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    Clinical Trial Results:
    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

    Summary
    EudraCT number
    		 2014-002666-76
    Trial protocol
    		 GB   Outside EU/EEA  
    Global end of trial date

    Results information
    Results version number
    		 v1
    This version publication date
    23 Jun 2017
    First version publication date
    23 Jun 2017
    Other versions
    		 v2 , v3

    Trial information

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    Trial identification
    Sponsor protocol code
    200363
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 -
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline
    Sponsor organisation address
    980 Great West Road, Brentford, Middlesex, United Kingdom,
    Public contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
    Scientific contact
    GSK Response Center, GlaxoSmithKline, 1 866-435-7343,
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-000069-PIP02-10
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Interim
    Date of interim/final analysis
    31 Mar 2017
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    07 Dec 2016
    Global end of trial reached?
    No
    General information about the trial
    Main objective of the trial
    Pharmacokinetic/Pharmacodynamic Phase (Part A): - To characterize the pharmacokinetics of mepolizumab administered subcutaneously to subjects aged 6 to 11 years old with severe eosinophilic asthma - To characterize the pharmacodynamics of mepolizumab administered subcutaneously to subjects aged 6 to 11 years old with severe eosinophilic asthma Long-Term Safety / Long-Term Pharmacodynamic Phase (Part B): - To assess the long-term (52 weeks) safety and tolerability of mepolizumab when administered subcutaneously to subjects aged 6 to 11 years old with severe eosinophilic asthma
    Protection of trial subjects
    Numbing cream or spray was permitted at the site of injection and rescue medications (salbuterol/albuterol) are available to the participant throughout the study.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    25 Aug 2015
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Ethical reason
    Long term follow-up duration
    		 2 Years
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Japan: 7
    Country: Number of subjects enrolled
    Poland: 11
    Country: Number of subjects enrolled
    United Kingdom: 17
    Country: Number of subjects enrolled
    United States: 9
    Worldwide total number of subjects
    44
    EEA total number of subjects
    28
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    43
    Adolescents (12-17 years)
    1
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 This was a multi-centre, open-label study to assess the pharmacokinetics (PK) and pharmacodynamics (PD) of three (4-weekly) doses of mepolizumab 40 or 100 milligrams (mg) subcutaneously (SC), administered to participants with severe eosinophilic asthma aged 6-11 years. The results presented are based on the interim analysis, following Part A.

    Pre-assignment
    Screening details
    		 This study consisted of two phases: Part A consist of pre-screening/ screening/ run-in, treatment, and Follow-up. Part B consisted of long-term treatment and Follow-up. A total of 44 participants were screened and 36 were enrolled to treatment in Part A. Study was conducted at 13 sites in 4 countries (Japan, Poland, United Kingdom and United States

    Period 1
    Period 1 title
    Part A (20 weeks) (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Mepolizumab 40 mg SC
    Arm 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.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Mepolizumab 40 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants with bodyweight < 40 kg received 0.4 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh. Investigational product was administered subcutaneously by 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.

    Arm title
    		 Mepolizumab 100 mg SC
    Arm description
    		 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.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Mepolizumab 100 mg
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Participants with bodyweight >= 40 kg received 1.0 mL of reconstituted mepolizumab subcutaneously every four weeks, in upper arm or thigh. Investigational product was administered subcutaneously by 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.

    Number of subjects in period 1 [1]
    		Mepolizumab 40 mg SC Mepolizumab 100 mg SC
    Started
    26
    10
    Completed
    22
    10
    Not completed
    4
    0
         Physician decision
    1
    -
         AE of Asthma Exacerbation
    1
    -
         Consent withdrawn by subject
    2
    -
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: A total of 44 participants were screened and 36 were enrolled to treatment in Part A.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Mepolizumab 40 mg SC
    Reporting 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.

    Reporting group title
    Mepolizumab 100 mg SC
    Reporting group description
    		 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.

    Reporting group values
    		 Mepolizumab 40 mg SC Mepolizumab 100 mg SC Total
    Number of subjects
    		 26 10
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 8 ( 1.79 ) 10 ( 1.33 ) -
    Gender categorical
    Units: Subjects
        Female
    		 6 5 11
        Male
    		 20 5 25
    Race/Ethnicity, Customized
    Units: Subjects
        Central/South Asian Heritage (Her.)
    		 1 0 1
        Japanese Her.
    		 6 1 7
        Black or African American (B or Af Am)
    		 4 3 7
        White/Caucasian/European Her.
    		 14 6 20
        B or Af Am and White-White/Caucasian/European Her.
    		 1 0 1

    End points

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    End points reporting groups
    Reporting group title
    Mepolizumab 40 mg SC
    Reporting 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.

