Pharmacokinetics and Pharmacodynamics of Mepolizumab Administered Subcutaneously in Children

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02377427
• Collaborator: (none)
• Enrollment: 36
• Locations: 16
• Arms: 2
• Actual Duration (Months): 29.2
• Patients Per Site: 2.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

Mepolizumab is a humanized immunoglobulin G (IgG1) monoclonal antibody (mAb) that exhibits dose proportional and time-independent pharmacokinetics. The study will be conducted in 2 parts. Part A: it will be pharmacokinetic (PK) and pharmacodynamic (PD) study conducted to support the use of mepolizumab in children aged 6 to 11 years with severe eosinophilic asthma and characterize the PK/PD of mepolizumab 40 milligrams (mg) or 100 mg administered subcutaneously depending on participant body weight. Part B: It is a long-term safety / pharmacodynamic phase in which extended treatment for a further 52 weeks will be offered on an optional basis to those subjects eligible for continued treatment. Participants with bodyweight <40 kilogram (kg) will be dosed with mepolizumab 40 mg and participants with body weight >=40 kg will be dosed with mepolizumab 100 mg subcutaneously in upper arm or thigh at Visit 2 (Week 0). Approximately 40 male or female participants aged 6 to 11 years will be screened to achieve approximately 28 eligible participants entering the treatment phase to allow availability of 20 evaluable participants, with a minimum of six participants enrolled in the <40 kg bodyweight group. The total duration of the study will be 22 weeks and will include a run-in period of 1-2 weeks, a treatment period of 12 weeks and a follow-up phase of 8 weeks. A participant will be considered having completed the study if the participant completes all phases of the study including the follow-up phase (Week 20 [visit 8]).

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 36 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: An Open-label Study to Characterize the Pharmacokinetics and Pharmacodynamics of Mepolizumab Administered Subcutaneously in Children From 6 to 11 Years of Age With Severe Eosinophilic Asthma
• Actual Study Start Date: Aug 25, 2015
• Actual Primary Completion Date: Dec 7, 2016
• Actual Study Completion Date: Jan 31, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mepolizumab 40 mg in Part A and B Participants with bodyweight < 40 kg will receive 0.4 milliliter (mL) of reconstituted mepolizumab subcutaneously, in upper arm or thigh.	Drug: Mepolizumab; Mepolizumab is supplied as 100 mg lyophilised cake in sterile vials for subcutaneous administration in upper arm or thigh. The vial will be reconstituted with sterile water for injection prior to individual use.
Experimental: Mepolizumab 100 mg in Part A and B Participants with bodyweight >= 40 kg will receive 1.0 mL of reconstituted mepolizumab subcutaneously, in upper arm or thigh.	Drug: Mepolizumab; Mepolizumab is supplied as 100 mg lyophilised cake in sterile vials for subcutaneous administration in upper arm or thigh. The vial will be reconstituted with sterile water for injection prior to individual use.

Outcome Measures

Primary Outcome Measures

1. Maximum Plasma Concentration (Cmax) of Mepolizumab for Part A [Pre-dose on Weeks 4 and 8; Weeks 9, 12, 16 and 20 post-dose]

   PK of mepolizumab was evaluated in participants using Cmax. PK samples were collected at pre-dose on Weeks 4 and 8; and at Weeks 9, 12, 16 and 20 post-dose. Cmax was evaluated by population PK methods and mean and standard error from the final model has been tabulated. Estimates have been presented from the final model centered to mean bodyweights of 27 kg, 50 kg and 70 kg. Note the average bodyweight of 70 kg (mean body weight observed in adults) was not investigated in the study. PK Population included all participants receiving at least one dose of mepolizumab beginning at Visit 2 (Week 0) and having at least one blood sample taken at Visit 3 (Week 4) or thereafter with measurable mepolizumab plasma concentration.

2. Area Under Concentration Time Curve to Infinity (AUC [0-inf]) of Mepolizumab for Part A [Pre-dose on Weeks 4 and 8; Weeks 9, 12, 16 and 20 post-dose]

   PK of mepolizumab was evaluated in participants using AUC (0-inf). PK samples were collected at pre-dose on Weeks 4 and 8; and at Weeks 9, 12, 16 and 20 post-dose. AUC (0-inf) was evaluated by population PK methods and mean and standard error from the final model has been tabulated. Estimates have been presented from the final model centered to mean bodyweights of 27 kg, 50 kg and 70 kg. Note the average bodyweight of 70kg (mean body weight observed in adults) was not investigated in the study.

3. Terminal Phase Elimination Half-life (T1/2) of Mepolizumab During Treatment Period for Part A [Pre-dose on Weeks 4 and 8; Weeks 9, 12, 16 and 20 post-dose]

   PK of mepolizumab was evaluated in participants using t1/2. PK samples were collected at pre-dose on Weeks 4 and 8; and at Weeks 9, 12, 16 and 20 post-dose. T1/2 was evaluated by population PK methods and mean and standard error from the final model has been tabulated. Estimates have been presented from the final model centered to mean bodyweights of 27 kg, 50 kg and 70 kg. Note the average bodyweight of 70kg (mean body weight observed in adults) was not investigated in the study.

4. Plasma Apparent Clearance (CL/F) of Mepolizumab in Part A [Pre-dose on Weeks 4 and 8; Weeks 9, 12, 16 and 20 post-dose]

   PK of mepolizumab was evaluated in participants using CL/F. PK samples were collected at pre-dose on Weeks 4 and 8; and at Weeks 9, 12, 16 and 20 post-dose. CL was evaluated by population PK methods and mean and standard error from the final model has been tabulated. Estimates have been presented from the final model centered to mean bodyweights of 27 kg, 50 kg and 70 kg. Note the average bodyweight of 70kg (mean body weight observed in adults) was not investigated in the study.

5. Ratio to Baseline in Absolute Blood Eosinophil Count at Week 12 for Part A [Baseline and Week 12]

   PD of mepolizumab was evaluated in participants using ratio to Baseline in absolute blood eosinophil count. Blood samples were collected at indicated time points. Baseline was defined as the latest value recorded prior to the first dose of mepolizumab. Ratio to Baseline was calculated as post-dose visit value/Baseline value. It was evaluated by Pharmacodynamic Eosinophils (PDe) Population which included all participants receiving at least one dose of mepolizumab beginning at Visit 2 (Week 0) and having at least one Part A blood sample evaluable for blood eosinophil count.

6. Number of Participants With on Treatment Serious Adverse Events (SAEs) and Non-SAEs for Part B [From Week 20 and up to Week 72]

   An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinemia are to be categorized as SAE. On-treatment SAEs and non-SAEs are defined as events occurring from the first Part B dose until 28 days following the last Part B dose. Safety Population includes all participants who received at least one dose of mepolizumab beginning at Visit 9.

7. Number of Participants With Positive Anti-mepolizumab Binding Antibodies and Neutralizing Antibodies Response for Part B [From Week 20 and up to Week 80]

   Blood sample were collected for the determination of anti-mepolizumab binding antibodies and neutralizing antibodies response in Part B at Weeks 44, 68 and 80 prior to study treatment administration. Participant was considered 'Positive' if they had at least one positive post-Baseline anti-drug antibody assay result. All Part B visits (including scheduled and unscheduled) post-Baseline were considered for Any-time Post-Baseline visit derivation. The number of participants with positive anti-mepolizumab binding antibodies and neutralizing antibodies response at Any Time Post Baseline has been presented. The neutralizing antibodies response results only presented for participants with positive anti-drug antibody assay.

8. Change From Baseline in Sitting Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) for Part B [Baseline and Weeks 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 80]

   Sitting blood pressure measurements included SBP and DBP. Measurements were done pre-infusion/injection with the participant sitting, having rested in this position for at least 5 minutes before each reading. The Baseline was defined as the latest value recorded prior to the first dose of mepolizumab. Change from Baseline was defined as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

9. Change From Baseline in Sitting Pulse Rate for Part B [Baseline and Weeks 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 80]

   Sitting pulse rate measurements were performed pre-infusion/injection with the participant sitting, having rested in this position for at least 5 minutes before each reading. The Baseline was defined as the latest value recorded prior to the first dose of mepolizumab in Part A. Change from Baseline was defined as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

10. Number of Participants With Any Time Change From Baseline Relative to Normal Range in Clinical Chemistry Parameters for Part B [Baseline, from Week 20 and up to Week 72]

    Blood samples were collected for analysis of alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), albumin, protein, bilirubin, creatinine, urate, direct bilirubin, calcium, carbon dioxide (CO2), chloride, glucose, potassium, sodium and urea. Baseline was defined as the latest value recorded prior to the first dose of mepolizumab in Part A. Change from Baseline was defined as value at indicated time point minus Baseline value. All Part B visits (scheduled and unscheduled) post-Baseline were considered for Any-time Post-Baseline visit derivation. If participant had at least one value for categories "To Low" and/or "To High" along with "To Normal or No Change" then participant was counted under "To Low" and/or "To High". If participant had values which belong only to "To Normal or No Change" then participant was counted under "To Normal or No Change" only. Any Time Post-Baseline values have been presented.

11. Number of Participants With Any Time Change From Baseline Relative to Normal Range in Hematology Parameters for Part B [Baseline, from Week 20 and up to Week 80]

    Blood samples were collected for analysis of basophils, eosinophils, leukocyte, monocyte, neutrophils, lymphocyte, platelets, mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), hemoglobin (Hgb), mean corpuscular volume (MCV), erythrocytes, hematocrit, and reticulocytes/erythrocytes (Ret/Ery). Baseline was defined as the latest value recorded prior to first dose of mepolizumab in Part A. Change from Baseline was defined as value at indicated time point minus Baseline value. All Part B visits (scheduled and unscheduled) post-Baseline were considered for Any-time Post-Baseline visit derivation. If participant had at least one value for categories "To Low" and/or "To High" along with "To Normal or No Change" then participant was counted under "To Low" and/or "To High". If participant had values which belong only to "To Normal or No Change" then participant was counted under "To Normal or No Change" only. Any Time Post-Baseline values have been presented.

12. Number of Participants With Abnormal Findings for Urinalysis Parameters in Part B [From Week 20 and up to Week 72]

    Urine samples were collected from participants at indicated time points for analysis of urinalysis parameters including Specific gravity and potential of hydrogen (pH) of urine, presence of glucose, protein, blood and ketones in urine by dipstick test. Microscopic examination was performed if blood or protein was abnormal. Only those participants with data available at the specified time points were analyzed.

Secondary Outcome Measures

1. Body Weight-adjusted Apparent Clearance of Mepolizumab for Part A [Pre-dose on Weeks 4 and 8; Weeks 9, 12, 16 and 20 post-dose]

   PK samples were collected at pre-dose on Weeks 4 and 8; and at Weeks 9, 12, 16 and 20 post-dose. The body weight-adjusted apparent clearance was compared between adults and participants aged 6 to 11 years old with severe eosinophilic asthma when mepolizumab was administered subcutaneously. Point estimate and 90% confidence interval (CI) for participants aged 6 to 11 years (centered to a mean bodyweight of 70 kg) was compared with the historic adult estimated body-weight adjusted clearance of 0.22 L/day, around which a proposed 80-125% interval was applied i.e. 0.18-0.28 L/day. Assuming an absolute bioavailability of 75% this corresponds to an apparent clearance of 0.29 L/day with the proposed 80% to 125% interval of 0.23 to 0.36 L/day. Note the average bodyweight of 70kg (mean body weight observed in adults) was not observed in the study.

2. Change From Baseline in Asthma Control Questionnaire-7 (ACQ-7) at Week 12 in Part A [Baseline and Week 12]

   ACQ-7 is a simple questionnaire to measure the adequacy of asthma control and change in asthma control which occurs either spontaneously or a result of treatment. The ACQ-7 uses a 7-point scale (0=no impairment, 6= maximum impairment for symptoms and rescue use; and 7 = category for forced expiratory volume in 1 second [FEV1]%). The instrument has a reported high test-retest reproducibility with an intraclass correlation coefficient =0.90. The minimally important change in score is 0.5. Baseline was defined as the latest value recorded prior to the first dose of mepolizumab. Change from Baseline was calculated as score obtained at Week 12 minus Baseline Score. Pharmacodynamic Outcome (PDo) Population included all participants who received at least one dose of mepolizumab beginning at Visit 2 and having at least one Part A assessment of pharmacodynamic outcomes.

