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Clinical Trial Results:
A Double-blind, Randomised, Placebo-controlled Study to Investigate the Efficacy and Safety of Mepolizumab in the Treatment of Eosinophilic Granulomatosis with Polyangiitis in Subjects Receiving Standard of Care Therapy.

Summary
EudraCT number	2012-004385-17
Trial protocol	BE DE GB IT ES
Global end of trial date	05 Sep 2016

Results information
Results version number	v1
This version publication date	14 Sep 2017
First version publication date	14 Sep 2017
Other versions	v2 , v3 , v4

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

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Trial information

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Sponsor protocol code

115921

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-PIP04-13

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?

Analysis stage

Final

Date of interim/final analysis

09 Dec 2016

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

05 Sep 2016

Was the trial ended prematurely?

Main objective of the trial

To investigate the efficacy of mepolizumab plus standard of care compared with placebo plus standard of care on duration of clinical remission, defined as accrued duration in weeks where a subject achieves a BVAS=0 and corticosteroid dose ≤4 mg/day prednisolone/prednisone, in subjects with relapsing or refractory eosinophilic granulomatosis with polyangiitis (EGPA) receiving standard of care therapy including corticosteroid therapy reduction/withdrawal. To investigate the durability of response to treatment with mepolizumab plus standard of care compared with placebo plus standard of care, assessed by the proportion of subjects in remission at both Weeks 36 and 48.

Protection of trial subjects

Not applicable

Background therapy

Evidence for comparator

Actual start date of recruitment

05 Feb 2014

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Belgium: 3

Country: Number of subjects enrolled

Canada: 6

Country: Number of subjects enrolled

France: 13

Country: Number of subjects enrolled

Germany: 19

Country: Number of subjects enrolled

Italy: 13

Country: Number of subjects enrolled

Japan: 6

Country: Number of subjects enrolled

Spain: 4

Country: Number of subjects enrolled

United Kingdom: 13

Country: Number of subjects enrolled

United States: 59

Worldwide total number of subjects

136

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)

119

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Eligible participants at screening and run-in visit, entered a 52 week study treatment phase followed by 8-week follow-up phase. The total duration for the study participation was approximately 64 weeks.

Screening details

A total of 151 participants with a history of relapsing or refractory Eosinophilic Granulomatosis with Polyangiitis (EGPA) were screened, out of which 4 were screen failures and 11 were run-in failures. 136 participants completed run-in period and received Mepolizumab 300 milligram (mg) or placebo in a randomized manner in the treatment phase.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Investigator, Monitor, Data analyst, Carer, Subject, Assessor

Are arms mutually exclusive

Yes

Placebo

Arm description

Participants received placebo injection via subcutaneous (SC) route once every 4 weeks along with standard of care (SOC) drugs up to Week 48.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Randomized participants received placebo (0.9 percent sodium chloride) injection via subcutaneous route once every 4 weeks along with standard of care treatment.

Mepolizumab 300mg

Arm description

Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.

Arm type

Experimental

Investigational medicinal product name

Mepolizumab 300 mg

Investigational medicinal product code

Other name

Pharmaceutical forms

Injection

Routes of administration

Subcutaneous use

Dosage and administration details

Randomized participants received Mepolizumab 300 mg injection via subcutaneous route once every 4 weeks along with standard of care treatment.

Number of subjects in period 1	Placebo	Mepolizumab 300mg
Started	68	68
Completed	61	65
Not completed	7	3
Adverse event, serious fatal	-	1
Physician decision	2	-
Consent withdrawn by subject	3	2
Lost to follow-up	1	-
Lack of efficacy	1	-

Baseline characteristics

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Reporting group title

Placebo

Reporting group description

Participants received placebo injection via subcutaneous (SC) route once every 4 weeks along with standard of care (SOC) drugs up to Week 48.

Reporting group title

Mepolizumab 300mg

Reporting group description

Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.

Reporting group values	Placebo	Mepolizumab 300mg	Total
Number of subjects	68	68
Age categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (standard deviation)	48.2 ( 14.32 )	48.7 ( 12.39 )	-
Gender categorical
Units: Subjects
Female	38	42	80
Male	30	26	56
Race/Ethnicity, Customized
Units: Subjects
American Indian or Alaskan Native	0	1	1
Asian - Japanese Heritage	3	3	6
Asian - South East Asian Heritage	2	0	2
White - Arabic/North African Heritage	0	2	2
White - White/Caucasian/European Heritage	61	62	123
Mixed Race	2	0	2

End points

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Reporting group title

Placebo

Reporting group description

Participants received placebo injection via subcutaneous (SC) route once every 4 weeks along with standard of care (SOC) drugs up to Week 48.

Reporting group title

Mepolizumab 300mg

Reporting group description

Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.

Primary: Total accrued number of weeks where remission achieved over the study treatment period

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End point title

Total accrued number of weeks where remission achieved over the study treatment period

End point description

Total accrued duration of remission is the accrued number of weeks where Birmingham Vasculitis Activity Score (BVAS) =0 plus prednisolone/prednisone dose <=4 mg/day over the 52 week study treatment period was reported. The accrued duration was categorized into zero, >0 to <12 weeks, 12 to <24 weeks, 24 to <36 weeks and >=36 weeks. Statistical analysis was based on a proportional odds regression model with covariates including treatment group, Baseline prednisolone/prednisone daily dose, Baseline BVAS score and region. Intent-to-Treat (ITT) Population was used for the analysis and was defined as all participants who were randomized and received at least one dose of trial medication. Randomized participants were assumed to have received study treatment unless definitive evidence to the contrary exists. The odds ratio for treatment difference and associated probability (p)-value and 95 percent confidence interval (CI) were calculated.

End point type

Primary

End point timeframe

Up to Week 52

End point values	Placebo	Mepolizumab 300mg
Number of subjects analysed	68 ^[1]	68 ^[2]
Units: Weeks
Zero	55	32
>0 to <12 weeks	8	8
12 to <24 weeks	3	9
24 to <36 weeks	0	10
>=36 weeks	2	9

Notes
[1] - ITT Population
[2] - ITT Population

Statistical analysis 1

Comparison groups

Mepolizumab 300mg v Placebo

Number of subjects included in analysis

136

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[3]

Method

Proportional odds regression model

Parameter type

Odds ratio (OR)

Point estimate

5.91

Confidence interval

level

95%

sides

2-sided

lower limit

2.68

upper limit

13.03

Notes
[3] - P- value was based on a proportional odds regression model with covariates including treatment group, Baseline prednisolone/prednisone daily dose, Baseline BVAS score and region.

Primary: Number of participants who are in remission at 36 and 48 weeks

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End point title

Number of participants who are in remission at 36 and 48 weeks

End point description

The proportion of participants who were in remission (i.e., BVAS=0 and prednisolone/prednisone <=4 mg/day) at both Weeks 36 and 48 of the study treatment period was reported. The statistical analysis was performed using a logistic regression model on ITT Population. The odds ratio for treatment difference and associated p-value and 95 percent CI were calculated.

End point type

Primary

End point timeframe

Week 36 and Week 48

End point values	Placebo	Mepolizumab 300mg
Number of subjects analysed	68 ^[4]	68 ^[5]
Units: Participants
Participants	2	22

Notes
[4] - ITT Population
[5] - ITT Population

Statistical analysis 1

Comparison groups

Mepolizumab 300mg v Placebo

Number of subjects included in analysis

136

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

16.74

Confidence interval

level

95%

sides

2-sided

lower limit

3.61

upper limit

77.56

Secondary: Time to first EGPA relapse

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End point title

Time to first EGPA relapse

End point description

EGPA relapse was defined as worsening or persistence of active disease since the last visit characterized by active vasculitis or active asthma symptoms and/or signs with a corresponding worsening in Asthma Control Questionnaire-6 (ACQ-6) score or active nasal and/or sinus disease, with a corresponding worsening in at least one of the sino-nasal symptom questions warranting: i) an increased dose of OCS therapy (or other systemic corticosteroid therapy) to >4 mg/day prednisolone total daily dose or equivalent; OR ii) an increased dose or addition of immunosuppressive therapy; OR iii) hospitalization related to EGPA worsening. Participants who completed study, or withdrawn prematurely from the study without experiencing the event were censored.

End point type

Secondary

End point timeframe

Up to Week 52

End point values	Placebo	Mepolizumab 300mg
Number of subjects analysed	68 ^[6]	68 ^[7]
Units: Participants
Endpoint (event)	56	38
Censored	12	30

Notes
[6] - ITT Population
[7] - ITT Population

Statistical analysis 1

Comparison groups

Mepolizumab 300mg v Placebo

Number of subjects included in analysis

136

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[8]

Method

Wald Chi-Square

Parameter type

Cox proportional hazard

Point estimate

0.322

Confidence interval

level

95%

sides

2-sided

lower limit

0.206

upper limit

0.502

Notes
[8] - p-value was based on a cox proportional hazards model with covariates of treatment group, Baseline prednisolone/prednisone daily dose, Baseline BVAS score and region.

Secondary: Average daily prednisolone/prednisone dose during the last 4 weeks of the Study Treatment Period

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End point title

Average daily prednisolone/prednisone dose during the last 4 weeks of the Study Treatment Period

End point description

The number of participants with an average daily prednisolone/prednisone dose during the last 4 weeks of the Study Treatment Period (48 through 52) was calculated. The average dose was categorized into zero, >0 to <=4.0mg, >4.0 to <=7.5mg and >7.5mg. The statistical analysis was performed using a proportional odds regression model with Baseline covariates of treatment group, Baseline prednisolone/prednisone daily dose, Baseline BVAS score and region and the comparison between treatment groups was presented as an odds ratio, p-value and 95 percent CI.

End point type

Secondary

End point timeframe

Week 48 and Week52

End point values	Placebo	Mepolizumab 300mg
Number of subjects analysed	68 ^[9]	68 ^[10]
Units: Milligrams (mg)
number (not applicable)
Zero	2	12
>0 to <=4.0mg	3	18
>4.0 to <=7.5mg	18	10
>7.5mg	45	28

Notes
[9] - ITT Population
[10] - ITT Population

Statistical analysis 1

Comparison groups

Mepolizumab 300mg v Placebo

Number of subjects included in analysis

136

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[11]

Method

Proportional odds regression model

Parameter type

Odds ratio (OR)

Point estimate

0.2

Confidence interval

level

95%

sides

2-sided

lower limit

0.09

upper limit

0.41

Notes
[11] - p-value was based on a proportional odds regression model with Baseline covariates of treatment group, Baseline prednisolone/prednisone daily dose, Baseline BVAS score and region.

Secondary: Number of participants who achieved remission within the first 24 weeks and remained in remission for the remainder of the treatment period

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End point title

Number of participants who achieved remission within the first 24 weeks and remained in remission for the remainder of the treatment period

End point description

The number of participants who achieved remission (i.e., BVAS=0 and prednisolone/prednisone<=4 mg/day) within the first 24 weeks and remain in remission for the remainder of the study treatment period was reported. The statistical analysis was performed using a logistic regression model on ITT Population. The odds ratio for treatment difference and associated p-value and 95 percent CI were calculated.

End point type

Secondary

End point timeframe

Up to Week 52

End point values	Placebo	Mepolizumab 300mg
Number of subjects analysed	68 ^[12]	68 ^[13]
Units: Participants
Participants	1	13

Notes
[12] - ITT Population
[13] - ITT Population

Statistical analysis 1

Comparison groups

Placebo v Mepolizumab 300mg

Number of subjects included in analysis

136

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.007

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

19.65

Confidence interval

level

95%

sides

2-sided

lower limit

2.3

upper limit

167.93

Secondary: Total accrued number of weeks where remission achieved over the study treatment period

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End point title

Total accrued number of weeks where remission achieved over the study treatment period

End point description

Total accrued duration of remission, i.e., the accrued number of weeks where Birmingham Vasculitis Activity Score (BVAS) =0 plus prednisolone/prednisone dose <=7.5mg/day over the 52 week study treatment period was reported. BVAS is a validated, clinician-completed tool used for the comprehensive multisystem clinical assessment of disease activity in systemic vasculitis. The duration was categorized into zero, >0 to <12 weeks, 12 to <24 weeks, 24 to <36 weeks and >=36 weeks. Statistical analysis was performed on ITT Population and was based on a proportional odds regression model with covariates including treatment group, Baseline prednisolone/prednisone daily dose, Baseline BVAS score and region. The odds ratio for treatment difference and associated p-value and 95 percent CI were calculated.

End point type

Secondary

End point timeframe

Up to Week 52

End point values	Placebo	Mepolizumab 300mg
Number of subjects analysed	68 ^[14]	68 ^[15]
Units: Weeks
Zero	36	15
>0 to <12 weeks	19	15
12 to <24 weeks	0	7
24 to <36 weeks	7	9
>=36 weeks	6	22

Notes
[14] - ITT Population
[15] - ITT Population

Statistical analysis 1

Comparison groups

Placebo v Mepolizumab 300mg

Number of subjects included in analysis

136

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[16]

Method

Proportional odds regression model

Parameter type

Odds ratio (OR)

Point estimate

5.31

Confidence interval

level

95%

sides

2-sided

lower limit

2.63

upper limit

10.74

Notes
[16] - P- value was based on a proportional odds regression model with covariates including treatment group, Baseline prednisolone/prednisone daily dose, Baseline BVAS score and region.

Secondary: Number of participants who are in remission at 36 and 48 weeks

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End point title

Number of participants who are in remission at 36 and 48 weeks

End point description

The proportion of participants who were in remission (i.e., BVAS=0 and prednisolone/prednisone <=7.5 mg/day) at both Weeks 36 and 48 of the study treatment period was reported. The statistical analysis was performed using a logistic regression model with covariates including treatment group, Baseline prednisolone/prednisone daily dose, Baseline BVAS score and region. Statistical analysis was performed on ITT Population. The odds ratio for treatment difference and associated p-value and 95 percent CI were calculated.

End point type

Secondary

End point timeframe

Week 36 and Week 48

End point values	Placebo	Mepolizumab 300mg
Number of subjects analysed	68 ^[17]	68 ^[18]
Units: Participants
Participants	7	28

Notes
[17] - ITT Population
[18] - ITT Population

Statistical analysis 1

Comparison groups

Placebo v Mepolizumab 300mg

Number of subjects included in analysis

136

Analysis specification

Pre-specified

Analysis type

other

P-value

< 0.001 ^[19]

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

7.19

Confidence interval

level

95%

sides

2-sided

lower limit

2.6

upper limit

19.87

Notes
[19] - P- value was based on logistic regression model with covariates including treatment group, Baseline prednisolone/prednisone daily dose, Baseline BVAS score and region.

Secondary: Number of participants who achieved remission (BVAS=0 and prednisolone/prednisone <=7.5 mg/day) within the first 24 weeks and remained in remission for the remainder of the treatment period

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End point title

Number of participants who achieved remission (BVAS=0 and prednisolone/prednisone <=7.5 mg/day) within the first 24 weeks and remained in remission for the remainder of the treatment period

End point description

The proportion of participants who achieved remission (i.e., BVAS=0 and prednisolone/prednisone <=7.5 mg/day) within the first 24 weeks of the study and remain in remission for the reminder of the study treatment period was reported. The statistical analysis was performed using a logistic regression model with covariates including treatment group, Baseline prednisolone/prednisone daily dose, Baseline BVAS score and region. Statistical analysis was performed on ITT Population. The odds ratio for treatment difference and associated p-value and 95 percent CI were calculated.

