Download PDF

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	31 Jan 2018

Results information
Results version number	v3(current)
This version publication date	09 Aug 2018
First version publication date	23 Jun 2017
Other versions	v1 , v2
Version creation reason

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

Collapse all Expand all

Trial information

Top of page

Sponsor protocol code

200363

ISRCTN number

US NCT number

WHO universal trial number (UTN)

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,

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?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

31 Jan 2018

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

31 Jan 2018

Was the trial ended prematurely?

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?

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

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

Top of page

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.

Screening details

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).

Period 1 title

Part A (20 weeks)

Is this the baseline period?

Yes

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Part A: 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.

Part A: 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]	Part A: Mepolizumab 40 mg SC	Part A: 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.

Period 2 title

Part B (From Week 20 and up to Week 80)

Is this the baseline period?

Allocation method

Not applicable

Blinding used

Not blinded

Are arms mutually exclusive

Yes

Part B: Mepolizumab 40 mg SC

Arm 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.

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

Part B: Mepolizumab 100 mg SC

Arm description

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

Part B: Mepolizumab 40/100 mg SC

Arm description

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 k g at any subsequent visit.

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

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

Number of subjects in period 2 ^[2]	Part B: Mepolizumab 40 mg SC	Part B: Mepolizumab 100 mg SC	Part B: Mepolizumab 40/100 mg SC
Started	16	10	4
Completed	15	10	4
Not completed	1	0	0
Protocol deviation	1	-	-

Notes
[2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
Justification: A total of 44 participants were screened, of which 36 were enrolled to receive treatment in Part A.

Baseline characteristics

Top of page

Reporting group title

Part A: Mepolizumab 40 mg SC

Reporting group description

Reporting group title

Part A: Mepolizumab 100 mg SC

Reporting group description

Reporting group values	Part A: Mepolizumab 40 mg SC	Part A: Mepolizumab 100 mg SC	Total
Number of subjects	26	10
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	8.0 ( 1.79 )	10.0 ( 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

Top of page

Reporting group title

Part A: Mepolizumab 40 mg SC

Reporting group description

Reporting group title

Part A: Mepolizumab 100 mg SC

Reporting group description

Reporting group title

Part B: Mepolizumab 40 mg SC

Reporting group description

Reporting group title

Part B: Mepolizumab 100 mg SC

Reporting group description

Reporting group title

Part B: Mepolizumab 40/100 mg SC

Reporting group description

Subject analysis set title

Part A: 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.

Subject analysis set title

Part B: Mepolizumab 40 mg SC

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

Part B: Mepolizumab 100 mg SC

Subject analysis set type

Sub-group analysis

Subject analysis set description

Subject analysis set title

Part B: Mepolizumab 40/100 mg SC

Subject analysis set type

Sub-group analysis

Subject analysis set description

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

Top of page

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 Weeks 4 and 8; and at Weeks 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 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. 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

Pre-dose on Weeks 4 and 8; Weeks 9, 12, 16 and 20 post-dose

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	Part A: Mepolizumab SC
Number of subjects analysed	36 ^[2]
Units: Microgram (ug) per mL
arithmetic mean (standard error)
70 kg	12.8188 ( 0.7843 )
50 kg	16.3412 ( 0.6364 )
27 kg	10.1960 ( 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

Top of page

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 at pre-dose on Weeks 4 and 8; and at Weeks 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 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.

End point type

Primary

End point timeframe

Pre-dose on Weeks 4 and 8; Weeks 9, 12, 16 and 20 post-dose

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	Part A: Mepolizumab SC
Number of subjects analysed	36 ^[4]
Units: Day*ug per mL
arithmetic mean (standard error)
70 kg	508.23 ( 41.8036 )
50 kg	675.20 ( 35.8980 )
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

Top of page

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 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.

End point type

Primary

End point timeframe

Pre-dose on Weeks 4 and 8; Weeks 9, 12, 16 and 20 post-dose

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	Part A: Mepolizumab SC
Number of subjects analysed	36 ^[6]
Units: Days
arithmetic mean (standard error)
70 kg	20.9583 ( 1.6520 )
50 kg	21.8420 ( 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

Top of page

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 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.

