A Study to Investigate Mepolizumab in the Treatment of Eosinophilic Granulomatosis With Polyangiitis

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Completed

CT.gov ID

NCT02020889

Collaborator

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

136

Enrollment

Locations

Arms

Actual Duration (Months)

4.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this randomized, double-blind study is to investigate the efficacy and safety of mepolizumab (300 milligram [mg] administered subcutaneously [SC] every 4 weeks) compared with placebo over a 52-week study treatment period in subjects with relapsing or refractory Eosinophilic Granulomatosis with Polyangiitis (EGPA) receiving standard of care therapy including background corticosteroid therapy with or without immunosuppressive therapy. During the treatment period, in accordance with standard of care, corticosteroid dose will be tapered. The key outcomes in the study focus on evaluation of clinical remission, defined as Birmingham Vasculitis Activity Score (BVAS)=0 with a corticosteroid dose of <=4 mg/day prednisolone/prednisone, reduction in disease relapse and reduction in corticosteroid requirement.

Condition or Disease	Intervention/Treatment	Phase
Churg-Strauss Syndrome	Biological: Mepolizumab Drug: Placebo	Phase 3

Study Design

Study Type:

Interventional

Actual Enrollment :

136 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Feb 5, 2014

Actual Primary Completion Date :

Sep 5, 2016

Actual Study Completion Date :

Sep 5, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mepolizumab 300 mg Each subject will receive mepolizumab 300 mg subcutaneous (SC) injection every 4 weeks (13 administrations) along with standard care. It will be administered as 3 separate injections (100 mg each- total dose 300 mg); individual injection sites will be separated by at least 5 cm. It will be administered into any of the upper arm, thigh or anterior abdominal wall.	Biological: Mepolizumab Mepolizumab will be provided as a lyophilized cake in sterile vials for individual use to be reconstituted with sterile water for Injection, just prior to use.
Placebo Comparator: Placebo Each subject will receive placebo (0.9% sodium chloride) SC injection every 4 weeks (13 administrations) along with standard care. It will be administered as 3 separate injections; individual injection sites will be separated by at least 5 cm. It will be administered into any of the upper arm, thigh or anterior abdominal wall.	Drug: Placebo Placebo will be available as 0.9% sodium chloride

Arm

Intervention/Treatment

Experimental: Mepolizumab 300 mg

Each subject will receive mepolizumab 300 mg subcutaneous (SC) injection every 4 weeks (13 administrations) along with standard care. It will be administered as 3 separate injections (100 mg each- total dose 300 mg); individual injection sites will be separated by at least 5 cm. It will be administered into any of the upper arm, thigh or anterior abdominal wall.

Biological: Mepolizumab

Mepolizumab will be provided as a lyophilized cake in sterile vials for individual use to be reconstituted with sterile water for Injection, just prior to use.

Placebo Comparator: Placebo

Each subject will receive placebo (0.9% sodium chloride) SC injection every 4 weeks (13 administrations) along with standard care. It will be administered as 3 separate injections; individual injection sites will be separated by at least 5 cm. It will be administered into any of the upper arm, thigh or anterior abdominal wall.

Drug: Placebo

Placebo will be available as 0.9% sodium chloride

Outcome Measures

Primary Outcome Measures

Number of Participants in Each Category of Accrued Duration of Remission [Up to Week 52]
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.
Number of Participants Who Are in Remission at 36 and 48 Weeks [Week 36 and Week 48]
The number 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.

Secondary Outcome Measures

Time to First EGPA Relapse [Up to Week 52]
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. The number of participants with at least one EGPA relapse during the planned study treatment period are presented.
Number of Participants in Each Category of Average Daily Prednisolone/Prednisone Dose During the Last 4 Weeks of the Study Treatment Period. [Week 48 and Week52]
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.
Number of Participants Who Achieved Remission Within the First 24 Weeks and Remained in Remission for the Remainder of the Treatment Period [Up to Week 52]
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.
Number of Participants in Each Category of Accrued Duration of Remission [Up to Week 52]
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.
Number of Participants Who Are in Remission at 36 and 48 Weeks [Week 36 and Week 48]
The number of participants who were in remission (i.e ., BVAS=0 and prednisolone /prednisone <=7.5mg/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.
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 [Up to Week 52]
The number of participants who were in remission (i.e ., BVAS=0 and prednisolone /prednisone <=7.5mg/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.
Number of Participants With Local and Systemic Adverse Events (AEs) [Up to Week 52]
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.
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 [Baseline and up to Week 60]
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.
Change From Baseline in Clinical Chemistry Parameters of Albumin and Protein Levels [Baseline and up to Week 60]
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.
Change From Baseline in Clinical Chemistry Parameters of Direct, Indirect and Total Bilirubin and Creatinine Levels [Baseline and up to Week 60]
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.
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 [Baseline and up to Week 60]
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. NA indicates that data were not available.
Change From Baseline in Clinical Chemistry Parameter of Troponin Levels [Baseline and up to Week 60]
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.
Change From Baseline in Hematology Parameters of Basophils, Eosinophil, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Levels [Baseline and up to Week 60]
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.
Change From Baseline in Hematology Parameters of Mean Corpuscle Hemoglobin Concentration (MCHC) and Hemoglobin Levels [Baseline and up to Week 60]
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.
Change From Baseline in Hematology Parameters of Mean Corpuscle Volume (MCV) Levels [Baseline and up to Week 60]
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.
Change From Baseline in Hematology Parameters of Mean Corpuscle Hemoglobin (MCH) Levels [Baseline and up to Week 60]
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.
Change From Baseline in Hematology Parameters of Erythrocytes Levels [Baseline and up to Week 60]
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.
Number of Participants With Anti-Mepolizumab Antibodies [Up to Week 60]
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.
Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Levels [Baseline up to Week 60]
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.
Change From Baseline in Pulse Rate [Baseline and up to Week 60]
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.
Change From Baseline in Body Temperature [Baseline and up to Week 60]
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.
Mean Change From Baseline in QT Interval Corrected by Fridericia's Method (QTcF) and QT Interval Corrected by Bazett's Method (QTcB) Values [Baseline and up to Week 60]
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).
Maximum Change From Baseline in QTcF and QTcB Values [Baseline and up to Week 60]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Informed Consent: Able to give written informed consent prior to participation in the study, which will include the ability to comply with the requirements and restrictions listed in the consent form. Subjects must be able to read, comprehend, and write at a level sufficient to complete study related materials.
Age and gender: Male or female subjects age 18 years or older.
EGPA diagnosis: subjects who have been diagnosed with EGPA for at least 6 months based on the history or presence of: asthma plus eosinophilia (>1.0x10^9/Liter and/or >10% of leucocytes) plus at least two of the following additional features of EGPA; a biopsy showing histopathological evidence of eosinophilic vasculitis, or perivascular eosinophilic infiltration, or eosinophil-rich granulomatous inflammation; neuropathy, mono or poly (motor deficit or nerve conduction abnormality); pulmonary infiltrates, non-fixed; sino-nasal abnormality; cardiomyopathy (established by echocardiography or Magnetic Resonance Imaging); glomerulonephritis (haematuria, red cell casts, proteinuria); alveolar haemorrhage (by bronchoalveolar lavage); palpable purpura; anti neutrophil cytoplasmic anti-body (ANCA) positive (Myeloperoxidase or proteinease 3).
History of relapsing OR refractory disease defined as: Relapsing disease:

