MUPPITS-2: A Trial of Mepolizumab Adjunctive Therapy for the Prevention of Asthma Exacerbations in Urban Children

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT03292588
• Collaborator: Inner-City Asthma Consortium (Other), GlaxoSmithKline (Industry), Rho Federal Systems Division, Inc. (Industry)
• Enrollment: 335
• Locations: 9
• Arms: 2
• Actual Duration (Months): 41.4
• Patients Per Site: 37.2
• Patients Per Site Per Month: 0.9

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Biological: Mepolizumab; Drug: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 335 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Mechanisms Underlying Asthma Exacerbations Prevented and Persistent With Immune-Based Therapy: A Systems Approach Phase 2 (ICAC-30)
• Actual Study Start Date: Nov 7, 2017
• Actual Primary Completion Date: Apr 20, 2021
• Actual Study Completion Date: Apr 20, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mepolizumab Intervention: Mepolizumab plus guidelines-based standard of care asthma treatment.	Biological: 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.; Other Names: Nucala® anti-Interleukin 5 (IL5) antagonist monoclonal antibody
Placebo Comparator: Placebo Intervention: Placebo for mepolizumab plus guidelines-based standard of care asthma treatment.	Drug: 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.; Other Names: Placebo for Mepolizumab

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. 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

7. 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

8. 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).

9. 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.

10. 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.

11. 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.

12. 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.

Other Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. EXPLORATORY:Bronchodilator Responsiveness [Baseline (prior to treatment initiation), Week 56 (Completion of Treatment)]

   A measure to determine whether mepolizumab improves pulmonary outcomes.

6. 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.

7. 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..

8. 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.

9. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts 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.

Exclusion Criteria:

Individual(s) who meets any of the following criteria are not eligible for enrollment or randomization-

• Is not able or willing to give written informed consent or comply with the study protocol;

• Has concurrent (existing) medical problems that would require systemic corticosteroids or other immunomodulator treatments during the study;

• Is currently receiving immunotherapy;

• Is currently receiving treatment with omalizumab or has had omalizumab treatment within 6 months prior to planned participant randomization to treatment assignment;

• Is currently requiring greater than fluticasone 500 mcg administered twice daily plus a long-acting beta agonist (LABA) one puff twice daily or its equivalent, and/or

--Individuals using oral corticosteroids daily or every other day for more than 14 days at the time of Visit 0 (Screening).

• Is currently pregnant or lactating, or plans to become pregnant during the time of study participation

--Note: Females of child-bearing potential (post-menarche) must be abstinent or use a medically acceptable birth control method throughout the study (e.g. oral subcutaneous, mechanical, or surgical contraception).

• Has a known, pre-existing clinically important lung condition other than asthma;

• Has a current malignancy or previous history of cancer in remission for less than 12 months prior to randomization;

• Has known, pre-existing, unstable liver disease;

• Is a current smoker or has a smoking history of 10 or more pack years;

• Has a known immunodeficiency disease;

• Has other conditions that could lead to elevated eosinophils such as hypereosinophilic syndromes, including eosinophilic granulomatosis with polyangiitis;

• Has a known, active pre-existing parasitic infestation or is undergoing treatment for a parasitic infestation

--Note: Once the individual has been successfully treated, the interested study applicant may be reevaluated for study eligibility.

• Positive for use of investigational drugs within 4 weeks of randomization;

• Has a past or current medical problems or findings from physical examination or laboratory testing that are not listed above, which, in the opinion of the study clinician,

• May pose additional risks from participation in this study,

• May interfere with the participant's ability to comply with study requirements, or

• May impact the quality or interpretation of the data obtained from the study.

• In the event that the study applicant will not allow the study clinician, an asthma specialist, to manage their disease for the duration of the study or who are not willing to change their asthma medications to follow the protocol;

• Has a known history of allergic reaction to previous biologic therapy for asthma; or

• Has had a life threatening asthma exacerbation in the last 2 years requiring intubation, mechanical ventilation or resulting in a hypoxic seizure.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital Colorado	Aurora	Colorado	United States	80045
2	Children's National Medical Center	Washington	District of Columbia	United States	20010
3	Ann and Robert Lurie Children's Hospital of Chicago	Chicago	Illinois	United States	60611
4	Boston Medical Center	Boston	Massachusetts	United States	02118
5	Henry Ford Health System	Detroit	Michigan	United States	48202
6	St. Louis Children's Hospital	Saint Louis	Missouri	United States	63110
7	Columbia University Medical Center	New York	New York	United States	10032
8	Cincinnati Children's Hospital	Cincinnati	Ohio	United States	45229
9	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)
• Inner-City Asthma Consortium
• GlaxoSmithKline
• Rho Federal Systems Division, Inc.

