Trial Outcomes & Findings for A Safety and Efficacy Study of Mepolizumab in Subjects With Severe Asthma (NCT NCT03562195)

Last Updated: 2024-09-19

Results Overview

Clinically significant exacerbation is defined as worsening of asthma which requires use of systemic corticosteroids and/or hospitalizations and/or Emergency Department (ED) visits. Analysis of the number of exacerbations was performed using a negative binomial model with covariates of treatment group, baseline maintenance Oral Corticosteroids (OCS) therapy (OCS vs. no OCS), region, exacerbations in the year prior to the study (as an ordinal variable) and baseline % predicted Forced Expiratory Volume in 1 second (FEV1), and with logarithm of time on treatment as an offset variable.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

300 participants

Primary outcome timeframe

Up to Week 52

Results posted on

2024-09-19

Participant Flow

Approximately 371 participants with severe asthma and eosinophilic inflammation who meet the protocol defined inclusion criteria were screened. Off these, 300 participants were randomized in 1:1 ratio to mepolizumab: placebo arms. 149 participants in the mepolizumab treatment group and 151 participants in the placebo treatment group.

Participant milestones

Participant milestones
Measure	Mepolizumab 100mg Participants received 100mg of Mepolizumab subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline Standard of Care (SOC) treatment for asthma. Participants received salbutamol as a rescue medication on need basis.	Placebo Participants received placebo matching to Mepolizumab administered subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline SOC treatment for asthma. Participants received salbutamol as a rescue medication on need basis.
Overall Study STARTED	149	151
Overall Study COMPLETED	145	138
Overall Study NOT COMPLETED	4	13

Reasons for withdrawal

Reasons for withdrawal
Measure	Mepolizumab 100mg Participants received 100mg of Mepolizumab subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline Standard of Care (SOC) treatment for asthma. Participants received salbutamol as a rescue medication on need basis.	Placebo Participants received placebo matching to Mepolizumab administered subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline SOC treatment for asthma. Participants received salbutamol as a rescue medication on need basis.
Overall Study Adverse Event	0	6
Overall Study Lack of Efficacy	0	5
Overall Study Protocol Violation	0	1
Overall Study Lost to Follow-up	0	1
Overall Study Physician Decision	1	0
Overall Study Withdrawal by Subject	3	0

Baseline Characteristics

A Safety and Efficacy Study of Mepolizumab in Subjects With Severe Asthma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Mepolizumab 100mg n=149 Participants Participants received 100mg of Mepolizumab subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline Standard of Care (SOC) treatment for asthma. Participants received salbutamol as a rescue medication on need basis.	Placebo n=151 Participants Participants received placebo matching to Mepolizumab administered subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline SOC treatment for asthma. Participants received salbutamol as a rescue medication on need basis.	Total n=300 Participants Total of all reporting groups
Age, Continuous	50.8 Years STANDARD_DEVIATION 12.59 • n=5 Participants	53.7 Years STANDARD_DEVIATION 13.59 • n=7 Participants	52.2 Years STANDARD_DEVIATION 13.16 • n=5 Participants
Sex: Female, Male Female	81 Participants n=5 Participants	83 Participants n=7 Participants	164 Participants n=5 Participants
Sex: Female, Male Male	68 Participants n=5 Participants	68 Participants n=7 Participants	136 Participants n=5 Participants
Race/Ethnicity, Customized Asian - East Asian Heritage	149 Participants n=5 Participants	151 Participants n=7 Participants	300 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Week 52

Population: The analysis was performed on the Modified Intent-to-Treat (MITT) Set that included all randomized participants who received at least one dose of trial medication. 'Modified' implies that participants who were randomized but did not receive study treatment were excluded.

Outcome measures

Outcome measures
Measure	Mepolizumab 100mg n=149 Participants Participants received 100mg of Mepolizumab subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline Standard of Care (SOC) treatment for asthma. Participants received salbutamol as a rescue medication on need basis.	Placebo n=151 Participants Participants received placebo matching to Mepolizumab administered subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline SOC treatment for asthma. Participants received salbutamol as a rescue medication on need basis.
Rate of Clinically Significant Exacerbations of Asthma	0.45 Exacerbations per year	1.31 Exacerbations per year