End point type

Primary

End point timeframe

Pre-dose on Weeks 4 and 8; Weeks 9, 12, 16 and 20 post-dose

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	Part A: Mepolizumab SC
Number of subjects analysed	36 ^[8]
Units: Liter (L) per 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

Top of page

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

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	Part A: Mepolizumab 40 mg SC	Part A: Mepolizumab 100 mg SC
Number of subjects analysed	22 ^[10]	10 ^[11]
Units: Ratio of eosinophils in blood
geometric mean (confidence interval 95%)
Ratio of eosinophils in blood	0.115 (0.067 to 0.196)	0.166 (0.087 to 0.318)

Notes
[10] - PDe Population
[11] - PDe Population

No statistical analyses for this end point

Primary: Number of participants with on treatment serious adverse events (SAEs) and non-SAEs for Part B

Top of page

End point title

Number of participants with on treatment serious adverse events (SAEs) and non-SAEs for Part B ^[12]

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 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.

End point type

Primary

End point timeframe

From Week 20 up to Week 72

Notes
[12] - 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	Part B: Mepolizumab 40 mg SC	Part B: Mepolizumab 100 mg SC	Part B: Mepolizumab 40/100 mg SC
Number of subjects analysed	16 ^[13]	10 ^[14]	4 ^[15]
Units: Participants
Any SAE	4	2	1
Any non-SAE	15	8	4

Notes
[13] - Safety Population
[14] - Safety Population
[15] - Safety Population

No statistical analyses for this end point

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

Top of page

End point title

Number of participants with positive anti-mepolizumab binding antibodies and neutralizing antibodies response for Part B ^[16]

End point 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.

End point type

Primary

End point timeframe

From Week 20 up to Week 80

Notes
[16] - 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	Part B: Mepolizumab 40 mg SC	Part B: Mepolizumab 100 mg SC	Part B: Mepolizumab 40/100 mg SC
Number of subjects analysed	16 ^[17]	10 ^[18]	4 ^[19]
Units: Participants
Anti-drug antibody	0	0	0
Neutralizing antibody	0	0	0

Notes
[17] - Safety Population
[18] - Safety Population
[19] - Safety Population

No statistical analyses for this end point

Primary: Change from Baseline in sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP) for Part B

Top of page

End point title

Change from Baseline in sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP) for Part B ^[20]

End point 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).

End point type

Primary

End point timeframe

Baseline and Weeks 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 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	Part B: Mepolizumab 40 mg SC	Part B: Mepolizumab 100 mg SC	Part B: Mepolizumab 40/100 mg SC
Number of subjects analysed	16 ^[21]	10 ^[22]	4 ^[23]
Units: Millimeter of mercury (mmHg)
arithmetic mean (standard deviation)
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 )

Notes
[21] - Safety Population
[22] - Safety Population
[23] - Safety Population

No statistical analyses for this end point

Primary: Change from Baseline in sitting pulse rate for Part B

Top of page

End point title

Change from Baseline in sitting pulse rate for Part B ^[24]

End point 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).

End point type

Primary

End point timeframe

Baseline and Weeks 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 80

Notes
[24] - 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	Part B: Mepolizumab 40 mg SC	Part B: Mepolizumab 100 mg SC	Part B: Mepolizumab 40/100 mg SC
Number of subjects analysed	16 ^[25]	10 ^[26]	4 ^[27]
Units: Beats per minute
arithmetic mean (standard deviation)
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 )

Notes
[25] - Safety Population
[26] - Safety Population
[27] - Safety Population

No statistical analyses for this end point

Primary: Number of participants with any time change from Baseline relative to normal range in clinical chemistry parameters for Part B

Top of page

End point title

Number of participants with any time change from Baseline relative to normal range in clinical chemistry parameters for Part B ^[28]

End point 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.