Investigators

• Study Chair: Daniel J Jackson, MD, University of Wisconsin, Madison
• Study Chair: William W Busse, MD, University of Wisconsin, Madison

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Apr 1, 2021

More Information

Additional Information:

• National Institute of Allergy and Infectious Diseases (NIAID) website
• Division of Allergy, Immunology, and Transplantation (DAIT) website

Publications

None provided.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT03292588
• Other Study ID Numbers: DAIT ICAC-30; UM1AI114271; NIAID CRMS ID#: 38189
• First Posted: Sep 25, 2017
• Last Update Posted: Jul 20, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID): 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
• Additional relevant MeSH terms: Asthma

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Mepolizumab	Placebo
Arm/Group Description	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.	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.
Period Title: Overall Study
STARTED	146	144
COMPLETED	126	122
NOT COMPLETED	20	22

Baseline Characteristics

Arm/Group Title	Mepolizumab	Placebo	Total
Arm/Group Description	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.	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.	Total of all reporting groups
Overall Participants	146	144	290
Age (Count of Participants)
<=18 years	146 100%	144 100%	290 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	10.8 (2.87)	10.8 (2.88)	10.8 (2.87)
Sex: Female, Male (Count of Participants)
Female	71 48.6%	55 38.2%	126 43.4%
Male	75 51.4%	89 61.8%	164 56.6%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	35 24%	37 25.7%	72 24.8%
Not Hispanic or Latino	111 76%	107 74.3%	218 75.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	146 100%	144 100%	290 100%

Outcome Measures

1. Primary Outcome

Title	Number of Asthma Exacerbations During the Treatment Period
Description	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

Outcome Measure Data

Analysis Population Description

All participants who were randomized and received at least one dose of study treatment

Arm/Group Title	Mepolizumab	Placebo
Arm/Group Description	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.	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.
Measure Participants	146	144
Mean (Standard Error) [Exacerbations during treatment]	0.96 (0.10)	1.30 (0.13)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments	Negative binomial model for the rate of exacerbations in the first year. The model included an offset term to account for differential follow-up among participants. To account for adaptive randomization, the model was also adjusted for study site, number of exacerbations in year prior to study (2 or 3+), peripheral blood eosinophils (< or ≥400 cells/μl), BMI (< or ≥95th percentile for age), total serum IgE (< or ≥540 kUA/L) and treatment dose (40 mg or 100 mg).
Statistical Test of Hypothesis	p-Value	0.027
	Comments
	Method	Regression, Negative Binomial
	Comments	Adjusted relative rate of exacerbations in the first year.
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.73
	Confidence Interval	(2-Sided) 95%; 0.56 to 0.96
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Composite Asthma Severity Index (CASI)
Description	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

Outcome Measure Data

Analysis Population Description

All participants who were randomized and received at least one dose of study treatment