Subject must have a past history of at least one confirmed EGPA relapse (i.e., requiring increase in oral corticosteroids (OCS) dose, initiation/increased dose of immunosuppressive therapy or hospitalisation) within the past 2 years which occurred at least 12 weeks prior to Screening (Visit 1) whilst receiving a dose of prednisolone (or equivalent) of >=7.5 milligram per day (mg/day). Refractory disease: Either: Failure to attain remission (BVAS=0 and OCS dose <=7.5 mg/day prednisolone or equivalent) within the last 6 months following induction treatment with a standard regimen, administered for at least 3 months. Note: a) Subjects who have received a cyclophosphamide (CYC) induction regimen may be included a minimum of 2 weeks after the last dose of daily oral CYC, or 3 weeks after the last dose of pulsed intravenous CYC prior to Baseline (Visit 2), if their total white blood cells (WBC) is >=4x10^9/Liter (tested at the local laboratory, if necessary) prior to randomisation. b) Subjects who have received a methotrexate, azathioprine, or mycophenolate mofetil induction regimen may be included if on a stable dose for at least 4 weeks prior to Baseline (Visit 2). c) Subjects who have received an induction regimen comprising corticosteroids alone may be included only if they have failed to attain remission after 3 months of treatment AND the corticosteroid dose is >=15 mg/day prednisolone or equivalent for the 4 weeks prior to Baseline (Visit 2). Or: Within 6 months prior to Screening (Visit 1), recurrence of symptoms of EGPA (not necessarily meeting the protocol definition of relapse) whilst tapering OCS, occurring at any dose level >=7.5 mg/day prednisolone or equivalent.

Corticosteroid therapy: Subject must be on a stable dose of oral prednisolone or prednisone of >=7.5 mg/day (but not >50 mg/day) for at least 4 weeks prior to Baseline (Visit 2).
Immunosuppressive therapy: If receiving immunosuppressive therapy (excluding cyclophosphamide) the dosage must be stable for the 4 weeks prior to Baseline (Visit

and during the study (dose reductions for safety reasons will be permitted).

ECG measurements: QTc(F)<450 msec or QTc(F)<480 msec for patients with bundle branch block. The QTc is the QT interval corrected for heart rate according to either Bazett's formula (QTcB), Fridericia's formula (QTcF), or another method, machine or manual overread. For subject eligibility and withdrawal decisions, QTcFwill be used. For purposes of data analysis, QTcF will be used as primary though data using both correction formulas will be collected and analysed. The QTc should be based on single or averaged QTc values of triplicate electrocardiograms (ECGs) obtained over a brief recording period.
Female subjects: To be eligible for entry into the study, females of childbearing potential (FCBP) must commit to consistent and correct use of an acceptable method of birth control (as discussed in the protocol) beginning with consent, for the duration of the trial and for 4 months after the last study drug administration.
French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
Liver Function Tests: obtained at Screening (Visit 1): ALT<2x ULN (upper limit of normal) or if subject is on background methotrexate or azathioprine <3x ULN; AST<2x ULN or if subject is on background methotrexate or azathioprine <3x ULN; Alkaline Phosphatase ≤2.0x ULN;Bilirubin ≤ 1.5x ULN (isolated bilirubin>1.5x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)

Exclusion Criteria:

GPA or MPA: Diagnosed with granulomatosis with polyangiitis (GPA; previously known as Wegener's granulomatosis) or microscopic polyangiitis (MPA).
Organ-threatening EGPA: Organ-threatening EGPA as per European league against rheumatism (EULAR) criteria, i.e., organ failure due to active vasculitis, creatinine

5.8 gram per deciliter (g/dL) (>513 micromole per liter [µmol/L]) within 3 months prior to Screening (Visit 1).