End point type

Primary

End point timeframe

Baseline, from Week 20 and up to Week 72

Notes
[28] - 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	Part B: Mepolizumab 40 mg SC	Part B: Mepolizumab 100 mg SC	Part B: Mepolizumab 40/100 mg SC
Number of subjects analysed	16 ^[29]	10 ^[30]	4 ^[31]
Units: Participants
ALT; To Low	0	0	0
ALT; To Normal or No Change	16	10	4
ALT; To High	0	0	0
Albumin; To Low	0	0	0
Albumin; To Normal or No Change	15	10	4
Albumin; To High	1	0	0
ALP; To Low	0	0	0
ALP; To Normal or No Change	16	10	4
ALP;To High	0	0	0
AST; To Low	0	0	0
AST; To Normal or No Change	16	10	4
AST; To High	0	0	0
Bilirubin; To Low	0	0	0
Bilirubin; To Normal or No Change	16	9	4
Bilirubin; To High	0	1	0
Calcium; To Low	0	0	0
Calcium; To Normal or No Change	16	7	3
Calcium; To High	0	3	1
CO2; To Low	6	3	3
CO2; To Normal or No Change	10	7	1
CO2; To High	0	0	0
Chloride; To Low	0	0	0
Chloride; To Normal or No Change	16	9	4
Chloride; To High	0	1	0
Creatinine; To Low	2	2	0
Creatinine; To Normal or No Change	13	7	4
Creatinine; To High	1	1	0
Direct Bilirubin; To Low	0	0	0
Direct Bilirubin; To Normal or No	16	10	4
Direct Bilirubin; To High	0	0	0
GGT; To Low	0	0	0
GGT; To Normal or No Change	16	10	4
GGT; To High	0	0	0
Glucose; To Low	1	2	0
Glucose; To Normal or No Change	10	4	1
Glucose; To High	5	4	3
Potassium; To Low	0	1	0
Potassium; To Normal or No Change	16	9	4
Potassium; To High	0	0	0
Protein; To Low	0	0	0
Protein; To Normal or No Change	15	10	4
Protein; To High	1	0	0
Sodium; To Low	0	0	0
Sodium; To Normal or No Change	16	10	4
Sodium; To High	0	0	0
Urate; To Low	0	0	0
Urate; To Normal or No Change	16	10	4
Urate; To High	0	0	0
Urea; To Low	2	1	1
Urea; To Normal or No Change	14	9	3
Urea; To High	0	0	0

Notes
[29] - Safety Population
[30] - Safety Population
[31] - Safety Population

No statistical analyses for this end point

Primary: Number of participants with any time change from Baseline relative to normal range in hematology parameters for Part B

Top of page

End point title

Number of participants with any time change from Baseline relative to normal range in hematology parameters for Part B ^[32]

End point 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.

End point type

Primary

End point timeframe

Baseline, from Week 20 and up to Week 80

Notes
[32] - 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	Part B: Mepolizumab 40 mg SC	Part B: Mepolizumab 100 mg SC	Part B: Mepolizumab 40/100 mg SC
Number of subjects analysed	16 ^[33]	10 ^[34]	4 ^[35]
Units: Participants
Basophils; To Low	0	0	0
Basophils; To Normal or No Change	16	10	4
Basophils; To High	0	0	0
Eosinophils;To Low	11	6	3
Eosinophils; To Normal or No Change	5	4	0
Eosinophils;To High	0	0	1
MCH; To Low	0	1	0
MCH; To Normal or No Change	16	9	4
MCH; To High	0	0	0
MCHC;To Low	0	1	0
MCHC; To Normal or No Change	16	9	4
MCHC; To High	0	0	0
MCV; To Low	0	1	0
MCV; To Normal or No Change	16	9	4
MCV; To High	0	0	0
Erythrocytes; To Low	0	0	0
Erythrocytes; To Normal or No Change	15	8	3
Erythrocytes; To High	1	2	1
Hematocrit; To Low	0	2	0
Hematocrit; To Normal or No Change	16	7	4
Hematocrit; To High	0	1	0
Hgb; To Low	0	1	0
Hgb; To Normal or No Change	16	8	4
Hgb; To High	0	1	0
Leukocytes; To Low	5	2	1
Leukocytes; To Normal or No Change	11	7	2
Leukocytes; To High	0	1	1
Lymphocytes; To Low	0	0	0
Lymphocytes; To Normal or No Change	15	9	2
Lymphocytes; To High	1	1	2
Monocytes; To Low	6	2	1
Monocytes; To Normal or No Change	10	8	3
Monocytes; To High	0	0	0
Neutrophils; To Low	3	2	2
Neutrophils; To Normal or No Change	13	5	1
Neutrophils; To High	0	3	1
Platelets; To Low	0	0	0
Platelets; To Normal or No Change	15	10	4
Platelets; To High	1	0	0
Ret/Ery; To Low	2	3	1
Ret/Ery; To Normal or No Change	12	7	3
Ret/Ery;To High	2	0	0