End point type

Secondary

End point timeframe

Up to Week 52

End point values	Placebo	Mepolizumab 300mg
Number of subjects analysed	68 ^[20]	68 ^[21]
Units: Participants
Participants	2	16

Notes
[20] - ITT Population
[21] - ITT Population

Statistical analysis 1

Comparison groups

Placebo v Mepolizumab 300mg

Number of subjects included in analysis

136

Analysis specification

Pre-specified

Analysis type

other

P-value

= 0.003

Method

Regression, Logistic

Parameter type

Odds ratio (OR)

Point estimate

11.39

Confidence interval

level

95%

sides

2-sided

lower limit

2.35

upper limit

55.24

Secondary: Number of participants with local and systemic Adverse Events (AEs)

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End point title

Number of participants with local and systemic Adverse Events (AEs)

End point description

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. AEs including systemic allergic and non-allergic reactions as well as local site injection-related reactions were counted throughout treatment phase and follow up phase. Systemic allergic reactions included Facial paralysis, flushing, hypersensitivity and rash pruritic. Injection related reactions were considered as systemic non-allergic reactions. Local site reactions included injection site bruising, erythema, pain and reaction. The analysis was performed on Safety Population which comprised of all participants who receive at least one dose of study treatment.

End point type

Secondary

End point timeframe

Up to Week 52

End point values	Placebo	Mepolizumab 300mg
Number of subjects analysed	68 ^[22]	68 ^[23]
Units: Participants
Facial paralysis	1	0
Flushing	0	1
Hypersensitivity	0	1
Rash pruritic	0	1
Injection related reactions	0	1
Injection site bruising	0	1
Injection site erythema	1	1
Injection site pain	1	0
Injection site reaction	7	9

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

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameters of alanine aminotransferase (ALT), alkaline phosphatase (Alk.phosph.), aspartate aminotransferase (AST), creatinine kinase, gamma glutamyl transaminase (GGT) and lactate dehydrogenase (dehydro) levels

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End point title

Change from Baseline in clinical chemistry parameters of alanine aminotransferase (ALT), alkaline phosphatase (Alk.phosph.), aspartate aminotransferase (AST), creatinine kinase, gamma glutamyl transaminase (GGT) and lactate dehydrogenase (dehydro) levels

End point description

Blood samples were collected to evaluate change from Baseline in ALT, Alk.phosph., AST, creatinine kinase, GGT and lactate dehydro values at Baseline throughout the 52 weeks study treatment and 8-weeks follow up period. Baseline values were taken at Visit 2 and change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and standard deviation (SD) were measured.

End point type

Secondary

End point timeframe

Baseline and up to Week 60

End point values	Placebo	Mepolizumab 300mg
Number of subjects analysed	68 ^[24]	68 ^[25]
Units: International Unit per Liter (IU/L)
arithmetic mean (standard deviation)
Absolute ALT; Baseline; n= 68, 68	19.9 ( 8.91 )	21.3 ( 14.22 )
ALT; Week 4; n= 68, 68	0.2 ( 6.17 )	-2.2 ( 8.59 )
ALT; Week 8; n= 67, 66	-0.9 ( 5.66 )	-1.7 ( 10.14 )
ALT; Week 12; n= 65, 68	-0.9 ( 4.53 )	-0.7 ( 12.65 )
ALT; Week 16; n= 65, 68	-0.4 ( 6.56 )	-2.2 ( 9.73 )
ALT; Week 20; n= 63, 68	-0.3 ( 6.25 )	-1.2 ( 12.3 )
ALT; Week 24; n= 63, 66	-1.3 ( 5.38 )	-0.2 ( 15.77 )
ALT; Week 28; n= 62, 66	-0.9 ( 6.73 )	-0.4 ( 13.62 )
ALT; Week 32; n= 61, 67	-0.7 ( 6.79 )	-2.4 ( 11.3 )
ALT; Week 36; n= 60, 67	-0.1 ( 6.21 )	-3 ( 11.66 )
ALT; Week 40; n= 61, 66	0.3 ( 9.01 )	-2.3 ( 11.7 )
ALT; Week 44; n= 61, 66	0.9 ( 9.68 )	-2.7 ( 9.51 )
ALT; Week 48; n= 61, 64	1.7 ( 9.04 )	-1.6 ( 15.47 )
ALT; Week 52; n= 60, 65	1.5 ( 10.42 )	-2.8 ( 12.87 )
ALT; Week 56; n= 61, 63	-0.1 ( 7.35 )	-3.6 ( 12.79 )
ALT; Week 60; n= 60, 65	-0.3 ( 7.33 )	-4.7 ( 14.11 )
Absolute Alk.phosph.; Baseline; n= 68, 68	61.2 ( 17.83 )	60.4 ( 20.9 )
Alk.phosph.; Week 4; n= 68, 68	-0.9 ( 6.65 )	-3.2 ( 10.01 )
Alk.phosph.; Week 8; n= 67, 66	-1.7 ( 9.95 )	-1.7 ( 11.56 )
Alk. phosph.; Week 12; n= 65, 68	-1.9 ( 8.36 )	-1.1 ( 12.99 )
Alk. phosph.; Week 16; n= 65, 68	-1.3 ( 9.35 )	-1.1 ( 14.61 )
Alk. phosph.; Week 20; n= 63, 68	0 ( 11.24 )	4.4 ( 21.9 )
Alk. phosph.; Week 24; n= 63, 66	-1.1 ( 10.65 )	2.8 ( 17.64 )
Alk. phosph.; Week 28; n= 62, 66	0.2 ( 10.95 )	4.9 ( 17.17 )
Alk. phosph.; Week 32; n= 61, 67	0.2 ( 11.14 )	4.4 ( 15.83 )
Alk. phosph.; Week 36; n= 60, 67	0.2 ( 10.42 )	4.8 ( 14.71 )
Alk. phosph.; Week 40; n= 61, 66	1 ( 10.08 )	6.2 ( 18.43 )
Alk. phosph.; Week 44; n= 61, 66	1.1 ( 12.55 )	5.1 ( 16.53 )
Alk. phosph.; Week 48; n= 61, 64	1.2 ( 11.66 )	5.1 ( 17.56 )
Alk. phosph.; Week 52; n= 60, 65	0.3 ( 12.3 )	2.3 ( 14.47 )
Alk. phosph.; Week 56; n= 61, 63	-0.9 ( 12.04 )	1.7 ( 16.42 )
Alk. phosph.; Week 60; n= 60, 65	-1.5 ( 13.16 )	1 ( 15.08 )
Absolute AST; Baseline; n= 68, 68	19.3 ( 6.11 )	21.8 ( 10.73 )
AST; Week 4; n= 68, 68	0 ( 4.41 )	-1.7 ( 8.61 )
AST; Week 8; n= 67, 66	-0.4 ( 4.77 )	-1 ( 8.21 )
AST; Week 12; n= 65, 68	0.5 ( 4.41 )	-0.7 ( 9.62 )
AST; Week 16; n= 65, 68	0.4 ( 5.48 )	-0.6 ( 7.9 )
AST; Week 20; n= 63, 68	0.8 ( 4.66 )	-0.6 ( 8.49 )
AST; Week 24; n= 63, 66	0 ( 4.46 )	-0.4 ( 10.44 )
AST; Week 28; n= 61, 66	-0.9 ( 5.34 )	-0.4 ( 10.59 )
AST; Week 32; n= 61, 67	-0.2 ( 4.91 )	-1.3 ( 10.67 )
AST; Week 36; n= 60, 67	0.2 ( 4.68 )	-2.2 ( 9.61 )
AST; Week 40; n= 61, 66	0.5 ( 5.51 )	-1.6 ( 8.97 )
AST; Week 44; n= 61, 66	0.4 ( 5.77 )	-2.4 ( 9.02 )
AST; Week 48; n= 61, 64	1.1 ( 6.86 )	-2.3 ( 10.14 )
AST; Week 52; n= 60, 65	0.9 ( 6.84 )	-3 ( 10.49 )
AST; Week 56; n= 61, 63	-0.2 ( 4.92 )	-2.8 ( 10.64 )
AST; Week 60; n= 60, 65	-0.4 ( 5.24 )	-3.7 ( 10.92 )
Absolute Creatinine kinase; Baseline; n= 68, 68	99 ( 75.99 )	88.8 ( 75.18 )
Creatinine kinase; Week 4; n= 68, 68	-2.4 ( 83.23 )	2 ( 60.92 )
Creatinine kinase; Week 8; n= 67, 66	-5 ( 62.41 )	3.5 ( 50.48 )
Creatinine kinase; Week 12; n= 65, 68	5.4 ( 93.24 )	6.1 ( 40.86 )
Creatinine kinase; Week 16; n= 65, 68	15.8 ( 125.84 )	0.5 ( 49.65 )
Creatinine kinase; Week 20; n= 63, 68	1.3 ( 78.35 )	6.5 ( 54.83 )
Creatinine kinase; Week 24; n= 63, 66	-0.6 ( 56.55 )	6 ( 66.69 )
Creatinine kinase; Week 28; n= 62, 66	-15.9 ( 59.38 )	6.3 ( 55.84 )
Creatinine kinase; Week 32; n= 61, 67	-13.1 ( 59.29 )	0.2 ( 49.68 )
Creatinine kinase; Week 36; n= 60, 67	-12 ( 65.11 )	4.9 ( 52.71 )
Creatinine kinase; Week 40; n= 61, 66	2.6 ( 91.89 )	2.8 ( 62.74 )
Creatinine kinase; Week 44; n= 61, 66	5.8 ( 86.76 )	-2.4 ( 62.13 )
Creatinine kinase; Week 48; n= 61, 64	-8.1 ( 70.09 )	-2.6 ( 90.09 )
Creatinine kinase; Week 52; n= 60, 65	0.9 ( 67.51 )	0.2 ( 53.45 )
Creatinine kinase; Week 56; n= 61, 63	-8.7 ( 60.58 )	-0.2 ( 62.08 )
Creatinine kinase; Week 60; n= 60, 65	-10.3 ( 65.83 )	0.4 ( 61.45 )
Absolute GGT; Baseline; n= 68, 68	30.8 ( 25.49 )	30.1 ( 27.24 )
GGT; Week 4; n= 68, 68	0.2 ( 11.7 )	-2 ( 9.68 )
GGT; Week 8; n= 67, 66	-1 ( 8.59 )	-0.6 ( 17.99 )
GGT; Week 12; n= 65, 68	-2.9 ( 6.68 )	-1.9 ( 18.7 )
GGT; Week 16; n= 65, 68	-2.1 ( 10.18 )	-1.5 ( 21.36 )
GGT; Week 20; n= 63, 68	1.7 ( 19.02 )	-1.1 ( 24.5 )
GGT; Week 24; n= 63, 66	-1.7 ( 11.83 )	-3.3 ( 22.52 )
GGT; Week 28; n= 62, 66	-1.9 ( 11.71 )	-3.1 ( 16.86 )
GGT; Week 32; n= 61, 67	-1.5 ( 15.77 )	-3.6 ( 17.87 )
GGT; Week 36; n= 60, 67	-2.1 ( 10.64 )	-4.7 ( 14.96 )
GGT; Week 40; n= 61, 66	-0.2 ( 16.05 )	-0.3 ( 19.75 )
GGT; Week 44; n= 61, 66	-2.9 ( 8.26 )	-2.7 ( 15.25 )
GGT; Week 48; n= 61, 64	0.9 ( 18.91 )	-3 ( 16.51 )
GGT; Week 52; n= 60, 65	-1.6 ( 16.44 )	-4.2 ( 13.53 )
GGT; Week 56; n= 61, 63	-5 ( 16.77 )	-3.6 ( 17.02 )
GGT; Week 60; n= 60, 65	-4.8 ( 16.45 )	-5.6 ( 15.37 )
Absolute Lactate dehydro; Baseline; n= 68, 68	186.5 ( 47.82 )	179.6 ( 38.88 )
Lactate dehydro; Week 4; n= 68, 68	-3.6 ( 19.73 )	-2.3 ( 27.8 )
Lactate dehydro; Week 8; n= 67, 66	-8.2 ( 29.91 )	-5.3 ( 24.46 )
Lactate dehydro; Week 12; n= 65, 68	-2.2 ( 27.17 )	-7.7 ( 25.56 )
Lactate dehydro; Week 16; n= 65, 68	-2.6 ( 32.13 )	-10.6 ( 26.12 )
Lactate dehydro; Week 20; n= 63, 68	2.2 ( 26.8 )	-13.7 ( 25.79 )
Lactate dehydro; Week 24; n= 63, 66	-4.3 ( 26.22 )	-13.5 ( 26.99 )
Lactate dehydro; Week 28; n= 61, 66	-8.5 ( 27.77 )	-15.9 ( 30.44 )
Lactate dehydro; Week 32; n= 61, 67	-8.3 ( 25.49 )	-17.1 ( 24.88 )
Lactate dehydro; Week 36; n= 60, 67	-3.6 ( 36.45 )	-16.2 ( 30.54 )
Lactate dehydro; Week 40; n= 61, 66	-4.5 ( 35.81 )	-13.5 ( 36.31 )
Lactate dehydro; Week 44; n= 61, 66	-2.7 ( 33.4 )	-17 ( 31.37 )
Lactate dehydro; Week 48; n= 61, 64	0.8 ( 43.82 )	-19 ( 30.66 )
Lactate dehydro; Week 52; n= 60, 65	-0.1 ( 34.99 )	-17.8 ( 33.45 )
Lactate dehydro; Week 56; n= 61, 63	-5.2 ( 32.69 )	-16 ( 30.87 )
Lactate dehydro; Week 60; n= 60, 65	-3.5 ( 34.15 )	-12.4 ( 33.23 )

Notes
[24] - Safety Population
[25] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameters of albumin and protein levels

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End point title

Change from Baseline in clinical chemistry parameters of albumin and protein levels

End point description

Blood samples were collected to evaluate change from Baseline in albumin and protein levels values at Baseline throughout the 52 weeks study treatment and 8-weeks follow up period. Baseline values were taken at Visit 2 and change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and standard deviation (SD) were measured.