Life-threatening EGPA: Imminently life-threatening EGPA disease defined as any of the following within 3 months prior to Screening (Visit 1); Intensive care required; Severe alveolar haemorrhage or haemoptysis requiring transfusion or ventilation or haemoglobin < 8 gram per liter (g/dL) (<80 g/L) or drop in haemoglobin > 2 g/dL (>20 g/L) over a 48 hour period due to alveolar haemorrhage; Rapidly progressive glomerulonephritis (RPGN) with creatinine > 2.5 milligram per deciliter (mg/dL) (>221 µmol/L) or rise in creatinine > 2 mg/dL (>177 µmol/L) over a 48 hour period; Severe gastrointestinal (GI) involvement, e.g., gangrene, bleeding requiring surgery; Severe central nervous system (CNS) involvement; Severe cardiac involvement, e.g., life-threatening arrhythmia, cardiac failure: ejection fraction < 20%, New York Heart Association Class III/IV (as discussed in protocol), acute myocardial infarction.
Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior screening (Subjects that had localized carcinoma (i.e., basal or squamous cell) of the skin which was resected for cure will not be excluded).
Liver disease: Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices or persistent jaundice), cirrhosis, and known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).
Cardiovascular: Subjects who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment including but not limited to: Known ejection fraction of <30%, OR Severe heart failure that meets New York Heart Association Class IV (as discussed in protocol), OR Hospitalised in the 12 months prior to Visit 1 for severe heart failure meeting New York Heart Association Class III (as discussed in protocol), OR Angina diagnosed less than 3 months prior to or at Visit 1 (Screening).
Other concurrent medical conditions: Subjects who have known, pre-existing, clinically significant endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, haematological, respiratory or any other system abnormalities that are not associated with EGPA and are uncontrolled with standard treatment.
Infectious disease: Chronic or ongoing active infectious disease requiring systemic treatment.
Parasitic infection: Subjects with a parasitic infestation within 6 months prior to Screening (Visit 1).
Hepatitis status: Diagnosis of chronic hepatitis B, as evidenced by positive Hepatitis B surface antigen (HBsAg) at Screening (Visit 1). Japan only: Subjects positive for HBsAg , antibodies to HBsAg, i.e., HBsAb, or Hepatitis B core antigen, i.e., HBcAb, at Screening (Visit 1). Note: Subjects with antibodies to HBsAg, i.e., HBsAb positive, only (i.e., negative for HBsAg and HBcAb) with a history of hepatitis B vaccination can be included.
HIV: Subjects with a known human immunodeficiency virus infection.
Hypersensitivity: Subjects with a known allergy or intolerance to a monoclonal antibody or biologic therapy.
Previous mepolizumab: Subjects who have previously received mepolizumab within a 1 year period prior to Screening (Visit 1).
Prohibited medications: Subjects receiving any of the following: OCS: Subject requires an oral corticosteroid dose of >50 mg/day prednisolone/prednisone in the 4-week period prior to Baseline (Visit 2); Intravenous or SC corticosteroids in the 4-week period prior to Baseline (Visit 2); Omalizumab within 130 days prior to Screening (Visit 1); Cyclophosphamide: oral CYC within 2 weeks prior to Baseline (Visit 2) and IV CYC within 3 weeks prior to Baseline (Visit 2), if their total WBC is >=4x10^9/Liter (measured using the local laboratory if necessary); Rituximab within 12 months prior to Screening (Visit 1); in addition, the subject must have shown recovery of peripheral B-cell count to within the normal range; IV or SC immunoglobulin within 6 months prior to Screening (Visit 1); Interferon-α within 6 months prior to Screening (Visit 1); Anti-TNF therapy within 12 weeks prior to Screening (Visit 1); Anti-CD52 (alemtuzumab) within 6 months prior to Screening (Visit 1).
Other laboratory parameter exclusions: Creatinine > 2.5 mg/dL (221 µmol/L); WBC < 4 x10^{9/Liter, Platelet count <120,000/millimetre cube (mm}3), Haemoglobin <8 g/dL (<80 g/L)
Pregnancy: Subjects who are pregnant or breastfeeding. Subjects should not be enrolled if they plan to become pregnant during the time of study participation.
Alcohol/substance abuse: A history (or suspected history) of alcohol misuse or substance abuse within 2 years prior to Screening (Visit 1).
Other investigational product: Subjects who have received treatment with an investigational drug within the past 30 days or 5 terminal phase half-lives of the drug whichever is longer, prior to Screening (Visit 1) (this also includes investigational formulations of marketed products).
Other clinical study: Subject is currently participating in any other interventional clinical study.
Adherence: Subjects who have known evidence of lack of adherence to controller medications and/or ability to follow physician's recommendations.
French subjects: the French subject has participated in any study using an investigational drug during the previous 30 days or 5 half-lives (whichever is longer).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Denver	Colorado	United States	80206
2	GSK Investigational Site	Bethesda	Maryland	United States	20892
3	GSK Investigational Site	Boston	Massachusetts	United States	02118-2307
4	GSK Investigational Site	Boston	Massachusetts	United States	02215
5	GSK Investigational Site	Rochester	Minnesota	United States	55905
6	GSK Investigational Site	Cleveland	Ohio	United States	44195
7	GSK Investigational Site	Philadelphia	Pennsylvania	United States	19104
8	GSK Investigational Site	Salt Lake City	Utah	United States	84132
9	GSK Investigational Site	Bruxelles		Belgium	1070
10	GSK Investigational Site	Hamilton	Ontario	Canada	L8N 4A6
11	GSK Investigational Site	Toronto	Ontario	Canada	M5T 3L9
12	GSK Investigational Site	Bron Cedex		France	69677
13	GSK Investigational Site	Marseille cedex 20		France	13915
14	GSK Investigational Site	Montpellier cedex 5		France	34295
15	GSK Investigational Site	Paris		France	75014
16	GSK Investigational Site	Suresnes		France	92151
17	GSK Investigational Site	Freiburg	Baden-Wuerttemberg	Germany	79106
18	GSK Investigational Site	Fulda	Hessen	Germany	36043
19	GSK Investigational Site	Bad Bramstedt	Schleswig-Holstein	Germany	24576
20	GSK Investigational Site	Jena	Thueringen	Germany	07740
21	GSK Investigational Site	Hamburg		Germany	22767
22	GSK Investigational Site	Kirchheim unter Teck		Germany	73230
23	GSK Investigational Site	Milano	Lombardia	Italy	20132
24	GSK Investigational Site	Milano	Lombardia	Italy	20162
25	GSK Investigational Site	Firenze	Toscana	Italy	50134
26	GSK Investigational Site	Pisa	Toscana	Italy	56126
27	GSK Investigational Site	Kanagawa		Japan	252-0392
28	GSK Investigational Site	Miyagi		Japan	980-8574
29	GSK Investigational Site	Barcelona		Spain	08036
30	GSK Investigational Site	Cambridge		United Kingdom	CB2 2QQ
31	GSK Investigational Site	Leicester		United Kingdom	LE3 9QP
32	GSK Investigational Site	Portsmouth		United Kingdom	PO6 3LY