    Reporting group title
    Mepolizumab 100 mg SC
    Reporting group description
    		 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.

    Subject analysis set title
    mepolizumab sc
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set 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.

    Primary: Maximum plasma concentration (Cmax) of mepolizumab for Part A

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    End point title
    		 Maximum plasma concentration (Cmax) of mepolizumab for Part A [1]
    End point description
    PK of mepolizumab was evaluated in participants using Cmax. PK samples were collected at pre-dose on Week 4 and 8; and at Week 9, 12, 16 and 20. 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 centred to mean bodyweights of 27kg, 50kg and 70kg. Note the average bodyweight of 70kg (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.
    End point type
    Primary
    End point timeframe
    Week 4, 8, 9, 12, 16 and 20
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 mepolizumab sc
    Number of subjects analysed
    36 [2]
    Units: Microgram (ug)/mL
    arithmetic mean (standard error)
        70 kg
    12.8188 ( 0.7843 )
        50 kg
    16.3412 ( 0.6364 )
        27 kg
    10.196 ( 0.3345 )
    Notes
    [2] - PK Population
    No statistical analyses for this end point

    Primary: Area under concentration time curve to infinity (AUC [0-inf]) of mepolizumab for Part A

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    End point title
    		 Area under concentration time curve to infinity (AUC [0-inf]) of mepolizumab for Part A [3]
    End point description
    PK of mepolizumab was evaluated in participants using AUC (0-inf). PK samples were collected pre-dose on Week 4 and 8; and at Week 9, 12, 16 and 20. 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 centred to mean bodyweights of 27kg, 50kg and 70kg. Note the average bodyweight of 70kg (mean body weight observed in adults) was not investigated in the study.
    End point type
    Primary
    End point timeframe
    Week 4, 8, 9, 12, 16 and 20
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 mepolizumab sc
    Number of subjects analysed
    36 [4]
    Units: Day*ug/mL
    arithmetic mean (standard error)
        70 kg
    508.23 ( 41.8036 )
        50 kg
    675.2 ( 35.898 )
        27 kg
    454.39 ( 15.8876 )
    Notes
    [4] - PK Population
    No statistical analyses for this end point

    Primary: Terminal phase elimination half-life (t1/2) of mepolizumab during treatment period for Part A

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    End point title
    		 Terminal phase elimination half-life (t1/2) of mepolizumab during treatment period for Part A [5]
    End point description
    PK of mepolizumab was evaluated in participants using t1/2. PK samples were collected at pre-dose on Week 4 and 8; and at Week 9, 12, 16 and 20. 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 centred to mean bodyweights of 27kg, 50kg and 70kg. Note the average bodyweight of 70kg (mean body weight observed in adults) was not investigated in the study.
    End point type
    Primary
    End point timeframe
    Week 4, 8, 9, 12, 16 and 20
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 mepolizumab sc
    Number of subjects analysed
    36 [6]
    Units: Days
    arithmetic mean (standard error)
        70 kg
    20.9583 ( 1.652 )
        50 kg
    21.842 ( 1.0999 )
        27 kg
    23.5582 ( 0.8406 )
    Notes
    [6] - PK Population
    No statistical analyses for this end point

    Primary: Plasma Apparent Clearance (CL/F) of mepolizumab in Part A

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    End point title
    		 Plasma Apparent Clearance (CL/F) of mepolizumab in Part A [7]
    End point description
    PK of mepolizumab was evaluated in participants using CL/F. PK samples were collected at pre-dose on Week 4 and 8; and at Week 9, 12, 16 and 20. 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 centred to mean bodyweights of 27kg, 50kg and 70kg. Note the average bodyweight of 70kg (mean body weight observed in adults) was not investigated in the study.
    End point type
    Primary
    End point timeframe
    Week 4, 8, 9, 12, 16 and 20
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 mepolizumab sc
    Number of subjects analysed
    36 [8]
    Units: Liter (L)/ day
    arithmetic mean (standard error)
        70 kg
    0.1968 ( 0.01618 )
        50 kg
    0.1481 ( 0.007874 )
        27 kg
    0.08803 ( 0.003078 )
    Notes
    [8] - PK Population
    No statistical analyses for this end point