3. Change From Baseline in Asthma Control Questionnaire-7 (ACQ-7) at Weeks 4,8,16 and 20 in Part A [Baseline and Weeks 4,8,16 and 20]

   ACQ-7 is a simple questionnaire to measure the adequacy of asthma control and change in asthma control which occurs either spontaneously or a result of treatment. The ACQ-7 uses a 7-point scale (0=no impairment, 6= maximum impairment for symptoms and rescue use; and 7=category for FEV1%). The instrument has a reported high test-retest reproducibility with an intraclass correlation coefficient =0.90. The minimally important change in score is 0.5. Baseline was defined as the latest value recorded prior to the first dose of mepolizumab. Change from Baseline was calculated as score obtained at the indicated time point minus Baseline Score. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

4. Change From Baseline in Childhood Asthma Control Test (C-ACT) at Week 12 for Part A [Baseline and Week 12]

   The C-ACT assesses asthma control in children 4-11 years of age. The C-ACT is a 7-question, 2-part questionnaire, with items 1 to 4 were completed by the child (with assistance from a caregiver, as needed) and items 5 to 7 were completed by the caregiver. A total sum score based upon responses to all items was calculated to provide an overall measure of asthma control. The derived C-ACT score ranges from 0 (maximum impairment) to 27 (no impairment), where higher scores represent a better outcome. Baseline was defined as the latest value recorded prior to the first dose of mepolizumab. Change from Baseline was calculated as score obtained at Week 12 minus Baseline Score.

5. Change From Baseline in C-ACT at Weeks 4,8,16 and 20 in Part A [Baseline and Weeks 4,8,16 and 20]

   The C-ACT assesses asthma control in children 4-11 years of age. The C-ACT is a 7-question, 2-part questionnaire, with items 1 to 4 were completed by the child (with assistance from a caregiver, as needed) and items 5 to 7 were completed by the caregiver. A total sum score based upon responses to all items was calculated to provide an overall measure of asthma control. The derived C-ACT score ranges from 0 (maximum impairment) to 27 (no impairment), where higher scores represent a better outcome. Baseline was defined as the latest value recorded prior to the first dose of mepolizumab. Change from Baseline was calculated as score obtained at the indicated time point minus Baseline Score. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

6. Number of Participants With on Treatment SAEs and Non-SAEs in Part A [Up to Week 20]

   An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinemia were categorized as SAE. Participants who received any of the study treatment and had any on-treatment non-SAE or SAE (defined as events occurring from the first dose until 28 days after the last dose of mepolizumab) were considered for analysis.

7. Number of Participants With Any Time Change From Baseline Relative to Normal Range in Hematology Parameters in Part A [Baseline and up to Week 20]

   Blood samples were collected for analysis of basophils, eosinophils, leukocyte, monocyte, neutrophils, lymphocyte, platelet count, MCH, MCHC, Hgb, MCV, erythrocytes, hematocrit, and Ret/Ery. The Baseline was the latest value recorded prior to the first dose of mepolizumab. Change from Baseline was defined as value at indicated time point minus Baseline value. Any time post Baseline = all visits (scheduled and unscheduled) post Baseline was considered for this visit derivation. If participant had at least one value for categories "To Low" and/or "To High" along with "To Normal or No Change" then participant was counted under "To Low" and/or "To High". If participant had values which belong only to "To Normal or No Change" then participant was counted under "To Normal or No Change" only. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). Any Time Post-Baseline values have been presented.

8. Number of Participants With Any Time Change From Baseline Relative to Normal Range in Clinical Chemistry Parameters in Part A [Baseline and up to Week 20]

   Blood samples were collected for analysis of ALT, ALP, AST, GGT, albumin, protein, total billirubin, creatinine, direct billirubin, urate, calcium, CO2, chloride, glucose, potassium, sodium and urea. Baseline was defined as the latest value recorded prior to the first dose of mepolizumab. Change from Baseline was defined as value at indicated time point minus Baseline value. Any time post Baseline = all visits (including scheduled and unscheduled) post Baseline was considered for this visit derivation. If participant had at least one value for categories "To Low" and/or "To High" along with "To Normal or No Change" then participant was counted under "To Low" and/or "To High". If participant had values which belong only to "To Normal or No Change" then participant was counted under "To Normal or No Change" only. Any Time Post-Baseline values have been presented.

9. Number of Participants With Abnormal Findings for Urinalysis in Part A [Up to Week 20]

   Urine samples were collected from participants at indicated time points for analysis of urinalysis parameters including specific gravity and pH of urine, presence of glucose, protein, blood and ketones in urine by dipstick test. Microscopic examination was performed if blood or protein was abnormal. Only those participants with data available at the specified time points were analyzed.

10. Number of Participants With Positive Anti-mepolizumab Binding Antibodies and Neutralizing Antibodies Response in Part A [Baseline and Weeks 16 and 20]

    Blood sample for immunogenicity was collected for anti-mepolizumab binding antibodies and neutralizing antibodies response in Part A at indicated time points prior to study treatment administration. Number of participants with positive anti-mepolizumab binding antibodies and neutralizing antibodies response was summarized. Participant was considered 'Positive' if they had at least one positive post-baseline assay result. Any Time Post Baseline has been presented, which included all visits (including scheduled and unscheduled) post-baseline was considered for this visit derivation. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

11. Change From Baseline in Sitting SBP and DBP in Part A [Baseline and Weeks 4, 8, 9, 12, 16 and 20]

    Sitting blood pressure measurements were performed in Part A at indicated time points. Measurements were done pre-infusion/injection with the participant sitting, having rested in this position for at least 5 minutes before each reading. The Baseline was defined as the latest value recorded prior to the first dose of mepolizumab. Change from Baseline was defined as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

12. Change From Baseline in Sitting Pulse Rate in Part A [Baseline and Weeks 4, 8, 9, 12, 16 and 20]

    Sitting pulse rate measurements was performed in Part A at indicated time points. Measurements were done pre-infusion/injection with the participant sitting, having rested in this position for at least 5 minutes before each reading. The Baseline was defined as the latest value recorded prior to the first dose of mepolizumab. Change from Baseline was defined as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

13. Ratio to Baseline in Absolute Blood Eosinophil Count at Weeks 32, 44, 56, 68, 72 and 80 for Part B [Baseline and Weeks 32, 44, 56, 68, 72 and 80]

    Blood samples were collected at the indicated time points for the analysis of eosinophil count. Baseline was defined as the latest value recorded prior to the first dose of mepolizumab in Part A. Ratio to Baseline was calculated as post-dose visit value/Baseline value. The analysis was based on Pharmacodynamic (Blood Eosinophils) (PDe) Population comprised of all participants receiving at least one dose of mepolizumab beginning at Visit 9 and having at least one Part B blood sample taken for blood eosinophil count. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 11 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Between 6 and 11 years of age inclusive, at the time of screening.

• Diagnosis of severe asthma, defined by the regional asthma guidelines (i.e., National Institute of Health (NIH), Global Initiative for Asthma (GINA), etc.), for at least 12 months prior to Visit 1. If the participant is naïve to the study site, the participant/guardian must self-report a physician diagnosis of asthma and the investigator must confirm by review of medical history with the participant/guardian.

• Eosinophilic airway inflammation that is related to asthma characterized as eosinophilic in nature as indicated by: elevated peripheral blood eosinophil count of

=300 cells per microliter (cells/μL) demonstrated in the past 12 months OR elevated peripheral blood eosinophil count of >=150/μL at visit 1.

• A well-documented requirement for regular treatment with inhaled corticosteroid (>200 μg/day fluticasone propionate drug powder inhaler [DPI] or equivalent daily) in the 12 months prior to Visit 1 with or without maintenance oral corticosteroids (OCS). The ICS dose should represent medium or high dose in children aged 6-11 years of age [GINA, 2015].

• Current treatment with an additional controller medication for at least 3 months or a documented failure in the past 12 months of an additional controller medication for at least 3 successive months. [e.g., long-acting beta-2-agonist (LABA), leukotriene receptor antagonist (LTRA), or theophylline.]

• Forced expiratory volume in one second (FEV1): Persistent airflow obstruction at either Visit 1 or Visit 2 (FEV1 performed prior to first dose of study medication) as indicated by: A pre-bronchodilator FEV1 <110% predicted (Quanjer, 2012) OR FEV1: Forced vital capacity (FVC) ratio <0.8.

• Previously confirmed history of two or more exacerbations requiring treatment with systemic corticosteroids (CS) (intramuscular [IM], intravenous, or oral), in the 12 months prior to visit 1, despite the use of high-dose inhaled corticosteroids (ICS). For participants receiving maintenance CS, the CS treatment for the exacerbations must have been a two-fold increase or greater in the dose.

• No changes in the dose or regimen of baseline ICS and/or additional controller medication during the run-in period.

• Male or female: Females of childbearing potential must commit to consistent and correct use of an acceptable method of contraception for the duration of the trial and for 4 months after the last dose of investigational product. A urine pregnancy test is required of girls of childbearing potential. This test will be performed at the initial screening visit (visit 1) and will be performed at each scheduled study visit prior to the administration of investigational product, and during the early withdrawal and follow-up visits.

• Parent(s)/guardian able to give written informed consent prior to participation in the study, which will include the ability to comply with the requirements and restrictions listed in the consent form. If applicable, the participant must be able and willing to give assent to take part in the study according to the local requirement.

• For Part B: The subject has completed all study assessments up-to and including Visit 8 and received all 3 doses of investigational product (IP) in Part A

• For Part B: The Principal Investigator (PI) has performed a benefit/risk assessment and this assessment supports continued therapy with mepolizumab.

• The subject's parents (or guardian) have given consent and the subject has given assent for continued treatment

Exclusion Criteria:

• Participants with any history of life threatening asthma (e.g. requiring intubation), immunosuppressive medications intake or immunodeficiency disorder.

• Participants with any medical condition or circumstance making the volunteer unsuitable for participation in the study.

• Significant abnormality of rate, interval, conduction or rhythm in the 12-lead electrocardiogram (ECG), determined by the investigator in conjunction with the age and gender of the child at Visit 1.

• Alanine aminotransferase (ALT), and bilirubin >2x upper limit of normal (ULN) (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) at Visit 1.

• Positive Hepatitis B Surface Antigen or positive Hepatitis C antibody at Visit 1.

• Parent/guardian has a history of psychiatric disease, intellectual deficiency, substance abuse, or other condition (e.g. inability to read, comprehend and write) which will limit the validity of consent to participate in this study.

• Unwillingness or inability of the participant or parent/guardian to follow the procedures outlined in the protocol.

• Participant who is mentally or legally incapacitated.

• Children who are wards of the state or government.

• A participant will not be eligible for this study if he/she is an immediate family member of the participating investigator, sub-investigator, study coordinator, or employee of the participating investigator.

• Omalizumab: Participants who have received omalizumab within 130 days of Visit 1.

• Other Biologics: Participants who have received any biological (other than omalizumab) to treat inflammatory disease within 5 half-lives of visit 1.

• History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation.

• Hypersensitivity: Participants with allergy/intolerance to a monoclonal antibody or biologic.