Sponsors and Collaborators

GlaxoSmithKline
National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT02020889

Other Study ID Numbers:

115921

First Posted:

Dec 25, 2013

Last Update Posted:

Jan 31, 2018

Last Verified:

Jan 1, 2018

Keywords provided by GlaxoSmithKline

eosinophils

SB 240563

Churg-Strauss Syndrome

Eosinophilic granulomatosis with polyangiitis

Additional relevant MeSH terms:

Granulomatosis with Polyangiitis

Systemic Vasculitis

Churg-Strauss Syndrome

Study Results

Participant Flow

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.
Pre-assignment Detail	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.

Arm/Group Title	Placebo	Mepolizumab 300mg
Arm/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.	Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.
Period Title: Overall Study
STARTED	68	68
COMPLETED	61	65
NOT COMPLETED	7	3

Baseline Characteristics

Arm/Group Title	Placebo	Mepolizumab 300mg	Total
Arm/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.	Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.	Total of all reporting groups
Overall Participants	68	68	136
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	48.2 (14.32)	48.7 (12.39)	48.5 (13.34)
Sex: Female, Male (Count of Participants)
Female	38 55.9%	42 61.8%	80 58.8%
Male	30 44.1%	26 38.2%	56 41.2%
Race/Ethnicity, Customized (Count of Participants)
American Indian or Alaskan Native	0 0%	1 1.5%	1 0.7%
Asian - Japanese Heritage	3 4.4%	3 4.4%	6 4.4%
Asian - South East Asian Heritage	2 2.9%	0 0%	2 1.5%
White - Arabic/North African Heritage	0 0%	2 2.9%	2 1.5%
White - White/Caucasian/European Heritage	61 89.7%	62 91.2%	123 90.4%
Mixed Race	2 2.9%	0 0%	2 1.5%

Outcome Measures

1. Primary Outcome

Title	Number of Participants in Each Category of Accrued Duration of Remission
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.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	Placebo	Mepolizumab 300mg
Arm/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.	Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.
Measure Participants	68	68
Zero	55 80.9%	32 47.1%
>0 to <12 weeks	8 11.8%	8 11.8%
12 to <24 weeks	3 4.4%	9 13.2%
24 to <36 weeks	0 0%	10 14.7%
>=36 weeks	2 2.9%	9 13.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mepolizumab 300mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Proportional odds regression model
	Comments	Proportional odds regression model with covariates including treatment group, Baseline prednisolone/prednisone daily dose, Baseline BVAS score, region

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.91
	Confidence Interval	(2-Sided) 95% 2.68 to 13.03
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mepolizumab 300mg/Placebo

2. Primary Outcome

Title	Number of Participants Who Are in Remission at 36 and 48 Weeks
Description	The number 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.
Time Frame	Week 36 and Week 48

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	Placebo	Mepolizumab 300mg
Arm/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.	Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.
Measure Participants	68	68
Number [Participants]	2 2.9%	22 32.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mepolizumab 300mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments	Logistic regression model with covariates including treatment group, Baseline prednisolone/prednisone daily dose, Baseline BVAS score and region

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	16.74
	Confidence Interval	(2-Sided) 95% 3.61 to 77.56
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mepolizumab 300mg/Placebo

3. Secondary Outcome

Title	Time to First EGPA Relapse
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. The number of participants with at least one EGPA relapse during the planned study treatment period are presented.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	Placebo	Mepolizumab 300mg
Arm/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.	Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.
Measure Participants	68	68
Number [Participants]	56 82.4%	38 55.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mepolizumab 300mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cox Proportional Hazard regression
	Comments	Cox proportional hazards model with covariates of treatment group, Baseline prednisolone/prednisone daily dose, Baseline BVAS score and region

Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.322
	Confidence Interval	(2-Sided) 95% 0.206 to 0.502
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mepolizumab 300mg/Placebo

4. Secondary Outcome

Title	Number of Participants in Each Category of Average Daily Prednisolone/Prednisone Dose During the Last 4 Weeks of the Study Treatment Period.
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.
Time Frame	Week 48 and Week52

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	Placebo	Mepolizumab 300mg
Arm/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.	Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.
Measure Participants	68	68
Zero	2 2.9%	12 17.6%
>0 to <=4.0mg	3 4.4%	18 26.5%
>4.0 to <=7.5mg	18 26.5%	10 14.7%
>7.5mg	45 66.2%	28 41.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mepolizumab 300mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Proportional odds regression model
	Comments	Proportional odds regression model with covariates including treatment group, Baseline prednisolone/prednisone daily dose, Baseline BVAS score, region

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.20
	Confidence Interval	(2-Sided) 95% 0.09 to 0.41
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mepolizumab 300mg/Placebo

5. Secondary Outcome

Title	Number of Participants Who Achieved Remission Within the First 24 Weeks and Remained in Remission for the Remainder of the Treatment Period
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.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	Placebo	Mepolizumab 300mg
Arm/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.	Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.
Measure Participants	68	68
Number [Participants]	1 1.5%	13 19.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mepolizumab 300mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	Regression, Logistic
	Comments	Logistic regression model with covariates including treatment group, Baseline prednisolone/prednisone daily dose, Baseline BVAS score and region

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	19.65
	Confidence Interval	(2-Sided) 95% 2.30 to 167.93
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mepolizumab 300mg/Placebo