    Primary: Ratio to Baseline in absolute blood eosinophil count at Week 12 for Part A

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    End point title
    		 Ratio to Baseline in absolute blood eosinophil count at Week 12 for Part A [9]
    End point description
    PD of mepolizumab was evaluated in participants using ratio to Baseline in absolute blood eosinophil count. Blood samples were collected at Screening and at Week 0, 4, 8, 9, 12, 16 and 20. 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.
    End point type
    Primary
    End point timeframe
    Baseline and Week 12
    Notes
    [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 Mepolizumab 40 mg SC Mepolizumab 100 mg SC
    Number of subjects analysed
    26 [10]
    10
    Units: 10^9/ L
    geometric mean (confidence interval 95%)
        10^9/ L
    0.115 (0.067 to 0.196)
    0.166 (0.087 to 0.318)
    Notes
    [10] - PDe Population
    No statistical analyses for this end point

    Primary: Number of participants with any adverse event (AE) and any serious adverse events (SAE) in Part B

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    End point title
    		 Number of participants with any adverse event (AE) and any serious adverse events (SAE) in Part B [11]
    End point 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 hyperbilirubinaemia are to be categorized as SAE. Safety Population includes all participants who received at least one dose of mepolizumab beginning at Visit 9. Participants who enter into Part B of the study and receive any of the study treatment and have any on-treatment AE or SAE (defined as events occurring from the first dose until 28 days after the last dose of mepolizumab) is planned to be considered for analysis.
    End point type
    Primary
    End point timeframe
    From Week 20 up to Week 80
    Notes
    [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 Mepolizumab 40 mg SC Mepolizumab 100 mg SC
    Number of subjects analysed
    0 [12]
    0 [13]
    Units: Participants
    Notes
    [12] - Part B data is not available and so will not be posted until August 2018.
    [13] - Part B data is not available and so will not be posted until August 2018.
    No statistical analyses for this end point

    Primary: Number of participants with positive anti-mepolizumab binding antibodies and neutralizing antibodies response in Part B

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    End point title
    		 Number of participants with positive anti-mepolizumab binding antibodies and neutralizing antibodies response in Part B [14]
    End point description
    Blood samples for immunogenicity are to be collected for anti-mepolizumab binding antibodies and neutralizing antibodies response in Part B at Week 44, 68 and 80. Number of participants with positive anti-mepolizumab binding antibodies and neutralizing antibodies response is planned to be summarized.
    End point type
    Primary
    End point timeframe
    From Week 20 up to Week 80
    Notes
    [14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 Mepolizumab 40 mg SC Mepolizumab 100 mg SC
    Number of subjects analysed
    0 [15]
    0 [16]
    Units: Participants
    Notes
    [15] - Part B data is not available and so will not be posted until August 2018.
    [16] - Part B data is not available and so will not be posted until August 2018.
    No statistical analyses for this end point

    Primary: Number of participants with clinically significant changes in vital sign measurements in Part B

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    End point title
    		 Number of participants with clinically significant changes in vital sign measurements in Part B [17]
    End point description
    Sitting pulse rate and blood pressure measurements are to be performed in Part B at Week 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72 and 80. Mean change from baseline and standard deviation in vital sign measurements are planned to be summarized.
    End point type
    Primary
    End point timeframe
    From Week 20 up to Week 80
    Notes
    [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 Mepolizumab 40 mg SC Mepolizumab 100 mg SC
    Number of subjects analysed
    0 [18]
    0 [19]
    Units: Participants
        arithmetic mean (standard deviation)
    ( )
    ( )
    Notes
    [18] - Part B is not available and so will not be posted until August 2018.
    [19] - Part B data is not available and so will not be posted until August 2018.
    No statistical analyses for this end point

    Primary: Number of participants with clinically significant changes in clinical laboratory parameters in Part B

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    End point title
    		 Number of participants with clinically significant changes in clinical laboratory parameters in Part B [20]
    End point description
    Blood samples are to be collected at Week 32, 44, 56, 68, 72 and 80 in Part B to perform hematology and clinical chemistry. Number of participants with clinically significant changes in clinical laboratory parameters are planned to be summarized.
    End point type
    Primary
    End point timeframe
    From Week 20 up to Week 80
    Notes
    [20] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: There are no statistical data to report.
    End point values
    		 Mepolizumab 40 mg SC Mepolizumab 100 mg SC
    Number of subjects analysed
    0 [21]
    0 [22]
    Units: Participants
    Notes
    [21] - Part B is not available and so will not be posted until August 2018.
    [22] - Part B data is not available and so will not be posted until August 2018.
    No statistical analyses for this end point