Arm/Group Title	Mepolizumab	Placebo
Arm/Group Description	Mepolizumab (anti-IL-5 antagonist monoclonal antibody) by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg	Placebo by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg
Measure Participants	146	144
Week 12	6.17 (0.2)	6.45 (0.20)
Week 24	5.94 (0.23)	6.01 (0.23)
Week 36	5.48 (0.22)	5.99 (0.23)
Week 48	5.16 (0.22)	5.23 (0.22)
Week 52	5.03 (0.23)	5.00 (0.23)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab, Placebo
	Comments	Week 12
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.290
	Comments
	Method	Mixed Models Analysis
	Comments	The difference in least square mean of CASI scores for week 12.
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-0.28
	Confidence Interval	(2-Sided) 95%; -0.81 to 0.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab, Placebo
	Comments	Week 24
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.820
	Comments
	Method	Mixed Models Analysis
	Comments	The difference in least square mean of CASI scores for week 24.
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-0.07
	Confidence Interval	(2-Sided) 95%; -0.69 to 0.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab, Placebo
	Comments	Week 36
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.096
	Comments
	Method	Mixed Models Analysis
	Comments	The difference in least square mean of CASI scores for week 36.
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-0.51
	Confidence Interval	(2-Sided) 95%; -1.11 to 0.09
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab, Placebo
	Comments	Week 48
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.831
	Comments
	Method	Mixed Models Analysis
	Comments	The difference in least square mean of CASI scores for week 48.
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-0.06
	Confidence Interval	(2-Sided) 95%; -0.65 to 0.52
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab, Placebo
	Comments	Week 52
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.947
	Comments
	Method	Mixed Models Analysis
	Comments	The difference in least square mean of CASI scores for week 52.
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	0.02
	Confidence Interval	(2-Sided) 95%; -0.60 to 0.64
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Participant Quality of Life Measured Using the Physician Global Assessment Tool
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Mepolizumab	Placebo
Arm/Group Description	Mepolizumab (anti-IL-5 antagonist monoclonal antibody) by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg	Placebo by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg
Measure Participants	129	122
Physician Global Assessment Tool - Significantly Improved	58 39.7%	54 37.5%
Physician Global Assessment Tool - Moderately Improved	27 18.5%	33 22.9%
Physician Global Assessment Tool - Mildly Improved	22 15.1%	17 11.8%
Physician Global Assessment Tool - No Change	20 13.7%	17 11.8%
Physician Global Assessment Tool - Mildly Worse	1 0.7%	1 0.7%
Physician Global Assessment Tool - Moderately Worse	0 0%	0 0%
Physician Global Assessment Tool - Significantly Worse	1 0.7%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab, Placebo
	Comments	Physician Global Assessment Tool
	Type of Statistical Test	Superiority
	Comments	A generalized logit model was used to analyze Physician Global Assessment Tool at Visit 14. The model included treatment arm as fixed effect as primary exposure but was also adjusted for study site, # of exacerbations in year prior to study (2 or 3+), peripheral blood eosinophils ((< or ≥400 cells/μl), BMI (< or ≥95th percentile for age) & total serum IgE (< or ≥540 kUA/L). No imputation of missing data was used for participants who weren't assessed for quality of life measurements at Visit 14.
Statistical Test of Hypothesis	p-Value	0.974
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.01
	Confidence Interval	(2-Sided) 95%; 0.62 to 1.64
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Participant Quality of Life Measured Using the Patient Global Assessment, at Visit 14
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Mepolizumab	Placebo
Arm/Group Description	Mepolizumab (anti-IL-5 antagonist monoclonal antibody) by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg	Placebo by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg
Measure Participants	129	124
Patient Global Assessment Tool - Significantly Improved	82 56.2%	87 60.4%
Patient Global Assessment Tool - Moderately Improved	27 18.5%	23 16%
Patient Global Assessment Tool - Mildly Improved	11 7.5%	12 8.3%
Patient Global Assessment Tool - No Change	7 4.8%	2 1.4%
Patient Global Assessment Tool - Mildly Worse	2 1.4%	0 0%
Patient Global Assessment Tool - Moderately Worse	0 0%	0 0%
Patient Global Assessment Tool - Significantly Worse	0 0%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab, Placebo
	Comments	Patient Global Assessment Tool
	Type of Statistical Test	Superiority
	Comments	A generalized logit model was used to analyze the Patient Global Assessment Tool at Visit 14. The model included treatment arm as fixed effect as the primary exposure but was adjusted for study site, # of exacerbations in year prior to study (2 or 3+), peripheral blood eosinophils ((< or ≥400 cells/μl), BMI (< or ≥95th percentile for age) & total serum IgE (< or ≥540 kUA/L). No imputation of missing data was used for participants who weren't assessed for quality of life measurements at Visit 14.
Statistical Test of Hypothesis	p-Value	0.238
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.72
	Confidence Interval	(2-Sided) 95%; 0.42 to 1.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Lung Function as Assessed by Spirometry
Description	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