Notes
[33] - Safety Population
[34] - Safety Population
[35] - Safety Population

No statistical analyses for this end point

Primary: Number of participants with abnormal findings for urinalysis parameters in Part B

Top of page

End point title

Number of participants with abnormal findings for urinalysis parameters in Part B ^[36]

End point 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.

End point type

Primary

End point timeframe

From Week 20 and up to Week 72

Notes
[36] - 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	Part B: Mepolizumab 40 mg SC	Part B: Mepolizumab 100 mg SC	Part B: Mepolizumab 40/100 mg SC
Number of subjects analysed	10 ^[37]	9 ^[38]	1 ^[39]
Units: Participants	7	6	0

Notes
[37] - Safety Population
[38] - Safety Population
[39] - Safety Population

No statistical analyses for this end point

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

Top of page

End point title

Body weight-adjusted apparent clearance of Mepolizumab for Part A

End point description

PK samples were collected at pre-dose on Weeks 4 and 8; and at Week 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 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

Pre-dose on Weeks 4 and 8; Weeks 9, 12, 16 and 20 post-dose

End point values	Part A: Mepolizumab SC
Number of subjects analysed	36 ^[40]
Units: L per 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	0.0880 (0.0828 to 0.0932)

Notes
[40] - 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

Top of page

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

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	Part A: Mepolizumab 40 mg SC	Part A: Mepolizumab 100 mg SC
Number of subjects analysed	23 ^[41]	10 ^[42]
Units: Scores on a scale
arithmetic mean (standard deviation)
Scores on a scale	-0.414 ( 1.1354 )	0.082 ( 1.3432 )

Notes
[41] - PDo Population
[42] - PDo Population

No statistical analyses for this end point

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

Top of page

End point title

Change from Baseline in Asthma Control Questionnaire-7 (ACQ-7) at Weeks 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 = 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).

End point type

Secondary

End point timeframe

Baseline and Weeks 4,8,16 and 20

End point values	Part A: Mepolizumab 40 mg SC	Part A: Mepolizumab 100 mg SC
Number of subjects analysed	26 ^[43]	10 ^[44]
Units: Scores 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 ( 1.2270 )	-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 )

Notes
[43] - PDo Population
[44] - 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

Top of page

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 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.

End point type

Secondary

End point timeframe

Baseline and Week 12

End point values	Part A: Mepolizumab 40 mg SC	Part A: Mepolizumab 100 mg SC
Number of subjects analysed	22 ^[45]	10 ^[46]
Units: Scores on a scale
arithmetic mean (standard deviation)
Scores on a scale	2.1 ( 4.45 )	-0.3 ( 5.19 )

Notes
[45] - PDo Population
[46] - PDo Population

No statistical analyses for this end point

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

Top of page

End point title

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

End point description

End point type

Secondary

End point timeframe

Baseline and Weeks 4, 8, 16, and 20

End point values	Part A: Mepolizumab 40 mg SC	Part A: Mepolizumab 100 mg SC
Number of subjects analysed	26 ^[47]	10 ^[48]
Units: Scores 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	3.0 ( 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 )

Notes
[47] - PDo Population
[48] - PDo Population

No statistical analyses for this end point

Secondary: Number of participants with treatment emergent SAEs and non-SAEs in Part A

Top of page

End point title

Number of participants with treatment emergent SAEs and non-SAEs 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 hyperbilirubinemia 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	Part A: Mepolizumab 40 mg SC	Part A: Mepolizumab 100 mg SC
Number of subjects analysed	26 ^[49]	10 ^[50]
Units: Participants
Any non-SAE	18	6
Any SAE	5	1

Notes
[49] - Safety Population
[50] - 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

Top of page

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 for analysis of basophils, eosinophils, leukocyte, monocyte, neutrophils, lymphocyte, platelet count, MCH, MCHC, Hgb, MCV, erythrocytes, hematocrit, 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.