    Secondary: Body weight-adjusted apparent clearance of Mepolizumab for Part A

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    End point title
    		 Body weight-adjusted apparent clearance of Mepolizumab for Part A
    End point description
    PK samples were collected at pre-dose on Week 4 and 8; and at Week 9, 12, 16 and 20. 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% CI for participants aged 6 to 11 years (centred to a mean bodyweight of 70kg) was compared with the historic adult estimated body-weight adjusted clearance of 0.22 Liter (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.
    End point type
    Secondary
    End point timeframe
    Week 4, 8, 9, 12, 16 and 20
    End point values
    		 mepolizumab sc
    Number of subjects analysed
    36 [23]
    Units: L/day
    arithmetic mean (confidence interval 90%)
        Weight 70kg
    0.1968 (0.1694 to 0.2241)
        Weight 50kg
    0.1481 (0.1348 to 0.1614)
        Weight 27kg
    0.088 (0.0828 to 0.0932)
    Notes
    [23] - PK Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in Asthma Control Questionnaire-7 (ACQ-7) at Week 12 in Part A

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    End point title
    		 Change from Baseline in Asthma Control Questionnaire-7 (ACQ-7) at Week 12 in Part A
    End point 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 categories 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.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Mepolizumab 40 mg SC Mepolizumab 100 mg SC
    Number of subjects analysed
    23 [24]
    10
    Units: Score on a scale
    arithmetic mean (standard deviation)
        Score on a scale
    -0.414 ( 1.1354 )
    0.082 ( 1.3432 )
    Notes
    [24] - PDo Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in Asthma Control Questionnaire-7 (ACQ-7) at Week 4,8,16 and 20 in Part A

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    End point title
    		 Change from Baseline in Asthma Control Questionnaire-7 (ACQ-7) at Week 4,8,16 and 20 in Part A
    End point 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 categories 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).
    End point type
    Secondary
    End point timeframe
    Baseline and up to Week 20
    End point values
    		 Mepolizumab 40 mg SC Mepolizumab 100 mg SC
    Number of subjects analysed
    26 [25]
    10
    Units: Score on a scale
    arithmetic mean (standard deviation)
        Week 4, n=26, 10
    -0.548 ( 1.1351 )
    -0.473 ( 0.9607 )
        Week 8, n=26, 10
    -0.652 ( 1.227 )
    -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 )
    Notes
    [25] - PDo Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in Childhood Asthma Control Test (C-ACT) at Week 12 for Part A

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    End point title
    		 Change from Baseline in Childhood Asthma Control Test (C-ACT) at Week 12 for Part A
    End point 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 one through 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. 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.
    End point type
    Secondary
    End point timeframe
    Baseline and Week 12
    End point values
    		 Mepolizumab 40 mg SC Mepolizumab 100 mg SC
    Number of subjects analysed
    22 [26]
    10
    Units: Score on a scale
    arithmetic mean (standard deviation)
        Score on a scale
    2.1 ( 4.45 )
    -0.3 ( 5.19 )
    Notes
    [26] - PDo Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in C-ACT at Week 4,8,16 and 20 in Part A

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    End point title
    		 Change from Baseline in C-ACT at Week 4,8,16 and 20 in Part A
    End point 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 one through 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. 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).
    End point type
    Secondary
    End point timeframe
    Baseline and up to Week 20
    End point values
    		 Mepolizumab 40 mg SC Mepolizumab 100 mg SC
    Number of subjects analysed
    26 [27]
    10
    Units: Score on a scale
    arithmetic mean (standard deviation)
        Week 4, n=26, 10
    1.8 ( 4.19 )
    2.4 ( 4.55 )
        Week 8, n=26, 10
    3 ( 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 ( 4.23 )
    0.9 ( 4.28 )
    Notes
    [27] - PDo Population
    No statistical analyses for this end point

    Secondary: Number of participants with any AE and any SAE in Part A

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    End point title
    		 Number of participants with any AE and any SAE in Part A
    End point 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 hyperbilirubinaemia were categorized as SAE. Participants who received any of the study treatment and had any on-treatment AE or SAE (defined as events occurring from the first dose until 28 days after the last dose of mepolizumab) were considered for analysis.
    End point type
    Secondary
    End point timeframe
    Up to Week 20
    End point values
    		 Mepolizumab 40 mg SC Mepolizumab 100 mg SC
    Number of subjects analysed
    26 [28]
    10
    Units: Participants
        Any AE
    18
    6
        Any SAE
    5
    1
    Notes
    [28] - Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants with any time change from Baseline relative to normal range in hematology parameters in Part A

