Participants |
| Mepolizumab | Participant Quality of Life Measured Using the Physician Global Assessment Tool | Physician Global Assessment Tool - Significantly Worse | 1 Participants |
| Mepolizumab | Participant Quality of Life Measured Using the Physician Global Assessment Tool | Physician Global Assessment Tool - Significantly Improved | 58 Participants |
| Placebo | Participant Quality of Life Measured Using the Physician Global Assessment Tool | Physician Global Assessment Tool - Significantly Worse | 0 Participants |
| Placebo | Participant Quality of Life Measured Using the Physician Global Assessment Tool | Physician Global Assessment Tool - Significantly Improved | 54 Participants |
| Placebo | Participant Quality of Life Measured Using the Physician Global Assessment Tool | Physician Global Assessment Tool - Moderately Improved | 33 Participants |
| Placebo | Participant Quality of Life Measured Using the Physician Global Assessment Tool | Physician Global Assessment Tool - Mildly Improved | 17 Participants |
| Placebo | Participant Quality of Life Measured Using the Physician Global Assessment Tool | Physician Global Assessment Tool - No Change | 17 Participants |
| Placebo | Participant Quality of Life Measured Using the Physician Global Assessment Tool | Physician Global Assessment Tool - Mildly Worse | 1 Participants |
| Placebo | Participant Quality of Life Measured Using the Physician Global Assessment Tool | Physician Global Assessment Tool - Moderately Worse | 0 Participants |
Comparison: Physician Global Assessment Toolp-value: 0.97495% CI: [0.62, 1.64]Regression, Logistic
Secondary
Rate of Exacerbations (Mepolizumab vs. Placebo) During the Treatment Period for Participants Who Did Not Fit the FDA-approved Dosing Table for Omalizumab Therapy.
Looking at the rate of exacerbations similarly to the primary endpoint. This outcome measure also took into consideration FDA- approved dosing of omalizumab. The FDA-approved dosing table is based off of age, weight and pre-treatment Serum IGE
Time frame: Up to 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mepolizumab | Rate of Exacerbations (Mepolizumab vs. Placebo) During the Treatment Period for Participants Who Did Not Fit the FDA-approved Dosing Table for Omalizumab Therapy. | 1.11 Exacerbations during treatment | Standard Error 0.21 |
| Placebo | Rate of Exacerbations (Mepolizumab vs. Placebo) During the Treatment Period for Participants Who Did Not Fit the FDA-approved Dosing Table for Omalizumab Therapy. | 1.31 Exacerbations during treatment | Standard Error 0.25 |
Comparison: Did not meet FDA-approved dosingp-value: 0.45895% CI: [0.55, 1.31]Mixed Models Analysis
Secondary
Rate of Exacerbations (Mepolizumab vs. Placebo) During the Treatment Period for Participants Who Fit the FDA-approved Dosing Table.
Looking at the rate of exacerbations similarly to the primary endpoint. This outcome measure also took into consideration FDA- approved dosing of omalizumab. The FDA-approved dosing table is based off of age, weight and pre-treatment Serum IGE
Time frame: Up to 12 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Mepolizumab | Rate of Exacerbations (Mepolizumab vs. Placebo) During the Treatment Period for Participants Who Fit the FDA-approved Dosing Table. | 0.87 Exacerbations during treatment | Standard Error 0.13 |
| Placebo | Rate of Exacerbations (Mepolizumab vs. Placebo) During the Treatment Period for Participants Who Fit the FDA-approved Dosing Table. | 1.30 Exacerbations during treatment | Standard Error 0.18 |
Comparison: Fit FDA-approved dosingp-value: 0.02595% CI: [0.47, 0.95]Regression, Negative Binomial
Secondary
Time to First Asthma Exacerbation
A Cox PH model was also used to model the time to first asthma exacerbation during the treatment period. The Cox PH model included treatment arm as the primary exposure but was also adjusted for study site, number of exacerbations in year prior to study (2 or 3+), peripheral blood eosinophils (above or below 400 cells/μl), BMI (above or below 95th percentile for age) and total serum IgE (above or below 540 kUA/L).
Time frame: Up to 12 months
Population: All participants who were randomized and received at least one dose of study treatment
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Mepolizumab | Time to First Asthma Exacerbation | 241 Days |
| Placebo | Time to First Asthma Exacerbation | 224 Days |
p-value: 0.358795% CI: [0.63, 1.18]Regression, Cox
Other Pre-specified
EXPLORATORY:Bronchodilator Responsiveness
A measure to determine whether mepolizumab improves pulmonary outcomes.
Time frame: Baseline (prior to treatment initiation), Week 56 (Completion of Treatment)
Other Pre-specified
EXPLORATORY:Childhood Asthma Control Test (ACT)/c-ACT
A validated tool to assess overall asthma control (over the last 4 weeks) in participants.
Time frame: Visits (V) 4 (Week 4 Treatment Initiation) , V4 (Week 16), V7 (Week 28), V10 (Week 40), V13 (Week 52) and V14 (Week 56, Completion of Treatment)
Other Pre-specified
EXPLORATORY: Gene Expression in Nasal Lavage Samples
Whole genome transcriptomics of nasal lavage samples to identify inflammatory pathways affected by mepolizumab.
Time frame: Visits (V) 1 (Week 4 Treatment Initiation) , V3(Week 12), and V14 (Week 56, Completion of Treatment)
Other Pre-specified
EXPLORATORY: Gene Expression in Whole Blood RNA Samples
Whole genome transcriptomics of whole blood RNA samples to identify inflammatory pathways affected by mepolizumab..
Time frame: Visits (V) 1 (Week 4 Treatment Initiation) , V3(Week 12), and V14 (Week 56, Completion of Treatment)
Other Pre-specified
EXPLORATORY:Levels of Antibody to Mepolizumab
An assay for detection/measurement of levels of antibody to mepolizumab. Analysis will include participants randomized to mepolizumab.
Time frame: Visit (V) 1 (Week 4, prior to treatment initiation), V3 (Week 12), and Visit 14 (Week 56, Completion of Treatment)
Other Pre-specified
EXPLORATORY:Maximum Number of Asthma Symptom Days
Defined as the highest value among the following variables over a two-week period: * number of days with wheezing, tightness in the chest, or cough; * number of nights with disturbed sleep as a result of asthma; and * number of days on which the participant had to slow down or discontinue play/physical activities.
Time frame: Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)
Other Pre-specified
EXPLORATORY:Number of Respiratory Virus-Induced Exacerbations
Measured by an exacerbation associated with a respiratory virus detected using nasal mucus samples obtained at the time of an exacerbation.
Time frame: Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)
Other Pre-specified
EXPLORATORY:Other Potential Biomarkers Not Specified to Date
Plasma, nasal samples, RNA and DNA will be banked for possible future study of potential biomarkers associated with asthma and asthma exacerbations.
Time frame: Visit (V) 1 (Week 4, prior to treatment initiation), V3 (Week 12), and Visit 14 (Week 56, Completion of Treatment)
Other Pre-specified
EXPLORATORY: Time to First Respiratory Virus-Induced Exacerbation
As measured by an exacerbation associated with a respiratory virus detected using nasal mucus samples obtained at the time of an exacerbation.
Time frame: Week 4 (Treatment Initiation) to Week 56 (Completion of Treatment)