End point type

Secondary

End point timeframe

Baseline and up to Week 60

End point values	Placebo	Mepolizumab 300mg
Number of subjects analysed	68 ^[26]	68 ^[27]
Units: gram per liter (g/L)
arithmetic mean (standard deviation)
Absolute Albumin; Baseline; n= 68, 68	43.4 ( 2.45 )	43.5 ( 3.01 )
Albumin; Week 4; n= 68, 68	-0.6 ( 2.25 )	-0.1 ( 2.16 )
Albumin; Week 8; n= 67, 66	-0.8 ( 2.16 )	-0.6 ( 2.72 )
Albumin; Week 12; n= 65, 68	-0.2 ( 2.47 )	-0.4 ( 2.64 )
Albumin; Week 16; n= 65, 68	-0.6 ( 2.57 )	-0.6 ( 2.54 )
Albumin; Week 20; n= 63, 68	-0.1 ( 2.35 )	-0.2 ( 2.92 )
Albumin; Week 24; n= 63, 66	0 ( 2.8 )	0.1 ( 2.72 )
Albumin; Week 28; n= 62, 66	-0.2 ( 2.67 )	0.1 ( 2.67 )
Albumin; Week 32; n= 61, 67	-0.4 ( 2.71 )	-0.1 ( 2.69 )
Albumin; Week 36; n= 60, 67	-0.1 ( 2.58 )	0.3 ( 3.01 )
Albumin; Week 40; n= 61, 66	-0.2 ( 2.98 )	0.2 ( 2.82 )
Albumin; Week 44; n= 61, 66	0.3 ( 2.95 )	-0.3 ( 2.87 )
Albumin; Week 48; n= 61, 64	-0.4 ( 2.74 )	-0.3 ( 2.77 )
Albumin; Week 52; n= 60, 65	-0.5 ( 2.45 )	-0.3 ( 3.1 )
Albumin; Week 56; n= 61, 63	-0.7 ( 2.84 )	-0.5 ( 2.88 )
Albumin; Week 60; n= 60, 65	-0.9 ( 2.55 )	-0.7 ( 3.04 )
Absolute Protein; Baseline; n= 68, 68	67.7 ( 4.26 )	67.3 ( 4.46 )
Protein; Week 4; n= 68, 68	-0.8 ( 3 )	-0.5 ( 3.19 )
Protein; Week 8; n= 67, 66	-1.5 ( 2.97 )	-0.9 ( 3.6 )
Protein; Week 12; n= 65, 68	-0.6 ( 3.57 )	-0.6 ( 3.3 )
Protein; Week 16; n= 65, 68	-0.3 ( 3.56 )	-0.8 ( 3.93 )
Protein; Week 20; n= 63, 68	0 ( 3.21 )	0.1 ( 4.28 )
Protein; Week 24; n= 63, 66	0.2 ( 3.99 )	0 ( 3.96 )
Protein; Week 28; n= 62, 66	-0.2 ( 4.13 )	-0.1 ( 3.59 )
Protein; Week 32; n= 61, 67	-0.5 ( 4.09 )	-0.4 ( 3.91 )
Protein; Week 36; n= 60, 67	-0.2 ( 3.82 )	0.2 ( 4.45 )
Protein; Week 40; n= 61, 66	-0.4 ( 3.48 )	0.1 ( 3.98 )
Protein; Week 44; n= 61, 66	0.4 ( 4.43 )	-0.6 ( 4.19 )
Protein; Week 48; n= 61, 64	-0.5 ( 3.94 )	-0.5 ( 4.29 )
Protein; Week 52; n= 60, 65	-0.3 ( 3.75 )	-0.4 ( 4.08 )
Protein; week 56; n= 61, 63	-0.1 ( 4.77 )	-0.5 ( 4.21 )
Protein; Week 60; n= 60, 65	-0.4 ( 5.88 )	-0.7 ( 4.17 )

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

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameters of direct, indirect and total bilirubin and creatinine levels

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End point title

Change from Baseline in clinical chemistry parameters of direct, indirect and total bilirubin and creatinine levels

End point description

Blood samples were collected to evaluate change from Baseline in direct, indirect and total bilirubin and creatinine values at Baseline throughout the 52 weeks study treatment and 8-weeks follow up period. Baseline values were taken at Visit 2 and change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and standard deviation (SD) were measured.

End point type

Secondary

End point timeframe

Baseline and up to Week 60

End point values	Placebo	Mepolizumab 300mg
Number of subjects analysed	68 ^[28]	68 ^[29]
Units: micromole per liter (µmol/L)
arithmetic mean (standard deviation)
Absolute Total bilirubin; Baseline; n= 68, 68	9.8 ( 6.14 )	8.8 ( 4.1 )
Total bilirubin; week 4; n= 68, 68	-0.9 ( 4.02 )	0.1 ( 3.48 )
Total bilirubin; Week 8; n= 67, 66	-1.2 ( 4.38 )	0 ( 3.5 )
Total bilirubin; Week 12; n= 65, 68	-0.3 ( 3.01 )	0.1 ( 3.27 )
Total bilirubin; Week 16; n= 65, 68	-1.1 ( 4.15 )	0 ( 4.14 )
Total bilirubin; Week 20; n= 63, 68	-0.5 ( 2.9 )	0.3 ( 3.57 )
Total bilirubin; Week 24; n= 63, 66	-0.3 ( 3.36 )	0 ( 2.71 )
Total bilirubin; Week 28; n= 62, 66	-0.8 ( 3.13 )	0.3 ( 4.43 )
Total bilirubin; Week 32; n= 61, 67	-1.1 ( 3.07 )	-0.1 ( 3.63 )
Total bilirubin; Week 36; n= 60, 67	-0.7 ( 3.39 )	0.1 ( 4.09 )
Total bilirubin; Week 40; n= 61, 66	-0.2 ( 3.22 )	-0.3 ( 3.78 )
Total bilirubin; Week 44; n= 61, 66	0 ( 2.5 )	0.1 ( 3.64 )
Total bilirubin; Week 48; n= 61, 64	-0.2 ( 2.59 )	-0.1 ( 3.77 )
Total bilirubin; Week 52; n= 60, 65	-0.1 ( 3.41 )	0.7 ( 3.92 )
Total bilirubin; Week 56; n= 61, 63	-0.8 ( 3.17 )	0.5 ( 3.24 )
Total bilirubin; Week 60; n= 60, 65	-0.5 ( 3.21 )	0 ( 3.42 )
Absolute Creatinine; Baseline; n= 68, 68	75.49 ( 12.878 )	73 ( 12.289 )
Creatinine; Week 4; n= 68, 68	0.69 ( 7.195 )	2.09 ( 5.533 )
Creatinine; Week 8; n= 67, 66	1.87 ( 7.505 )	1.15 ( 6.737 )
Creatinine; Week 12; n= 65, 68	1.5 ( 9.029 )	0.34 ( 7.006 )
Creatinine; Week 16; n= 65, 68	1.53 ( 10.012 )	2.72 ( 6.702 )
Creatinine; Week 20; n= 63, 68	1.73 ( 6.916 )	2.6 ( 7.739 )
Creatinine; Week 24; n= 63, 66	0.74 ( 7.775 )	0.06 ( 6.538 )
Creatinine; Week 28; n= 62, 66	0.96 ( 7.504 )	1.02 ( 7.764 )
Creatinine; Week 32; n= 61, 67	1.89 ( 9.809 )	1.85 ( 8.589 )
Creatinine; Week 36; n= 60, 67	1.42 ( 6.957 )	0.4 ( 7.839 )
Creatinine; Week 40; n= 61, 66	1.16 ( 8.253 )	0.34 ( 8.119 )
Creatinine; Week 44; n= 61, 66	2.14 ( 8.991 )	0.04 ( 9.07 )
Creatinine; Week 48; n= 61, 64	1.53 ( 7.972 )	-2.25 ( 7.398 )
Creatinine; Week 52; n= 60, 65	0.52 ( 7.719 )	-1.35 ( 7.182 )
Creatinine; Week 56; n= 61, 63	1.39 ( 7.367 )	-0.3 ( 8.695 )
Creatinine; Week 60; n= 60, 65	0.34 ( 7.014 )	-1.22 ( 10.896 )
Absolute Direct bilirubin; Baseline; n= 68, 68	2.1 ( 1.33 )	1.9 ( 0.98 )
Direct bilirubin; Week 4; n= 68, 68	0 ( 1.06 )	0 ( 0.84 )
Direct bilirubin; Week 8; n= 67, 66	0 ( 1.01 )	0.1 ( 0.96 )
Direct bilirubin; Week 12; n= 65, 68	0 ( 0.97 )	0 ( 1.04 )
Direct bilirubin; Week 16; n= 65, 68	-0.2 ( 0.96 )	-0.1 ( 1.2 )
Direct bilirubin; Week 20; n= 63, 68	0 ( 0.86 )	0.1 ( 1.03 )
Direct bilirubin; Week 24; n= 63, 66	0.1 ( 0.9 )	0 ( 0.88 )
Direct bilirubin; Week 28; n= 62, 66	-0.1 ( 1.2 )	0.2 ( 1.15 )
Direct bilirubin; Week 32; n= 61, 67	-0.2 ( 0.99 )	0.1 ( 0.99 )
Direct bilirubin; Week 36; n= 60, 67	-0.1 ( 1.11 )	0.1 ( 1.17 )
Direct bilirubin; Week 40; n= 61, 66	0 ( 1.11 )	0 ( 0.94 )
Direct bilirubin; Week 44; n= 61, 66	0.1 ( 0.93 )	0 ( 1.12 )
Direct bilirubin; Week 48; n= 61, 64	0.1 ( 0.99 )	0 ( 1.17 )
Direct bilirubin; Week 52; n= 60, 65	0.1 ( 1.05 )	0.2 ( 1.06 )
Direct bilirubin; Week 56; n= 61, 63	0.1 ( 1.08 )	0.1 ( 1.06 )
Direct bilirubin; Week 60; n= 60, 65	0.1 ( 1.1 )	0.1 ( 1.07 )
Absolute Indirect bilirubin; Baseline; n= 68, 68	7.7 ( 5.09 )	6.9 ( 3.38 )
Indirect bilirubin; Week 4; n= 68, 68	-0.8 ( 3.68 )	0 ( 3.06 )
Indirect bilirubin; Week 8; n= 67, 66	-1.2 ( 3.86 )	-0.1 ( 2.94 )
Indirect bilirubin; Week 12; n= 65, 68	-0.3 ( 2.61 )	0.1 ( 2.79 )
Indirect bilirubin; Week 16; n= 65, 68	-0.9 ( 3.67 )	0.1 ( 3.37 )
Indirect bilirubin; Week 20; n= 63, 68	-0.5 ( 2.37 )	0.2 ( 3 )
Indirect bilirubin; Week 24; n= 63, 66	-0.4 ( 2.94 )	0 ( 2.37 )
Indirect bilirubin; Week 28; n= 62, 66	-0.7 ( 2.6 )	0.1 ( 3.71 )
Indirect bilirubin; Week 32; n= 61, 66	-0.9 ( 2.48 )	-0.2 ( 3.02 )
Indirect bilirubin; Week 36; n= 60, 67	-0.6 ( 2.77 )	0 ( 3.3 )
Indirect bilirubin; Week 40; n= 61, 66	-0.1 ( 2.56 )	-0.2 ( 3.16 )
Indirect bilirubin; Week 44; n= 61, 66	-0.1 ( 2.19 )	0.1 ( 2.99 )
Indirect bilirubin; Week 48; n= 61, 64	-0.3 ( 2.19 )	-0.1 ( 3.13 )
Indirect bilirubin; Week 52; n= 60, 65	-0.2 ( 2.84 )	0.5 ( 3.32 )
Indirect bilirubin; Week 56; n= 61, 63	-0.9 ( 2.72 )	0.4 ( 2.64 )
Indirect bilirubin; Week 60; n= 60, 65	-0.6 ( 2.64 )	-0.1 ( 2.81 )

Notes
[28] - Safety Population
[29] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in calcium, chloride, cholesterol, glucose, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, phosphorus, potassium, sodium, urea nitrogen and very low density lipoprotein (VLDL) cholesterol levels

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End point title

Change from Baseline in calcium, chloride, cholesterol, glucose, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, phosphorus, potassium, sodium, urea nitrogen and very low density lipoprotein (VLDL) cholesterol levels

End point description

Blood samples were collected to evaluate change from Baseline in calcium, chloride, cholesterol, glucose, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, phosphorus, potassium, sodium, urea nitrogen and very low density lipoprotein (VLDL) cholesterol values at Baseline throughout the 52 weeks study treatment and 8-weeks follow up period. Baseline values were taken at Visit 2 and change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and standard deviation (SD) were measured. 99999 indicates that data were not available.