6. Secondary Outcome

Title	Number of Participants in Each Category of Accrued Duration of Remission
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.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	Placebo	Mepolizumab 300mg
Arm/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.	Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.
Measure Participants	68	68
Zero	36 52.9%	15 22.1%
>0 to <12 weeks	19 27.9%	15 22.1%
12 to <24 weeks	0 0%	7 10.3%
24 to <36 weeks	7 10.3%	9 13.2%
>=36 weeks	6 8.8%	22 32.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mepolizumab 300mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Proportional odds regression model
	Comments	Proportional odds regression model with covariates including treatment group, Baseline prednisolone/prednisone daily dose, Baseline BVAS score, region

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	5.31
	Confidence Interval	(2-Sided) 95% 2.63 to 10.74
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mepolizumab 300mg/Placebo

7. Secondary Outcome

Title	Number of Participants Who Are in Remission at 36 and 48 Weeks
Description	The number of participants who were in remission (i.e ., BVAS=0 and prednisolone /prednisone <=7.5mg/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.
Time Frame	Week 36 and Week 48

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	Placebo	Mepolizumab 300mg
Arm/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.	Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.
Measure Participants	68	68
Number [Participants]	7 10.3%	28 41.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mepolizumab 300mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments	Logistic regression model with covariates including treatment group, Baseline prednisolone/prednisone daily dose, Baseline BVAS score and region

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	7.19
	Confidence Interval	(2-Sided) 95% 2.60 to 19.87
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mepolizumab 300mg/Placebo

8. Secondary Outcome

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
Description	The number of participants who were in remission (i.e ., BVAS=0 and prednisolone /prednisone <=7.5mg/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.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description
ITT Population

Arm/Group Title	Placebo	Mepolizumab 300mg
Arm/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.	Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.
Measure Participants	68	68
Number [Participants]	2 2.9%	16 23.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mepolizumab 300mg
	Comments
	Type of Statistical Test	Other
	Comments

Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Regression, Logistic
	Comments	Logistic regression model with covariates including treatment group, Baseline prednisolone/prednisone daily dose, Baseline BVAS score and region.

Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	11.39
	Confidence Interval	(2-Sided) 95% 2.35 to 55.24
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mepolizumab 300mg/Placebo

9. Secondary Outcome

Title	Number of Participants With Local and Systemic Adverse Events (AEs)
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.
Time Frame	Up to Week 52

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Placebo	Mepolizumab 300mg
Arm/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.	Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.
Measure Participants	68	68
Facial paralysis	1 1.5%	0 0%
Flushing	0 0%	1 1.5%
Hypersensitivity	0 0%	1 1.5%
Rash pruritic	0 0%	1 1.5%
Injection related reactions	0 0%	1 1.5%
Injection site bruising	0 0%	1 1.5%
Injection site erythema	1 1.5%	1 1.5%
Injection site pain	1 1.5%	0 0%
Injection site reaction	7 10.3%	9 13.2%

10. Secondary Outcome

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
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.
Time Frame	Baseline and up to Week 60

Outcome Measure Data

Analysis Population Description
Safety population

Arm/Group Title	Placebo	Mepolizumab 300mg
Arm/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.	Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.
Measure Participants	68	68
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 (12.30)
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 (11.30)
ALT; Week 36; n= 60, 67	-0.1 (6.21)	-3.0 (11.66)
ALT; Week 40; n= 61, 66	0.3 (9.01)	-2.3 (11.70)
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 (20.90)
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	0.0 (11.24)	4.4 (21.90)
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	1.0 (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 (12.30)	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)	1.0 (15.08)
Absolute AST; Baseline; n= 68, 68	19.3 (6.11)	21.8 (10.73)
AST; Week 4; n= 68, 68	0.0 (4.41)	-1.7 (8.61)
AST; Week 8; n= 67, 66	-0.4 (4.77)	-1.0 (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 (7.90)
AST; Week 20; n= 63, 68	0.8 (4.66)	-0.6 (8.49)
AST; Week 24; n= 63, 66	0.0 (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)	-3.0 (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	99.0 (75.99)	88.8 (75.18)
Creatinine kinase; Week 4; n= 68, 68	-2.4 (83.23)	2.0 (60.92)
Creatinine kinase; Week 8; n= 67, 66	-5.0 (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)	6.0 (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	-12.0 (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 (11.70)	-2.0 (9.68)
GGT; Week 8; n= 67, 66	-1.0 (8.59)	-0.6 (17.99)
GGT; Week 12; n= 65, 68	-2.9 (6.68)	-1.9 (18.70)
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 (24.50)
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)	-3.0 (16.51)
GGT; Week 52; n= 60, 65	-1.6 (16.44)	-4.2 (13.53)
GGT; Week 56; n= 61, 63	-5.0 (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 (27.80)
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 (26.80)	-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 (33.40)	-17.0 (31.37)
Lactate dehydro; Week 48; n= 61, 64	0.8 (43.82)	-19.0 (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)	-16.0 (30.87)
Lactate dehydro; Week 60; n= 60, 65	-3.5 (34.15)	-12.4 (33.23)

11. Secondary Outcome

Title	Change From Baseline in Clinical Chemistry Parameters of Albumin and Protein Levels
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.
Time Frame	Baseline and up to Week 60

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Placebo	Mepolizumab 300mg
Arm/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.	Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.
Measure Participants	68	68
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	0.0 (2.80)	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 (3.10)
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 (3.00)	-0.5 (3.19)
Protein; Week 8; n= 67, 66	-1.5 (2.97)	-0.9 (3.60)
Protein; Week 12; n= 65, 68	-0.6 (3.57)	-0.6 (3.30)
Protein; Week 16; n= 65, 68	-0.3 (3.56)	-0.8 (3.93)
Protein; Week 20; n= 63, 68	0.0 (3.21)	0.1 (4.28)
Protein; Week 24; n= 63, 66	0.2 (3.99)	0.0 (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)

12. Secondary Outcome

Title	Change From Baseline in Clinical Chemistry Parameters of Direct, Indirect and Total Bilirubin and Creatinine Levels
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.
Time Frame	Baseline and up to Week 60