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    End point title
    		 Number of participants with any time change from Baseline relative to normal range in hematology parameters in Part A
    End point description
    Blood samples were collected at Screening and at Week 0, 4, 8, 9, 12, 16 and 20 in Part A to perform basophils, eosinophils, leukocyte (also called as white blood cells), monocyte, neutrophils, lymphocyte, platelet count, mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), hemoglobin (Hgb), mean corpuscular volume (MCV), erythrocytes, hematocrit, reticulocytes/erythrocytes. The Baseline was the latest value recorded prior to the first dose of mepolizumab. 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. n=X:Number of participants with data analyzed at specified time points.
    End point type
    Secondary
    End point timeframe
    Up to Week 20
    End point values
    		 Mepolizumab 40 mg SC Mepolizumab 100 mg SC
    Number of subjects analysed
    26 [29]
    10
    Units: Participants
        Basophils, To low, n=26, 10
    0
    0
        Basophils, To Normal or No Change n=26, 10
    25
    10
        Basophils, To high n=26, 10
    1
    0
        Eosinophils, To low n=26, 10
    15
    6
        Eosinophils, To Normal or No Change n=26, 10
    10
    4
        Eosinophils, To high n=26, 10
    1
    0
        Leukocyte, To low n=26, 10
    8
    2
        Leukocyte, To Normal or No Change n=26, 10
    17
    8
        Leukocyte, To high n=26, 10
    1
    0
        Monocyte, To low n=26, 10
    6
    3
        Monocyte, To Normal or No Change n=26, 10
    19
    7
        Monocyte, To high n=26, 10
    1
    0
        Neutrophils, To low n=26, 10
    8
    3
        Neutrophils, To Normal or No Change n=26, 10
    16
    7
        Neutrophils, To high n=26, 10
    2
    0
        Lymphocyte, To low n=26, 10
    4
    1
        Lymphocyte, To Normal or No Change n=26, 10
    20
    8
        Lymphocyte, To high n=26, 10
    2
    1
        Platelet count, To low n=25, 10
    0
    1
        Platelet count, To Normal or No change n=25,10
    22
    9
        Platelet count, To high n=25, 10
    3
    0
        MCH, To low n=26, 10
    2
    0
        MCH, To Normal or No Change n=26, 10
    24
    10
        MCH, To high n=26, 10
    0
    0
        MCHC, To low n=26, 10
    1
    1
        MCHC, To Normal or No Change n=26, 10
    25
    9
        MCHC, To high n=26, 10
    0
    0
        Hgb, To low n=26, 10
    0
    1
        Hgb, To Normal or No Change n=26, 10
    26
    9
        Hgb, To high n=26, 10
    0
    0
        MCV, To low n=26, 10
    2
    0
        MCV, To Normal or No Change n=26, 10
    24
    10
        MCV, To high n=26, 10
    0
    0
        Erythrocytes, To low n=26, 10
    0
    0
        Erythrocytes, To Normal or No Change n=26, 10
    21
    8
        Erythrocytes, To high n=26, 10
    5
    2
        Hematocrit, To low n=26, 10
    0
    2
        Hematocrit, To Normal or No Change n=26, 10
    26
    8
        Hematocrit, To high n=26, 10
    0
    0
        Reticulocytes(Ret)/erythrocytes(Ery),To lown=26,10
    8
    1
        Ret/Ery, To Normal or No change n=26,10
    15
    9
        Ret/Ery, To high n=26,10
    3
    0
    Notes
    [29] - Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants with any time change from Baseline relative to normal range in clinical chemistry parameters in Part A