End point type

Secondary

End point timeframe

Baseline and up to Week 20

End point values	Part A: Mepolizumab 40 mg SC	Part A: Mepolizumab 100 mg SC
Number of subjects analysed	26 ^[51]	10 ^[52]
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
Ret/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
[51] - Safety Population
[52] - 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

Top of page

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 for analysis of ALT, ALP, AST, GGT, albumin, protein, total billirubin, creatinine, direct billirubin, urate, calcium, CO2, chloride, glucose, potassium, sodium and urea. 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. 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 valued have been presented.

End point type

Secondary

End point timeframe

Baseline and up to Week 20

End point values	Part A: Mepolizumab 40 mg SC	Part A: Mepolizumab 100 mg SC
Number of subjects analysed	26 ^[53]	10 ^[54]
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
[53] - Safety Population
[54] - Safety Population

No statistical analyses for this end point

Secondary: Number of participants with abnormal findings for urinalysis parameters in Part A

Top of page

End point title

Number of participants with abnormal findings for urinalysis parameters in Part A

End point description

End point type

Secondary

End point timeframe

Up to Week 20

End point values	Part A: Mepolizumab 40 mg SC	Part A: Mepolizumab 100 mg SC
Number of subjects analysed	15 ^[55]	7 ^[56]
Units: Participants	5	4

Notes
[55] - Safety Population
[56] - 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

Top of page

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 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).

End point type

Secondary

End point timeframe

Baseline and Weeks 16 and 20

End point values	Part A: Mepolizumab 40 mg SC	Part A: Mepolizumab 100 mg SC
Number of subjects analysed	26 ^[57]	10 ^[58]
Units: Participants
Anti-drug antibody,Any time post-baseline,n=25,10	1	1
Neutralizing antibody,Any time post-baseline,n=1,1	0	0

Notes
[57] - Safety Population
[58] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in sitting SBP and DBP in Part A

Top of page

End point title

Change from Baseline in sitting SBP and DBP in Part A

End point 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).

End point type

Secondary

End point timeframe

Baseline and Weeks 4, 8, 9, 12, 16 and 20

End point values	Part A: Mepolizumab 40 mg SC	Part A: Mepolizumab 100 mg SC
Number of subjects analysed	26 ^[59]	10 ^[60]
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 20, , n=24, 10	0.7 ( 6.94 )	5.1 ( 7.03 )
Sitting DBP, Week 16, , n=23, 10	0.6 ( 6.99 )	3.9 ( 7.06 )
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 )

Notes
[59] - Safety Population
[60] - Safety Population

No statistical analyses for this end point

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

Top of page

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 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).

End point type

Secondary

End point timeframe

Baseline and Weeks 4, 8, 9, 12, 16 and 20

End point values	Part A: Mepolizumab 40 mg SC	Part A: Mepolizumab 100 mg SC
Number of subjects analysed	26 ^[61]	10 ^[62]
Units: Beats per minute
arithmetic mean (standard deviation)
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 )

Notes
[61] - Safety Population
[62] - Safety Population

No statistical analyses for this end point

Secondary: Ratio to Baseline in absolute blood eosinophil count at Weeks 32, 44, 56, 68, 72 and 80 for Part B

Top of page

End point title

Ratio to Baseline in absolute blood eosinophil count at Weeks 32, 44, 56, 68, 72 and 80 for Part B

End point 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. 99999 indicates data was not available due to insufficient number of participants. 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 Weeks 32, 44, 56, 68, 72 and 80