SECONDARY outcome

Timeframe: Week 16, 32 and 52

Outcome measures

Outcome measures
Measure	Mepolizumab 100mg n=149 Participants Participants received 100mg of Mepolizumab subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline Standard of Care (SOC) treatment for asthma. Participants received salbutamol as a rescue medication on need basis.	Placebo n=151 Participants Participants received placebo matching to Mepolizumab administered subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline SOC treatment for asthma. Participants received salbutamol as a rescue medication on need basis.
Percent Probability of First Clinically Significant Exacerbations at Week 16, Week 32, and Week 52 Week 32	18.1 Percent probability Interval 12.82 to 25.32	47.9 Percent probability Interval 40.18 to 56.25
Percent Probability of First Clinically Significant Exacerbations at Week 16, Week 32, and Week 52 Week 16	14.1 Percent probability Interval 9.43 to 20.79	34.7 Percent probability Interval 27.64 to 42.87
Percent Probability of First Clinically Significant Exacerbations at Week 16, Week 32, and Week 52 Week 52	28.4 Percent probability Interval 21.86 to 36.44	53.6 Percent probability Interval 45.74 to 61.84

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: The analysis was performed on the MITT Set that included all randomized participants who received at least one dose of trial medication. 'Modified' implies that participants who were randomized but did not receive study treatment were excluded. Number of participants analyzed signifies those participants who were evaluable for this outcome measure.

The SGRQ Questionnaire is a well-established, self-completed tool, with 50 questions comprising three domains: Symptoms, Activity, and Impacts scores (each ranging from 0 to 100; where higher score indicates worst outcome). SGRQ total score was calculated by summing weights from all positive items, divided by sum of weights for all items in SGRQ questionnaire and multiplying by 100. The SGRQ total score ranges from 0 to 100, with 0 implying the best possible health status and 100 implying worst possible health status. Analysis was performed using mixed model repeated measures with covariates of baseline, baseline maintenance OCS therapy (OCS vs. no OCS), exacerbations in the year prior to the study (as an ordinal variable), baseline % predicted FEV1, treatment and visit, plus interaction terms for visit by baseline and visit by treatment group.

Outcome measures

Outcome measures
Measure	Mepolizumab 100mg n=136 Participants Participants received 100mg of Mepolizumab subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline Standard of Care (SOC) treatment for asthma. Participants received salbutamol as a rescue medication on need basis.	Placebo n=124 Participants Participants received placebo matching to Mepolizumab administered subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline SOC treatment for asthma. Participants received salbutamol as a rescue medication on need basis.
Mean Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) at Week 52	-14.29 Scores on a scale Standard Error 1.526	-7.20 Scores on a scale Standard Error 1.577

SECONDARY outcome

Timeframe: Up to Week 52

An exacerbation is defined as worsening of asthma requiring the use of systemic corticosteroids and/or emergency department visit, or hospitalization. The number of exacerbations requiring hospitalization including incubation and admittance to an Intensive care unit (ICU) or ED visits were evaluated. Analysis of number of exacerbations was performed using a negative binomial model with covariates of treatment group, baseline maintenance OCS therapy (OCS vs. no OCS), exacerbations in the year prior to the study (as an ordinal variable) and baseline % predicted FEV1, and with logarithm of time on treatment as an offset variable. The data for participants with 0, 1, 2 and 3 exacerbations requiring hospitalization (including intubation and admittance to an ICU) or ED visits are summarized.

Outcome measures

Outcome measures
Measure	Mepolizumab 100mg n=149 Participants Participants received 100mg of Mepolizumab subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline Standard of Care (SOC) treatment for asthma. Participants received salbutamol as a rescue medication on need basis.	Placebo n=151 Participants Participants received placebo matching to Mepolizumab administered subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline SOC treatment for asthma. Participants received salbutamol as a rescue medication on need basis.
Number of Participants With Clinically Significant Exacerbations Requiring Hospitalization (Including Intubation and Admittance to an Intensive Care Unit [ICU]) or Emergency Department (ED) Visits 0 exacerbation	144 Participants	133 Participants
Number of Participants With Clinically Significant Exacerbations Requiring Hospitalization (Including Intubation and Admittance to an Intensive Care Unit [ICU]) or Emergency Department (ED) Visits 1 exacerbation	3 Participants	14 Participants
Number of Participants With Clinically Significant Exacerbations Requiring Hospitalization (Including Intubation and Admittance to an Intensive Care Unit [ICU]) or Emergency Department (ED) Visits 2 exacerbations	2 Participants	3 Participants
Number of Participants With Clinically Significant Exacerbations Requiring Hospitalization (Including Intubation and Admittance to an Intensive Care Unit [ICU]) or Emergency Department (ED) Visits 3 exacerbations	0 Participants	1 Participants