End point type

Secondary

End point timeframe

Baseline and up to Week 60

End point values	Placebo	Mepolizumab 300mg
Number of subjects analysed	68 ^[30]	68 ^[31]
Units: millimoles per liter (mmol/L)
arithmetic mean (standard deviation)
Absolute Calcium; Baseline; n= 68, 68	2.365 ( 0.0864 )	2.382 ( 0.1189 )
Calcium; Week 4; n= 68, 68	-0.011 ( 0.0836 )	-0.012 ( 0.12 )
Calcium; Week 8; n= 67, 66	-0.013 ( 0.0877 )	-0.01 ( 0.1003 )
Calcium; Week 12; n= 65, 68	-0.013 ( 0.0844 )	-0.026 ( 0.0889 )
Calcium; Week 16; n= 65, 68	0 ( 0.1091 )	-0.029 ( 0.1018 )
Calcium; Week 20; n= 63, 68	0.002 ( 0.0882 )	-0.016 ( 0.1032 )
Calcium; Week 24; n= 63, 66	0.001 ( 0.0901 )	-0.013 ( 0.1111 )
Calcium; Week 28; n= 61, 66	0.001 ( 0.0962 )	-0.001 ( 0.1039 )
Calcium; Week 32; n= 61, 67	0 ( 0.0911 )	-0.006 ( 0.0977 )
Calcium; Week 36; n= 60, 67	-0.006 ( 0.0931 )	-0.006 ( 0.1133 )
Calcium; Week 40; n= 61, 66	0.014 ( 0.1126 )	0.005 ( 0.1115 )
Calcium; Week 44; n= 61, 66	0.016 ( 0.1144 )	-0.02 ( 0.1115 )
Calcium; Week 48; n= 61, 64	-0.007 ( 0.1007 )	-0.018 ( 0.1002 )
Calcium; Week 52; n= 60, 65	-0.008 ( 0.1001 )	-0.027 ( 0.111 )
Calcium; Week 56; n= 61, 63	-0.008 ( 0.0931 )	-0.015 ( 0.0994 )
Calcium; Week 60; n= 60, 65	-0.025 ( 0.0946 )	-0.019 ( 0.1058 )
Absolute Chloride; Baseline; n= 68, 68	103.4 ( 2.05 )	104 ( 2.21 )
Chloride; Week 4; n= 68, 68	0.6 ( 1.97 )	0.2 ( 2 )
Chloride; Week 8; n= 67, 66	0.9 ( 2.05 )	0.5 ( 2.06 )
Chloride; Week 12; n= 65, 68	0.7 ( 2.32 )	0.7 ( 2.2 )
Chloride; Week 16; n= 65, 68	0.5 ( 2.08 )	0.8 ( 1.95 )
Chloride; Week 20; n= 63, 68	0.3 ( 2.38 )	0.7 ( 2.04 )
Chloride; Week 24; n= 63, 66	0.6 ( 2.51 )	0.8 ( 2.2 )
Chloride; Week 28; n= 62, 66	0.7 ( 2.17 )	0.8 ( 2.59 )
Chloride; Week 32; n= 61, 67	0.4 ( 2.24 )	0.5 ( 2.32 )
Chloride; Week 36; n= 60, 67	0.8 ( 2.53 )	0.6 ( 2.08 )
Chloride; Week 40; n= 61, 66	0.9 ( 2.22 )	0.7 ( 2.13 )
Chloride; Week 44; n= 61, 66	0.5 ( 2.13 )	0.6 ( 2.55 )
Chloride; Week 48; n= 61, 64	0.5 ( 2.38 )	0.5 ( 2.34 )
Chloride; Week 52; n= 60, 65	0.3 ( 2.26 )	0.4 ( 2.24 )
Chloride; Week 56; n= 61, 63	0.7 ( 2.27 )	0.2 ( 2.06 )
Chloride; Week 60; n= 60, 65	0.4 ( 2.01 )	0.4 ( 2.2 )
Absolute Cholesterol; Baseline; n= 68, 68	5.771 ( 1.2033 )	5.788 ( 1.2386 )
Cholesterol; Week 8; n= 2, 0	-0.25 ( 0.1414 )	99999 ( 99999 )
Cholesterol; Week 12; n= 1, 0	0.05 ( 99999 )	99999 ( 99999 )
Cholesterol; Week 16; n= 1, 1	-0.4 ( 99999 )	-0.3 ( 99999 )
Cholesterol; Week 20; n= 1, 1	0.05 ( 99999 )	-0.3 ( 99999 )
Cholesterol; Week 24; n= 0, 1	99999 ( 99999 )	-0.56 ( 99999 )
Cholesterol; Week 36; n= 0, 1	99999 ( 99999 )	0.42 ( 99999 )
Cholesterol; Week 52; n= 60, 65	-0.006 ( 0.9364 )	-0.384 ( 0.8798 )
Cholesterol; Week 56; n= 1, 0	-0.22 ( 99999 )	99999 ( 99999 )
Absolute Glucose; Baseline; n= 68, 68	5.76 ( 2 )	5.35 ( 1.195 )
Glucose; Week 4; n= 68, 68	0.27 ( 1.619 )	-0.01 ( 1.05 )
Glucose; Week 8; n= 67, 66	0.09 ( 1.695 )	0.07 ( 0.986 )
Glucose; Week 12; n= 65, 68	0.27 ( 1.961 )	0.26 ( 1.079 )
Glucose; Week 16; n= 65, 68	0.03 ( 1.454 )	0.04 ( 1.077 )
Glucose; Week 20; n= 63, 68	0.25 ( 1.644 )	-0.03 ( 1.351 )
Glucose; Week 24; n= 63, 66	0.02 ( 1.588 )	0.16 ( 1.211 )
Glucose; Week 28; n= 62, 66	0.14 ( 1.613 )	0.21 ( 1.551 )
Glucose; Week 32; n= 61, 67	-0.03 ( 1.808 )	-0.14 ( 1.162 )
Glucose; Week 36; n= 60, 67	0.11 ( 1.525 )	0.03 ( 1.003 )
Glucose; Week 40; n= 61, 66	0.34 ( 1.831 )	-0.03 ( 1.305 )
Glucose; Week 44; n= 61, 66	0.21 ( 1.766 )	-0.05 ( 0.891 )
Glucose; Week 48; n= 61, 64	0.32 ( 2.065 )	0.21 ( 1.74 )
Glucose; Week 52; n= 60, 65	-0.17 ( 1.65 )	0.02 ( 1.258 )
Glucose; Week 56; n= 61, 63	0.01 ( 1.718 )	0.13 ( 1.852 )
Glucose; Week 60; n= 60, 65	0.2 ( 1.664 )	0.11 ( 1.483 )
Absolute HDL cholesterol; Baseline; n= 68, 68	1.837 ( 0.454 )	1.937 ( 0.5606 )
HDL cholesterol; Week 8; n= 2, 0	-0.075 ( 0.0354 )	99999 ( 99999 )
HDL cholesterol; Week 12; n= 1, 0	-0.1 ( 99999 )	99999 ( 99999 )
HDL cholesterol; Week 16; n= 1, 1	0.4 ( 99999 )	-0.15 ( 99999 )
HDL cholesterol; Week 20; n= 1, 1	0 ( 99999 )	-0.25 ( 99999 )
HDL cholesterol; Week 24; n= 0, 1	99999 ( 99999 )	-0.39 ( 99999 )
HDL cholesterol; Week 36; n= 0, 1	99999 ( 99999 )	0.4 ( 99999 )
HDL cholesterol; Week 52; n= 60, 65	-0.045 ( 0.2832 )	-0.15 ( 0.3146 )
HDL cholesterol; Week 56; n= 1, 0	-0.06 ( 99999 )	99999 ( 99999 )
Absolute LDL cholesterol; Baseline; n= 67, 68	3.261 ( 1.0808 )	3.205 ( 1.0992 )
LDL cholesterol; Week 8; n= 1, 0	-0.35 ( 99999 )	99999 ( 99999 )
LDL cholesterol; Week 12; n= 1, 0	0.19 ( 99999 )	99999 ( 99999 )
LDL cholesterol; Week 16; n= 1, 1	-0.73 ( 99999 )	-0.79 ( 99999 )
LDL cholesterol; Week 20; n= 1, 1	-0.15 ( 99999 )	-0.54 ( 99999 )
LDL cholesterol; Week 24; n= 0, 1	99999 ( 99999 )	0.04 ( 99999 )
LDL cholesterol; Week 36; n= 0, 1	99999 ( 99999 )	0.25 ( 99999 )
LDL cholesterol; Week 52; n= 58, 64	0.016 ( 0.7717 )	-0.215 ( 0.8079 )
LDL cholesterol; Week 56; n= 1, 0	0.1 ( 99999 )	99999 ( 99999 )
Absolute Phosphate; Baseline; n= 68, 68	1.068 ( 0.1797 )	1.066 ( 0.1939 )
Phosphate; Week 4; n= 68, 68	-0.027 ( 0.2183 )	0.014 ( 0.1833 )
Phosphate; Week 8; n= 67, 66	-0.004 ( 0.1577 )	0.024 ( 0.2239 )
Phosphate; Week 12; n= 65, 68	0.003 ( 0.1821 )	0.019 ( 0.2181 )
Phosphate; Week 16; n= 65, 68	0.016 ( 0.1819 )	0.016 ( 0.2205 )
Phosphate; Week 20; n= 63, 68	-0.001 ( 0.1611 )	0.019 ( 0.2087 )
Phosphate; Week 24; n= 63, 66	-0.042 ( 0.1565 )	0.007 ( 0.2142 )
Phosphate; Week 28; n= 62, 66	-0.025 ( 0.1819 )	0.003 ( 0.2539 )
Phosphate; Week 32; n= 61, 67	-0.018 ( 0.1975 )	0.04 ( 0.2172 )
Phosphate; Week 36; n= 60, 67	-0.038 ( 0.2159 )	0.023 ( 0.226 )
Phosphate; Week 40; n= 61, 66	-0.029 ( 0.1822 )	0.026 ( 0.2213 )
Phosphate; Week 44; n= 61, 66	-0.018 ( 0.2104 )	0.041 ( 0.224 )
Phosphate; Week 48; n= 61, 64	-0.053 ( 0.1931 )	-0.02 ( 0.2443 )
Phosphate; Week 52; n= 60, 65	0.005 ( 0.1939 )	0.053 ( 0.2988 )
Phosphate; Week 56; n= 61, 63	0.019 ( 0.2962 )	0.043 ( 0.3066 )
Phosphate; Week 60; n= 60, 65	-0.035 ( 0.2125 )	-0.007 ( 0.2322 )
Absolute Potassium; Baseline; n= 68, 68	4.11 ( 0.348 )	4.1 ( 0.359 )
Potassium; Week 4; n= 68, 68	0.05 ( 0.378 )	-0.02 ( 0.345 )
Potassium; Week 8; n= 67, 66	0.01 ( 0.309 )	0.02 ( 0.323 )
Potassium; Week 12; n= 65, 68	-0.04 ( 0.318 )	0.01 ( 0.296 )
Potassium; Week 16; n= 65, 68	0.06 ( 0.34 )	0.05 ( 0.317 )
Potassium; Week 20; n= 63, 68	0.08 ( 0.382 )	0.01 ( 0.372 )
Potassium; Week 24; n= 63, 66	-0.02 ( 0.298 )	0.04 ( 0.35 )
Potassium; Week 28; n= 61, 66	0.07 ( 0.338 )	0.1 ( 0.382 )
Potassium; Week 32; n= 61, 67	0.04 ( 0.34 )	0.11 ( 0.305 )
Potassium; Week 36; n= 60, 67	0.02 ( 0.291 )	0.01 ( 0.351 )
Potassium; Week 40; n= 61, 66	0.08 ( 0.419 )	0.14 ( 0.313 )
Potassium; Week 44; n= 61, 66	0.08 ( 0.383 )	0.09 ( 0.341 )
Potassium; Week 48; n= 61, 64	0.09 ( 0.367 )	0.05 ( 0.349 )
Potassium; Week 52; n= 60, 65	0.05 ( 0.344 )	0.01 ( 0.329 )
Potassium; Week 56; n= 61, 63	0.08 ( 0.379 )	0.08 ( 0.378 )
Potassium; Week 60; n= 60, 65	0 ( 0.358 )	0.1 ( 0.39 )
Absolute Sodium; Baseline; n= 68, 68	139.8 ( 2.03 )	140.3 ( 1.83 )
Sodium; Week 4; n= 68, 68	0.2 ( 1.86 )	0.3 ( 2.03 )
Sodium; Week 8; n= 67, 66	0.4 ( 2.06 )	0.2 ( 1.89 )
Sodium; Week 12; n= 65, 68	0.1 ( 1.99 )	-0.1 ( 2.28 )
Sodium; Week 16; n= 65, 68	0 ( 1.46 )	-0.1 ( 1.91 )
Sodium; Week 20; n= 63, 68	0 ( 1.88 )	0.1 ( 2.09 )
Sodium; Week 24; n= 63, 66	0.2 ( 1.94 )	0 ( 1.95 )
Sodium; Week 28; n= 62, 66	0.5 ( 1.71 )	0 ( 2.23 )
Sodium; Week 32; n= 61, 67	0.3 ( 1.92 )	0.1 ( 2.13 )
Sodium; Week 36; n= 60, 67	0.4 ( 2.1 )	0 ( 1.95 )
Sodium; Week 40; n= 61, 66	0.2 ( 2.42 )	0 ( 2.18 )
Sodium; Week 44; n= 61, 66	0.1 ( 1.77 )	-0.2 ( 2.02 )
Sodium; Week 48; n= 61, 64	0.1 ( 2.03 )	-0.4 ( 1.97 )
Sodium; Week 52; n= 60, 65	0.4 ( 1.79 )	-0.2 ( 2.17 )
Sodium; Week 56; n= 61, 63	0.4 ( 2.15 )	-0.5 ( 2.08 )
Sodium; Week 60; n= 60, 65	-0.1 ( 2.04 )	-0.3 ( 2.36 )
Absolute Urea; Baseline; n= 68, 68	5.94 ( 1.451 )	5.79 ( 1.629 )
Urea; Week 4; n= 68, 68	-0.08 ( 1.412 )	0.09 ( 1.241 )
Urea; Week 8; n= 67, 66	-0.23 ( 1.564 )	0.2 ( 1.206 )
Urea; Week 12; n= 65, 68	-0.15 ( 1.414 )	-0.1 ( 1.217 )
Urea; Week 16; n= 65, 68	-0.07 ( 1.569 )	0 ( 1.317 )
Urea; Week 20; n= 63, 68	-0.21 ( 1.465 )	-0.23 ( 1.286 )
Urea; Week 24; n= 63, 66	-0.28 ( 1.513 )	-0.12 ( 1.172 )
Urea; Week 28; n= 62, 66	-0.21 ( 1.525 )	-0.22 ( 1.35 )
Urea; Week 32; n= 61, 67	-0.11 ( 1.32 )	-0.23 ( 1.359 )
Urea; Week 36; n= 60, 67	-0.27 ( 1.407 )	-0.32 ( 1.391 )
Urea; Week 40; n= 61, 66	-0.44 ( 1.377 )	-0.23 ( 1.375 )
Urea; Week 44; n= 61, 66	-0.32 ( 1.731 )	-0.19 ( 1.698 )
Urea; Week 48; n= 61, 64	-0.36 ( 1.422 )	-0.09 ( 1.429 )
Urea; Week 52; n= 60, 65	-0.19 ( 1.737 )	-0.18 ( 1.128 )
Urea; Week 56; n= 61, 63	-0.11 ( 1.495 )	-0.13 ( 1.539 )
Urea; Week 60; n= 60, 65	-0.09 ( 1.546 )	-0.1 ( 1.17 )
Absolute VLDL cholesterol; Baseline; n= 67, 68	0.68 ( 0.2846 )	0.646 ( 0.2841 )
VLDL cholesterol; Week 8; n= 1, 0	0.1 ( 99999 )	99999 ( 99999 )
VLDL cholesterol; Week 12; n= 1, 0	-0.04 ( 99999 )	99999 ( 99999 )
VLDL cholesterol; Week 16; n= 1, 1	-0.07 ( 99999 )	0.64 ( 99999 )
VLDL cholesterol; Week 20; n= 1, 1	0.2 ( 99999 )	0.49 ( 99999 )
VLDL cholesterol; Week 24; n= 0, 1	99999 ( 99999 )	-0.21 ( 99999 )
VLDL cholesterol; Week 36; n= 0, 1	99999 ( 99999 )	-0.23 ( 99999 )
VLDL cholesterol; Week 52; n= 58, 64	-0.019 ( 0.3229 )	-0.051 ( 0.1927 )
VLDL cholesterol; Week 56; n= 1, 0	-0.26 ( 99999 )	99999 ( 99999 )

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

No statistical analyses for this end point

Secondary: Change from Baseline in clinical chemistry parameter of troponin levels

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End point title

Change from Baseline in clinical chemistry parameter of troponin levels

End point description

Blood samples were collected to evaluate change from Baseline in troponin values at Baseline throughout the 52 weeks study treatment and 8-weeks follow up period. Baseline values were taken at Visit 2 and change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and standard deviation (SD) were measured.