End point values	Part B: Mepolizumab 40 mg SC	Part B: Mepolizumab 100 mg SC	Part B: Mepolizumab 40/100 mg SC
Number of subjects analysed	16 ^[63]	10 ^[64]	4 ^[65]
Units: Ratio of eosinophils in blood
geometric mean (confidence interval 95%)
Week 32; n= 15, 10, 4	0.161 (0.100 to 0.259)	0.176 (0.089 to 0.346)	0.072 (0.021 to 0.247)
Week 44; n= 15, 10, 4	0.157 (0.093 to 0.263)	0.189 (0.090 to 0.398)	0.147 (0.012 to 1.781)
Week 56; n= 15, 10, 4	0.149 (0.090 to 0.246)	0.172 (0.094 to 0.314)	0.058 (0.015 to 0.220)
Week 68; n= 14, 10, 4	0.133 (0.078 to 0.227)	0.214 (0.111 to 0.415)	0.108 (0.009 to 1.271)
Week 72; n = 15, 10, 4	0.148 (0.086 to 0.254)	0.134 (0.064 to 0.279)	0.098 (0.073 to 0.130)
Week 80; n =9, 7, 0	0.591 (0.245 to 1.429)	0.647 (0.269 to 1.560)	99999 (99999 to 99999)

Notes
[63] - PDe Population
[64] - PDe Population
[65] - PDe Population

No statistical analyses for this end point

Adverse events

Top of page

Timeframe for reporting adverse events

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 additional 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.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

20.1

Reporting group title

Part A: Mepolizumab 40 mg SC

Reporting group description

Reporting group title

Part A: Mepolizumab 100 mg SC

Reporting group description

Reporting group title

Part B: Mepolizumab 40 mg SC

Reporting group description

Reporting group title

Part B: Mepolizumab 100 mg SC

Reporting group description

Reporting group title

Part B: Mepolizumab 40/100 mg SC

Reporting group description

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
Total subjects affected by serious adverse events
subjects affected / exposed	5 / 26 (19.23%)	1 / 10 (10.00%)	4 / 16 (25.00%)	2 / 10 (20.00%)	1 / 4 (25.00%)
number of deaths (all causes)	0	0	0	0	0
number of deaths resulting from adverse events
Nervous system disorders
Dizziness
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Headache
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
General disorders and administration site conditions
Chest pain
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pain
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Immune system disorders
Anaphylactic shock
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastrointestinal disorders
Nausea
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	3 / 26 (11.54%)	0 / 10 (0.00%)	2 / 16 (12.50%)	2 / 10 (20.00%)	1 / 4 (25.00%)
occurrences causally related to treatment / all	1 / 3	0 / 0	0 / 2	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Epistaxis
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Cellulitis
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Lower respiratory tract infection
subjects affected / exposed	1 / 26 (3.85%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 3%