SECONDARY outcome

Timeframe: Up to Week 52

An exacerbation is defined as worsening of asthma requiring the use of systemic corticosteroids and/or emergency department visit, or hospitalization. Analysis of number of exacerbations was performed using a negative binomial model with covariates of treatment group, baseline maintenance OCS therapy (OCS vs. no OCS), exacerbations in the year prior to the study (as an ordinal variable) and baseline % predicted FEV1, and with logarithm of time on treatment as an offset variable. The summary data for participants with 0, 1, 2 and 3 exacerbations requiring hospitalization are summarized.

Outcome measures

Outcome measures
Measure	Mepolizumab 100mg n=149 Participants Participants received 100mg of Mepolizumab subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline Standard of Care (SOC) treatment for asthma. Participants received salbutamol as a rescue medication on need basis.	Placebo n=151 Participants Participants received placebo matching to Mepolizumab administered subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline SOC treatment for asthma. Participants received salbutamol as a rescue medication on need basis.
Number of Participants With Clinically Significant Exacerbations Requiring Hospitalization 3 exacerbations	0 Participants	1 Participants
Number of Participants With Clinically Significant Exacerbations Requiring Hospitalization 0 exacerbation	145 Participants	139 Participants
Number of Participants With Clinically Significant Exacerbations Requiring Hospitalization 1 exacerbation	3 Participants	10 Participants
Number of Participants With Clinically Significant Exacerbations Requiring Hospitalization 2 exacerbations	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Baseline and Week 52

FEV1 is the volume of air that can be forced out in one second after taking a deep breath. Prebronchodilator FEV1 were measured via spirometer at Baseline and Week 52. Analysis was performed using mixed model repeated measures with covariates of baseline, baseline maintenance OCS therapy (OCS vs. no OCS), exacerbations in the year prior to the study (as an ordinal variable), treatment and visit, plus interaction terms for visit by baseline and visit by treatment group.

Outcome measures

Outcome measures
Measure	Mepolizumab 100mg n=130 Participants Participants received 100mg of Mepolizumab subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline Standard of Care (SOC) treatment for asthma. Participants received salbutamol as a rescue medication on need basis.	Placebo n=114 Participants Participants received placebo matching to Mepolizumab administered subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline SOC treatment for asthma. Participants received salbutamol as a rescue medication on need basis.
Mean Change From Baseline in Clinic Prebronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 52	262.79 Milliliter (mL) Standard Error 34.341	125.67 Milliliter (mL) Standard Error 35.488

SECONDARY outcome

Timeframe: Up to Week 52

AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Systemic reactions and local injection site reactions are adverse events of special interest (AESIs).

Outcome measures

Outcome measures
Measure	Mepolizumab 100mg n=149 Participants Participants received 100mg of Mepolizumab subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline Standard of Care (SOC) treatment for asthma. Participants received salbutamol as a rescue medication on need basis.	Placebo n=151 Participants Participants received placebo matching to Mepolizumab administered subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline SOC treatment for asthma. Participants received salbutamol as a rescue medication on need basis.
Number of Participants With Adverse Events (AEs) Including Systemic (i.e., Allergic [Type I Hypersensitivity] and Other Systemic) and Injection Site Reactions Participants with AE	135 Participants	146 Participants
Number of Participants With Adverse Events (AEs) Including Systemic (i.e., Allergic [Type I Hypersensitivity] and Other Systemic) and Injection Site Reactions Participants with Systemic Reactions	4 Participants	2 Participants
Number of Participants With Adverse Events (AEs) Including Systemic (i.e., Allergic [Type I Hypersensitivity] and Other Systemic) and Injection Site Reactions Participants with Local Injection Site Reactions	3 Participants	2 Participants

SECONDARY outcome

Timeframe: Baseline and Week 52

Blood samples was collected for the assessment of change from baseline in hematology parameter Platelets count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Outcome measures