• The participant has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	San Diego	California	United States	92123
2	GSK Investigational Site	Oklahoma City	Oklahoma	United States	73112
3	GSK Investigational Site	Medford	Oregon	United States	97504
4	GSK Investigational Site	Madison	Wisconsin	United States	53792-9988
5	GSK Investigational Site	Fukuoka		Japan	811-1394
6	GSK Investigational Site	Hiroshima		Japan	720-8520
7	GSK Investigational Site	Hiroshima		Japan	721-8511
8	GSK Investigational Site	Wakayama		Japan	646-8558
9	GSK Investigational Site	Lodz		Poland	90-329
10	GSK Investigational Site	Tarnow		Poland	33-100
11	GSK Investigational Site	Glasgow		United Kingdom	G514TF
12	GSK Investigational Site	Liverpool		United Kingdom	L12 2AP
13	GSK Investigational Site	London		United Kingdom	SE5 9RS
14	GSK Investigational Site	London		United Kingdom	SW3 6NP
15	GSK Investigational Site	Oxford		United Kingdom	OX3 9DU
16	GSK Investigational Site	Sheffield		United Kingdom	S10 2TH

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

• Study Protocol - Jan 18, 2017
• Statistical Analysis Plan - Dec 9, 2016

More Information

Publications

• Gupta A, Ikeda M, Geng B, Azmi J, Price RG, Bradford ES, Yancey SW, Steinfeld J. Long-term safety and pharmacodynamics of mepolizumab in children with severe asthma with an eosinophilic phenotype. J Allergy Clin Immunol. 2019 Nov;144(5):1336-1342.e7. doi: 10.1016/j.jaci.2019.08.005. Epub 2019 Aug 16.
• Gupta A, Pouliquen I, Austin D, Price RG, Kempsford R, Steinfeld J, Bradford ES, Yancey SW. Subcutaneous mepolizumab in children aged 6 to 11 years with severe eosinophilic asthma. Pediatr Pulmonol. 2019 Dec;54(12):1957-1967. doi: 10.1002/ppul.24508. Epub 2019 Sep 9.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT02377427
• Other Study ID Numbers: 200363; 2014-002666-76
• First Posted: Mar 3, 2015
• Last Update Posted: Dec 3, 2019
• Last Verified: Nov 1, 2019

• 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
• Keywords provided by GlaxoSmithKline: pharmacokinetics; pediatric; Mepolizumab; subcutaneous; eosinophilic asthma; pharmacodynamics
• Additional relevant MeSH terms: Asthma

Study Results

Participant Flow

Recruitment Details	This was a multi-center, open-label study to assess the pharmacokinetics (PK) and pharmacodynamics (PD) of mepolizumab 40 or 100 milligrams (mg) subcutaneously administered to participants with severe eosinophilic asthma aged 6-11 years. This study consisted of two parts: Part A and Part B.
Pre-assignment Detail	Part A consisted of pre-screening/ screening/ run-in, treatment, and Follow-up. Part B was long-term treatment and Follow-up phase. A total of 44 participants were screened and 36 were enrolled in Part A. Of which, 30 participants continued on treatment in Part B. Study was conducted in 4 countries (Japan, Poland, United Kingdom and United States).

Arm/Group Title	Part A: Mepolizumab 40 mg SC	Part A: Mepolizumab 100 mg SC	Part B: Mepolizumab 40 mg SC	Part B: Mepolizumab 100 mg SC	Part B: Mepolizumab 40/100 mg SC
Arm/Group Description	Participants with bodyweight < 40 kilograms (kg) received 0.4 milliliter (mL) of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Participant's weight at Week 0 (Visit 2) was considered to select dosage in Part A. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product.	Participants with bodyweight >= 40 kg received 1.0 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. On investigator discretion, injected volume was split between two injection sites and was given as 2 injections of 0.5 mL each if required.	Participants with bodyweight < 40 kg received 0.4 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product.	Participants with bodyweight >= 40 kg received 1.0 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. On investigator discretion, injected volume was split between two injection sites and was given as 2 injections of 0.5 mL each if required.	Participants received either 0.4 mL or 1.0 mL of reconstituted mepolizumab depending upon the bodyweight, administered subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. Participants enrolled to <40 kg at Visit 9 (Week 20) were summarized in the 40/100 mg SC group if they had weight >=40 kg at any subsequent visit.
Period Title: Part A (Up to Week 20)
STARTED	26	10	0	0	0
COMPLETED	22	10	0	0	0
NOT COMPLETED	4	0	0	0	0
Period Title: Part A (Up to Week 20)
STARTED	0	0	16	10	4
COMPLETED	0	0	15	10	4
NOT COMPLETED	0	0	1	0	0

Baseline Characteristics

Arm/Group Title	Part A: Mepolizumab 40 mg SC	Part A: Mepolizumab 100 mg SC	Total
Arm/Group Description	Participants with bodyweight < 40 kilogram (kg) received 0.4 milliliter (mL) of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Participant's weight at Week 0 (Visit 2) was considered to select dosage in Part A. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product.	Participants with bodyweight >= 40 kg received 1.0 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. On investigator discretion, injected volume was split between two injection sites and was given as 2 injections of 0.5 mL each if required.	Total of all reporting groups
Overall Participants	26	10	36
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	8.0 (1.79)	10.0 (1.33)	8.6 (1.89)
Sex: Female, Male (Count of Participants)
Female	6 23.1%	5 50%	11 30.6%
Male	20 76.9%	5 50%	25 69.4%
Race/Ethnicity, Customized (Count of Participants)
Central/South Asian Heritage (Her.)	1 3.8%	0 0%	1 2.8%
Japanese Her.	6 23.1%	1 10%	7 19.4%
Black or African American (B or Af Am)	4 15.4%	3 30%	7 19.4%
White/Caucasian/European Her.	14 53.8%	6 60%	20 55.6%
B or Af Am and White-White/Caucasian/European Her.	1 3.8%	0 0%	1 2.8%

Outcome Measures

1. Primary Outcome

Title	Maximum Plasma Concentration (Cmax) of Mepolizumab for Part A
Description	PK of mepolizumab was evaluated in participants using Cmax. PK samples were collected at pre-dose on Weeks 4 and 8; and at Weeks 9, 12, 16 and 20 post-dose. Cmax was evaluated by population PK methods and mean and standard error from the final model has been tabulated. Estimates have been presented from the final model centered to mean bodyweights of 27 kg, 50 kg and 70 kg. Note the average bodyweight of 70 kg (mean body weight observed in adults) was not investigated in the study. PK Population included all participants receiving at least one dose of mepolizumab beginning at Visit 2 (Week 0) and having at least one blood sample taken at Visit 3 (Week 4) or thereafter with measurable mepolizumab plasma concentration.
Time Frame	Pre-dose on Weeks 4 and 8; Weeks 9, 12, 16 and 20 post-dose

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Part A: Mepolizumab SC
Arm/Group Description	Participants received mepolizumab 40 or 100 mg SC, depending on participant's bodyweight (40 mg for <40 kg and 100 mg for >=40 kg). Participants received 0.4 mL of reconstituted mepolizumab subcutaneously (for 40 mg dose) or 1.0 mL of reconstituted mepolizumab subcutaneously (for 100 mg dose) every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product.
Measure Participants	36
70 kg	12.8188 (0.7843)
50 kg	16.3412 (0.6364)
27 kg	10.1960 (0.3345)

2. Primary Outcome

Title	Area Under Concentration Time Curve to Infinity (AUC [0-inf]) of Mepolizumab for Part A
Description	PK of mepolizumab was evaluated in participants using AUC (0-inf). PK samples were collected at pre-dose on Weeks 4 and 8; and at Weeks 9, 12, 16 and 20 post-dose. AUC (0-inf) was evaluated by population PK methods and mean and standard error from the final model has been tabulated. Estimates have been presented from the final model centered to mean bodyweights of 27 kg, 50 kg and 70 kg. Note the average bodyweight of 70kg (mean body weight observed in adults) was not investigated in the study.
Time Frame	Pre-dose on Weeks 4 and 8; Weeks 9, 12, 16 and 20 post-dose

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Part A: Mepolizumab SC
Arm/Group Description	Participants received mepolizumab 40 or 100 mg SC, depending on participant's bodyweight (40 mg for <40 kg and 100 mg for >=40 kg). Participants received 0.4 mL of reconstituted mepolizumab subcutaneously (for 40 mg dose) or 1.0 mL of reconstituted mepolizumab subcutaneously (for 100 mg dose) every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product.
Measure Participants	36
70 kg	508.23 (41.8036)
50 kg	675.20 (35.8980)
27 kg	454.39 (15.8876)

3. Primary Outcome

Title	Terminal Phase Elimination Half-life (T1/2) of Mepolizumab During Treatment Period for Part A
Description	PK of mepolizumab was evaluated in participants using t1/2. PK samples were collected at pre-dose on Weeks 4 and 8; and at Weeks 9, 12, 16 and 20 post-dose. T1/2 was evaluated by population PK methods and mean and standard error from the final model has been tabulated. Estimates have been presented from the final model centered to mean bodyweights of 27 kg, 50 kg and 70 kg. Note the average bodyweight of 70kg (mean body weight observed in adults) was not investigated in the study.
Time Frame	Pre-dose on Weeks 4 and 8; Weeks 9, 12, 16 and 20 post-dose

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Part A: Mepolizumab SC
Arm/Group Description	Participants received mepolizumab 40 or 100 mg SC, depending on participant's bodyweight (40 mg for <40 kg and 100 mg for >=40 kg). Participants received 0.4 mL of reconstituted mepolizumab subcutaneously (for 40 mg dose) or 1.0 mL of reconstituted mepolizumab subcutaneously (for 100 mg dose) every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product.
Measure Participants	36
70 kg	20.9583 (1.6520)
50 kg	21.8420 (1.0999)
27 kg	23.5582 (0.8406)

4. Primary Outcome

Title	Plasma Apparent Clearance (CL/F) of Mepolizumab in Part A
Description	PK of mepolizumab was evaluated in participants using CL/F. PK samples were collected at pre-dose on Weeks 4 and 8; and at Weeks 9, 12, 16 and 20 post-dose. CL was evaluated by population PK methods and mean and standard error from the final model has been tabulated. Estimates have been presented from the final model centered to mean bodyweights of 27 kg, 50 kg and 70 kg. Note the average bodyweight of 70kg (mean body weight observed in adults) was not investigated in the study.
Time Frame	Pre-dose on Weeks 4 and 8; Weeks 9, 12, 16 and 20 post-dose

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Part A: Mepolizumab SC
Arm/Group Description	Participants received mepolizumab 40 or 100 mg SC, depending on participant's bodyweight (40 mg for <40 kg and 100 mg for >=40 kg). Participants received 0.4 mL of reconstituted mepolizumab subcutaneously (for 40 mg dose) or 1.0 mL of reconstituted mepolizumab subcutaneously (for 100 mg dose) every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product.
Measure Participants	36
70 kg	0.1968 (0.01618)
50 kg	0.1481 (0.007874)
27 kg	0.08803 (0.003078)

5. Primary Outcome

Title	Ratio to Baseline in Absolute Blood Eosinophil Count at Week 12 for Part A
Description	PD of mepolizumab was evaluated in participants using ratio to Baseline in absolute blood eosinophil count. Blood samples were collected at indicated time points. Baseline was defined as the latest value recorded prior to the first dose of mepolizumab. Ratio to Baseline was calculated as post-dose visit value/Baseline value. It was evaluated by Pharmacodynamic Eosinophils (PDe) Population which included all participants receiving at least one dose of mepolizumab beginning at Visit 2 (Week 0) and having at least one Part A blood sample evaluable for blood eosinophil count.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

PDe Population. Only those participants with data available at specific time point were analyzed.

Arm/Group Title	Part A: Mepolizumab 40 mg SC	Part A: Mepolizumab 100 mg SC
Arm/Group Description	Participants with bodyweight < 40 kilogram (kg) received 0.4 milliliter (mL) of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Participant's weight at Week 0 (Visit 2) was considered to select dosage in Part A. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product.	Participants with bodyweight >= 40 kg received 1.0 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. On investigator discretion, injected volume was split between two injection sites and was given as 2 injections of 0.5 mL each if required.
Measure Participants	22	10
Geometric Mean (95% Confidence Interval) [Ratio of eosinophils in blood]	0.115	0.166

6. Primary Outcome

Title	Number of Participants With on Treatment Serious Adverse Events (SAEs) and Non-SAEs for Part B
Description	An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinemia are to be categorized as SAE. On-treatment SAEs and non-SAEs are defined as events occurring from the first Part B dose until 28 days following the last Part B dose. Safety Population includes all participants who received at least one dose of mepolizumab beginning at Visit 9.
Time Frame	From Week 20 and up to Week 72

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part B: Mepolizumab 40 mg SC	Part B: Mepolizumab 100 mg SC	Part B: Mepolizumab 40/100 mg SC
Arm/Group Description	Participants with bodyweight < 40 kg received 0.4 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product.	Participants with bodyweight >= 40 kg received 1.0 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. On investigator discretion, injected volume was split between two injection sites and was given as 2 injections of 0.5 mL each if required.	Participants received either 0.4 mL or 1.0 mL of reconstituted mepolizumab depending upon the bodyweight, administered subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. Participants enrolled to <40 kg at Visit 9 (Week 20) were summarized in the 40/100 mg SC group if they had weight >=40 kg at any subsequent visit.
Measure Participants	16	10	4
Any SAE	4 15.4%	2 20%	1 2.8%
Any Non-SAE	15 57.7%	8 80%	4 11.1%