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    End point title
    		 Number of participants with any time change from Baseline relative to normal range in clinical chemistry parameters in Part A
    End point description
    Blood samples were collected at Screening and at Week 4, 8, 12 and 20 in Part A to perform alanine aminotransferase (ALT), alkaline phosphatase (ALP), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), albumin, protein, total billirubin, creatinine, direct billirubin, urate, calcium, carbon dioxide (CO2), chloride, glucose, potassium, sodium and urea. The Baseline was defined as the latest value recorded prior to the first dose of mepolizumab. 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.
    End point type
    Secondary
    End point timeframe
    Up to Week 20
    End point values
    		 Mepolizumab 40 mg SC Mepolizumab 100 mg SC
    Number of subjects analysed
    26 [30]
    10
    Units: Participants
        ALT, To low
    0
    0
        ALT, To Normal or No Change
    26
    10
        ALT, To high
    0
    0
        AST, To low
    0
    0
        AST, To Normal or No Change
    26
    10
        AST, To high
    0
    0
        ALP, To low
    0
    0
        ALP, To Normal or No Change
    26
    10
        ALP, To high
    0
    0
        GGT, To low
    0
    0
        GGT, To Normal or No Change
    26
    10
        GGT, To high
    0
    0
        Albumin, To low
    0
    0
        Albumin, To Normal or No Change
    22
    10
        Albumin, To high
    4
    0
        Protein, To low
    0
    0
        Protein, To Normal or No Change
    23
    10
        Protein, To high
    3
    0
        Total billirubin, To low
    0
    0
        Total billirubin, To Normal or No Change
    26
    10
        Total billirubin, To high
    0
    0
        Creatinine, To low
    4
    1
        Creatinine, To Normal or No Change
    22
    9
        Creatinine, To high
    0
    0
        Direct billirubin, To low
    0
    0
        Direct billirubin, To Normal or No Change
    26
    10
        Direct billirubin, To high
    0
    0
        Urate, To low
    1
    0
        Urate, To Normal or No Change
    25
    10
        Urate, To high
    0
    0
        Calcium, To low
    0
    0
        Calcium, To Normal or No Change
    22
    8
        Calcium, To high
    4
    2
        CO2, To low
    12
    3
        CO2, To Normal or No Change
    14
    7
        CO2, To high
    0
    0
        Chloride, To low
    0
    0
        Chloride, To Normal or No Change
    23
    9
        Chloride, To high
    3
    1
        Glucose, To low
    2
    0
        Glucose, To Normal or No Change
    17
    8
        Glucose, To high
    7
    2
        Potassium, To low
    0
    0
        Potassium, To Normal or No Change
    26
    10
        Potassium, To high
    0
    0
        Sodium, To low
    0
    0
        Sodium, To Normal or No Change
    26
    10
        Sodium, To high
    0
    0
        Urea, To low
    1
    3
        Urea, To Normal or No Change
    25
    7
        Urea, To high
    0
    0
    Notes
    [30] - Safety Population
    No statistical analyses for this end point

    Secondary: Number of participants with positive anti-mepolizumab binding antibodies and neutralizing antibodies response in Part A

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    End point title
    		 Number of participants with positive anti-mepolizumab binding antibodies and neutralizing antibodies response in Part A
    End point description
    Blood sample for immunogenicity was collected for anti-mepolizumab binding antibodies and neutralizing antibodies response in Part A at Week 0, 16 and 20 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, X in the category titles).
    End point type
    Secondary
    End point timeframe
    Up to Week 20
    End point values
    		 Mepolizumab 40 mg SC Mepolizumab 100 mg SC
    Number of subjects analysed
    26 [31]
    10
    Units: Participants
    number (not applicable)
        Anti-drug antibody,Any time post-baseline,n=25,10
    1
    1
        Neutralizing antibody,Any time post-baseline,n=1,1
    0
    0
    Notes
    [31] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Part A

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    End point title
    		 Change from Baseline in sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Part A
    End point description
    Sitting blood pressure measurements were performed in Part A at Screening and at Week 0, 4, 8, 9, 12, 16 and 20. 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, X in the category titles).
    End point type
    Secondary
    End point timeframe
    Up to Week 20
    End point values
    		 Mepolizumab 40 mg SC Mepolizumab 100 mg SC
    Number of subjects analysed
    26 [32]
    10
    Units: mmHg
    arithmetic mean (standard deviation)
        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 ( 11.1 )
        Sitting SBP, Week 16, , n=23, 10
    4.3 ( 11.53 )
    -4.6 ( 9.94 )
        Sitting SBP, Week 20, , n=24, 10
    5 ( 9.21 )
    1.4 ( 9.91 )
    Notes
    [32] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Baseline in sitting pulse rate in Part A