Outcome measures
Measure	Mepolizumab 100mg n=142 Participants Participants received 100mg of Mepolizumab subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline Standard of Care (SOC) treatment for asthma. Participants received salbutamol as a rescue medication on need basis.	Placebo n=127 Participants Participants received placebo matching to Mepolizumab administered subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline SOC treatment for asthma. Participants received salbutamol as a rescue medication on need basis.
Change From Baseline in Platelets Count	0.6 Giga cells per liter (10^9/L) Standard Deviation 35.46	-3.5 Giga cells per liter (10^9/L) Standard Deviation 45.09

SECONDARY outcome

Timeframe: Baseline and Week 52

Blood samples was collected for the assessment of change from baseline in hematology parameter Erythrocytes count. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Outcome measures

Outcome measures
Measure	Mepolizumab 100mg n=142 Participants Participants received 100mg of Mepolizumab subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline Standard of Care (SOC) treatment for asthma. Participants received salbutamol as a rescue medication on need basis.	Placebo n=127 Participants Participants received placebo matching to Mepolizumab administered subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline SOC treatment for asthma. Participants received salbutamol as a rescue medication on need basis.
Change From Baseline in Erythrocytes Count	-0.03 Tera cells per liter (10^12/L) Standard Deviation 0.257	-0.05 Tera cells per liter (10^12/L) Standard Deviation 0.257

SECONDARY outcome

Timeframe: Baseline and Week 52

Blood samples was collected for the assessment of change from baseline in hematology parameter Hematocrit. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Outcome measures

Outcome measures
Measure	Mepolizumab 100mg n=142 Participants Participants received 100mg of Mepolizumab subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline Standard of Care (SOC) treatment for asthma. Participants received salbutamol as a rescue medication on need basis.	Placebo n=127 Participants Participants received placebo matching to Mepolizumab administered subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline SOC treatment for asthma. Participants received salbutamol as a rescue medication on need basis.
Change From Baseline in Hematocrit	-0.004 Fraction of 1 Standard Deviation 0.0257	-0.003 Fraction of 1 Standard Deviation 0.0260

SECONDARY outcome

Timeframe: Baseline and Week 52

Blood samples was collected for the assessment of change from baseline in WBC) count with differential (neutrophils, lymphocytes, monocytes. eosinophils and basophils). Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

Outcome measures

Outcome measures
Measure	Mepolizumab 100mg n=142 Participants Participants received 100mg of Mepolizumab subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline Standard of Care (SOC) treatment for asthma. Participants received salbutamol as a rescue medication on need basis.	Placebo n=127 Participants Participants received placebo matching to Mepolizumab administered subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline SOC treatment for asthma. Participants received salbutamol as a rescue medication on need basis.
Percent Change From Baseline in Mean White Blood Cell (WBC) Count With Differential (Neutrophils, Lymphocytes, Monocytes. Eosinophils and Basophils) Monocytes/Leukocytes	0.30 Percent change Interval -5.4 to 4.3	0.30 Percent change Interval -16.7 to 5.9
Percent Change From Baseline in Mean White Blood Cell (WBC) Count With Differential (Neutrophils, Lymphocytes, Monocytes. Eosinophils and Basophils) Basophils/Leukocytes	0.00 Percent change Interval -1.0 to 1.2	0.20 Percent change Interval -0.8 to 1.3
Percent Change From Baseline in Mean White Blood Cell (WBC) Count With Differential (Neutrophils, Lymphocytes, Monocytes. Eosinophils and Basophils) Eosinophils/Leukocytes	-4.95 Percent change Interval -26.4 to 5.3	-0.80 Percent change Interval -13.8 to 15.1
Percent Change From Baseline in Mean White Blood Cell (WBC) Count With Differential (Neutrophils, Lymphocytes, Monocytes. Eosinophils and Basophils) Lymphocytes/Leukocytes	0.45 Percent change Interval -20.8 to 17.3	0.20 Percent change Interval -26.4 to 15.1
Percent Change From Baseline in Mean White Blood Cell (WBC) Count With Differential (Neutrophils, Lymphocytes, Monocytes. Eosinophils and Basophils) Neutrophils/Leukocytes	4.65 Percent change Interval -18.7 to 28.0	-0.50 Percent change Interval -16.7 to 35.4

SECONDARY outcome

Timeframe: Baseline and Week 52

Blood samples was collected for the assessment of change from baseline in clinical parameter Alkaline Phosphatase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Outcome measures