7. Primary Outcome

Title	Number of Participants With Positive Anti-mepolizumab Binding Antibodies and Neutralizing Antibodies Response for Part B
Description	Blood sample were collected for the determination of anti-mepolizumab binding antibodies and neutralizing antibodies response in Part B at Weeks 44, 68 and 80 prior to study treatment administration. Participant was considered 'Positive' if they had at least one positive post-Baseline anti-drug antibody assay result. All Part B visits (including scheduled and unscheduled) post-Baseline were considered for Any-time Post-Baseline visit derivation. The number of participants with positive anti-mepolizumab binding antibodies and neutralizing antibodies response at Any Time Post Baseline has been presented. The neutralizing antibodies response results only presented for participants with positive anti-drug antibody assay.
Time Frame	From Week 20 and up to Week 80

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part B: Mepolizumab 40 mg SC	Part B: Mepolizumab 100 mg SC	Part B: Mepolizumab 40/100 mg SC
Arm/Group Description	Participants with bodyweight < 40 kg received 0.4 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product.	Participants with bodyweight >= 40 kg received 1.0 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. On investigator discretion, injected volume was split between two injection sites and was given as 2 injections of 0.5 mL each if required.	Participants received either 0.4 mL or 1.0 mL of reconstituted mepolizumab depending upon the bodyweight, administered subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. Participants enrolled to <40 kg at Visit 9 (Week 20) were summarized in the 40/100 mg SC group if they had weight >=40 kg at any subsequent visit.
Measure Participants	16	10	4
Anti-drug antibody	0 0%	0 0%	0 0%
Neutralizing antibody	0 0%	0 0%	0 0%

8. Primary Outcome

Title	Change From Baseline in Sitting Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) for Part B
Description	Sitting blood pressure measurements included SBP and DBP. Measurements were done pre-infusion/injection with the participant sitting, having rested in this position for at least 5 minutes before each reading. The Baseline was defined as the latest value recorded prior to the first dose of mepolizumab. Change from Baseline was defined as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame	Baseline and Weeks 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 80

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part B: Mepolizumab 40 mg SC	Part B: Mepolizumab 100 mg SC	Part B: Mepolizumab 40/100 mg SC
Arm/Group Description	Participants with bodyweight < 40 kg received 0.4 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product.	Participants with bodyweight >= 40 kg received 1.0 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. On investigator discretion, injected volume was split between two injection sites and was given as 2 injections of 0.5 mL each if required.	Participants received either 0.4 mL or 1.0 mL of reconstituted mepolizumab depending upon the bodyweight, administered subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. Participants enrolled to <40 kg at Visit 9 (Week 20) were summarized in the 40/100 mg SC group if they had weight >=40 kg at any subsequent visit.
Measure Participants	16	10	4
Sitting DBP, Week 24, n=16,9, 4	1.4 (4.22)	-0.9 (6.68)	-0.8 (3.59)
Sitting DBP, Week 28, n=15,9, 3	5.7 (7.13)	1.6 (5.53)	-4.0 (7.00)
Sitting DBP, Week 32, n=15 ,9,3	2.3 (5.65)	3.0 (7.37)	1.0 (12.49)
Sitting DBP, Week 36, n=15,8,3	3.6 (4.73)	4.9 (11.14)	1.7 (8.62)
Sitting DBP, Week 40, n=15,9,3	2.3 (8.40)	4.2 (6.82)	-3.7 (4.73)
Sitting DBP, Week 44, n=15,9 ,3	1.4 (5.62)	6.2 (7.61)	3.7 (11.85)
Sitting DBP, Week 48, n=15,9,3	3.5 (7.50)	4.1 (6.15)	8.7 (3.21)
Sitting DBP, Week 52, n=15,9,3	3.5 (7.55)	1.4 (5.05)	-3.3 (9.61)
Sitting DBP, Week 56, n=15,9,3	2.2 (8.47)	3.6 (7.14)	-0.3 (8.02)
Sitting DBP, Week 60, n=15,9,3	0.8 (4.80)	6.3 (10.77)	-2.3 (8.08)
Sitting DBP, Week 64, n=15,9,3	1.7 (3.48)	3.9 (8.12)	0.7 (3.06)
Sitting DBP, Week 68, n=15,9,3	3.3 (7.08)	5.3 (7.60)	-2.0 (10.58)
Sitting DBP, Week 72, n=15,10,4	2.5 (6.15)	5.4 (10.42)	0.5 (10.21)
Sitting DBP, Week 80, n=12 ,9,2	1.3 (4.60)	7.4 (7.60)	0.5 (13.44)
Sitting SBP, Week 24, n=16, 9, 4	3.3 (7.44)	-2.4 (13.87)	-6.3 (6.95)
Sitting SBP, Week 28, n=15, 9, 3	9.3 (6.11)	-0.6 (13.47)	-1.0 (5.57)
Sitting SBP, Week 32, n=15, 9, 3	2.9 (5.59)	5.6 (12.04)	-2.7 (16.50)
Sitting SBP, Week 36, n=15, 8, 3	6.3 (9.13)	9.4 (11.84)	-1.3 (6.43)
Sitting SBP, Week 40, n=15, 9, 3	5.5 (7.85)	4.6 (9.74)	-9.3 (12.22)
Sitting SBP, Week 44, n=15, 9, 3	4.3 (8.50)	3.8 (8.32)	3.0 (9.54)
Sitting SBP, Week 48, n=15, 9, 3	5.5 (8.25)	4.2 (11.09)	3.3 (11.68)
Sitting SBP, Week 52, n=15, 9, 3	7.8 (7.19)	-1.2 (12.04)	-5.0 (17.32)
Sitting SBP, Week 56, n=15, 9, 3	4.9 (7.81)	2.1 (10.33)	-9.7 (15.04)
Sitting SBP, Week 60, n=15, 9, 3	5.7 (8.33)	2.3 (16.50)	-3.3 (17.62)
Sitting SBP, Week 64, n=15, 9, 3	5.5 (7.98)	5.2 (12.09)	-1.3 (15.89)
Sitting SBP, Week 68, n=15, 9, 3	8.6 (8.58)	5.6 (8.75)	4.3 (10.02)
Sitting SBP, Week 72, n=15, 10, 4	6.4 (5.79)	2.7 (10.93)	-3.3 (9.22)
Sitting SBP, Week 80, n= 12, 9, 2	3.3 (4.33)	3.6 (11.82)	11.5 (0.71)

9. Primary Outcome

Title	Change From Baseline in Sitting Pulse Rate for Part B
Description	Sitting pulse rate measurements were performed pre-infusion/injection with the participant sitting, having rested in this position for at least 5 minutes before each reading. The Baseline was defined as the latest value recorded prior to the first dose of mepolizumab in Part A. Change from Baseline was defined as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame	Baseline and Weeks 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 80

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part B: Mepolizumab 40 mg SC	Part B: Mepolizumab 100 mg SC	Part B: Mepolizumab 40/100 mg SC
Arm/Group Description	Participants with bodyweight < 40 kg received 0.4 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product.	Participants with bodyweight >= 40 kg received 1.0 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. On investigator discretion, injected volume was split between two injection sites and was given as 2 injections of 0.5 mL each if required.	Participants received either 0.4 mL or 1.0 mL of reconstituted mepolizumab depending upon the bodyweight, administered subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. Participants enrolled to <40 kg at Visit 9 (Week 20) were summarized in the 40/100 mg SC group if they had weight >=40 kg at any subsequent visit.
Measure Participants	16	10	4
Sitting pulse rate, Week 24, n= 16, 9, 4	-3.8 (5.80)	4.3 (7.50)	7.0 (16.51)
Sitting pulse rate, Week 28, n= 15, 9, 3	-7.0 (9.02)	2.7 (4.92)	1.7 (9.61)
Sitting pulse rate, Week 32, n= 15, 9, 3	-4.8 (9.75)	4.7 (10.30)	-7.7 (12.01)
Sitting pulse rate, Week 36, n= 15, 8, 3	-0.5 (11.30)	7.3 (12.28)	8.0 (7.00)
Sitting pulse rate, Week 40, n= 15, 9, 3	-4.5 (10.84)	1.7 (14.04)	-4.0 (4.00)
Sitting pulse rate, Week 44, n= 15, 9, 3	-0.7 (13.56)	3.4 (12.30)	4.0 (19.31)
Sitting pulse rate, Week 48, n= 15, 9, 3	-2.3 (11.29)	-0.6 (5.64)	-3.0 (8.19)
Sitting pulse rate, Week 52, n= 15, 9, 3	-1.3 (8.41)	-2.1 (9.03)	11.7 (4.16)
Sitting pulse rate, Week 56, n= 15, 9, 3	-3.8 (8.90)	-1.9 (10.99)	-0.3 (6.66)
Sitting pulse rate, Week 60, n= 15, 9, 3	-3.4 (11.18)	-1.0 (13.86)	6.3 (14.43)
Sitting pulse rate, Week 64, n= 15, 9, 3	-2.0 (11.16)	5.0 (11.26)	8.3 (16.86)
Sitting pulse rate, Week 68, n= 15, 9, 3	-0.9 (8.03)	-2.4 (9.18)	-4.3 (10.97)
Sitting pulse rate, Week 72, n= 15, 10, 4	-5.3 (8.66)	-0.3 (14.21)	-6.0 (6.83)
Sitting pulse rate, Week 80, n= 11, 9, 2	-2.5 (3.33)	2.1 (7.24)	13.0 (9.90)

10. Primary Outcome

Title	Number of Participants With Any Time Change From Baseline Relative to Normal Range in Clinical Chemistry Parameters for Part B
Description	Blood samples were collected for analysis of alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), albumin, protein, bilirubin, creatinine, urate, direct bilirubin, calcium, carbon dioxide (CO2), chloride, glucose, potassium, sodium and urea. Baseline was defined as the latest value recorded prior to the first dose of mepolizumab in Part A. Change from Baseline was defined as value at indicated time point minus Baseline value. All Part B visits (scheduled and unscheduled) post-Baseline were considered for Any-time Post-Baseline visit derivation. If participant had at least one value for categories "To Low" and/or "To High" along with "To Normal or No Change" then participant was counted under "To Low" and/or "To High". If participant had values which belong only to "To Normal or No Change" then participant was counted under "To Normal or No Change" only. Any Time Post-Baseline values have been presented.
Time Frame	Baseline, from Week 20 and up to Week 72

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part B: Mepolizumab 40 mg SC	Part B: Mepolizumab 100 mg SC	Part B: Mepolizumab 40/100 mg SC
Arm/Group Description	Participants with bodyweight < 40 kg received 0.4 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product.	Participants with bodyweight >= 40 kg received 1.0 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. On investigator discretion, injected volume was split between two injection sites and was given as 2 injections of 0.5 mL each if required.	Participants received either 0.4 mL or 1.0 mL of reconstituted mepolizumab depending upon the bodyweight, administered subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. Participants enrolled to <40 kg at Visit 9 (Week 20) were summarized in the 40/100 mg SC group if they had weight >=40 kg at any subsequent visit.
Measure Participants	16	10	4
ALT; To Low	0 0%	0 0%	0 0%
ALT; To Normal or No Change	16 61.5%	10 100%	4 11.1%
ALT; To High	0 0%	0 0%	0 0%
Albumin; To Low	0 0%	0 0%	0 0%
Albumin; To Normal or No Change	15 57.7%	10 100%	4 11.1%
Albumin; To High	1 3.8%	0 0%	0 0%
ALP; To Low	0 0%	0 0%	0 0%
ALP; To Normal or No Change	16 61.5%	10 100%	4 11.1%
ALP;To High	0 0%	0 0%	0 0%
AST; To Low	0 0%	0 0%	0 0%
AST; To Normal or No Change	16 61.5%	10 100%	4 11.1%
AST; To High	0 0%	0 0%	0 0%
Bilirubin; To Low	0 0%	0 0%	0 0%
Bilirubin; To Normal or No Change	16 61.5%	9 90%	4 11.1%
Bilirubin; To High	0 0%	1 10%	0 0%
Calcium; To Low	0 0%	0 0%	0 0%
Calcium; To Normal or No Change	16 61.5%	7 70%	3 8.3%
Calcium; To High	0 0%	3 30%	1 2.8%
CO2; To Low	6 23.1%	3 30%	3 8.3%
CO2; To Normal or No Change	10 38.5%	7 70%	1 2.8%
CO2; To High	0 0%	0 0%	0 0%
Chloride; To Low	0 0%	0 0%	0 0%
Chloride; To Normal or No Change	16 61.5%	9 90%	4 11.1%
Chloride; To High	0 0%	1 10%	0 0%
Creatinine; To Low	2 7.7%	2 20%	0 0%
Creatinine; To Normal or No Change	13 50%	7 70%	4 11.1%
Creatinine; To High	1 3.8%	1 10%	0 0%
Direct Bilirubin; To Low	0 0%	0 0%	0 0%
Direct Bilirubin; To Normal or No Change	16 61.5%	10 100%	4 11.1%
Direct Bilirubin; To High	0 0%	0 0%	0 0%
GGT; To Low	0 0%	0 0%	0 0%
GGT; To Normal or No Change	16 61.5%	10 100%	4 11.1%
GGT; To High	0 0%	0 0%	0 0%
Glucose; To Low	1 3.8%	2 20%	0 0%
Glucose; To Normal or No Change	10 38.5%	4 40%	1 2.8%
Glucose; To High	5 19.2%	4 40%	3 8.3%
Potassium; To Low	0 0%	1 10%	0 0%
Potassium; To Normal or No Change	16 61.5%	9 90%	4 11.1%
Potassium; To High	0 0%	0 0%	0 0%
Protein; To Low	0 0%	0 0%	0 0%
Protein; To Normal or No Change	15 57.7%	10 100%	4 11.1%
Protein; To High	1 3.8%	0 0%	0 0%
Sodium; To Low	0 0%	0 0%	0 0%
Sodium; To Normal or No Change	16 61.5%	10 100%	4 11.1%
Sodium; To High	0 0%	0 0%	0 0%
Urate; To Low	0 0%	0 0%	0 0%
Urate; To Normal or No Change	16 61.5%	10 100%	4 11.1%
Urate; To High	0 0%	0 0%	0 0%
Urea; To Low	2 7.7%	1 10%	1 2.8%
Urea; To Normal or No Change	14 53.8%	9 90%	3 8.3%
Urea; To High	0 0%	0 0%	0 0%