End point type

Secondary

End point timeframe

Baseline and up to Week 60

End point values	Placebo	Mepolizumab 300mg
Number of subjects analysed	68 ^[32]	68 ^[33]
Units: µg/L
arithmetic mean (standard deviation)
Absolute Troponin; Baseline; n= 68, 68	0.013 ( 0.011 )	0.013 ( 0.0092 )
Troponin; Week 4; n= 68, 66	-0.001 ( 0.0106 )	0.008 ( 0.0717 )
Troponin; Week 8; n= 67, 67	-0.002 ( 0.0111 )	0.001 ( 0.0089 )
Troponin; Week 12; n= 64, 67	-0.002 ( 0.0108 )	-0.001 ( 0.0053 )
Troponin; Week 16; n= 65, 68	-0.002 ( 0.0104 )	0.002 ( 0.0272 )
Troponin; Week 20; n= 61, 68	-0.002 ( 0.0105 )	-0.001 ( 0.0089 )
Troponin; Week 24; n= 62, 67	-0.002 ( 0.0098 )	0.004 ( 0.0535 )
Troponin; Week 28; n= 63, 66	-0.003 ( 0.0102 )	-0.002 ( 0.009 )
Troponin; Week 32; n= 61, 67	-0.003 ( 0.01 )	-0.002 ( 0.0092 )
Troponin; Week 36; n= 61, 67	-0.002 ( 0.0107 )	0 ( 0.0185 )
Troponin; Week 40; n= 61, 66	-0.001 ( 0.0117 )	-0.002 ( 0.009 )
Troponin; Week 44; n= 61, 65	0 ( 0.0068 )	-0.001 ( 0.0095 )
Troponin; Week 48; n= 60, 65	0.017 ( 0.1479 )	-0.001 ( 0.0101 )
Troponin; Week 52; n= 60, 65	-0.002 ( 0.0114 )	-0.001 ( 0.0111 )
Troponin; Week 56; n= 61, 63	-0.003 ( 0.0112 )	-0.002 ( 0.0086 )
Troponin; Week 60; n= 59, 65	-0.003 ( 0.0109 )	-0.001 ( 0.0093 )

Notes
[32] - Safety Population
[33] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in hematology parameters of basophils, eosinophil, leukocytes, lymphocytes, monocytes, neutrophils, platelets levels

Top of page

End point title

Change from Baseline in hematology parameters of basophils, eosinophil, leukocytes, lymphocytes, monocytes, neutrophils, platelets levels

End point description

Blood samples were collected to evaluate change from Baseline in basophils, eosinophils, leukocytes, lymphocytes, monocytes, neutrophils and platelet values at Baseline throughout the 52 weeks study treatment and 8-weeks follow up period. Baseline values were taken at Visit 2 and change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and standard deviation (SD) were measured.

End point type

Secondary

End point timeframe

Baseline and up to Week 60

End point values	Placebo	Mepolizumab 300mg
Number of subjects analysed	68 ^[34]	68 ^[35]
Units: 10^9/L
arithmetic mean (standard deviation)
Absolute Basophils; Baselin; n= 68, 68	0.03 ( 0.0253 )	0.028 ( 0.0236 )
Basophils; Week 4; n= 66, 66	-0.002 ( 0.0302 )	-0.007 ( 0.0282 )
Basophils; Week 8; n= 65, 66	0.005 ( 0.0285 )	-0.002 ( 0.0261 )
Basophils; Week 12; n= 63, 65	0.007 ( 0.0351 )	-0.007 ( 0.0222 )
Basophils; Week 16; n= 64, 68	0.005 ( 0.0333 )	-0.004 ( 0.0295 )
Basophils; Week 20; n= 61, 66	0.005 ( 0.0338 )	-0.002 ( 0.0287 )
Basophils; Week 24; n= 61, 66	0.004 ( 0.0341 )	-0.002 ( 0.0328 )
Basophils; Week 28; n= 62, 65	0.006 ( 0.0411 )	-0.005 ( 0.0297 )
Basophils; Week 32; n= 61, 66	0.01 ( 0.0467 )	0.002 ( 0.0355 )
Basophils; Week 36; n= 60, 66	0.009 ( 0.0321 )	0.005 ( 0.0424 )
Basophils; Week 40; n= 61, 65	0.005 ( 0.0357 )	-0.002 ( 0.0356 )
Basophils; Week 44; n= 59, 61	0.008 ( 0.0328 )	0 ( 0.0296 )
Basophils; Week 48; n= 59, 64	0.003 ( 0.0408 )	-0.004 ( 0.03 )
Basophils; Week 52; n= 60, 64	0.004 ( 0.0289 )	-0.003 ( 0.0284 )
Basophils; Week 56; n= 59, 61	0.009 ( 0.0381 )	-0.003 ( 0.0286 )
Basophils; Week 60; n= 58, 64	0.002 ( 0.0316 )	-0.006 ( 0.0248 )
Absolute Eosinophils; Baseline; n= 68, 68	0.362 ( 0.5835 )	0.398 ( 0.8415 )
Eosinophils; Week 4; n= 66, 66	-0.054 ( 0.3309 )	-0.339 ( 0.6794 )
Eosinophils; Week 8; n= 65, 66	0.103 ( 0.2921 )	-0.37 ( 0.8092 )
Eosinophils; Week 12; n= 63, 65	0.027 ( 0.3515 )	-0.364 ( 0.8407 )
Eosinophils; Week 16; n= 64, 68	0.058 ( 0.4092 )	-0.355 ( 0.828 )
Eosinophils; Week 20; n= 61, 66	0.162 ( 0.59 )	-0.347 ( 0.8266 )
Eosinophils; Week 24; n= 61, 66	0.136 ( 0.4044 )	-0.364 ( 0.8211 )
Eosinophils; Week 28; n= 62, 65	0.172 ( 0.4365 )	-0.36 ( 0.8258 )
Eosinophils; Week 32; n= 61, 66	0.079 ( 0.3759 )	-0.347 ( 0.831 )
Eosinophils; Week 36; n= 60, 66	0.086 ( 0.3758 )	-0.347 ( 0.8388 )
Eosinophils; Week 40; n= 61, 65	0.022 ( 0.4448 )	-0.358 ( 0.8396 )
Eosinophils; Week 44; n= 59, 61	0.051 ( 0.4472 )	-0.365 ( 0.8604 )
Eosinophils; Week 48; n= 59, 64	0.109 ( 0.3873 )	-0.364 ( 0.854 )
Eosinophils; Week 52; n= 60, 64	0.055 ( 0.3764 )	-0.341 ( 0.8456 )
Eosinophils; Week 56; n= 59, 61	0.071 ( 0.4137 )	-0.351 ( 0.8624 )
Eosinophils; Week 60; n= 58, 64	0.111 ( 0.4666 )	-0.302 ( 0.8352 )
Absolute Leukocytes; Baseline; n= 68, 68	9.91 ( 2.714 )	9.54 ( 3.13 )
Leukocytes; Week 4; 66, 66	-0.11 ( 2.109 )	-0.77 ( 2.356 )
Leukocytes; Week 8; n= 65, 66	-0.18 ( 2.562 )	-0.83 ( 2.511 )
Leukocytes; Week 12; n= 63, 65	-0.53 ( 1.765 )	-1.24 ( 2.716 )
Leukocytes; ; Week 16; n= 64, 68	0.01 ( 2.567 )	-1.16 ( 2.827 )
Leukocytes; Week 20; n= 61, 66	-0.13 ( 2.269 )	-1.43 ( 2.649 )
Leukocytes; Week 24; n= 61, 66	-0.73 ( 2.11 )	-1.47 ( 2.738 )
Leukocytes; Week 28; n= 62, 65	-0.01 ( 2.297 )	-1.66 ( 2.804 )
Leukocytes; week 32; n= 61, 66	-0.33 ( 2.218 )	-1.54 ( 2.725 )
Leukocytes; Week 36; n= 60, 66	-0.17 ( 2.501 )	-1.37 ( 2.578 )
Leukocytes; Week 40; n= 61, 65	0.17 ( 2.912 )	-1.28 ( 3.284 )
Leukocytes; Week 44; n= 59, 61	0.25 ( 3.166 )	-1.57 ( 2.198 )
Leukocytes; Week 48; n= 59, 64	-0.1 ( 3.092 )	-1.46 ( 2.546 )
Leukocytes; Week 52; n= 60, 64	-0.12 ( 3.114 )	-1.5 ( 2.521 )
Leukocytes; Week 56; n= 59, 61	-0.05 ( 3.357 )	-1.5 ( 2.84 )
Leukocytes; Week 60; n= 58, 64	0.19 ( 3.533 )	-1.2 ( 2.396 )
Absolute Lymphocytes; Baseline; n= 68, 68	1.638 ( 0.9375 )	1.508 ( 0.823 )
Lymphocytes; Week 4; n= 66, 66	0.031 ( 0.899 )	0.145 ( 0.7485 )
Lymphocytes; Week 8; n= 65, 66	0.245 ( 0.8804 )	-0.048 ( 0.6388 )
Lymphocytes; Week 12; n= 63, 65	0.16 ( 0.9043 )	-0.071 ( 0.7665 )
Lymphocytes; Week 16; n= 64, 68	0.078 ( 1.0337 )	0.079 ( 0.7254 )
Lymphocytes; Week 20; n= 61, 66	0.137 ( 0.7984 )	0.127 ( 0.7096 )
Lymphocytes; Week 24; n= 61, 66	0.056 ( 0.8778 )	0.011 ( 0.8077 )
Lymphocytes; Week 28; n= 62, 65	0.261 ( 1.0966 )	0.004 ( 0.7328 )
Lymphocytes; Week 32; n= 61, 66	0.244 ( 0.9633 )	0.031 ( 0.7986 )
Lymphocytes; Week 36; n= 60, 66	0.156 ( 1.0399 )	0.031 ( 0.5939 )
Lymphocytes; Week 40; n= 61, 65	0.064 ( 1.0537 )	0.037 ( 0.6391 )
Lymphocytes; Week 44; n= 59, 61	0.13 ( 0.8773 )	0.059 ( 0.6471 )
Lymphocytes; Week 48; n=59, 64	0.106 ( 0.8396 )	0.035 ( 0.7368 )
Lymphocytes; Week 52; n= 60, 64	0.144 ( 0.9262 )	0.031 ( 0.6244 )
Lymphocytes; Week 56; n= 59, 61	0.2 ( 0.8356 )	0.128 ( 0.7824 )
Lymphocytes; Week 60; n= 58, 64	0.076 ( 0.8821 )	-0.101 ( 0.6848 )
Absolute Monocytes; Baseline; n= 68, 68	0.377 ( 0.2126 )	0.405 ( 0.2376 )
Monocytes; week 4; n= 66, 66	0.038 ( 0.2444 )	0.014 ( 0.2127 )
Monocytes; Week 8; n= 65, 66	0.052 ( 0.2271 )	0.039 ( 0.1988 )
Monocytes; Week 12; n= 63, 65	0.077 ( 0.2468 )	-0.004 ( 0.1985 )
Monocytes; Week 16; n= 64, 68	0.086 ( 0.279 )	0.031 ( 0.2157 )
Monocytes; Week 20; n= 61, 66	0.132 ( 0.2684 )	0.03 ( 0.1967 )
Monocytes; Week 24; n= 61, 66	0.061 ( 0.229 )	0.013 ( 0.2412 )
Monocytes; Week 28; n= 62, 65	0.107 ( 0.2363 )	0.035 ( 0.235 )
Monocytes; Week 32; n= 61, 66	0.108 ( 0.2839 )	0.057 ( 0.2069 )
Monocytes; Week 36; n= 60, 66	0.089 ( 0.2992 )	0.072 ( 0.2416 )
Monocytes; Week 40; n= 61, 65	0.084 ( 0.2495 )	0.05 ( 0.2096 )
Monocytes; Week 44; n= 59, 61	0.09 ( 0.2494 )	0.077 ( 0.2176 )
Monocytes; Week 48; n= 59, 64	0.078 ( 0.2261 )	0.025 ( 0.2235 )
Monocytes; Week 52; n= 60, 64	0.075 ( 0.2407 )	0.024 ( 0.2098 )
Monocytes; Week 56; n= 59, 61	0.051 ( 0.2104 )	0.037 ( 0.2303 )
Monocytes; Week 60; n= 58, 64	0.052 ( 0.26 )	0.001 ( 0.2165 )
Absolute Neutrophils; Baseline; n= 68, 68	7.5 ( 2.7424 )	7.198 ( 2.9732 )
Neutrophils; Week 4; n= 66, 66	-0.124 ( 2.617 )	-0.583 ( 2.2703 )
Neutrophils; Week 8; n= 65, 66	-0.572 ( 2.6791 )	-0.443 ( 2.56476 )
Neutrophils; Week 12; n= 63, 65	-0.797 ( 2.2948 )	-0.799 ( 2.6278 )
Neutrophils; Week 16; n= 64, 68	-0.222 ( 2.7666 )	-0.914 ( 2.6034 )
Neutrophils; Week 20; n= 61, 66	-0.56 ( 2.3679 )	-1.243 ( 2.6857 )
Neutrophils; Week 24; n= 61, 66	-0.98 ( 2.3151 )	-1.12 ( 2.8349 )
Neutrophils; Week 28; n= 62, 65	-0.555 ( 2.3719 )	-1.335 ( 2.9428 )
Neutrophils; Week 32; n= 61, 66	-0.762 ( 2.4952 )	-1.286 ( 2.6995 )
Neutrophils; Week 36; n= 60, 66	-0.509 ( 2.8231 )	-1.131 ( 2.4261 )
Neutrophils; Week 40; n= 61, 65	-0.009 ( 3.0467 )	-1.01 ( 3.3999 )
Neutrophils; Week 44; n= 59, 61	-0.02 ( 3.3497 )	-1.344 ( 2.1031 )
Neutrophils; Week 48; n= 59, 64	-0.403 ( 3.2656 )	-1.151 ( 2.5806 )
Neutrophils; Week 52; n= 60, 64	-0.391 ( 3.4463 )	-1.211 ( 2.2815 )
Neutrophils; Week 56; n= 59, 61	-0.381 ( 3.4297 )	-1.311 ( 3.0024 )
Neutrophils; Week 60; n= 58, 64	-0.048 ( 3.5724 )	-0.795 ( 2.6501 )
Absolute Platelets; Baseline; n= 68, 68	259.8 ( 61.16 )	270.3 ( 60.86 )
Platelets; Week 4; n= 66, 67	4.5 ( 38.14 )	-1.4 ( 33.79 )
Platelets; Week 8; n= 66, 66	5 ( 43.97 )	4.1 ( 26.48 )
Platelets; Week 12; n= 63, 65	3.1 ( 50.6 )	-4.3 ( 37.89 )
Platelets; Week 16; n= 64, 68	15.4 ( 71.2 )	1.8 ( 40.25 )
Platelets; Week 20; n= 61, 68	12.3 ( 49.92 )	6.1 ( 52.76 )
Platelets; Week 24; n= 62, 65	10.9 ( 50.38 )	-4.2 ( 40.07 )
Platelets; Week 28; n= 62, 66	13.3 ( 55.12 )	5.4 ( 41.57 )
Platelets; Week 32; n= 61, 67	12.1 ( 45.36 )	0.7 ( 43.85 )
Platelets; Week 36; n= 60, 66	9.3 ( 42.64 )	0.6 ( 37.87 )
Platelets; Week 40; n= 61, 65	14.7 ( 45.63 )	2 ( 42.12 )
Platelets; Week 44; n= 60, 63	19.3 ( 48.88 )	4.9 ( 40.27 )
Platelets; Week 48; n= 59, 64	14.2 ( 53.93 )	5.4 ( 44.8 )
Platelets; Week 52; n= 60, 64	14.7 ( 48.19 )	-3.7 ( 46.34 )
Platelets; Week 56; n= 59, 61	20.3 ( 47.35 )	-1 ( 48.51 )
Platelets; Week 60; n= 59, 64	13 ( 50.07 )	-2 ( 41.32 )

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

No statistical analyses for this end point

Secondary: Change from Baseline in hematology parameters of Mean Corpuscle Hemoglobin Concentration (MCHC) and hemoglobin levels

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End point title

Change from Baseline in hematology parameters of Mean Corpuscle Hemoglobin Concentration (MCHC) and hemoglobin levels

End point description

Blood samples were collected to evaluate change from Baseline in MCHC and hemoglobin values at Baseline throughout the 52 weeks study treatment and 8-weeks follow up period. Baseline values were taken at Visit 2 and change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and standard deviation (SD) were measured.