Outcome Measure Data

Analysis Population Description

All participants who were randomized and received at least one dose of study treatment

Arm/Group Title	Mepolizumab	Placebo
Arm/Group Description	Mepolizumab (anti-IL-5 antagonist monoclonal antibody) by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg	Placebo by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg
Measure Participants	146	144
FEV1/FVC - Week 12	0.747 (0.007)	0.752 (0.007)
FEV1/FVC - Week 24	0.755 (0.007)	0.766 (0.007)
FEV1/FVC - Week 36	0.758 (0.008)	0.747 (0.008)
FEV1/FVC - Week 48	0.755 (0.008)	0.742 (0.008)
FEV1/FVC - Week 52	0.761 (0.008)	0.763 (0.008)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab, Placebo
	Comments	FEV1/FVC Week 12
	Type of Statistical Test	Superiority
	Comments	A generalized mixed model as described in section 8.3.1 was used to analyze each spirometry and impulse oscillometry parameter, separately, at each visit where the lung function was collected.
Statistical Test of Hypothesis	p-Value	0.591
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-0.005
	Confidence Interval	(2-Sided) 95%; -0.023 to 0.013
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab, Placebo
	Comments	FEV1/FVC Week 24
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.265
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-0.011
	Confidence Interval	(2-Sided) 95%; -0.031 to 0.008
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab, Placebo
	Comments	FEV1/FVC Week 36
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.345
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	0.011
	Confidence Interval	(2-Sided) 95%; -0.012 to 0.033
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab, Placebo
	Comments	FEV1/FVC Week 48
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.248
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	0.013
	Confidence Interval	(2-Sided) 95%; -0.009 to 0.036
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab, Placebo
	Comments	FEV1/FVC Week 52
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.864
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-0.002
	Confidence Interval	(2-Sided) 95%; -0.023 to 0.020
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Lung Function as Assessed by Impulse Oscillometry
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mepolizumab	Placebo
Arm/Group Description	Mepolizumab (anti-IL-5 antagonist monoclonal antibody) by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg	Placebo by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg
Measure Participants	146	144
FEV1PP - Week 12	91.9 (1.27)	92.3 (1.27)
FEV1PP - Week 24	90.8 (1.46)	94.2 (1.49)
FEV1PP - Week 36	91.5 (1.45)	89.9 (1.46)
FEV1PP - Week 48	90.4 (1.46)	89.8 (1.48)
FEV1PP - Week 52	90.9 (1.45)	93.5 (1.43)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab, Placebo
	Comments	FEV1PP Week 12
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.816
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-0.4
	Confidence Interval	(2-Sided) 95%; -3.8 to 3.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab, Placebo
	Comments	FEV1PP Week 24
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.095
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-3.4
	Confidence Interval	(2-Sided) 95%; -7.4 to 0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab, Placebo
	Comments	FEV1PP Week 36
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.444
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	1.5
	Confidence Interval	(2-Sided) 95%; -2.4 to 5.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab, Placebo
	Comments	FEV1PP Week 48
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.751
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	0.6
	Confidence Interval	(2-Sided) 95%; -3.3 to 4.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab, Placebo
	Comments	FEV1PP Week 52
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.184
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Least Square Mean Difference
	Estimated Value	-2.6
	Confidence Interval	(2-Sided) 95%; -6.5 to 1.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Rate of Exacerbations (Mepolizumab vs. Placebo) During the Treatment Period for Participants Who Did Not Fit the FDA-approved Dosing Table for Omalizumab Therapy.
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mepolizumab	Placebo
Arm/Group Description	Mepolizumab (anti-IL-5 antagonist monoclonal antibody) by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg	Placebo by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg
Measure Participants	57	51
Mean (Standard Error) [Exacerbations during treatment]	1.11 (0.21)	1.31 (0.25)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab, Placebo
	Comments	Did not meet FDA-approved dosing
	Type of Statistical Test	Superiority
	Comments	Negative binomial model for the rate of exacerbations (per year. The model included an offset term to account for differential follow-up among participants. To account for adaptive randomization, the model was also adjusted for study site, number of exacerbations in year prior to study (2 or 3+), peripheral blood eosinophils (< or ≥400 cells/μl), BMI (< or ≥95th percentile for age), total serum IgE (< or ≥540 kUA/L) and treatment dose (40 mg or 100 mg).
Statistical Test of Hypothesis	p-Value	0.458
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.55 to 1.31
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Rate of Exacerbations (Mepolizumab vs. Placebo) During the Treatment Period for Participants Who Fit the FDA-approved Dosing Table.
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Mepolizumab	Placebo
Arm/Group Description	Mepolizumab (anti-IL-5 antagonist monoclonal antibody) by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg	Placebo by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg
Measure Participants	89	93
Mean (Standard Error) [Exacerbations during treatment]	0.87 (0.13)	1.30 (0.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab, Placebo
	Comments	Fit FDA-approved dosing
	Type of Statistical Test	Superiority
	Comments	Negative binomial model for the rate of exacerbations (per year. The model included an offset term to account for differential follow-up among participants. To account for adaptive randomization, the model was also adjusted for study site, number of exacerbations in year prior to study (2 or 3+), peripheral blood eosinophils (< or ≥400 cells/μl), BMI (< or ≥95th percentile for age), total serum IgE (< or ≥540 kUA/L) and treatment dose (40 mg or 100 mg).
Statistical Test of Hypothesis	p-Value	0.025
	Comments
	Method	Regression, Negative Binomial
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.67
	Confidence Interval	(2-Sided) 95%; 0.47 to 0.95
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Time to First Asthma Exacerbation
Description	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