11. Primary Outcome

Title	Number of Participants With Any Time Change From Baseline Relative to Normal Range in Hematology Parameters for Part B
Description	Blood samples were collected for analysis of basophils, eosinophils, leukocyte, monocyte, neutrophils, lymphocyte, platelets, mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), hemoglobin (Hgb), mean corpuscular volume (MCV), erythrocytes, hematocrit, and reticulocytes/erythrocytes (Ret/Ery). Baseline was defined as the latest value recorded prior to first dose of mepolizumab in Part A. Change from Baseline was defined as value at indicated time point minus Baseline value. All Part B visits (scheduled and unscheduled) post-Baseline were considered for Any-time Post-Baseline visit derivation. If participant had at least one value for categories "To Low" and/or "To High" along with "To Normal or No Change" then participant was counted under "To Low" and/or "To High". If participant had values which belong only to "To Normal or No Change" then participant was counted under "To Normal or No Change" only. Any Time Post-Baseline values have been presented.
Time Frame	Baseline, from Week 20 and up to Week 80

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part B: Mepolizumab 40 mg SC	Part B: Mepolizumab 100 mg SC	Part B: Mepolizumab 40/100 mg SC
Arm/Group Description	Participants with bodyweight < 40 kg received 0.4 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product.	Participants with bodyweight >= 40 kg received 1.0 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. On investigator discretion, injected volume was split between two injection sites and was given as 2 injections of 0.5 mL each if required.	Participants received either 0.4 mL or 1.0 mL of reconstituted mepolizumab depending upon the bodyweight, administered subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. Participants enrolled to <40 kg at Visit 9 (Week 20) were summarized in the 40/100 mg SC group if they had weight >=40 kg at any subsequent visit.
Measure Participants	16	10	4
Basophils; To Low	0 0%	0 0%	0 0%
Basophils; To Normal or No Change	16 61.5%	10 100%	4 11.1%
Basophils; To High	0 0%	0 0%	0 0%
Eosinophils;To Low	11 42.3%	6 60%	3 8.3%
Eosinophils; To Normal or No Change	5 19.2%	4 40%	0 0%
Eosinophils;To High	0 0%	0 0%	1 2.8%
MCH; To Low	0 0%	1 10%	0 0%
MCH; To Normal or No Change	16 61.5%	9 90%	4 11.1%
MCH; To High	0 0%	0 0%	0 0%
MCHC;To Low	0 0%	1 10%	0 0%
MCHC; To Normal or No Change	16 61.5%	9 90%	4 11.1%
MCHC; To High	0 0%	0 0%	0 0%
MCV; To Low	0 0%	1 10%	0 0%
MCV; To Normal or No Change	16 61.5%	9 90%	4 11.1%
MCV; To High	0 0%	0 0%	0 0%
Erythrocytes; To Low	0 0%	0 0%	0 0%
Erythrocytes; To Normal or No Change	15 57.7%	8 80%	3 8.3%
Erythrocytes; To High	1 3.8%	2 20%	1 2.8%
Hematocrit; To Low	0 0%	2 20%	0 0%
Hematocrit; To Normal or No Change	16 61.5%	7 70%	4 11.1%
Hematocrit; To High	0 0%	1 10%	0 0%
Hgb; To Low	0 0%	1 10%	0 0%
Hgb; To Normal or No Change	16 61.5%	8 80%	4 11.1%
Hgb; To High	0 0%	1 10%	0 0%
Leukocytes; To Low	5 19.2%	2 20%	1 2.8%
Leukocytes; To Normal or No Change	11 42.3%	7 70%	2 5.6%
Leukocytes; To High	0 0%	1 10%	1 2.8%
Lymphocytes; To Low	0 0%	0 0%	0 0%
Lymphocytes; To Normal or No Change	15 57.7%	9 90%	2 5.6%
Lymphocytes; To High	1 3.8%	1 10%	2 5.6%
Monocytes; To Low	6 23.1%	2 20%	1 2.8%
Monocytes; To Normal or No Change	10 38.5%	8 80%	3 8.3%
Monocytes; To High	0 0%	0 0%	0 0%
Neutrophils; To Low	3 11.5%	2 20%	2 5.6%
Neutrophils; To Normal or No Change	13 50%	5 50%	1 2.8%
Neutrophils; To High	0 0%	3 30%	1 2.8%
Platelets; To Low	0 0%	0 0%	0 0%
Platelets; To Normal or No Change	15 57.7%	10 100%	4 11.1%
Platelets; To High	1 3.8%	0 0%	0 0%
Ret/Ery; To Low	2 7.7%	3 30%	1 2.8%
Ret/Ery; To Normal or No Change	12 46.2%	7 70%	3 8.3%
Ret/Ery;To High	2 7.7%	0 0%	0 0%

12. Primary Outcome

Title	Number of Participants With Abnormal Findings for Urinalysis Parameters in Part B
Description	Urine samples were collected from participants at indicated time points for analysis of urinalysis parameters including Specific gravity and potential of hydrogen (pH) of urine, presence of glucose, protein, blood and ketones in urine by dipstick test. Microscopic examination was performed if blood or protein was abnormal. Only those participants with data available at the specified time points were analyzed.
Time Frame	From Week 20 and up to Week 72

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part B: Mepolizumab 40 mg SC	Part B: Mepolizumab 100 mg SC	Part B: Mepolizumab 40/100 mg SC
Arm/Group Description	Participants with bodyweight < 40 kg received 0.4 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product.	Participants with bodyweight >= 40 kg received 1.0 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. On investigator discretion, injected volume was split between two injection sites and was given as 2 injections of 0.5 mL each if required.	Participants received either 0.4 mL or 1.0 mL of reconstituted mepolizumab depending upon the bodyweight, administered subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. Participants enrolled to <40 kg at Visit 9 (Week 20) were summarized in the 40/100 mg SC group if they had weight >=40 kg at any subsequent visit.
Measure Participants	10	9	1
Number [Participants]	7 26.9%	6 60%	0 0%

13. Secondary Outcome

Title	Body Weight-adjusted Apparent Clearance of Mepolizumab for Part A
Description	PK samples were collected at pre-dose on Weeks 4 and 8; and at Weeks 9, 12, 16 and 20 post-dose. The body weight-adjusted apparent clearance was compared between adults and participants aged 6 to 11 years old with severe eosinophilic asthma when mepolizumab was administered subcutaneously. Point estimate and 90% confidence interval (CI) for participants aged 6 to 11 years (centered to a mean bodyweight of 70 kg) was compared with the historic adult estimated body-weight adjusted clearance of 0.22 L/day, around which a proposed 80-125% interval was applied i.e. 0.18-0.28 L/day. Assuming an absolute bioavailability of 75% this corresponds to an apparent clearance of 0.29 L/day with the proposed 80% to 125% interval of 0.23 to 0.36 L/day. Note the average bodyweight of 70kg (mean body weight observed in adults) was not observed in the study.
Time Frame	Pre-dose on Weeks 4 and 8; Weeks 9, 12, 16 and 20 post-dose

Outcome Measure Data

Analysis Population Description

PK Population

Arm/Group Title	Part A: Mepolizumab SC
Arm/Group Description	Participants received mepolizumab 40 or 100 mg SC, depending on participant's bodyweight (40 mg for <40 kg and 100 mg for >=40 kg). Participants received 0.4 mL of reconstituted mepolizumab subcutaneously (for 40 mg dose) or 1.0 mL of reconstituted mepolizumab subcutaneously (for 100 mg dose) every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product.
Measure Participants	36
Weight 70kg	0.1968
Weight 50kg	0.1481
Weight 27kg	0.0880

14. Secondary Outcome

Title	Change From Baseline in Asthma Control Questionnaire-7 (ACQ-7) at Week 12 in Part A
Description	ACQ-7 is a simple questionnaire to measure the adequacy of asthma control and change in asthma control which occurs either spontaneously or a result of treatment. The ACQ-7 uses a 7-point scale (0=no impairment, 6= maximum impairment for symptoms and rescue use; and 7 = category for forced expiratory volume in 1 second [FEV1]%). The instrument has a reported high test-retest reproducibility with an intraclass correlation coefficient =0.90. The minimally important change in score is 0.5. Baseline was defined as the latest value recorded prior to the first dose of mepolizumab. Change from Baseline was calculated as score obtained at Week 12 minus Baseline Score. Pharmacodynamic Outcome (PDo) Population included all participants who received at least one dose of mepolizumab beginning at Visit 2 and having at least one Part A assessment of pharmacodynamic outcomes.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

PDo Population. Only those participants with data available at specific time point were analyzed.

Arm/Group Title	Part A: Mepolizumab 40 mg SC	Part A: Mepolizumab 100 mg SC
Arm/Group Description	Participants with bodyweight < 40 kilogram (kg) received 0.4 milliliter (mL) of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Participant's weight at Week 0 (Visit 2) was considered to select dosage in Part A. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product.	Participants with bodyweight >= 40 kg received 1.0 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. On investigator discretion, injected volume was split between two injection sites and was given as 2 injections of 0.5 mL each if required.
Measure Participants	23	10
Mean (Standard Deviation) [Scores on a scale]	-0.414 (1.1354)	0.082 (1.3432)

15. Secondary Outcome

Title	Change From Baseline in Asthma Control Questionnaire-7 (ACQ-7) at Weeks 4,8,16 and 20 in Part A
Description	ACQ-7 is a simple questionnaire to measure the adequacy of asthma control and change in asthma control which occurs either spontaneously or a result of treatment. The ACQ-7 uses a 7-point scale (0=no impairment, 6= maximum impairment for symptoms and rescue use; and 7=category for FEV1%). The instrument has a reported high test-retest reproducibility with an intraclass correlation coefficient =0.90. The minimally important change in score is 0.5. Baseline was defined as the latest value recorded prior to the first dose of mepolizumab. Change from Baseline was calculated as score obtained at the indicated time point minus Baseline Score. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame	Baseline and Weeks 4,8,16 and 20

Outcome Measure Data

Analysis Population Description

PDo Population

Arm/Group Title	Part A: Mepolizumab 40 mg SC	Part A: Mepolizumab 100 mg SC
Arm/Group Description	Participants with bodyweight < 40 kilogram (kg) received 0.4 milliliter (mL) of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Participant's weight at Week 0 (Visit 2) was considered to select dosage in Part A. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product.	Participants with bodyweight >= 40 kg received 1.0 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. On investigator discretion, injected volume was split between two injection sites and was given as 2 injections of 0.5 mL each if required.
Measure Participants	26	10
Week 4, n=26, 10	-0.548 (1.1351)	-0.473 (0.9607)
Week 8, n=26, 10	-0.652 (1.2270)	-0.302 (1.2445)
Week 16, n=23, 10	-0.154 (1.2336)	-0.087 (1.2541)
Week 20, n=24, 10	-0.261 (1.2303)	-0.088 (1.0632)

16. Secondary Outcome

Title	Change From Baseline in Childhood Asthma Control Test (C-ACT) at Week 12 for Part A
Description	The C-ACT assesses asthma control in children 4-11 years of age. The C-ACT is a 7-question, 2-part questionnaire, with items 1 to 4 were completed by the child (with assistance from a caregiver, as needed) and items 5 to 7 were completed by the caregiver. A total sum score based upon responses to all items was calculated to provide an overall measure of asthma control. The derived C-ACT score ranges from 0 (maximum impairment) to 27 (no impairment), where higher scores represent a better outcome. Baseline was defined as the latest value recorded prior to the first dose of mepolizumab. Change from Baseline was calculated as score obtained at Week 12 minus Baseline Score.
Time Frame	Baseline and Week 12

Outcome Measure Data

Analysis Population Description

PDo Population. Only those participants with data available at specific time point were analyzed.