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    End point title
    		 Change from Baseline in sitting pulse rate in Part A
    End point description
    Sitting pulse rate measurements was performed in Part A at Screening and at Week 0, 4, 8, 9, 12, 16 and 20. 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, X in the category titles).
    End point type
    Secondary
    End point timeframe
    Up to Week 20
    End point values
    		 Mepolizumab 40 mg SC Mepolizumab 100 mg SC
    Number of subjects analysed
    26 [33]
    10
    Units: Beats per minute
    arithmetic mean (standard deviation)
        Sitting pulse rate, Week 4, n=26, 10
    -4 ( 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 ( 10.2 )
        Sitting pulse rate, Week 20, , n=24, 10
    -3.9 ( 13.13 )
    1.8 ( 8.22 )
    Notes
    [33] - Safety Population
    No statistical analyses for this end point

    Secondary: Change from Week 0 (Visit 2) in absolute blood eosinophil count at Weeks 32, 44, 56, 68, 72 and 80

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    End point title
    		 Change from Week 0 (Visit 2) in absolute blood eosinophil count at Weeks 32, 44, 56, 68, 72 and 80
    End point description
    Long term durability of PD of mepolizumab is to be evaluated in participants using change from Week 0 in absolute blood eosinophil count. Change from Week 0 (Visit 2) is to be calculated as post-dose visit value minus Week 0 value in PDe Population.
    End point type
    Secondary
    End point timeframe
    Weeks 0, 32, 44, 56, 68, 72 and 80
    End point values
    		 Mepolizumab 40 mg SC Mepolizumab 100 mg SC
    Number of subjects analysed
    0 [34]
    0 [35]
    Units: 10^9/ L
        geometric mean (confidence interval 95%)
    ( to )
    ( to )
    Notes
    [34] - Part B is not available and so will not be posted until August 2018.
    [35] - Part B data is not available and so will not be posted until August 2018.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    On-treatment serious adverse events (SAEs) and non-serious AEs were defined as events occurring from the first dose until 28 days after the last dose of mepolizumab.
    Adverse event reporting additional description
    Serious adverse events (SAEs) and Non-serious AEs were collected in members of Safety Population, comprised of all participants who received at least one dose of open label mepolizumab medication.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    19.1
    Reporting groups
    Reporting group title
    Mepolizumab 100 mg SC
    Reporting group description
    		 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.

    Reporting group title
    Mepolizumab 40 mg SC
    Reporting 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.

    Serious adverse events
    		 Mepolizumab 100 mg SC Mepolizumab 40 mg SC
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 10 (10.00%)
    5 / 26 (19.23%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pain
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 10 (0.00%)
    3 / 26 (11.54%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Cellulitis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 26 (3.85%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 3%
    Non-serious adverse events
    		 Mepolizumab 100 mg SC Mepolizumab 40 mg SC
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    6 / 10 (60.00%)
    18 / 26 (69.23%)
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Body temperature increased
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Neutrophil count decreased
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Injury, poisoning and procedural complications
    Ankle fracture
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Dizziness postural
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Headache
         subjects affected / exposed
    2 / 10 (20.00%)
    3 / 26 (11.54%)
         occurrences all number
    3
    3
    Lethargy
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    Injection site reaction
         subjects affected / exposed
    0 / 10 (0.00%)
    5 / 26 (19.23%)
         occurrences all number
    0
    7
    Pain
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Pyrexia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Abdominal pain upper
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Constipation
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    2
    Gastritis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Nausea
         subjects affected / exposed
    0 / 10 (0.00%)
    3 / 26 (11.54%)
         occurrences all number
    0
    3
    Vomiting
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 26 (3.85%)
         occurrences all number
    1
    1
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    2
    Cough
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Dysphonia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Epistaxis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Fibrinous bronchitis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Nasal congestion
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Oropharyngeal pain
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    2
    Pharyngeal erythema
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 26 (3.85%)
         occurrences all number
    1
    1
    Productive cough
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 26 (0.00%)
         occurrences all number
    2
    0
    Upper respiratory tract inflammation
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Wheezing
         subjects affected / exposed
    1 / 10 (10.00%)
    2 / 26 (7.69%)
         occurrences all number
    1
    3
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Dermatitis allergic
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Dry skin
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Rash
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    4
    Renal and urinary disorders
    Urinary retention
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Musculoskeletal pain
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Infections and infestations
    Acute sinusitis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Bronchitis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Croup infectious
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Eczema infected
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Gastroenteritis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Nasopharyngitis
         subjects affected / exposed
    1 / 10 (10.00%)
    3 / 26 (11.54%)
         occurrences all number
    1
    3
    Oral herpes
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Otitis media acute
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Pharyngitis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Pneumonia
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Respiratory tract infection viral
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Rhinitis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 26 (0.00%)
         occurrences all number
    2
    0
    Sinusitis
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 26 (3.85%)
         occurrences all number
    1
    1
    Tinea infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 26 (3.85%)
         occurrences all number
    0
    1
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 10 (10.00%)
    2 / 26 (7.69%)
         occurrences all number
    1
    2
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 26 (7.69%)
         occurrences all number
    0
    2
    Wound infection
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Metabolism and nutrition disorders
    Hypercholesterolaemia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Hyperglycaemia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0
    Hypertriglyceridaemia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 26 (0.00%)
         occurrences all number
    1
    0