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Placebo	Mepolizumab 300mg
Arm/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.	Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.
Measure Participants	68	68
Absolute Total bilirubin; Baseline; n= 68, 68	9.8 (6.14)	8.8 (4.10)
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)	0.0 (3.50)
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)	0.0 (4.14)
Total bilirubin; Week 20; n= 63, 68	-0.5 (2.90)	0.3 (3.57)
Total bilirubin; Week 24; n= 63, 66	-0.3 (3.36)	0.0 (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	0.0 (2.50)	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)	0.0 (3.42)
Absolute Creatinine; Baseline; n= 68, 68	75.49 (12.878)	73.00 (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	1.50 (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)	2.60 (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)	0.40 (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 (9.070)
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)	-0.30 (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	0.0 (1.06)	0.0 (0.84)
Direct bilirubin; Week 8; n= 67, 66	0.0 (1.01)	0.1 (0.96)
Direct bilirubin; Week 12; n= 65, 68	0.0 (0.97)	0.0 (1.04)
Direct bilirubin; Week 16; n= 65, 68	-0.2 (0.96)	-0.1 (1.20)
Direct bilirubin; Week 20; n= 63, 68	0.0 (0.86)	0.1 (1.03)
Direct bilirubin; Week 24; n= 63, 66	0.1 (0.90)	0.0 (0.88)
Direct bilirubin; Week 28; n= 62, 66	-0.1 (1.20)	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	0.0 (1.11)	0.0 (0.94)
Direct bilirubin; Week 44; n= 61, 66	0.1 (0.93)	0.0 (1.12)
Direct bilirubin; Week 48; n= 61, 64	0.1 (0.99)	0.0 (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 (1.10)	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)	0.0 (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 (3.00)
Indirect bilirubin; Week 24; n= 63, 66	-0.4 (2.94)	0.0 (2.37)
Indirect bilirubin; Week 28; n= 62, 66	-0.7 (2.60)	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)	0.0 (3.30)
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)

13. Secondary Outcome

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
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. NA indicates that data were not available.
Time Frame	Baseline and up to Week 60

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Placebo	Mepolizumab 300mg
Arm/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.	Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.
Measure Participants	68	68
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 (0.1200)
Calcium; Week 8; n= 67, 66	-0.013 (0.0877)	-0.010 (0.1003)
Calcium; Week 12; n= 65, 68	-0.013 (0.0844)	-0.026 (0.0889)
Calcium; Week 16; n= 65, 68	0.000 (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	-0.000 (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)	-0.020 (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 (0.1110)
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)	104.0 (2.21)
Chloride; Week 4; n= 68, 68	0.6 (1.97)	0.2 (2.00)
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 (2.20)
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 (2.20)
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 (2.20)
Absolute Cholesterol; Baseline; n= 68, 68	5.771 (1.2033)	5.788 (1.2386)
Cholesterol; Week 8; n= 2, 0	-0.250 (0.1414)
Cholesterol; Week 12; n= 1, 0	0.050 (NA)
Cholesterol; Week 16; n= 1, 1	-0.400 (NA)	-0.300 (NA)
Cholesterol; Week 20; n= 1, 1	0.050 (NA)	-0.300 (NA)
Cholesterol; Week 24; n= 0, 1	-0.560 (NA)
Cholesterol; Week 36; n= 0, 1	0.420 (NA)
Cholesterol; Week 52; n= 60, 65	-0.006 (0.9364)	-0.384 (0.8798)
Cholesterol; Week 56; n= 1, 0	-0.220 (NA)
Absolute Glucose; Baseline; n= 68, 68	5.76 (2.000)	5.35 (1.195)
Glucose; Week 4; n= 68, 68	0.27 (1.619)	-0.01 (1.050)
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 (1.740)
Glucose; Week 52; n= 60, 65	-0.17 (1.650)	0.02 (1.258)
Glucose; Week 56; n= 61, 63	0.01 (1.718)	0.13 (1.852)
Glucose; Week 60; n= 60, 65	0.20 (1.664)	0.11 (1.483)
Absolute HDL cholesterol; Baseline; n= 68, 68	1.837 (0.4540)	1.937 (0.5606)
HDL cholesterol; Week 8; n= 2, 0	-0.075 (0.0354)
HDL cholesterol; Week 12; n= 1, 0	-0.100 (NA)
HDL cholesterol; Week 16; n= 1, 1	0.400 (NA)	-0.150 (NA)
HDL cholesterol; Week 20; n= 1, 1	0.000 (NA)	-0.250 (NA)
HDL cholesterol; Week 24; n= 0, 1	-0.390 (NA)
HDL cholesterol; Week 36; n= 0, 1	0.400 (NA)
HDL cholesterol; Week 52; n= 60, 65	-0.045 (0.2832)	-0.150 (0.3146)
HDL cholesterol; Week 56; n= 1, 0	-0.060 (NA)
Absolute LDL cholesterol; Baseline; n= 67, 68	3.261 (1.0808)	3.205 (1.0992)
LDL cholesterol; Week 8; n= 1, 0	-0.350 (NA)
LDL cholesterol; Week 12; n= 1, 0	0.190 (NA)
LDL cholesterol; Week 16; n= 1, 1	-0.730 (NA)	-0.790 (NA)
LDL cholesterol; Week 20; n= 1, 1	-0.150 (NA)	-0.540 (NA)
LDL cholesterol; Week 24; n= 0, 1	0.040 (NA)
LDL cholesterol; Week 36; n= 0, 1	0.250 (NA)
LDL cholesterol; Week 52; n= 58, 64	0.016 (0.7717)	-0.215 (0.8079)
LDL cholesterol; Week 56; n= 1, 0	0.100 (NA)
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)	0.040 (0.2172)
Phosphate; Week 36; n= 60, 67	-0.038 (0.2159)	0.023 (0.2260)
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 (0.2240)
Phosphate; Week 48; n= 61, 64	-0.053 (0.1931)	-0.020 (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)	4.10 (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 (0.340)	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 (0.350)
Potassium; Week 28; n= 61, 66	0.07 (0.338)	0.10 (0.382)
Potassium; Week 32; n= 61, 67	0.04 (0.340)	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	0.00 (0.358)	0.10 (0.390)
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	0.0 (1.46)	-0.1 (1.91)
Sodium; Week 20; n= 63, 68	0.0 (1.88)	0.1 (2.09)
Sodium; Week 24; n= 63, 66	0.2 (1.94)	0.0 (1.95)
Sodium; Week 28; n= 62, 66	0.5 (1.71)	0.0 (2.23)
Sodium; Week 32; n= 61, 67	0.3 (1.92)	0.1 (2.13)
Sodium; Week 36; n= 60, 67	0.4 (2.10)	0.0 (1.95)
Sodium; Week 40; n= 61, 66	0.2 (2.42)	0.0 (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)	0.20 (1.206)
Urea; Week 12; n= 65, 68	-0.15 (1.414)	-0.10 (1.217)
Urea; Week 16; n= 65, 68	-0.07 (1.569)	0.00 (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 (1.350)
Urea; Week 32; n= 61, 67	-0.11 (1.320)	-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)	-0.10 (1.170)
Absolute VLDL cholesterol; Baseline; n= 67, 68	0.680 (0.2846)	0.646 (0.2841)
VLDL cholesterol; Week 8; n= 1, 0	0.100 (NA)
VLDL cholesterol; Week 12; n= 1, 0	-0.040 (NA)
VLDL cholesterol; Week 16; n= 1, 1	-0.070 (NA)	0.640 (NA)
VLDL cholesterol; Week 20; n= 1, 1	0.200 (NA)	0.490 (NA)
VLDL cholesterol; Week 24; n= 0, 1	-0.210 (NA)
VLDL cholesterol; Week 36; n= 0, 1	-0.230 (NA)
VLDL cholesterol; Week 52; n= 58, 64	-0.019 (0.3229)	-0.051 (0.1927)
VLDL cholesterol; Week 56; n= 1, 0	-0.260 (NA)