End point type

Secondary

End point timeframe

Baseline and up to Week 60

End point values	Placebo	Mepolizumab 300mg
Number of subjects analysed	68 ^[36]	68 ^[37]
Units: g/L
arithmetic mean (standard deviation)
Absolute MCHC; Baseline; n= 68, 68	324.9 ( 7.53 )	324.4 ( 7.37 )
MCHC; Week 4; n= 66, 67	-1.2 ( 6.02 )	-1.1 ( 5.92 )
MCHC; Week 8; n= 66, 66	-1.5 ( 6.69 )	-1.5 ( 6.86 )
MCHC; Week 12; n= 63, 65	-1.3 ( 7.73 )	0.3 ( 6.6 )
MCHC; Week 16; n= 64, 68	-2.3 ( 7.11 )	-2.1 ( 7.88 )
MCHC; Week 20; n= 61, 68	-2.2 ( 6.65 )	-1.2 ( 7.88 )
MCHC; Week 24; n= 62, 66	-3.2 ( 10.19 )	-2.6 ( 7.39 )
MCHC; Week 28; n= 62, 66	-4.3 ( 7.07 )	-2.6 ( 7.33 )
MCHC; Week 32; n= 61, 67	-6.6 ( 8.19 )	-3.6 ( 7.56 )
MCHC; Week 36; n= 60, 66	-4.7 ( 8.05 )	-3.3 ( 8.37 )
MCHC; Week 40; n= 61, 65	-4.5 ( 8.04 )	-3.2 ( 8.96 )
MCHC; Week 44; n= 60, 64	-4.7 ( 8.51 )	-4.5 ( 9.4 )
MCHC; Week 48; n= 59, 64	-6 ( 8.03 )	-4.8 ( 10.56 )
MCHC; Week 52; n= 60, 64	-5.2 ( 7.79 )	-5.3 ( 7.72 )
MCHC; Week 56; n= 59, 61	-6.9 ( 7.74 )	-5.3 ( 7.47 )
MCHC; Week 60; n= 59, 64	-7.5 ( 7.41 )	-4.7 ( 9.9 )
Absolute Hemoglobin; Baseline; n= 68, 68	141.6 ( 12.67 )	140.6 ( 12.99 )
Hemoglobin; Week 4; n= 66, 67	-2.3 ( 6.86 )	-1.8 ( 6.43 )
Hemoglobin; Week 8; n= 66, 66	-2.5 ( 7.56 )	-1.1 ( 6.28 )
Hemoglobin; Week 12; n= 63, 65	-1.6 ( 8.28 )	-2.2 ( 7.17 )
Hemoglobin; Week 16; n= 64, 68	-1.6 ( 8.24 )	-1.9 ( 7.64 )
Hemoglobin; Week 20; n= 61, 68	-0.3 ( 6.85 )	-1.4 ( 7.64 )
Hemoglobin; Week 24; n= 62, 66	-1.1 ( 8.06 )	-1.6 ( 8.51 )
Hemoglobin; Week 28; n= 62, 66	-1.3 ( 7.48 )	-1.3 ( 8.94 )
Hemoglobin; Week 32; n= 61, 67	-1.3 ( 8.03 )	-1.6 ( 9.22 )
Hemoglobin; Week 36; n= 60, 66	-0.2 ( 8.5 )	-0.4 ( 10.23 )
Hemoglobin; Week 40; n= 61, 65	0.1 ( 8.35 )	-0.9 ( 9.74 )
Hemoglobin; Week 44; n= 60, 64	0.7 ( 9.59 )	-1.9 ( 10.47 )
Hemoglobin; Week 48; n= 59, 64	0.5 ( 8.2 )	-1.9 ( 11.07 )
Hemoglobin; Week 52; n= 60, 64	0.1 ( 8.57 )	-1.9 ( 10.36 )
Hemoglobin; Week 56; n= 59, 61	-1.5 ( 9.92 )	-1.9 ( 11.48 )
Hemoglobin; Week 60; n= 59, 64	-1.8 ( 9.86 )	-2.4 ( 11.36 )

Notes
[36] - Safety Population
[37] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in hematology parameters of Mean Corpuscle Volume (MCV) levels

Top of page

End point title

Change from Baseline in hematology parameters of Mean Corpuscle Volume (MCV) levels

End point description

Blood samples were collected to evaluate change from Baseline in MCV values at Baseline throughout the 52 weeks study treatment and 8-weeks follow up period. Baseline values were taken at Visit 2 and change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and standard deviation (SD) were measured.

End point type

Secondary

End point timeframe

Baseline and up to Week 60

End point values	Placebo	Mepolizumab 300mg
Number of subjects analysed	68 ^[38]	68 ^[39]
Units: femtoliter (fL)
arithmetic mean (standard deviation)
Absolute, Baseline; n= 68, 68	94.8 ( 9.02 )	94.8 ( 6.14 )
Week 4; n= 66, 67	0.4 ( 1.67 )	0 ( 2.33 )
Week 8; n= 66, 66	0.3 ( 2.5 )	0 ( 2.58 )
Week 12; n= 63, 65	0.2 ( 2 )	-0.7 ( 2.3 )
Week 16; n= 64, 68	0 ( 2.22 )	-0.4 ( 2.94 )
Week 20; n= 61, 68	-0.3 ( 1.87 )	-0.9 ( 2.66 )
Week 24; n= 62, 66	-0.5 ( 2.21 )	-1 ( 2.92 )
Week 28; n= 62, 66	-0.4 ( 2.86 )	-1.4 ( 3.48 )
Week 32; n= 61, 67	-0.2 ( 3.01 )	-1.7 ( 3.56 )
Week 36; n= 60, 66	-0.5 ( 3.55 )	-1.9 ( 3.74 )
Week 40; n= 61, 65	-0.9 ( 4.09 )	-1.4 ( 3.73 )
Week 44; n= 60, 64	-1.2 ( 5.06 )	-1.5 ( 3.91 )
Week 48; n= 59, 64	-1.1 ( 5.96 )	-1.5 ( 4.04 )
Week 52; n= 60, 64	-0.8 ( 6.52 )	-1.3 ( 4.29 )
Week 56; n= 59, 61	-0.5 ( 6.47 )	-1 ( 4.15 )
Week 60; n= 59, 64	-0.6 ( 6.57 )	-1 ( 4.49 )

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

No statistical analyses for this end point

Secondary: Change from Baseline in hematology parameters of Mean Corpuscle Hemoglobin (MCH) levels

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End point title

Change from Baseline in hematology parameters of Mean Corpuscle Hemoglobin (MCH) levels

End point description

Blood samples were collected to evaluate change from Baseline in MCH values at Baseline throughout the 52 weeks study treatment and 8-weeks follow up period. Baseline values were taken at Visit 2 and change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and standard deviation (SD) were measured.

End point type

Secondary

End point timeframe

Baseline and up to Week 60

End point values	Placebo	Mepolizumab 300mg
Number of subjects analysed	68 ^[40]	68 ^[41]
Units: Picogram (pg)
arithmetic mean (standard deviation)
Absolute, Baseline; n= 68, 68	30.77 ( 2.902 )	30.77 ( 2.255 )
Week 4; n= 66, 67	0.04 ( 0.331 )	-0.12 ( 0.785 )
Week 8; n= 66, 66	-0.02 ( 0.95 )	-0.16 ( 0.653 )
Week 12; n= 63, 65	-0.04 ( 0.55 )	-0.17 ( 0.769 )
Week 16; n= 64, 68	-0.21 ( 0.845 )	-0.34 ( 0.769 )
Week 20; n= 61, 68	-0.28 ( 0.665 )	-0.41 ( 0.851 )
Week 24; n= 62, 66	-0.45 ( 1.27 )	-0.59 ( 0.959 )
Week 28; n= 62, 66	-0.51 ( 0.618 )	-0.7 ( 1.184 )
Week 32; n= 61, 67	-0.66 ( 0.764 )	-0.88 ( 1.368 )
Week 36; n= 60, 66	-0.6 ( 0.91 )	-0.9 ( 1.395 )
Week 40; n= 61, 65	-0.67 ( 1.171 )	-0.79 ( 1.39 )
Week 44; n= 60, 64	-0.78 ( 1.566 )	-0.95 ( 1.484 )
Week 48; n= 59, 64	-0.87 ( 1.745 )	-0.96 ( 1.654 )
Week 52; n= 60, 64	-0.69 ( 1.908 )	-0.95 ( 1.585 )
Week 56; n= 59, 61	-0.79 ( 2.056 )	-0.83 ( 1.713 )
Week 60; n= 59, 64	-0.86 ( 2.094 )	-0.8 ( 1.818 )

Notes
[40] - Safety Population
[41] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in hematology parameters of erythrocytes levels

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End point title

Change from Baseline in hematology parameters of erythrocytes levels

End point description

Blood samples were collected to evaluate change from Baseline in erythrocytes values at Baseline throughout the 52 weeks study treatment and 8-weeks follow up period. Baseline values were taken at Visit 2 and change from Baseline was defined as post-dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and standard deviation (SD) were measured.

End point type

Secondary

End point timeframe

Baseline and up to Week 60

End point values	Placebo	Mepolizumab 300mg
Number of subjects analysed	68 ^[42]	68 ^[43]
Units: 10^12/ L
arithmetic mean (standard deviation)
Absolute, Baseline; n= 68, 68	4.64 ( 0.511 )	4.58 ( 0.456 )
Week 4; n= 66, 67	-0.07 ( 0.228 )	-0.03 ( 0.226 )
Week 8; n= 66, 66	-0.07 ( 0.278 )	-0.01 ( 0.211 )
Week 12; n= 63, 65	-0.04 ( 0.273 )	-0.04 ( 0.252 )
Week 16; n= 64, 68	-0.02 ( 0.266 )	-0.01 ( 0.243 )
Week 20; n= 61, 68	0.03 ( 0.243 )	0.03 ( 0.252 )
Week 24; n= 62, 66	0.02 ( 0.252 )	0.05 ( 0.265 )
Week 28; n= 62, 66	0.03 ( 0.286 )	0.08 ( 0.264 )
Week 32; n= 61, 67	0.06 ( 0.3 )	0.09 ( 0.273 )
Week 36; n= 60, 66	0.08 ( 0.314 )	0.14 ( 0.299 )
Week 40; n= 61, 65	0.09 ( 0.274 )	0.09 ( 0.27 )
Week 44; n= 60, 64	0.13 ( 0.332 )	0.08 ( 0.26 )
Week 48; n= 59, 64	0.14 ( 0.293 )	0.1 ( 0.271 )
Week 52; n= 60, 64	0.1 ( 0.309 )	0.09 ( 0.251 )
Week 56; n= 59, 61	0.06 ( 0.365 )	0.07 ( 0.284 )
Week 60; n= 59, 64	0.07 ( 0.384 )	0.05 ( 0.318 )

Notes
[42] - Safety Population
[43] - Safety Population

No statistical analyses for this end point

Secondary: Number of participants with anti-Mepolizumab antibodies

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End point title

Number of participants with anti-Mepolizumab antibodies

End point description

Blood samples were collected for the determination of anti-Mepolizumab antibodies. Participants who showed presence of anti-Mepolizumab antibody were termed as 'positive' and those who did not have anti-Mepolizumab antibody in blood sample were termed as 'negative'. Participants who did not have a positive ADA assay prior to the first dose of investigational product were included in the analysis.

End point type

Secondary

End point timeframe

Up to Week 60

End point values	Placebo	Mepolizumab 300mg
Number of subjects analysed	67 ^[44]	66 ^[45]
Units: Participants
Negative	66	65
Positive	1	1

Notes
[44] - Safety Population
[45] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels

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End point title

Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels

End point description

SBP and DBP were measured from Baseline throughout follow-up (till Week 60) before injection with the participant sitting, having rested in this position for at least 5 minutes before reading. The Baseline value was taken at Visit 2 and change from Baseline was defined as post dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and standard deviation (SD) were measured.

End point type

Secondary

End point timeframe

Baseline up to Week 60

End point values	Placebo	Mepolizumab 300mg
Number of subjects analysed	68 ^[46]	68 ^[47]
Units: millimeter of mercury (mm of Hg)
arithmetic mean (standard deviation)
Absolute SBP; Baseline; n= 68, 68	127.46 ( 17.794 )	122.46 ( 14.134 )
SBP; Week 4; n= 68, 68	0.47 ( 15.865 )	0.93 ( 12.37 )
SBP; Week 8; n= 67, 68	0.07 ( 14.192 )	1.29 ( 11.066 )
SBP; Week 12; n= 66, 68	-1.12 ( 14.38 )	-1.41 ( 12.071 )
SBP; Week 16; n= 64, 68	-0.97 ( 16.63 )	-0.41 ( 11.579 )
SBP; Week 20; n= 63, 68	-0.97 ( 15.028 )	-0.85 ( 12.019 )
SBP; Week 24; n= 63, 67	-1.54 ( 15.449 )	-1.57 ( 12.824 )
SBP; Week 28; n= 63, 67	-0.06 ( 14.337 )	-0.15 ( 13.24 )
SBP; Week 32; n= 62, 67	-2.35 ( 14.027 )	0.04 ( 11.181 )
SBP; Week 36; n= 62, 67	1.02 ( 14.663 )	0.48 ( 14.397 )
SBP; Week 40; n= 62, 66	0.9 ( 14.202 )	1.27 ( 12.075 )
SBP; Week 44; n= 61, 66	1.41 ( 16.143 )	-0.36 ( 13.694 )
SBP; Week 48; n= 61, 65	-0.41 ( 17.14 )	-0.22 ( 12.351 )
SBP: Week 52; n= 61, 65	-1.03 ( 13.2 )	-0.32 ( 13.091 )
SBP; Week 56; n= 62, 63	0.06 ( 15.216 )	1.02 ( 13.559 )
SBP; Week 60; n= 61, 65	0.61 ( 15.627 )	-0.63 ( 11.656 )
Absolute DBP; Baseline; n= 68, 68	80.21 ( 10.127 )	76.22 ( 9.646 )
DBP; Week 4; n= 68, 68	-2.26 ( 10.046 )	1.01 ( 10.13 )
DBP; Week 8; n= 67, 68	-2.04 ( 8.461 )	-0.34 ( 10.078 )
DBP; Week 12; n= 66, 68	-1.92 ( 10.115 )	-0.37 ( 9.167 )
DBP; Week 16; n= 64, 68	-1.36 ( 10.237 )	0.46 ( 9.824 )
DBP; Week 20; n= 63, 68	-1.25 ( 8.092 )	-1.19 ( 9.214 )
DBP; Week 24; n= 63, 67	-2.24 ( 8.751 )	-1.16 ( 9.629 )
DBP; Week 28; n= 63, 67	-2.02 ( 9.939 )	0.36 ( 10.071 )
DBP; Week 32; n= 62, 67	-4.27 ( 9.313 )	-0.49 ( 10.652 )
DBP; Week 36; n= 62, 67	-1.97 ( 10.995 )	0.16 ( 10.988 )
DBP; Week 40; n= 62, 66	-0.48 ( 9.625 )	-0.03 ( 8.868 )
DBP; Week 44; n= 61, 66	-0.79 ( 9.93 )	-1.03 ( 9.595 )
DBP; Week 48; n= 61, 65	-3.26 ( 10.466 )	-1.71 ( 9.239 )
DBP; Week 52; n= 61, 65	-3.66 ( 10.628 )	-0.06 ( 9.236 )
DBP; Week 56; n= 62, 63	-3.48 ( 10.57 )	0.11 ( 8.899 )
DBP; Week 60; n= 61, 65	-2.54 ( 11.278 )	-0.45 ( 9.836 )

Notes
[46] - Safety Population
[47] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in pulse rate

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End point title

Change from Baseline in pulse rate

End point description

Pulse rate was measured from Baseline throughout follow-up (till Week 60) before injection with the participant sitting, having rested in this position for at least 5 minutes before reading. The Baseline value was taken at Visit 2 and change from Baseline was defined as post dose visit value minus Baseline value. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and standard deviation (SD) were measured.