Arm/Group Title	Part A: Mepolizumab 40 mg SC	Part A: Mepolizumab 100 mg SC
Arm/Group Description	Participants with bodyweight < 40 kilogram (kg) received 0.4 milliliter (mL) of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Participant's weight at Week 0 (Visit 2) was considered to select dosage in Part A. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product.	Participants with bodyweight >= 40 kg received 1.0 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. On investigator discretion, injected volume was split between two injection sites and was given as 2 injections of 0.5 mL each if required.
Measure Participants	22	10
Mean (Standard Deviation) [Scores on a scale]	2.1 (4.45)	-0.3 (5.19)

17. Secondary Outcome

Title	Change From Baseline in C-ACT at Weeks 4,8,16 and 20 in Part A
Description	The C-ACT assesses asthma control in children 4-11 years of age. The C-ACT is a 7-question, 2-part questionnaire, with items 1 to 4 were completed by the child (with assistance from a caregiver, as needed) and items 5 to 7 were completed by the caregiver. A total sum score based upon responses to all items was calculated to provide an overall measure of asthma control. The derived C-ACT score ranges from 0 (maximum impairment) to 27 (no impairment), where higher scores represent a better outcome. Baseline was defined as the latest value recorded prior to the first dose of mepolizumab. Change from Baseline was calculated as score obtained at the indicated time point minus Baseline Score. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame	Baseline and Weeks 4,8,16 and 20

Outcome Measure Data

Analysis Population Description

PDo Population

Arm/Group Title	Part A: Mepolizumab 40 mg SC	Part A: Mepolizumab 100 mg SC
Arm/Group Description	Participants with bodyweight < 40 kilogram (kg) received 0.4 milliliter (mL) of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Participant's weight at Week 0 (Visit 2) was considered to select dosage in Part A. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product.	Participants with bodyweight >= 40 kg received 1.0 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. On investigator discretion, injected volume was split between two injection sites and was given as 2 injections of 0.5 mL each if required.
Measure Participants	26	10
Week 4, n=26, 10	1.8 (4.19)	2.4 (4.55)
Week 8, n=26, 10	3.0 (5.77)	1.5 (4.28)
Week 16, n=23, 10	1.5 (4.62)	-0.7 (5.19)
Week 20, n=24, 10	1.0 (4.23)	0.9 (4.28)

18. Secondary Outcome

Title	Number of Participants With on Treatment SAEs and Non-SAEs in Part A
Description	An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinemia were categorized as SAE. Participants who received any of the study treatment and had any on-treatment non-SAE or SAE (defined as events occurring from the first dose until 28 days after the last dose of mepolizumab) were considered for analysis.
Time Frame	Up to Week 20

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part A: Mepolizumab 40 mg SC	Part A: Mepolizumab 100 mg SC
Arm/Group Description	Participants with bodyweight < 40 kilogram (kg) received 0.4 milliliter (mL) of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Participant's weight at Week 0 (Visit 2) was considered to select dosage in Part A. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product.	Participants with bodyweight >= 40 kg received 1.0 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. On investigator discretion, injected volume was split between two injection sites and was given as 2 injections of 0.5 mL each if required.
Measure Participants	26	10
Any non-SAE	18 69.2%	6 60%
Any SAE	5 19.2%	1 10%

19. Secondary Outcome

Title	Number of Participants With Any Time Change From Baseline Relative to Normal Range in Hematology Parameters in Part A
Description	Blood samples were collected for analysis of basophils, eosinophils, leukocyte, monocyte, neutrophils, lymphocyte, platelet count, MCH, MCHC, Hgb, MCV, erythrocytes, hematocrit, and Ret/Ery. The Baseline was the latest value recorded prior to the first dose of mepolizumab. Change from Baseline was defined as value at indicated time point minus Baseline value. Any time post Baseline = all visits (scheduled and unscheduled) post Baseline was considered for this visit derivation. If participant had at least one value for categories "To Low" and/or "To High" along with "To Normal or No Change" then participant was counted under "To Low" and/or "To High". If participant had values which belong only to "To Normal or No Change" then participant was counted under "To Normal or No Change" only. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). Any Time Post-Baseline values have been presented.
Time Frame	Baseline and up to Week 20

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part A: Mepolizumab 40 mg SC	Part A: Mepolizumab 100 mg SC
Arm/Group Description	Participants with bodyweight < 40 kilogram (kg) received 0.4 milliliter (mL) of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Participant's weight at Week 0 (Visit 2) was considered to select dosage in Part A. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product.	Participants with bodyweight >= 40 kg received 1.0 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. On investigator discretion, injected volume was split between two injection sites and was given as 2 injections of 0.5 mL each if required.
Measure Participants	26	10
Basophils; To Low; n=26, 10	0 0%	0 0%
Basophils; To Normal or No Change; n=26, 10	25 96.2%	10 100%
Basophils; To High; n=26,10	1 3.8%	0 0%
Eosinophils; To Low; n=26, 10	15 57.7%	6 60%
Eosinophils; To Normal or No Change; n=26, 10	10 38.5%	4 40%
Eosinophils; To High; n=26, 10	1 3.8%	0 0%
Leukocyte; To Low; n=26, 10	8 30.8%	2 20%
Leukocyte; To Normal or No Change; n=26, 10	17 65.4%	8 80%
Leukocyte; To High; n=26, 10	1 3.8%	0 0%
Monocyte; To Low; n=26, 10	6 23.1%	3 30%
Monocyte; To Normal or No Change; n=26, 10	19 73.1%	7 70%
Monocyte; To High; n=26, 10	1 3.8%	0 0%
Neutrophils; To Low; n=26, 10	8 30.8%	3 30%
Neutrophils; To Normal or No Change; n=26, 10	16 61.5%	7 70%
Neutrophils; To High; n=26, 10	2 7.7%	0 0%
Lymphocyte; To Low; n=26, 10	4 15.4%	1 10%
Lymphocyte; To Normal or No Change; n=26, 10	20 76.9%	8 80%
Lymphocyte; To High; n=26, 10	2 7.7%	1 10%
Platelet count; To Low; n=25, 10	0 0%	1 10%
Platelet count; To Normal or No Change; n=25, 10	22 84.6%	9 90%
Platelet count; To High; n=25, 10	3 11.5%	0 0%
MCH; To Low; n=26, 10	2 7.7%	0 0%
MCH;To Normal or No Change; n=26, 10	24 92.3%	10 100%
MCH; To High; n=26, 10	0 0%	0 0%
MCHC; To Low n=26, 10	1 3.8%	1 10%
MCHC; To Normal or No Change; n=26, 10	25 96.2%	9 90%
MCHC; To High; n=26, 10	0 0%	0 0%
Hgb; To Low; n=26, 10	0 0%	1 10%
Hgb; To Normal or No Change; n=26, 10	26 100%	9 90%
Hgb; To High; n=26, 10	0 0%	0 0%
MCV; To Low; n=26, 10	2 7.7%	0 0%
MCV; To Normal or No Change; n=26, 10	24 92.3%	10 100%
MCV; To High; n=26, 10	0 0%	0 0%
Erythrocytes; To Low; n=26, 10	0 0%	0 0%
Erythrocytes; To Normal or No Change; n=26, 10	21 80.8%	8 80%
Erythrocytes; To High; n=26, 10	5 19.2%	2 20%
Hematocrit; To Low; n=26, 10	0 0%	2 20%
Hematocrit; To Normal or No Change; n=26, 10	26 100%	8 80%
Hematocrit; To High; n=26, 10	0 0%	0 0%
Reti/Ery; To Low; n=26,10	8 30.8%	1 10%
Reti/Ery;To Normal/No Change;n=26,10	15 57.7%	9 90%
Ret/Ery;To High; n=26,10	3 11.5%	0 0%

20. Secondary Outcome

Title	Number of Participants With Any Time Change From Baseline Relative to Normal Range in Clinical Chemistry Parameters in Part A
Description	Blood samples were collected for analysis of ALT, ALP, AST, GGT, albumin, protein, total billirubin, creatinine, direct billirubin, urate, calcium, CO2, chloride, glucose, potassium, sodium and urea. Baseline was defined as the latest value recorded prior to the first dose of mepolizumab. Change from Baseline was defined as value at indicated time point minus Baseline value. Any time post Baseline = all visits (including scheduled and unscheduled) post Baseline was considered for this visit derivation. If participant had at least one value for categories "To Low" and/or "To High" along with "To Normal or No Change" then participant was counted under "To Low" and/or "To High". If participant had values which belong only to "To Normal or No Change" then participant was counted under "To Normal or No Change" only. Any Time Post-Baseline values have been presented.
Time Frame	Baseline and up to Week 20

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part A: Mepolizumab 40 mg SC	Part A: Mepolizumab 100 mg SC
Arm/Group Description	Participants with bodyweight < 40 kilogram (kg) received 0.4 milliliter (mL) of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Participant's weight at Week 0 (Visit 2) was considered to select dosage in Part A. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product.	Participants with bodyweight >= 40 kg received 1.0 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. On investigator discretion, injected volume was split between two injection sites and was given as 2 injections of 0.5 mL each if required.
Measure Participants	26	10
ALT; To Low	0 0%	0 0%
ALT; To Normal or No chang	26 100%	10 100%
ALT; To High	0 0%	0 0%
AST;To Low	0 0%	0 0%
AST;To Normal or No Change	26 100%	10 100%
AST;To High	0 0%	0 0%
ALP;To Low	0 0%	0 0%
ALP;To Normal or No Change	26 100%	10 100%
ALP;To High	0 0%	0 0%
GGT;To Low	0 0%	0 0%
GGT;To Normal or No Change	26 100%	10 100%
GGT;To High	0 0%	0 0%
Albumin;To Low	0 0%	0 0%
Albumin;To Normal or No Change	22 84.6%	10 100%
Albumin;To High	4 15.4%	0 0%
Protein;To Low	0 0%	0 0%
Protein;To Normal or No Change	23 88.5%	10 100%
Protein;To High	3 11.5%	0 0%
Total billirubin;To Low	0 0%	0 0%
Total billirubin;To Normal or No Change	26 100%	10 100%
Total billirubin;To High	0 0%	0 0%
Creatinine;To Low	4 15.4%	1 10%
Creatinine;To Normal or No Change	22 84.6%	9 90%
Creatinine;To High	0 0%	0 0%
Direct billirubin;To Low	0 0%	0 0%
Direct billirubin;To Normal or No Change	26 100%	10 100%
Direct billirubin;To High	0 0%	0 0%
Urate;To Low	1 3.8%	0 0%
Urate;To Normal or No Change	25 96.2%	10 100%
Urate;To High	0 0%	0 0%
Calcium;To Low	0 0%	0 0%
Calcium;To Normal or No Change	22 84.6%	8 80%
Calcium; To High	4 15.4%	2 20%
CO2;To Low	12 46.2%	3 30%
CO2;To Normal or No Change	14 53.8%	7 70%
CO2;To High	0 0%	0 0%
Chloride;To Low	0 0%	0 0%
Chloride;To Normal or No Change	23 88.5%	9 90%
Chloride;To High	3 11.5%	1 10%
Glucose;To Low	2 7.7%	0 0%
Glucose;To Normal or No Change	17 65.4%	8 80%
Glucose;To High	7 26.9%	2 20%
Potassium;To Low	0 0%	0 0%
Potassium; To Normal or No Change	26 100%	10 100%
Potassium;To High	0 0%	0 0%
Sodium,To Low	0 0%	0 0%
Sodium;To Normal or No Change	26 100%	10 100%
Sodium;To High	0 0%	0 0%
Urea;To Low	1 3.8%	3 30%
Urea;To Normal or No Change	25 96.2%	7 70%
Urea;To High	0 0%	0 0%