Non-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
Total subjects affected by non serious adverse events
subjects affected / exposed	18 / 26 (69.23%)	6 / 10 (60.00%)	15 / 16 (93.75%)	8 / 10 (80.00%)	4 / 4 (100.00%)
Vascular disorders
Orthostatic hypotension
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0
General disorders and administration site conditions
Adverse food reaction
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0
Fatigue
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0
Injection site reaction
subjects affected / exposed	5 / 26 (19.23%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	7	0	0	0	0
Pain
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0
Pyrexia
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	1 / 16 (6.25%)	1 / 10 (10.00%)	0 / 4 (0.00%)
occurrences all number	1	0	1	1	0
Xerosis
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0
Immune system disorders
Hypersensitivity
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0
Seasonal allergy
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	2 / 16 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	2	0	4	0	0
Cough
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	1 / 16 (6.25%)	2 / 10 (20.00%)	0 / 4 (0.00%)
occurrences all number	1	0	1	3	0
Dysphonia
subjects affected / exposed	0 / 26 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0
Epistaxis
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	2 / 16 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	2	0	0
Fibrinous bronchitis
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0
Nasal congestion
subjects affected / exposed	0 / 26 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0
Oropharyngeal pain
subjects affected / exposed	2 / 26 (7.69%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)
occurrences all number	2	0	0	1	0
Pharyngeal erythema
subjects affected / exposed	1 / 26 (3.85%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	1	0	0	0
Productive cough
subjects affected / exposed	0 / 26 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	2	0	0	0
Upper respiratory tract inflammation
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0
Wheezing
subjects affected / exposed	2 / 26 (7.69%)	1 / 10 (10.00%)	0 / 16 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)
occurrences all number	3	1	0	2	0
Throat irritation
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0
Psychiatric disorders
Aggression
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	2 / 16 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	3	0	0
Anxiety
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0
Depressed mood
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0
Enuresis
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0
Investigations
Alanine aminotransferase increased
subjects affected / exposed	0 / 26 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0
Body temperature increased
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0
Neutrophil count decreased
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	1	0	0
Injury, poisoning and procedural complications
Ankle fracture
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0
Contusion
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0
Heat stroke
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0
Laceration
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0
Limb injury
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0
Nervous system disorders
Dizziness
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0
Dizziness postural
subjects affected / exposed	0 / 26 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0
Headache
subjects affected / exposed	3 / 26 (11.54%)	2 / 10 (20.00%)	4 / 16 (25.00%)	3 / 10 (30.00%)	1 / 4 (25.00%)
occurrences all number	3	3	5	9	1
Lethargy
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0
Orthostatic intolerance
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	1
Blood and lymphatic system disorders
lymphadenopathy
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0
Eye disorders
Eye pain
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0
Eye swelling
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	2	0
Eyelid haematoma
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	1 / 4 (25.00%)
occurrences all number	1	0	0	0	1
Abdominal pain upper
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	2 / 16 (12.50%)	1 / 10 (10.00%)	0 / 4 (0.00%)
occurrences all number	1	0	4	2	0
Constipation
subjects affected / exposed	2 / 26 (7.69%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 10 (0.00%)	1 / 4 (25.00%)
occurrences all number	2	0	1	0	1
Diarrhoea
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	2 / 16 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	2	0	0
Gastritis
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0
Nausea
subjects affected / exposed	3 / 26 (11.54%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	3	0	1	0	0
Vomiting
subjects affected / exposed	1 / 26 (3.85%)	1 / 10 (10.00%)	0 / 16 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)
occurrences all number	1	1	0	1	0
Hepatobiliary disorders
Hepatic function abnormal
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0
Skin and subcutaneous tissue disorders
Acne
subjects affected / exposed	0 / 26 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0
Dermatitis allergic
subjects affected / exposed	0 / 26 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0
Dry skin
subjects affected / exposed	0 / 26 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0
Rash
subjects affected / exposed	2 / 26 (7.69%)	0 / 10 (0.00%)	2 / 16 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	4	0	2	0	0
Eczema
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	2 / 16 (12.50%)	1 / 10 (10.00%)	0 / 4 (0.00%)
occurrences all number	0	0	2	1	0
Erythema
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	2	0
Haemorrhage subcutaneous
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0
Pruritus
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0
Rash generalised
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0
Urticaria
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0
Dermatitis atopic
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	1 / 10 (10.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	1	0
Renal and urinary disorders
Urinary retention
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0
Endocrine disorders
Adrenal suppression
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	1
Musculoskeletal and connective tissue disorders
Musculoskeletal pain
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0
Arthritis
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0
Back pain
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	2 / 16 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	2	0	0
Joint swelling
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0
Pain in extremity
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0
Infections and infestations
Acute sinusitis
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0
Bronchitis
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	5 / 16 (31.25%)	3 / 10 (30.00%)	1 / 4 (25.00%)
occurrences all number	1	0	5	3	1
Conjunctivitis
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	1 / 10 (10.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	1	0
Croup infectious
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	1	0	0
Ear infection
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 10 (10.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	1	1
Eczema infected
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0
Empyema
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	1
Gastroenteritis
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	2 / 16 (12.50%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	2	0	0
Gastroenteritis norovirus
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0
Nasopharyngitis
subjects affected / exposed	3 / 26 (11.54%)	1 / 10 (10.00%)	3 / 16 (18.75%)	1 / 10 (10.00%)	2 / 4 (50.00%)
occurrences all number	3	1	3	2	6
Oral herpes
subjects affected / exposed	0 / 26 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	2	0
Otitis media acute
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0
Pharyngitis
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	3 / 16 (18.75%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	3	0	0
Pneumonia
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0
Respiratory tract infection viral
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	0	0
Rhinitis
subjects affected / exposed	0 / 26 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	1 / 10 (10.00%)	1 / 4 (25.00%)
occurrences all number	0	2	0	2	1
Sinusitis
subjects affected / exposed	1 / 26 (3.85%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	1	1	0	0	0
Tinea infection
subjects affected / exposed	1 / 26 (3.85%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)
occurrences all number	1	0	0	1	0
Upper respiratory tract infection
subjects affected / exposed	2 / 26 (7.69%)	1 / 10 (10.00%)	2 / 16 (12.50%)	2 / 10 (20.00%)	1 / 4 (25.00%)
occurrences all number	2	1	7	7	1
Viral upper respiratory tract infection
subjects affected / exposed	2 / 26 (7.69%)	0 / 10 (0.00%)	2 / 16 (12.50%)	0 / 10 (0.00%)	1 / 4 (25.00%)
occurrences all number	2	0	4	0	2
Wound infection
subjects affected / exposed	0 / 26 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0
Gastroenteritis viral
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0
Hordeolum
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	1 / 10 (10.00%)	0 / 4 (0.00%)
occurrences all number	0	0	0	1	0
Impetigo
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	1 / 10 (10.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	1	0
Influenza
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	3 / 16 (18.75%)	0 / 10 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	4	0	1
Lower respiratory tract infection
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	1 / 10 (10.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	1	0
Paronychia
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0
Tracheitis
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0
Viral pharyngitis
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	1
Pnenumonia Bacterial
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	0	0	0	1
Metabolism and nutrition disorders
Hypercholesterolaemia
subjects affected / exposed	0 / 26 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0
Hyperglycaemia
subjects affected / exposed	0 / 26 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	1 / 4 (25.00%)
occurrences all number	0	1	0	0	1
Hypertriglyceridaemia
subjects affected / exposed	0 / 26 (0.00%)	1 / 10 (10.00%)	0 / 16 (0.00%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	1	0	0	0
Decreased appetite
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0
Hypoglycaemia
subjects affected / exposed	0 / 26 (0.00%)	0 / 10 (0.00%)	1 / 16 (6.25%)	0 / 10 (0.00%)	0 / 4 (0.00%)
occurrences all number	0	0	1	0	0