End point type

Secondary

End point timeframe

Baseline and up to Week 60

End point values	Placebo	Mepolizumab 300mg
Number of subjects analysed	68 ^[48]	68 ^[49]
Units: beats per minute (bpm)
arithmetic mean (standard deviation)
Absolute Baseline; n= 68, 68	77.38 ( 13.763 )	75.75 ( 10.404 )
Week 4; n= 68, 68	2.01 ( 12.294 )	1.87 ( 10.543 )
Week 8; n= 67, 68	0.97 ( 10.718 )	-1.01 ( 10.304 )
Week 12; n= 66, 68	1.52 ( 12.393 )	-0.12 ( 10.855 )
Week 16; n= 64, 68	0.59 ( 11.287 )	0.44 ( 11.411 )
Week 20; n= 63, 68	1.03 ( 11.521 )	-0.56 ( 9.687 )
Week 24; n= 63, 67	0.79 ( 12.134 )	0.37 ( 10.057 )
Week 28; n= 62, 67	1.29 ( 10.439 )	0.16 ( 10.093 )
Week 32; n= 62, 67	1.6 ( 11.703 )	-0.31 ( 10.53 )
Week 36; n= 62, 67	3.47 ( 12.538 )	-0.57 ( 11.422 )
Week 40; n= 62, 66	2.65 ( 12.297 )	0.74 ( 11.669 )
Week 44; n= 61, 66	3.1 ( 12.195 )	0.15 ( 12.763 )
Week 48; n= 61, 65	3.85 ( 12.383 )	-1.12 ( 10.315 )
Week 52; n= 61, 65	1.85 ( 11.987 )	-2.17 ( 9.596 )
Week 56; n= 62, 63	2.6 ( 14.041 )	-0.35 ( 9.986 )
Week 60; n= 61, 65	1.51 ( 12.793 )	0.09 ( 10.28 )

Notes
[48] - Safety Population
[49] - Safety Population

No statistical analyses for this end point

Secondary: Change from Baseline in body temperature

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End point title

Change from Baseline in body temperature

End point description

Body temperature was measured from Baseline throughout follow-up (till Week 60). The Baseline value was taken at Visit 2 and change from Baseline was defined as post dose visit value minus Baseline value. The analysis was performed on Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles). Mean and standard deviation (SD) were measured.

End point type

Secondary

End point timeframe

Baseline and up to Week 60

End point values	Placebo	Mepolizumab 300mg
Number of subjects analysed	68 ^[50]	68 ^[51]
Units: Degree celsius
arithmetic mean (standard deviation)
Absolute Baseline; n= 68, 68	36.52 ( 0.385 )	36.51 ( 0.462 )
Week 4; n= 68, 68	0.05 ( 0.439 )	-0.04 ( 0.411 )
Week 8; n= 67,68	-0.01 ( 0.379 )	-0.02 ( 0.425 )
Week 12; n= 66, 68	0.05 ( 0.41 )	-0.03 ( 0.447 )
Week 16; n= 64, 68	-0.01 ( 0.421 )	-0.03 ( 0.432 )
Week 20; n= 63, 68	-0.08 ( 0.351 )	-0.13 ( 0.376 )
Week 24; n= 62, 67	-0.06 ( 0.449 )	-0.06 ( 0.389 )
Week 28; n= 63, 67	-0.06 ( 0.499 )	-0.14 ( 0.411 )
Week 32; n= 62, 67	-0.09 ( 0.392 )	-0.07 ( 0.355 )
Week 36; n= 62, 67	-0.05 ( 0.431 )	0.03 ( 0.468 )
Week 40; n= 62, 66	-0.03 ( 0.53 )	-0.13 ( 0.406 )
Week 44; n= 61, 65	-0.03 ( 0.55 )	-0.08 ( 0.396 )
Week 48; n= 61, 64	-0.04 ( 0.452 )	-0.09 ( 0.414 )
Week 52; n= 60, 65	-0.04 ( 0.423 )	-0.12 ( 0.541 )
Week 56; n= 61, 63	-0.08 ( 0.53 )	0 ( 0.402 )
Week 60; n= 61, 64	0.03 ( 0.467 )	-0.02 ( 0.479 )

Notes
[50] - Safety Population
[51] - Safety Population

No statistical analyses for this end point

Secondary: Mean change from Baseline in QT interval corrected by Fridericia's method (QTcF) and QT interval corrected by Bazett's method (QTcB) values

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End point title

Mean change from Baseline in QT interval corrected by Fridericia's method (QTcF) and QT interval corrected by Bazett's method (QTcB) values

End point description

Single measurements of 12-lead electrocardiogram (ECGs) were obtained after 5 minutes rest in a supine position at Baseline throughout the 52 weeks treatment period and 8 weeks follow-up period using an ECG machine. Mean change from Baseline in QTcF and QTcB values were measured. Only those participants with data available at the specified data points were analyzed (represented by n= X in the category titles).

End point type

Secondary

End point timeframe

Baseline and up to Week 60

End point values	Placebo	Mepolizumab 300mg
Number of subjects analysed	68 ^[52]	68 ^[53]
Units: milliseconds (msec)
arithmetic mean (standard deviation)
QTcF; Week 8; n= 66, 66	0.1 ( 17.9 )	1 ( 15.03 )
QTcF; Week 16; n= 64, 66	0.8 ( 15.26 )	0.2 ( 14.05 )
QTcF; Week 24; n= 60, 66	2.8 ( 14.43 )	1.9 ( 16.66 )
QTcF; Week 32; n= 61, 66	6.2 ( 25.19 )	1.5 ( 17.16 )
QTcF; Week 40; n= 61, 65	-0.5 ( 15.25 )	-0.3 ( 17.53 )
QTcF; Week 52; n= 58, 64	2 ( 15.96 )	3 ( 16.04 )
QTcF; Week 60; n= 58, 63	3 ( 14.3 )	2.9 ( 14.97 )
QTcF; Any time post Baseline; n= 68, 68	16.9 ( 23.74 )	15.4 ( 13.79 )
QTcB; Week 8; n= 66, 66	-0.8 ( 19.05 )	0.9 ( 17.31 )
QTcB; Week 16; n= 64, 66	-0.1 ( 18.33 )	-0.9 ( 14.76 )
QTcB; Week 24; n= 60, 66	1.4 ( 17.89 )	1 ( 18.1 )
QTcB; Week 32; n= 61, 66	5.2 ( 29.63 )	0 ( 19.63 )
QTcB; Week 40; n= 61, 65	-0.6 ( 17.83 )	-1.4 ( 18.88 )
QTcB; Week 52; n= 58, 64	1.8 ( 17.64 )	0.7 ( 18.27 )
QTcB; Week 60; n= 58, 63	1.2 ( 16.56 )	2.7 ( 17.27 )
QTcB; Any time post Baseline; n= 68, 68	18.8 ( 26.46 )	18.1 ( 15.28 )

Notes
[52] - Safety Population
[53] - Safety Population

No statistical analyses for this end point

Secondary: Maximum change from Baseline in QTcF and QTcB values

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End point title

Maximum change from Baseline in QTcF and QTcB values

End point description

Single measurements of 12-lead ECGs were obtained after 5 minutes rest in a supine position at Baseline throughout the 52 weeks treatment period and 8 weeks follow-up period using an ECG machine. Maximum change from Baseline in QTcF and QTcB values were measured.

End point type

Secondary

End point timeframe

Baseline and up to Week 60

End point values	Placebo	Mepolizumab 300mg
Number of subjects analysed	68 ^[54]	68 ^[55]
Units: msec
arithmetic mean (standard deviation)
QTcB interval	18.8 ( 26.46 )	18.1 ( 15.28 )
QTcF interval	16.9 ( 23.74 )	15.4 ( 13.79 )

Notes
[54] - Safety Population
[55] - Safety Population

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

On-treatment Serious Adverse Events (SAEs) and non-serious Adverse Events (AEs) were collected from the start of the study treatment until week 52.

Adverse event reporting additional description

AEs and SAEs were collected in Safety Population which comprised of all participants who received at least one dose of study treatment.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

19.0

Reporting group title

Mepolizumab 300mg

Reporting group description

Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.

Reporting group title

Placebo

Reporting group description

Participants received placebo injection via subcutaneous (SC) route once every 4 weeks along with standard of care (SOC) drugs up to Week 48.

Serious adverse events	Mepolizumab 300mg	Placebo
Total subjects affected by serious adverse events
subjects affected / exposed	12 / 68 (17.65%)	18 / 68 (26.47%)
number of deaths (all causes)	1	0
number of deaths resulting from adverse events
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Testis cancer
subjects affected / exposed	0 / 68 (0.00%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	1 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Road traffic accident
subjects affected / exposed	0 / 68 (0.00%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Spinal fracture
subjects affected / exposed	0 / 68 (0.00%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Cardiac arrest
subjects affected / exposed	1 / 68 (1.47%)	0 / 68 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Coronary artery disease
subjects affected / exposed	0 / 68 (0.00%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Stress cardiomyopathy
subjects affected / exposed	0 / 68 (0.00%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Nervous system disorders
Cerebellar ischaemia
subjects affected / exposed	1 / 68 (1.47%)	0 / 68 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Dizziness
subjects affected / exposed	1 / 68 (1.47%)	0 / 68 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Facial paralysis
subjects affected / exposed	0 / 68 (0.00%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Facial paresis
subjects affected / exposed	1 / 68 (1.47%)	0 / 68 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lacunar infarction
subjects affected / exposed	1 / 68 (1.47%)	0 / 68 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Nystagmus
subjects affected / exposed	1 / 68 (1.47%)	0 / 68 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pachymeningitis
subjects affected / exposed	1 / 68 (1.47%)	0 / 68 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Toxic encephalopathy
subjects affected / exposed	0 / 68 (0.00%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Hernia
subjects affected / exposed	1 / 68 (1.47%)	0 / 68 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pyrexia
subjects affected / exposed	0 / 68 (0.00%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Immune system disorders
Allergic granulomatous angiitis
subjects affected / exposed	0 / 68 (0.00%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hypersensitivity
subjects affected / exposed	1 / 68 (1.47%)	0 / 68 (0.00%)
occurrences causally related to treatment / all	3 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 68 (1.47%)	0 / 68 (0.00%)
occurrences causally related to treatment / all	1 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	2 / 68 (2.94%)	4 / 68 (5.88%)
occurrences causally related to treatment / all	0 / 2	0 / 8
deaths causally related to treatment / all	0 / 0	0 / 0
Acute respiratory failure
subjects affected / exposed	0 / 68 (0.00%)	2 / 68 (2.94%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Lung infiltration
subjects affected / exposed	0 / 68 (0.00%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia aspiration
subjects affected / exposed	0 / 68 (0.00%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory failure
subjects affected / exposed	0 / 68 (0.00%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Psychiatric disorders
Mental status changes
subjects affected / exposed	0 / 68 (0.00%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Renal and urinary disorders
Acute kidney injury
subjects affected / exposed	0 / 68 (0.00%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Back pain
subjects affected / exposed	1 / 68 (1.47%)	0 / 68 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Influenza
subjects affected / exposed	0 / 68 (0.00%)	2 / 68 (2.94%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia
subjects affected / exposed	0 / 68 (0.00%)	2 / 68 (2.94%)
occurrences causally related to treatment / all	0 / 0	1 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	0 / 68 (0.00%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	0 / 68 (0.00%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 68 (0.00%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Corona virus infection
subjects affected / exposed	0 / 68 (0.00%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Enterococcal infection
subjects affected / exposed	1 / 68 (1.47%)	0 / 68 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 68 (0.00%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Herpes zoster
subjects affected / exposed	0 / 68 (0.00%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Lower respiratory infection
subjects affected / exposed	0 / 68 (0.00%)	2 / 68 (2.94%)
occurrences causally related to treatment / all	0 / 0	2 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Parainfluenzae virus infection
subjects affected / exposed	1 / 68 (1.47%)	0 / 68 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Perirectal abscess
subjects affected / exposed	1 / 68 (1.47%)	0 / 68 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pneumonia bacterial
subjects affected / exposed	0 / 68 (0.00%)	1 / 68 (1.47%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory tract infection
subjects affected / exposed	1 / 68 (1.47%)	0 / 68 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	1 / 68 (1.47%)	0 / 68 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