21. Secondary Outcome

Title	Number of Participants With Abnormal Findings for Urinalysis in Part A
Description	Urine samples were collected from participants at indicated time points for analysis of urinalysis parameters including specific gravity and pH of urine, presence of glucose, protein, blood and ketones in urine by dipstick test. Microscopic examination was performed if blood or protein was abnormal. Only those participants with data available at the specified time points were analyzed.
Time Frame	Up to Week 20

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part A: Mepolizumab 40 mg SC	Part A: Mepolizumab 100 mg SC
Arm/Group Description	Participants with bodyweight < 40 kilogram (kg) received 0.4 milliliter (mL) of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Participant's weight at Week 0 (Visit 2) was considered to select dosage in Part A. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product.	Participants with bodyweight >= 40 kg received 1.0 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. On investigator discretion, injected volume was split between two injection sites and was given as 2 injections of 0.5 mL each if required.
Measure Participants	15	7
Number [Participants]	5 19.2%	4 40%

22. Secondary Outcome

Title	Number of Participants With Positive Anti-mepolizumab Binding Antibodies and Neutralizing Antibodies Response in Part A
Description	Blood sample for immunogenicity was collected for anti-mepolizumab binding antibodies and neutralizing antibodies response in Part A at indicated time points prior to study treatment administration. Number of participants with positive anti-mepolizumab binding antibodies and neutralizing antibodies response was summarized. Participant was considered 'Positive' if they had at least one positive post-baseline assay result. Any Time Post Baseline has been presented, which included all visits (including scheduled and unscheduled) post-baseline was considered for this visit derivation. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame	Baseline and Weeks 16 and 20

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part A: Mepolizumab 40 mg SC	Part A: Mepolizumab 100 mg SC
Arm/Group Description	Participants with bodyweight < 40 kilogram (kg) received 0.4 milliliter (mL) of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Participant's weight at Week 0 (Visit 2) was considered to select dosage in Part A. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product.	Participants with bodyweight >= 40 kg received 1.0 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. On investigator discretion, injected volume was split between two injection sites and was given as 2 injections of 0.5 mL each if required.
Measure Participants	26	10
Anti-drug antibody,Any time post-baseline,n=25, 10	1 3.8%	1 10%
Neutralizing antibody,Any time post-baseline,n=1,1	0 0%	0 0%

23. Secondary Outcome

Title	Change From Baseline in Sitting SBP and DBP in Part A
Description	Sitting blood pressure measurements were performed in Part A at indicated time points. Measurements were done pre-infusion/injection with the participant sitting, having rested in this position for at least 5 minutes before each reading. The Baseline was defined as the latest value recorded prior to the first dose of mepolizumab. Change from Baseline was defined as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame	Baseline and Weeks 4, 8, 9, 12, 16 and 20

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part A: Mepolizumab 40 mg SC	Part A: Mepolizumab 100 mg SC
Arm/Group Description	Participants with bodyweight < 40 kilogram (kg) received 0.4 milliliter (mL) of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Participant's weight at Week 0 (Visit 2) was considered to select dosage in Part A. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product.	Participants with bodyweight >= 40 kg received 1.0 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. On investigator discretion, injected volume was split between two injection sites and was given as 2 injections of 0.5 mL each if required.
Measure Participants	26	10
Sitting DBP, Week 4, n=26, 10	0.4 (5.72)	2.1 (3.87)
Sitting DBP, Week 8, , n=26, 10	-0.4 (5.45)	3.4 (7.59)
Sitting DBP, Week 9, , n=22, 10	1.8 (9.82)	4.9 (9.13)
Sitting DBP, Week 12, , n=23, 10	1.5 (8.88)	0.3 (9.98)
Sitting DBP, Week 16, , n=23, 10	0.6 (6.99)	3.9 (7.06)
Sitting DBP, Week 20, , n=24, 10	0.7 (6.94)	5.1 (7.03)
Sitting SBP, Week 4, n=26, 10	3.6 (9.92)	-1.9 (8.81)
Sitting SBP, Week 8, , n=26, 10	1.8 (8.65)	-0.2 (6.23)
Sitting SBP, Week 9, , n=22, 10	2.8 (10.39)	-0.2 (12.04)
Sitting SBP, Week 12, , n=23, 10	4.3 (9.89)	-2.9 (11.10)
Sitting SBP, Week 16, , n=23, 10	4.3 (11.53)	-4.6 (9.94)
Sitting SBP, Week 20, , n=24, 10	5.0 (9.21)	1.4 (9.91)

24. Secondary Outcome

Title	Change From Baseline in Sitting Pulse Rate in Part A
Description	Sitting pulse rate measurements was performed in Part A at indicated time points. Measurements were done pre-infusion/injection with the participant sitting, having rested in this position for at least 5 minutes before each reading. The Baseline was defined as the latest value recorded prior to the first dose of mepolizumab. Change from Baseline was defined as value at indicated time point minus Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame	Baseline and Weeks 4, 8, 9, 12, 16 and 20

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	Part A: Mepolizumab 40 mg SC	Part A: Mepolizumab 100 mg SC
Arm/Group Description	Participants with bodyweight < 40 kilogram (kg) received 0.4 milliliter (mL) of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Participant's weight at Week 0 (Visit 2) was considered to select dosage in Part A. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product.	Participants with bodyweight >= 40 kg received 1.0 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. On investigator discretion, injected volume was split between two injection sites and was given as 2 injections of 0.5 mL each if required.
Measure Participants	26	10
Sitting pulse rate, Week 4, n=26, 10	-4.0 (10.91)	-1.1 (10.56)
Sitting pulse rate, Week 8, n=26, 10	-3.2 (9.11)	1.8 (7.42)
Sitting pulse rate, Week 9, n=22, 10	-2.9 (8.31)	2.3 (9.33)
Sitting pulse rate, Week 12, n=23, 10	-0.8 (8.31)	-0.5 (10.73)
Sitting pulse rate, Week 16, n=23, 10	-0.6 (7.65)	3.5 (10.20)
Sitting pulse rate, Week 20, n=24, 10	-3.9 (13.13)	1.8 (8.22)

25. Secondary Outcome

Title	Ratio to Baseline in Absolute Blood Eosinophil Count at Weeks 32, 44, 56, 68, 72 and 80 for Part B
Description	Blood samples were collected at the indicated time points for the analysis of eosinophil count. Baseline was defined as the latest value recorded prior to the first dose of mepolizumab in Part A. Ratio to Baseline was calculated as post-dose visit value/Baseline value. The analysis was based on Pharmacodynamic (Blood Eosinophils) (PDe) Population comprised of all participants receiving at least one dose of mepolizumab beginning at Visit 9 and having at least one Part B blood sample taken for blood eosinophil count. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame	Baseline and Weeks 32, 44, 56, 68, 72 and 80

Outcome Measure Data

Analysis Population Description

PDe Population

Arm/Group Title	Part B: Mepolizumab 40 mg SC	Part B: Mepolizumab 100 mg SC	Part B: Mepolizumab 40/100 mg SC
Arm/Group Description	Participants with bodyweight < 40 kg received 0.4 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product.	Participants with bodyweight >= 40 kg received 1.0 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. On investigator discretion, injected volume was split between two injection sites and was given as 2 injections of 0.5 mL each if required.	Participants received either 0.4 mL or 1.0 mL of reconstituted mepolizumab depending upon the bodyweight, administered subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. Participants enrolled to <40 kg at Visit 9 (Week 20) were summarized in the 40/100 mg SC group if they had weight >=40 kg at any subsequent visit.
Measure Participants	16	10	4
Week 32; n= 15, 10, 4	0.161	0.176	0.072
Week 44; n= 15, 10, 4	0.157	0.189	0.147
Week 56; n= 15, 10, 4	0.149	0.172	0.058
Week 68; n= 14, 10, 4	0.133	0.214	0.108
Week 72; n = 15, 10, 4	0.148	0.134	0.098
Week 80; n =9, 7, 0	0.591	0.647