Outcome measures
Measure	Mepolizumab 100mg n=142 Participants Participants received 100mg of Mepolizumab subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline Standard of Care (SOC) treatment for asthma. Participants received salbutamol as a rescue medication on need basis.	Placebo n=128 Participants Participants received placebo matching to Mepolizumab administered subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline SOC treatment for asthma. Participants received salbutamol as a rescue medication on need basis.
Change From Baseline in Alkaline Phosphatase	2.8 International Unit per Liter (IU/L) Standard Deviation 16.16	1.5 International Unit per Liter (IU/L) Standard Deviation 12.79

SECONDARY outcome

Timeframe: Baseline and Week 52

Blood samples was collected for the assessment of change from baseline in clinical parameter Alanine Aminotransferase, Aspartate Aminotransferase. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Outcome measures

Outcome measures
Measure	Mepolizumab 100mg n=142 Participants Participants received 100mg of Mepolizumab subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline Standard of Care (SOC) treatment for asthma. Participants received salbutamol as a rescue medication on need basis.	Placebo n=128 Participants Participants received placebo matching to Mepolizumab administered subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline SOC treatment for asthma. Participants received salbutamol as a rescue medication on need basis.
Change From Baseline in Alanine Aminotransferase and Aspartate Aminotransferase Alanine Aminotransferase	0.8 Units per liter (U/L) Standard Deviation 11.49	0.0 Units per liter (U/L) Standard Deviation 10.77
Change From Baseline in Alanine Aminotransferase and Aspartate Aminotransferase Aspartate Aminotransferase	1.5 Units per liter (U/L) Standard Deviation 7.38	-0.1 Units per liter (U/L) Standard Deviation 6.31

SECONDARY outcome

Timeframe: Baseline and Week 52

Blood samples was collected for the assessment of change from baseline in clinical parameter albumin, total protein. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Outcome measures

Outcome measures
Measure	Mepolizumab 100mg n=142 Participants Participants received 100mg of Mepolizumab subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline Standard of Care (SOC) treatment for asthma. Participants received salbutamol as a rescue medication on need basis.	Placebo n=128 Participants Participants received placebo matching to Mepolizumab administered subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline SOC treatment for asthma. Participants received salbutamol as a rescue medication on need basis.
Change From Baseline in Albumin and Total Protein Albumin	0.1 Gram per liter (g/L) Standard Deviation 2.55	-0.4 Gram per liter (g/L) Standard Deviation 2.39
Change From Baseline in Albumin and Total Protein Total Protein	-0.6 Gram per liter (g/L) Standard Deviation 3.53	-0.6 Gram per liter (g/L) Standard Deviation 3.70

SECONDARY outcome

Timeframe: Baseline and Week 52

Blood samples was collected for the assessment of change from baseline in clinical parameter including total and direct bilirubin, creatinine, glucose, calcium, sodium, potassium, urea. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was calculated by subtracting the post dose visit value from the Baseline value.

Outcome measures

Outcome measures
Measure	Mepolizumab 100mg n=142 Participants Participants received 100mg of Mepolizumab subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline Standard of Care (SOC) treatment for asthma. Participants received salbutamol as a rescue medication on need basis.	Placebo n=128 Participants Participants received placebo matching to Mepolizumab administered subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline SOC treatment for asthma. Participants received salbutamol as a rescue medication on need basis.
Change From Baseline in Clinical Chemistry Parameters Direct Bilirubin	0.4 Micro moles per liter (umol/L) Standard Deviation 0.55	0.3 Micro moles per liter (umol/L) Standard Deviation 0.60
Change From Baseline in Clinical Chemistry Parameters Glucose	0.16 Micro moles per liter (umol/L) Standard Deviation 0.921	0.09 Micro moles per liter (umol/L) Standard Deviation 1.448
Change From Baseline in Clinical Chemistry Parameters Total Bilirubin	-0.1 Micro moles per liter (umol/L) Standard Deviation 3.47	-0.7 Micro moles per liter (umol/L) Standard Deviation 3.43
Change From Baseline in Clinical Chemistry Parameters Calcium	0.014 Micro moles per liter (umol/L) Standard Deviation 0.0874	0.016 Micro moles per liter (umol/L) Standard Deviation 0.0773
Change From Baseline in Clinical Chemistry Parameters Creatinine	-0.7 Micro moles per liter (umol/L) Standard Deviation 6.89	-0.9 Micro moles per liter (umol/L) Standard Deviation 6.55
Change From Baseline in Clinical Chemistry Parameters Potassium	0.00 Micro moles per liter (umol/L) Standard Deviation 0.350	-0.04 Micro moles per liter (umol/L) Standard Deviation 0.328
Change From Baseline in Clinical Chemistry Parameters Sodium	-0.8 Micro moles per liter (umol/L) Standard Deviation 2.42	-0.7 Micro moles per liter (umol/L) Standard Deviation 2.39
Change From Baseline in Clinical Chemistry Parameters Urea	0.205 Micro moles per liter (umol/L) Standard Deviation 1.3284	-0.058 Micro moles per liter (umol/L) Standard Deviation 1.2335