Outcome Measure Data

Analysis Population Description

All participants who were randomized and received at least one dose of study treatment

Arm/Group Title	Mepolizumab	Placebo
Arm/Group Description	Mepolizumab (anti-IL-5 antagonist monoclonal antibody) by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg	Placebo by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg
Measure Participants	146	144
Median (Full Range) [Days]	241	224

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Mepolizumab, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3587
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.86
	Confidence Interval	(2-Sided) 95%; 0.63 to 1.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Number of Reported Adverse Events (AEs), Including Their Severity
Description	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)

Outcome Measure Data

Analysis Population Description

Number of Subjects with at Least One AE by severity

Arm/Group Title	Mepolizumab	Placebo
Arm/Group Description	Mepolizumab (anti-IL-5 antagonist monoclonal antibody) by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg	Placebo by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg
Measure Participants	113	94
Severity: Grade 1 - Mild	47 32.2%	39 27.1%
Severity: Grade 2 - Moderate	58 39.7%	51 35.4%
Severity: Grade 3 - Severe and undesirable	8 5.5%	3 2.1%
Severity: Grade 4 - Life-threatening or disabling	0 0%	1 0.7%
Severity: Grade 5 - Death	0 0%	0 0%

11. Secondary Outcome

Title	Number of Reported Adverse Events (AEs), Including Their Treatment Relatedness
Description	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)

Outcome Measure Data

Analysis Population Description

Number of Subjects with any study procedures related AEs

Arm/Group Title	Mepolizumab	Placebo
Arm/Group Description	Mepolizumab (anti-IL-5 antagonist monoclonal antibody) by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg	Placebo by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg
Measure Participants	146	144
Count of Participants [Participants]	46 31.5%	26 18.1%

12. Secondary Outcome

Title	Number of Reported Serious Adverse Events (SAEs) Inclusive of Severity. Please Refer to the Adverse Event Tables for Specifics.
Description	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)

Outcome Measure Data

Analysis Population Description

Number of subjects with Serious Adverse Events

Arm/Group Title	Mepolizumab	Placebo
Arm/Group Description	Mepolizumab (anti-IL-5 antagonist monoclonal antibody) by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg	Placebo by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg
Measure Participants	4	2
Severity: Grade 2 - Moderate	0 0%	1 0.7%
Severity: Grade 3 - Severe and undesirable	3 2.1%	1 0.7%
Severity: Grade 4 - Life threatening	0 0%	0 0%
Severity: Grade 5 - Death	1 0.7%	0 0%

13. Other Pre-specified Outcome

Title	EXPLORATORY: Time to First Respiratory Virus-Induced Exacerbation
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

14. Other Pre-specified Outcome

Title	EXPLORATORY:Number of Respiratory Virus-Induced Exacerbations
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