Adverse Events

Time Frame	On-treatment serious adverse events (SAEs) and non-SAEs were collected in Part A from first Part A dose until 28 days following last Part A dose (up to Week 20) and in Part B from first Part B dose until 28 days following last Part B dose (Up to Week 72).
Adverse Event Reporting Description	Serious adverse events (SAEs) and Non-SAEs were collected in members of Safety Population, comprised of all participants who received at least one dose of open label mepolizumab medication.
Arm/Group Title	Part A: Mepolizumab 40 mg SC		Part A: Mepolizumab 100 mg SC		Part B: Mepolizumab 40 mg SC		Part B: Mepolizumab 100 mg SC		Part B: Mepolizumab 40/100 mg SC
Arm/Group Description	Participants with bodyweight < 40 kilogram (kg) received 0.4 milliliter (mL) of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Participant's weight at Week 0 (Visit 2) was considered to select dosage in Part A. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product.		Participants with bodyweight >= 40 kg received 1.0 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. On investigator discretion, injected volume was split between two injection sites and was given as 2 injections of 0.5 mL each if required.		Participants with bodyweight < 40 kg received 0.4 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product.		Participants with bodyweight >= 40 kg received 1.0 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. On investigator discretion, injected volume was split between two injection sites and was given as 2 injections of 0.5 mL each if required.		Participants received either 0.4 mL or 1.0 mL of reconstituted mepolizumab depending upon the bodyweight, administered subcutaneously every four weeks, in upper arm or thigh directly from the investigator or designee, under medical supervision. Prior to administration, each vial of mepolizumab were reconstituted and swirled gently to enable complete dissolution of the product. Participants enrolled to <40 kg at Visit 9 (Week 20) were summarized in the 40/100 mg SC group if they had weight >=40 kg at any subsequent visit.
All Cause Mortality
	Part A: Mepolizumab 40 mg SC		Part A: Mepolizumab 100 mg SC		Part B: Mepolizumab 40 mg SC		Part B: Mepolizumab 100 mg SC		Part B: Mepolizumab 40/100 mg SC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		0/10 (0%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Serious Adverse Events
	Part A: Mepolizumab 40 mg SC		Part A: Mepolizumab 100 mg SC		Part B: Mepolizumab 40 mg SC		Part B: Mepolizumab 100 mg SC		Part B: Mepolizumab 40/100 mg SC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/26 (19.2%)		1/10 (10%)		4/16 (25%)		2/10 (20%)		1/4 (25%)
Gastrointestinal disorders
Nausea	1/26 (3.8%)		0/10 (0%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
General disorders
Chest pain	1/26 (3.8%)		0/10 (0%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Pain	1/26 (3.8%)		0/10 (0%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Immune system disorders
Anaphylactic shock	0/26 (0%)		0/10 (0%)		1/16 (6.3%)		0/10 (0%)		0/4 (0%)
Infections and infestations
Cellulitis	1/26 (3.8%)		0/10 (0%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Lower respiratory tract infection	1/26 (3.8%)		1/10 (10%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Pneumonia	0/26 (0%)		0/10 (0%)		0/16 (0%)		1/10 (10%)		0/4 (0%)
Musculoskeletal and connective tissue disorders
Back pain	1/26 (3.8%)		0/10 (0%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Nervous system disorders
Dizziness	1/26 (3.8%)		0/10 (0%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Headache	1/26 (3.8%)		0/10 (0%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	3/26 (11.5%)		0/10 (0%)		2/16 (12.5%)		2/10 (20%)		1/4 (25%)
Epistaxis	0/26 (0%)		0/10 (0%)		1/16 (6.3%)		0/10 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Part A: Mepolizumab 40 mg SC		Part A: Mepolizumab 100 mg SC		Part B: Mepolizumab 40 mg SC		Part B: Mepolizumab 100 mg SC		Part B: Mepolizumab 40/100 mg SC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/26 (69.2%)		6/10 (60%)		15/16 (93.8%)		8/10 (80%)		4/4 (100%)
Blood and lymphatic system disorders
Lymphadenopathy	0/26 (0%)		0/10 (0%)		0/16 (0%)		1/10 (10%)		0/4 (0%)
Endocrine disorders
Adrenal suppression	0/26 (0%)		0/10 (0%)		0/16 (0%)		0/10 (0%)		1/4 (25%)
Eye disorders
Eye pain	0/26 (0%)		0/10 (0%)		1/16 (6.3%)		0/10 (0%)		0/4 (0%)
Eye swelling	0/26 (0%)		0/10 (0%)		0/16 (0%)		1/10 (10%)		0/4 (0%)
Eyelid haematoma	0/26 (0%)		0/10 (0%)		1/16 (6.3%)		0/10 (0%)		0/4 (0%)
Gastrointestinal disorders
Abdominal pain	1/26 (3.8%)		0/10 (0%)		0/16 (0%)		0/10 (0%)		1/4 (25%)
Abdominal pain upper	1/26 (3.8%)		0/10 (0%)		2/16 (12.5%)		1/10 (10%)		0/4 (0%)
Constipation	2/26 (7.7%)		0/10 (0%)		1/16 (6.3%)		0/10 (0%)		1/4 (25%)
Gastritis	1/26 (3.8%)		0/10 (0%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Nausea	3/26 (11.5%)		0/10 (0%)		1/16 (6.3%)		0/10 (0%)		0/4 (0%)
Vomiting	1/26 (3.8%)		1/10 (10%)		0/16 (0%)		1/10 (10%)		0/4 (0%)
Diarrhoea	0/26 (0%)		0/10 (0%)		2/16 (12.5%)		0/10 (0%)		0/4 (0%)
General disorders
Injection site reaction	5/26 (19.2%)		0/10 (0%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Pain	1/26 (3.8%)		0/10 (0%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Pyrexia	1/26 (3.8%)		0/10 (0%)		1/16 (6.3%)		1/10 (10%)		0/4 (0%)
Adverse food reaction	0/26 (0%)		0/10 (0%)		1/16 (6.3%)		0/10 (0%)		0/4 (0%)
Fatigue	0/26 (0%)		0/10 (0%)		1/16 (6.3%)		0/10 (0%)		0/4 (0%)
Xerosis	0/26 (0%)		0/10 (0%)		0/16 (0%)		1/10 (10%)		0/4 (0%)
Hepatobiliary disorders
Hepatic function abnormal	0/26 (0%)		0/10 (0%)		1/16 (6.3%)		0/10 (0%)		0/4 (0%)
Immune system disorders
Hypersensitivity	1/26 (3.8%)		0/10 (0%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Seasonal allergy	0/26 (0%)		0/10 (0%)		1/16 (6.3%)		0/10 (0%)		0/4 (0%)
Infections and infestations
Acute sinusitis	1/26 (3.8%)		0/10 (0%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Bronchitis	1/26 (3.8%)		0/10 (0%)		5/16 (31.3%)		3/10 (30%)		1/4 (25%)
Croup infectious	1/26 (3.8%)		0/10 (0%)		1/16 (6.3%)		0/10 (0%)		0/4 (0%)
Eczema infected	1/26 (3.8%)		0/10 (0%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Gastroenteritis	1/26 (3.8%)		0/10 (0%)		2/16 (12.5%)		0/10 (0%)		0/4 (0%)
Nasopharyngitis	3/26 (11.5%)		1/10 (10%)		3/16 (18.8%)		1/10 (10%)		2/4 (50%)
Oral herpes	0/26 (0%)		1/10 (10%)		0/16 (0%)		1/10 (10%)		0/4 (0%)
Otitis media acute	1/26 (3.8%)		0/10 (0%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Pharyngitis	1/26 (3.8%)		0/10 (0%)		3/16 (18.8%)		0/10 (0%)		0/4 (0%)
Pneumonia	1/26 (3.8%)		0/10 (0%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Respiratory tract infection viral	1/26 (3.8%)		0/10 (0%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Rhinitis	0/26 (0%)		1/10 (10%)		0/16 (0%)		1/10 (10%)		1/4 (25%)
Sinusitis	1/26 (3.8%)		1/10 (10%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Tinea infection	1/26 (3.8%)		0/10 (0%)		0/16 (0%)		1/10 (10%)		0/4 (0%)
Upper respiratory tract infection	2/26 (7.7%)		1/10 (10%)		2/16 (12.5%)		2/10 (20%)		1/4 (25%)
Viral upper respiratory tract infection	2/26 (7.7%)		0/10 (0%)		2/16 (12.5%)		0/10 (0%)		1/4 (25%)
Wound infection	0/26 (0%)		1/10 (10%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Conjunctivitis	0/26 (0%)		0/10 (0%)		1/16 (6.3%)		1/10 (10%)		0/4 (0%)
Ear infection	0/26 (0%)		0/10 (0%)		0/16 (0%)		1/10 (10%)		1/4 (25%)
Empyema	0/26 (0%)		0/10 (0%)		0/16 (0%)		0/10 (0%)		1/4 (25%)
Gastroenteritis viral	0/26 (0%)		0/10 (0%)		1/16 (6.3%)		0/10 (0%)		0/4 (0%)
Gastroenteritis norovirus	0/26 (0%)		0/10 (0%)		1/16 (6.3%)		0/10 (0%)		0/4 (0%)
Hordeolum	0/26 (0%)		0/10 (0%)		0/16 (0%)		1/10 (10%)		0/4 (0%)
Impetigo	0/26 (0%)		0/10 (0%)		1/16 (6.3%)		1/10 (10%)		0/4 (0%)
Influenza	0/26 (0%)		0/10 (0%)		3/16 (18.8%)		0/10 (0%)		1/4 (25%)
Lower respiratory tract infection	0/26 (0%)		0/10 (0%)		1/16 (6.3%)		1/10 (10%)		0/4 (0%)
Paronychia	0/26 (0%)		0/10 (0%)		1/16 (6.3%)		0/10 (0%)		0/4 (0%)
Tracheitis	0/26 (0%)		0/10 (0%)		1/16 (6.3%)		0/10 (0%)		0/4 (0%)
Viral pharyngitis	0/26 (0%)		0/10 (0%)		0/16 (0%)		0/10 (0%)		1/4 (25%)
Pnenumonia Bacterial	0/26 (0%)		0/10 (0%)		0/16 (0%)		0/10 (0%)		1/4 (25%)
Injury, poisoning and procedural complications
Ankle fracture	1/26 (3.8%)		0/10 (0%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Contusion	0/26 (0%)		0/10 (0%)		1/16 (6.3%)		0/10 (0%)		0/4 (0%)
Heat stroke	0/26 (0%)		0/10 (0%)		1/16 (6.3%)		0/10 (0%)		0/4 (0%)
Laceration	0/26 (0%)		0/10 (0%)		0/16 (0%)		1/10 (10%)		0/4 (0%)
Limb injury	0/26 (0%)		0/10 (0%)		0/16 (0%)		1/10 (10%)		0/4 (0%)
Investigations
Alanine aminotransferase increased	0/26 (0%)		1/10 (10%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Body temperature increased	1/26 (3.8%)		0/10 (0%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Neutrophil count decreased	1/26 (3.8%)		0/10 (0%)		1/16 (6.3%)		0/10 (0%)		0/4 (0%)
Metabolism and nutrition disorders
Hypercholesterolaemia	0/26 (0%)		1/10 (10%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Hyperglycaemia	0/26 (0%)		1/10 (10%)		0/16 (0%)		0/10 (0%)		1/4 (25%)
Hypertriglyceridaemia	0/26 (0%)		1/10 (10%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Decreased appetite	0/26 (0%)		0/10 (0%)		1/16 (6.3%)		0/10 (0%)		0/4 (0%)
Hypoglycaemia	0/26 (0%)		0/10 (0%)		1/16 (6.3%)		0/10 (0%)		0/4 (0%)
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	1/26 (3.8%)		0/10 (0%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Arthritis	0/26 (0%)		0/10 (0%)		1/16 (6.3%)		0/10 (0%)		0/4 (0%)
Back pain	0/26 (0%)		0/10 (0%)		2/16 (12.5%)		0/10 (0%)		0/4 (0%)
Joint swelling	0/26 (0%)		0/10 (0%)		0/16 (0%)		1/10 (10%)		0/4 (0%)
Pain in extremity	0/26 (0%)		0/10 (0%)		0/16 (0%)		1/10 (10%)		0/4 (0%)
Nervous system disorders
Dizziness	1/26 (3.8%)		0/10 (0%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Dizziness postural	0/26 (0%)		1/10 (10%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Headache	3/26 (11.5%)		2/10 (20%)		4/16 (25%)		3/10 (30%)		1/4 (25%)
Lethargy	1/26 (3.8%)		0/10 (0%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Orthostatic intolerance	0/26 (0%)		0/10 (0%)		0/16 (0%)		0/10 (0%)		1/4 (25%)
Psychiatric disorders
Aggression	0/26 (0%)		0/10 (0%)		2/16 (12.5%)		0/10 (0%)		0/4 (0%)
Anxiety	0/26 (0%)		0/10 (0%)		1/16 (6.3%)		0/10 (0%)		0/4 (0%)
Depressed mood	0/26 (0%)		0/10 (0%)		1/16 (6.3%)		0/10 (0%)		0/4 (0%)
Enuresis	0/26 (0%)		0/10 (0%)		1/16 (6.3%)		0/10 (0%)		0/4 (0%)
Renal and urinary disorders
Urinary retention	1/26 (3.8%)		0/10 (0%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/26 (3.8%)		0/10 (0%)		2/16 (12.5%)		0/10 (0%)		0/4 (0%)
Cough	1/26 (3.8%)		0/10 (0%)		1/16 (6.3%)		2/10 (20%)		0/4 (0%)
Dysphonia	0/26 (0%)		1/10 (10%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Epistaxis	1/26 (3.8%)		0/10 (0%)		2/16 (12.5%)		0/10 (0%)		0/4 (0%)
Fibrinous bronchitis	1/26 (3.8%)		0/10 (0%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Nasal congestion	0/26 (0%)		1/10 (10%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Oropharyngeal pain	2/26 (7.7%)		0/10 (0%)		0/16 (0%)		1/10 (10%)		0/4 (0%)
Pharyngeal erythema	1/26 (3.8%)		1/10 (10%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Productive cough	0/26 (0%)		1/10 (10%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Upper respiratory tract inflammation	1/26 (3.8%)		0/10 (0%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Wheezing	2/26 (7.7%)		1/10 (10%)		0/16 (0%)		1/10 (10%)		0/4 (0%)
Throat irritation	0/26 (0%)		0/10 (0%)		1/16 (6.3%)		0/10 (0%)		0/4 (0%)
Skin and subcutaneous tissue disorders
Acne	0/26 (0%)		1/10 (10%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Dermatitis allergic	0/26 (0%)		1/10 (10%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Dry skin	0/26 (0%)		1/10 (10%)		0/16 (0%)		0/10 (0%)		0/4 (0%)
Rash	2/26 (7.7%)		0/10 (0%)		2/16 (12.5%)		0/10 (0%)		0/4 (0%)
Eczema	0/26 (0%)		0/10 (0%)		2/16 (12.5%)		1/10 (10%)		0/4 (0%)
Erythema	0/26 (0%)		0/10 (0%)		0/16 (0%)		1/10 (10%)		0/4 (0%)
Haemorrhage subcutaneous	0/26 (0%)		0/10 (0%)		1/16 (6.3%)		0/10 (0%)		0/4 (0%)
Pruritus	0/26 (0%)		0/10 (0%)		1/16 (6.3%)		0/10 (0%)		0/4 (0%)
Rash generalised	0/26 (0%)		0/10 (0%)		0/16 (0%)		1/10 (10%)		0/4 (0%)
Urticaria	0/26 (0%)		0/10 (0%)		1/16 (6.3%)		0/10 (0%)		0/4 (0%)
Dermatitis atopic	0/26 (0%)		0/10 (0%)		1/16 (6.3%)		1/10 (10%)		0/4 (0%)
Vascular disorders
Orthostatic hypotension	0/26 (0%)		0/10 (0%)		1/16 (6.3%)		0/10 (0%)		0/4 (0%)

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.