14. Secondary Outcome

Title	Change From Baseline in Clinical Chemistry Parameter of Troponin Levels
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.
Time Frame	Baseline and up to Week 60

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Placebo	Mepolizumab 300mg
Arm/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.	Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.
Measure Participants	68	68
Absolute Troponin; Baseline; n= 68, 68	0.013 (0.0110)	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 (0.0090)
Troponin; Week 32; n= 61, 67	-0.003 (0.0100)	-0.002 (0.0092)
Troponin; Week 36; n= 61, 67	-0.002 (0.0107)	0.000 (0.0185)
Troponin; Week 40; n= 61, 66	-0.001 (0.0117)	-0.002 (0.0090)
Troponin; Week 44; n= 61, 65	-0.000 (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)

15. Secondary Outcome

Title	Change From Baseline in Hematology Parameters of Basophils, Eosinophil, Leukocytes, Lymphocytes, Monocytes, Neutrophils, Platelets Levels
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.
Time Frame	Baseline and up to Week 60

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Placebo	Mepolizumab 300mg
Arm/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.	Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.
Measure Participants	68	68
Absolute Basophils; Baselin; n= 68, 68	0.030 (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	0.010 (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)	0.000 (0.0296)
Basophils; Week 48; n= 59, 64	0.003 (0.0408)	-0.004 (0.0300)
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)	-0.370 (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 (0.8280)
Eosinophils; Week 20; n= 61, 66	0.162 (0.5900)	-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)	-0.360 (0.8258)
Eosinophils; Week 32; n= 61, 66	0.079 (0.3759)	-0.347 (0.8310)
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 (0.8540)
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 (3.130)
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 (2.110)	-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	-0.10 (3.092)	-1.46 (2.546)
Leukocytes; Week 52; n= 60, 64	-0.12 (3.114)	-1.50 (2.521)
Leukocytes; Week 56; n= 59, 61	-0.05 (3.357)	-1.50 (2.840)
Leukocytes; Week 60; n= 58, 64	0.19 (3.533)	-1.20 (2.396)
Absolute Lymphocytes; Baseline; n= 68, 68	1.638 (0.9375)	1.508 (0.8230)
Lymphocytes; Week 4; n= 66, 66	0.031 (0.8990)	0.145 (0.7485)
Lymphocytes; Week 8; n= 65, 66	0.245 (0.8804)	-0.048 (0.6388)
Lymphocytes; Week 12; n= 63, 65	0.160 (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	0.130 (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	0.200 (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 (0.2790)	0.031 (0.2157)
Monocytes; Week 20; n= 61, 66	0.132 (0.2684)	0.030 (0.1967)
Monocytes; Week 24; n= 61, 66	0.061 (0.2290)	0.013 (0.2412)
Monocytes; Week 28; n= 62, 65	0.107 (0.2363)	0.035 (0.2350)
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)	0.050 (0.2096)
Monocytes; Week 44; n= 59, 61	0.090 (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 (0.2600)	0.001 (0.2165)
Absolute Neutrophils; Baseline; n= 68, 68	7.500 (2.7424)	7.198 (2.9732)
Neutrophils; Week 4; n= 66, 66	-0.124 (2.6170)	-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	-0.560 (2.3679)	-1.243 (2.6857)
Neutrophils; Week 24; n= 61, 66	-0.980 (2.3151)	-1.120 (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)	-1.010 (3.3999)
Neutrophils; Week 44; n= 59, 61	-0.020 (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	5.0 (43.97)	4.1 (26.48)
Platelets; Week 12; n= 63, 65	3.1 (50.60)	-4.3 (37.89)
Platelets; Week 16; n= 64, 68	15.4 (71.20)	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)	2.0 (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 (44.80)
Platelets; Week 52; n= 60, 64	14.7 (48.19)	-3.7 (46.34)
Platelets; Week 56; n= 59, 61	20.3 (47.35)	-1.0 (48.51)
Platelets; Week 60; n= 59, 64	13.0 (50.07)	-2.0 (41.32)

16. Secondary Outcome

Title	Change From Baseline in Hematology Parameters of Mean Corpuscle Hemoglobin Concentration (MCHC) and Hemoglobin Levels
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.
Time Frame	Baseline and up to Week 60