SECONDARY outcome

Timeframe: Baseline and Week 52

SBP and DBP were measured in a sitting position after 5 minutes rest. The normal range for SBP is 90-140 mmHg and DBP is 60-90 millimeters of mercury (mmHg).

Outcome measures

Outcome measures
Measure	Mepolizumab 100mg n=143 Participants Participants received 100mg of Mepolizumab subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline Standard of Care (SOC) treatment for asthma. Participants received salbutamol as a rescue medication on need basis.	Placebo n=131 Participants Participants received placebo matching to Mepolizumab administered subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline SOC treatment for asthma. Participants received salbutamol as a rescue medication on need basis.
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Diastolic Blood Pressure, Week 52	-0.9 Millimeters of mercury (mmHg) Standard Deviation 9.58	-1.1 Millimeters of mercury (mmHg) Standard Deviation 8.42
Mean Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Systolic Blood Pressure, Week 52	-1.3 Millimeters of mercury (mmHg) Standard Deviation 12.46	-0.5 Millimeters of mercury (mmHg) Standard Deviation 10.75

SECONDARY outcome

Timeframe: Baseline and Week 52

Pulse rate measurement were measured in a sitting position after 5 minutes rest.

Outcome measures

Outcome measures
Measure	Mepolizumab 100mg n=143 Participants Participants received 100mg of Mepolizumab subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline Standard of Care (SOC) treatment for asthma. Participants received salbutamol as a rescue medication on need basis.	Placebo n=131 Participants Participants received placebo matching to Mepolizumab administered subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline SOC treatment for asthma. Participants received salbutamol as a rescue medication on need basis.
Mean Change From Baseline in Pulse Rate	-1.3 Beats per minute (bpm) Standard Deviation 9.71	-1.1 Beats per minute (bpm) Standard Deviation 10.14

SECONDARY outcome

Timeframe: Up to Week 52

12-Lead electrocardiogram (ECG) measurements were obtained after the participants had rested in the supine position for 5 minutes. Clinically significant abnormal findings are based on the judgement of the investigator.

Outcome measures

Outcome measures
Measure	Mepolizumab 100mg n=143 Participants Participants received 100mg of Mepolizumab subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline Standard of Care (SOC) treatment for asthma. Participants received salbutamol as a rescue medication on need basis.	Placebo n=131 Participants Participants received placebo matching to Mepolizumab administered subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline SOC treatment for asthma. Participants received salbutamol as a rescue medication on need basis.
Number of Participants With Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) Findings	7 Participants	13 Participants

SECONDARY outcome

Timeframe: Up to Week 52

Blood samples were collected for detection of binding and neutralizing anti-mepolizumab antibodies. Samples with a positive screening result continued for confirmation analysis. Samples with a positive confirmation analysis were considered positive for mepolizumab Anti-drug antibody (ADA).

Outcome measures

Outcome measures
Measure	Mepolizumab 100mg n=149 Participants Participants received 100mg of Mepolizumab subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline Standard of Care (SOC) treatment for asthma. Participants received salbutamol as a rescue medication on need basis.	Placebo n=151 Participants Participants received placebo matching to Mepolizumab administered subcutaneously every 4 weeks during the total treatment period of 52 weeks in addition to their baseline SOC treatment for asthma. Participants received salbutamol as a rescue medication on need basis.
Number of Participants With Positive Anti-Mepolizumab Antibody	5 Participants	0 Participants

Adverse Events

Mepolizumab 100mg

Serious events: 18 serious events

Other events: 134 other events

Deaths: 0 deaths

Placebo

Serious events: 25 serious events

Other events: 146 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Email: [email protected]

Results disclosure agreements

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

Restriction type: OTHER