More information

Top of page

Were there any global substantial amendments to the protocol? Yes

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.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials

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

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

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

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

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

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

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

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

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

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

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

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

Primary: Number of participants with on treatment serious adverse events (SAEs) and non-SAEs for Part B

Primary: Number of participants with on treatment serious adverse events (SAEs) and non-SAEs for Part B

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

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

Primary: Change from Baseline in sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP) for Part B

Primary: Change from Baseline in sitting systolic blood pressure (SBP) and diastolic blood pressure (DBP) for Part B

Primary: Change from Baseline in sitting pulse rate for Part B

Primary: Change from Baseline in sitting pulse rate for Part B

Primary: Number of participants with any time change from Baseline relative to normal range in clinical chemistry parameters for Part B

Primary: Number of participants with any time change from Baseline relative to normal range in clinical chemistry parameters for Part B

Primary: Number of participants with any time change from Baseline relative to normal range in hematology parameters for Part B

Primary: Number of participants with any time change from Baseline relative to normal range in hematology parameters for Part B

Primary: Number of participants with abnormal findings for urinalysis parameters in Part B

Primary: Number of participants with abnormal findings for urinalysis parameters in Part B

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

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

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

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

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

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

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

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

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

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

Secondary: Number of participants with treatment emergent SAEs and non-SAEs in Part A

Secondary: Number of participants with treatment emergent SAEs and non-SAEs in Part A

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

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

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

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

Secondary: Number of participants with abnormal findings for urinalysis parameters in Part A

Secondary: Number of participants with abnormal findings for urinalysis parameters in Part A

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

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

Secondary: Change from Baseline in sitting SBP and DBP in Part A

Secondary: Change from Baseline in sitting SBP and DBP in Part A

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

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

Secondary: Ratio to Baseline in absolute blood eosinophil count at Weeks 32, 44, 56, 68, 72 and 80 for Part B

Secondary: Ratio to Baseline in absolute blood eosinophil count at Weeks 32, 44, 56, 68, 72 and 80 for Part B

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

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