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    10 Jun 2015
    - Addition of the C-ACT questionnaire to assess asthma control - To allow of the use of the ACQ tool to be administered in each country for which there is a validated translation available - Use of the Global Lung Function Initiative 2012 equations by Quanjer (2012) to estimate FEV1 predicted values - To add a copy of the ACQ-7, ACQ-IA and C-ACT questionnaire - To clarify that blood samples will be stored for up to 15 years after the end of the study. - To correct few typographical errors and few minor changes
    30 Sep 2015
    - To change the details of the Primary and Secondary Medical Monitors for the study. - To permit extended mepolizumab treatment for a minimum of 52 weeks upon completion of the pharmacokinetic/pharmacodynamic phase (Part A) of the protocol. - To add long-term safety (52 weeks) as the primary objective for the extended treatment phase (Part B). - To add long-term pharmacodynamic response as a secondary objective for the extended treatment phase. - To amend Section 9.3.2 to specify a pre-planned interim analyses to report results of the initial pharmacokinetic/pharmacodynamic phase upon completion of all required assessment for all subjects. - To add Section 9.5 to define the primary and secondary analysis plans for the extended treatment phase
    30 Mar 2016
    - Protocol Synopsis, Treatment Arms and Duration, Part B Treatment were updated to clarify the design and procedure - Section 4 Part A Follow-up: To change “positive neutralizing antibody” to “positive anti-mepolizumab antibody” and to clarify the timeline for obtaining a repeat sample - To clarify that subjects should be monitored for 1 hour post-dose during Part A only and thereafter monitoring in Part B will be according to standard practice at the site and to give guidance regarding the capability requirements at site during this monitoring. - To clarify that sample size is not determined for Part B and that all subjects completing Part A are eligible for Part B. - Changes in inclusion and exclusion criteria - Withdrawal/Stopping Criteria: To clarify that the Early Withdrawal Visit should be completed for subjects withdrawing from the study. - Permitted Medications and Non-Drug Therapies: To clarify that time of administration of concomitant medications is not required in the electronic case report form. To clarify that rescue medication will be provided for the study. To clarify that oral corticosteroids are permitted during this study and to clarify that baseline inhaled corticosteroids (ICS) and Baseline controller levels should not be changed between screening and Visit 2. - Few typographical corrections - To correct sample size assumptions, Secondary and Exploratory Analyses assumptions for Part B.
    05 May 2016
    - Inclusion Criteria for Part A: To correct an error in Protocol Amendment 03 when text was deleted from Inclusion Criterion 4 in error.
    18 Jan 2017
    - Protocol Synopsis, Rationale: To clarify that Part B follow-up is not required for subjects transitioning to the long-term access program. - Secondary and Exploratory Endpoints will be measured from Week 0 in Part A instead of Week 20 in Part B: - “Change from Week 20 (Visit 9)” is amended to “Change from Week 0 (Visit 2)” and that Secondary and Exploratory Endpoints will be measured at Week 80 only for subjects that will not transition to the long-term access program. To clarify that Part B follow-up is not required for subjects transitioning to the long term access program. - To clarify the definition of “completed subject” for subjects transitioning to the long-term access program and for those that do not transition. - Treatment After the Completion of Part A and Part B: Updated to include the long-term access program as an option for treatment of subjects after the end of Part B. - To clarify that immunoglobulin E (IgE) total only will be measured for this study. - Sample Size Considerations updated to clarify that the clearance mentioned in the section refers to apparent clearance. To quote the body-weight adjusted clearance value in adults (instead of the bodyweight-adjusted apparent clearance) and the 80-125% interval around this value, and to provide as additional information the value of the corresponding apparent clearance. - Abbreviations and Trademarks: Apparent clearance after extravascular (e.g., subcutaneous) administration added. - Reporting of SAEs to GlaxoSmithKline: clarification made to the point regarding reporting SAEs when the electronic system is down.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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