15. Other Pre-specified Outcome

Title	EXPLORATORY:Childhood Asthma Control Test (ACT)/c-ACT
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

16. Other Pre-specified Outcome

Title	EXPLORATORY:Maximum Number of Asthma Symptom Days
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

17. Other Pre-specified Outcome

Title	EXPLORATORY:Bronchodilator Responsiveness
Description	A measure to determine whether mepolizumab improves pulmonary outcomes.
Time Frame	Baseline (prior to treatment initiation), Week 56 (Completion of Treatment)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

18. Other Pre-specified Outcome

Title	EXPLORATORY: Gene Expression in Nasal Lavage Samples
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

19. Other Pre-specified Outcome

Title	EXPLORATORY: Gene Expression in Whole Blood RNA Samples
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

20. Other Pre-specified Outcome

Title	EXPLORATORY:Levels of Antibody to Mepolizumab
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

21. Other Pre-specified Outcome

Title	EXPLORATORY:Other Potential Biomarkers Not Specified to Date
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

22. Secondary Outcome

Title	Number of Reported Serious Adverse Events (SAEs) Inclusive of Treatment Relatedness. Please Refer to the Adverse Event Tables for Specifics.
Description	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)

Outcome Measure Data

Analysis Population Description

Number of subjects with any study procedures related Serious Adverse Events

Arm/Group Title	Mepolizumab	Placebo
Arm/Group Description	Mepolizumab (anti-IL-5 antagonist monoclonal antibody) by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg	Placebo by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg
Measure Participants	146	144
Count of Participants [Participants]	0 0%	1 0.7%

Adverse Events

Time Frame	Adverse events were collected from the time of consent until 1 year and the participant completes study participation or until 30 days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study.
Adverse Event Reporting Description	The safety population was used for reporting adverse events, which was defined as: participants who were randomized and received at least one dose of study treatment. Participants were analyzed according to the medication they actually received, regardless of the treatment arm to which they were randomized. Non-treatment emergent adverse events were summarized in all participants who were enrolled, while treatment emergent adverse events were summarized in the safety sample
Arm/Group Title	Mepolizumab		Placebo
Arm/Group Description	Mepolizumab (anti-IL-5 antagonist monoclonal antibody) by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg		Placebo by subcutaneous injection every 4 weeks at the following doses: Age 12 years and above-100 mg, Age 6-11 years-40mg, Participants 6 to 11 years of age and weighing ≥40 kg who were enrolled in Protocol ICAC-30 under the previous versions of the protocol and initially assigned a 100 mg dose will have their dose reduced to 40 mg
All Cause Mortality
	Mepolizumab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/146 (0.7%)		0/144 (0%)
Serious Adverse Events
	Mepolizumab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/146 (2.7%)		2/144 (1.4%)
Cardiac disorders
Cardio-respiratory arrest	1/146 (0.7%)	1	0/144 (0%)	0
Tachycardia	0/146 (0%)	0	1/144 (0.7%)	1
Gastrointestinal disorders
Abdominal pain	1/146 (0.7%)	2	0/144 (0%)	0
General disorders
All-Cause Mortality	0/146 (0%)	0	0/144 (0%)	0
Chest pain	0/146 (0%)	0	1/144 (0.7%)	1
Psychiatric disorders
Major depression	1/146 (0.7%)	1	0/144 (0%)	0
Suicidal ideation	1/146 (0.7%)	1	1/144 (0.7%)	1
Other (Not Including Serious) Adverse Events
	Mepolizumab		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	53/146 (36.3%)		42/144 (29.2%)
Gastrointestinal disorders
Vomiting	13/146 (8.9%)	15	12/144 (8.3%)	13
General disorders
Injection site reaction	13/146 (8.9%)	14	0/144 (0%)	0
Infections and infestations
Influenza	11/146 (7.5%)	11	11/144 (7.6%)	11
Pharyngitis streptococcal	7/146 (4.8%)	7	9/144 (6.3%)	9
Nervous system disorders
Headache	15/146 (10.3%)	19	7/144 (4.9%)	9
Respiratory, thoracic and mediastinal disorders
Epistaxis	8/146 (5.5%)	8	8/144 (5.6%)	14

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.