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

Non-serious adverse events	Mepolizumab 300mg	Placebo
Total subjects affected by non serious adverse events
subjects affected / exposed	65 / 68 (95.59%)	61 / 68 (89.71%)
Vascular disorders
Hot flush
subjects affected / exposed	3 / 68 (4.41%)	0 / 68 (0.00%)
occurrences all number	4	0
General disorders and administration site conditions
Fatigue
subjects affected / exposed	10 / 68 (14.71%)	10 / 68 (14.71%)
occurrences all number	13	14
Injection site reaction
subjects affected / exposed	9 / 68 (13.24%)	7 / 68 (10.29%)
occurrences all number	38	11
Pyrexia
subjects affected / exposed	7 / 68 (10.29%)	7 / 68 (10.29%)
occurrences all number	12	12
Asthenia
subjects affected / exposed	5 / 68 (7.35%)	3 / 68 (4.41%)
occurrences all number	43	18
Chest pain
subjects affected / exposed	1 / 68 (1.47%)	5 / 68 (7.35%)
occurrences all number	3	5
Injection site pain
subjects affected / exposed	2 / 68 (2.94%)	3 / 68 (4.41%)
occurrences all number	3	15
Oedema peripheral
subjects affected / exposed	3 / 68 (4.41%)	1 / 68 (1.47%)
occurrences all number	4	1
Influenza like illness
subjects affected / exposed	3 / 68 (4.41%)	0 / 68 (0.00%)
occurrences all number	3	0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	10 / 68 (14.71%)	7 / 68 (10.29%)
occurrences all number	14	11
Cough
subjects affected / exposed	5 / 68 (7.35%)	8 / 68 (11.76%)
occurrences all number	5	12
Oropharyngeal pain
subjects affected / exposed	8 / 68 (11.76%)	5 / 68 (7.35%)
occurrences all number	8	5
Productive cough
subjects affected / exposed	6 / 68 (8.82%)	7 / 68 (10.29%)
occurrences all number	8	15
Sinus congestion
subjects affected / exposed	6 / 68 (8.82%)	6 / 68 (8.82%)
occurrences all number	9	9
Wheezing
subjects affected / exposed	5 / 68 (7.35%)	6 / 68 (8.82%)
occurrences all number	9	7
Nasal congestion
subjects affected / exposed	4 / 68 (5.88%)	5 / 68 (7.35%)
occurrences all number	4	6
Upper-airway cough syndrome
subjects affected / exposed	2 / 68 (2.94%)	6 / 68 (8.82%)
occurrences all number	2	6
Dyspnoea
subjects affected / exposed	1 / 68 (1.47%)	4 / 68 (5.88%)
occurrences all number	1	4
Epistaxis
subjects affected / exposed	3 / 68 (4.41%)	2 / 68 (2.94%)
occurrences all number	3	8
Sneezing
subjects affected / exposed	3 / 68 (4.41%)	1 / 68 (1.47%)
occurrences all number	3	1
Psychiatric disorders
Insomnia
subjects affected / exposed	2 / 68 (2.94%)	4 / 68 (5.88%)
occurrences all number	3	5
Investigations
Alanine aminotransferase increased
subjects affected / exposed	5 / 68 (7.35%)	0 / 68 (0.00%)
occurrences all number	5	0
Weight increased
subjects affected / exposed	4 / 68 (5.88%)	1 / 68 (1.47%)
occurrences all number	5	1
Aspartate aminotransferase increased
subjects affected / exposed	3 / 68 (4.41%)	0 / 68 (0.00%)
occurrences all number	3	0
Gamma-glutamyltransferase increased
subjects affected / exposed	3 / 68 (4.41%)	0 / 68 (0.00%)
occurrences all number	3	0
Injury, poisoning and procedural complications
Laceration
subjects affected / exposed	3 / 68 (4.41%)	2 / 68 (2.94%)
occurrences all number	3	4
Ligament sprain
subjects affected / exposed	4 / 68 (5.88%)	1 / 68 (1.47%)
occurrences all number	4	1
Contusion
subjects affected / exposed	3 / 68 (4.41%)	1 / 68 (1.47%)
occurrences all number	3	1
Nervous system disorders
Headache
subjects affected / exposed	22 / 68 (32.35%)	12 / 68 (17.65%)
occurrences all number	50	20
Dizziness
subjects affected / exposed	3 / 68 (4.41%)	5 / 68 (7.35%)
occurrences all number	6	8
Paraesthesia
subjects affected / exposed	4 / 68 (5.88%)	3 / 68 (4.41%)
occurrences all number	4	4
Sinus headache
subjects affected / exposed	2 / 68 (2.94%)	3 / 68 (4.41%)
occurrences all number	4	4
Migraine
subjects affected / exposed	3 / 68 (4.41%)	1 / 68 (1.47%)
occurrences all number	3	1
Ear and labyrinth disorders
Vertigo
subjects affected / exposed	5 / 68 (7.35%)	1 / 68 (1.47%)
occurrences all number	5	1
Ear discomfort
subjects affected / exposed	1 / 68 (1.47%)	4 / 68 (5.88%)
occurrences all number	1	5
Eye disorders
Vision blurred
subjects affected / exposed	4 / 68 (5.88%)	2 / 68 (2.94%)
occurrences all number	4	2
Cataract
subjects affected / exposed	3 / 68 (4.41%)	2 / 68 (2.94%)
occurrences all number	3	2
Eye pruritus
subjects affected / exposed	3 / 68 (4.41%)	0 / 68 (0.00%)
occurrences all number	3	0
Gastrointestinal disorders
Nausea
subjects affected / exposed	11 / 68 (16.18%)	13 / 68 (19.12%)
occurrences all number	16	14
Diarrhoea
subjects affected / exposed	12 / 68 (17.65%)	8 / 68 (11.76%)
occurrences all number	16	9
Vomiting
subjects affected / exposed	11 / 68 (16.18%)	4 / 68 (5.88%)
occurrences all number	12	4
Abdominal pain upper
subjects affected / exposed	5 / 68 (7.35%)	5 / 68 (7.35%)
occurrences all number	11	5
Abdominal pain
subjects affected / exposed	2 / 68 (2.94%)	4 / 68 (5.88%)
occurrences all number	2	4
Gastrooesophageal reflux disease
subjects affected / exposed	1 / 68 (1.47%)	4 / 68 (5.88%)
occurrences all number	1	5
Dyspepsia
subjects affected / exposed	1 / 68 (1.47%)	3 / 68 (4.41%)
occurrences all number	3	3
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	9 / 68 (13.24%)	6 / 68 (8.82%)
occurrences all number	10	7
Pruritus
subjects affected / exposed	6 / 68 (8.82%)	1 / 68 (1.47%)
occurrences all number	7	1
Urticaria
subjects affected / exposed	4 / 68 (5.88%)	1 / 68 (1.47%)
occurrences all number	7	1
Skin lesion
subjects affected / exposed	3 / 68 (4.41%)	0 / 68 (0.00%)
occurrences all number	4	0
Endocrine disorders
Adrenal insufficiency
subjects affected / exposed	3 / 68 (4.41%)	0 / 68 (0.00%)
occurrences all number	3	0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	15 / 68 (22.06%)	12 / 68 (17.65%)
occurrences all number	17	22
Myalgia
subjects affected / exposed	6 / 68 (8.82%)	9 / 68 (13.24%)
occurrences all number	8	12
Back pain
subjects affected / exposed	8 / 68 (11.76%)	6 / 68 (8.82%)
occurrences all number	10	10
Pain in extremity
subjects affected / exposed	5 / 68 (7.35%)	6 / 68 (8.82%)
occurrences all number	5	7
Neck pain
subjects affected / exposed	8 / 68 (11.76%)	2 / 68 (2.94%)
occurrences all number	9	2
Musculoskeletal pain
subjects affected / exposed	6 / 68 (8.82%)	2 / 68 (2.94%)
occurrences all number	7	2
Joint swelling
subjects affected / exposed	2 / 68 (2.94%)	3 / 68 (4.41%)
occurrences all number	2	3
Muscle spasms
subjects affected / exposed	3 / 68 (4.41%)	2 / 68 (2.94%)
occurrences all number	3	4
Infections and infestations
Nasopharyngitis
subjects affected / exposed	12 / 68 (17.65%)	16 / 68 (23.53%)
occurrences all number	19	25
Sinusitis
subjects affected / exposed	14 / 68 (20.59%)	11 / 68 (16.18%)
occurrences all number	15	19
Upper respiratory tract infection
subjects affected / exposed	14 / 68 (20.59%)	11 / 68 (16.18%)
occurrences all number	21	14
Bronchitis
subjects affected / exposed	7 / 68 (10.29%)	8 / 68 (11.76%)
occurrences all number	9	9
Influenza
subjects affected / exposed	7 / 68 (10.29%)	6 / 68 (8.82%)
occurrences all number	9	6
Respiratory tract infection
subjects affected / exposed	5 / 68 (7.35%)	8 / 68 (11.76%)
occurrences all number	7	15
Urinary tract infection
subjects affected / exposed	5 / 68 (7.35%)	4 / 68 (5.88%)
occurrences all number	5	6
Acute sinusitis
subjects affected / exposed	6 / 68 (8.82%)	2 / 68 (2.94%)
occurrences all number	6	3
Conjunctivitis
subjects affected / exposed	4 / 68 (5.88%)	4 / 68 (5.88%)
occurrences all number	4	4
Rhinitis
subjects affected / exposed	5 / 68 (7.35%)	3 / 68 (4.41%)
occurrences all number	5	3
Ear infection
subjects affected / exposed	1 / 68 (1.47%)	6 / 68 (8.82%)
occurrences all number	1	8
Fungal skin infection
subjects affected / exposed	4 / 68 (5.88%)	3 / 68 (4.41%)
occurrences all number	4	3
Oral herpes
subjects affected / exposed	4 / 68 (5.88%)	3 / 68 (4.41%)
occurrences all number	6	5
Gastroenteritis
subjects affected / exposed	5 / 68 (7.35%)	1 / 68 (1.47%)
occurrences all number	5	1
Otitis media
subjects affected / exposed	3 / 68 (4.41%)	1 / 68 (1.47%)
occurrences all number	3	1
Viral infection
subjects affected / exposed	3 / 68 (4.41%)	1 / 68 (1.47%)
occurrences all number	3	1

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Were there any global substantial amendments to the protocol? Yes

15 Oct 2013

Generated to remove evaluation of ACQ-6 and sino-nasal symptoms at the time of relapse and to clarify the definition of time of onset of relapse; countryspecific requirements for Japan regarding hepatitis B screening added as well as clarification to text as needed and administrative changes

27 Aug 2014

Generated to clarify investigators can taper oral corticosteroids downward when BVAS≠0; to include additional statement in risk assessment table; to clarify that participants who become pregnant must be withdrawn from study treatment; to clarify requirements for collection of a fasting blood sample in diabetic participants; to clarify that collection of PK samples at Weeks 1 and 29 is optional; to delete requirement for measurement of eosinophil count as a liver event follow-up assessment; to amend the schedule for sputum sampling in the biomarker sub-study; to add country-specific change for Japan regarding definition of relapsing disease in inclusion criteria; to include SAMAs and LAMAs as bronchodilator to be withheld prior to reversibility testing; to clarify requirements for participant follow-up in the event study treatment is discontinued; to include reference to the Supplement to Version 12 of the Investigator’s Brochure and other administrative changes.

24 Jun 2016

Generated to add secondary endpoints including the remission definition as per the EULAR recommendations for conducting clinical trials in systemic vasculitis, i.e., BVAS=0 and prednisolone/prednisone dose ≤7.5 mg/day, to clarify relapse definition, to amend the statistical analysis plan in accordance with the addition of the new secondary endpoints, to clarify specific aspects of the Data Analysis and Statistical Considerations section and to include some administrative updates.

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

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Clinical trials

Clinical Trial Results: A Double-blind, Randomised, Placebo-controlled Study to Investigate the Efficacy and Safety of Mepolizumab in the Treatment of Eosinophilic Granulomatosis with Polyangiitis in Subjects Receiving Standard of Care Therapy.

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Total accrued number of weeks where remission achieved over the study treatment period

Primary: Total accrued number of weeks where remission achieved over the study treatment period

Primary: Number of participants who are in remission at 36 and 48 weeks

Primary: Number of participants who are in remission at 36 and 48 weeks

Secondary: Time to first EGPA relapse

Secondary: Time to first EGPA relapse

Secondary: Average daily prednisolone/prednisone dose during the last 4 weeks of the Study Treatment Period

Secondary: Average daily prednisolone/prednisone dose during the last 4 weeks of the Study Treatment Period

Secondary: Number of participants who achieved remission within the first 24 weeks and remained in remission for the remainder of the treatment period

Secondary: Number of participants who achieved remission within the first 24 weeks and remained in remission for the remainder of the treatment period

Secondary: Total accrued number of weeks where remission achieved over the study treatment period

Secondary: Total accrued number of weeks where remission achieved over the study treatment period

Secondary: Number of participants who are in remission at 36 and 48 weeks

Secondary: Number of participants who are in remission at 36 and 48 weeks

Secondary: Number of participants who achieved remission (BVAS=0 and prednisolone/prednisone <=7.5 mg/day) within the first 24 weeks and remained in remission for the remainder of the treatment period

Secondary: Number of participants who achieved remission (BVAS=0 and prednisolone/prednisone <=7.5 mg/day) within the first 24 weeks and remained in remission for the remainder of the treatment period

Secondary: Number of participants with local and systemic Adverse Events (AEs)

Secondary: Number of participants with local and systemic Adverse Events (AEs)

Secondary: Change from Baseline in clinical chemistry parameters of alanine aminotransferase (ALT), alkaline phosphatase (Alk.phosph.), aspartate aminotransferase (AST), creatinine kinase, gamma glutamyl transaminase (GGT) and lactate dehydrogenase (dehydro) levels

Secondary: Change from Baseline in clinical chemistry parameters of alanine aminotransferase (ALT), alkaline phosphatase (Alk.phosph.), aspartate aminotransferase (AST), creatinine kinase, gamma glutamyl transaminase (GGT) and lactate dehydrogenase (dehydro) levels

Secondary: Change from Baseline in clinical chemistry parameters of albumin and protein levels

Secondary: Change from Baseline in clinical chemistry parameters of albumin and protein levels

Secondary: Change from Baseline in clinical chemistry parameters of direct, indirect and total bilirubin and creatinine levels

Secondary: Change from Baseline in clinical chemistry parameters of direct, indirect and total bilirubin and creatinine levels

Secondary: Change from Baseline in calcium, chloride, cholesterol, glucose, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, phosphorus, potassium, sodium, urea nitrogen and very low density lipoprotein (VLDL) cholesterol levels

Secondary: Change from Baseline in calcium, chloride, cholesterol, glucose, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, phosphorus, potassium, sodium, urea nitrogen and very low density lipoprotein (VLDL) cholesterol levels

Secondary: Change from Baseline in clinical chemistry parameter of troponin levels

Secondary: Change from Baseline in clinical chemistry parameter of troponin levels

Secondary: Change from Baseline in hematology parameters of basophils, eosinophil, leukocytes, lymphocytes, monocytes, neutrophils, platelets levels

Secondary: Change from Baseline in hematology parameters of basophils, eosinophil, leukocytes, lymphocytes, monocytes, neutrophils, platelets levels

Secondary: Change from Baseline in hematology parameters of Mean Corpuscle Hemoglobin Concentration (MCHC) and hemoglobin levels

Secondary: Change from Baseline in hematology parameters of Mean Corpuscle Hemoglobin Concentration (MCHC) and hemoglobin levels

Secondary: Change from Baseline in hematology parameters of Mean Corpuscle Volume (MCV) levels

Secondary: Change from Baseline in hematology parameters of Mean Corpuscle Volume (MCV) levels

Secondary: Change from Baseline in hematology parameters of Mean Corpuscle Hemoglobin (MCH) levels

Secondary: Change from Baseline in hematology parameters of Mean Corpuscle Hemoglobin (MCH) levels

Secondary: Change from Baseline in hematology parameters of erythrocytes levels

Secondary: Change from Baseline in hematology parameters of erythrocytes levels

Secondary: Number of participants with anti-Mepolizumab antibodies

Secondary: Number of participants with anti-Mepolizumab antibodies

Secondary: Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels

Secondary: Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels

Secondary: Change from Baseline in pulse rate

Secondary: Change from Baseline in pulse rate

Secondary: Change from Baseline in body temperature

Secondary: Change from Baseline in body temperature

Secondary: Mean change from Baseline in QT interval corrected by Fridericia's method (QTcF) and QT interval corrected by Bazett's method (QTcB) values

Secondary: Mean change from Baseline in QT interval corrected by Fridericia's method (QTcF) and QT interval corrected by Bazett's method (QTcB) values

Secondary: Maximum change from Baseline in QTcF and QTcB values

Secondary: Maximum change from Baseline in QTcF and QTcB values

Adverse events

Adverse events

More information

Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

More information

Clinical Trial Results:
A Double-blind, Randomised, Placebo-controlled Study to Investigate the Efficacy and Safety of Mepolizumab in the Treatment of Eosinophilic Granulomatosis with Polyangiitis in Subjects Receiving Standard of Care Therapy.