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Placebo	Mepolizumab 300mg
Arm/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.	Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.
Measure Participants	68	68
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 (6.60)
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 (9.40)
MCHC; Week 48; n= 59, 64	-6.0 (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 (9.90)
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 (8.50)	-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 (8.20)	-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)

17. Secondary Outcome

Title	Change From Baseline in Hematology Parameters of Mean Corpuscle Volume (MCV) Levels
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.
Time Frame	Baseline and up to Week 60

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Placebo	Mepolizumab 300mg
Arm/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.	Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.
Measure Participants	68	68
Absolute, Baseline; n= 68, 68	94.8 (9.02)	94.8 (6.14)
Week 4; n= 66, 67	0.4 (1.67)	0.0 (2.33)
Week 8; n= 66, 66	0.3 (2.50)	0.0 (2.58)
Week 12; n= 63, 65	0.2 (2.00)	-0.7 (2.30)
Week 16; n= 64, 68	0.0 (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)	-1.0 (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)	-1.0 (4.15)
Week 60; n= 59, 64	-0.6 (6.57)	-1.0 (4.49)

18. Secondary Outcome

Title	Change From Baseline in Hematology Parameters of Mean Corpuscle Hemoglobin (MCH) Levels
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.
Time Frame	Baseline and up to Week 60

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Placebo	Mepolizumab 300mg
Arm/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.	Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.
Measure Participants	68	68
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 (0.950)	-0.16 (0.653)
Week 12; n= 63, 65	-0.04 (0.550)	-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 (1.270)	-0.59 (0.959)
Week 28; n= 62, 66	-0.51 (0.618)	-0.70 (1.184)
Week 32; n= 61, 67	-0.66 (0.764)	-0.88 (1.368)
Week 36; n= 60, 66	-0.60 (0.910)	-0.90 (1.395)
Week 40; n= 61, 65	-0.67 (1.171)	-0.79 (1.390)
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)	-0.80 (1.818)

19. Secondary Outcome

Title	Change From Baseline in Hematology Parameters of Erythrocytes Levels
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.
Time Frame	Baseline and up to Week 60

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Placebo	Mepolizumab 300mg
Arm/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.	Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.
Measure Participants	68	68
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 (0.300)	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 (0.270)
Week 44; n= 60, 64	0.13 (0.332)	0.08 (0.260)
Week 48; n= 59, 64	0.14 (0.293)	0.10 (0.271)
Week 52; n= 60, 64	0.10 (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)

20. Secondary Outcome

Title	Number of Participants With Anti-Mepolizumab Antibodies
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.
Time Frame	Up to Week 60

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Placebo	Mepolizumab 300mg
Arm/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.	Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.
Measure Participants	67	66
Negative	66 97.1%	65 95.6%
Positive	1 1.5%	1 1.5%

21. Secondary Outcome

Title	Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) Levels
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.
Time Frame	Baseline up to Week 60

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Placebo	Mepolizumab 300mg
Arm/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.	Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.
Measure Participants	68	68
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 (12.370)
SBP; Week 8; n= 67, 68	0.07 (14.192)	1.29 (11.066)
SBP; Week 12; n= 66, 68	-1.12 (14.380)	-1.41 (12.071)
SBP; Week 16; n= 64, 68	-0.97 (16.630)	-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 (13.240)
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	0.90 (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 (17.140)	-0.22 (12.351)
SBP: Week 52; n= 61, 65	-1.03 (13.200)	-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 (10.130)
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 (9.930)	-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 (10.570)	0.11 (8.899)
DBP; Week 60; n= 61, 65	-2.54 (11.278)	-0.45 (9.836)

22. Secondary Outcome

Title	Change From Baseline in Pulse Rate
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.
Time Frame	Baseline and up to Week 60

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Placebo	Mepolizumab 300mg
Arm/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.	Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.
Measure Participants	68	68
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	1.60 (11.703)	-0.31 (10.530)
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	3.10 (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	2.60 (14.041)	-0.35 (9.986)
Week 60; n= 61, 65	1.51 (12.793)	0.09 (10.280)

23. Secondary Outcome

Title	Change From Baseline in Body Temperature
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.
Time Frame	Baseline and up to Week 60

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Placebo	Mepolizumab 300mg
Arm/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.	Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.
Measure Participants	68	68
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 (0.410)	-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 (0.530)	-0.13 (0.406)
Week 44; n= 61, 65	-0.03 (0.550)	-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 (0.530)	-0.00 (0.402)
Week 60; n= 61, 64	0.03 (0.467)	-0.02 (0.479)

24. Secondary Outcome

Title	Mean Change From Baseline in QT Interval Corrected by Fridericia's Method (QTcF) and QT Interval Corrected by Bazett's Method (QTcB) Values
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).
Time Frame	Baseline and up to Week 60

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Placebo	Mepolizumab 300mg
Arm/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.	Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.
Measure Participants	68	68
QTcF; Week 8; n= 66, 66	0.1 (17.90)	1.0 (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	2.0 (15.96)	3.0 (16.04)
QTcF; Week 60; n= 58, 63	3.0 (14.30)	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)	1.0 (18.10)
QTcB; Week 32; n= 61, 66	5.2 (29.63)	0.0 (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)

25. Secondary Outcome

Title	Maximum Change From Baseline in QTcF and QTcB Values
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.
Time Frame	Baseline and up to Week 60

Outcome Measure Data

Analysis Population Description
Safety Population

Arm/Group Title	Placebo	Mepolizumab 300mg
Arm/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.	Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.
Measure Participants	68	68
QTcB interval	18.8 (26.46)	18.1 (15.28)
QTcF interval	16.9 (23.74)	15.4 (13.79)

Adverse Events

	Placebo		Mepolizumab 300mg
Time Frame	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 Description	AEs and SAEs were collected in Safety Population which comprised of all participants who received at least one dose of study treatment.

Arm/Group Title	Placebo		Mepolizumab 300mg
Arm/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.		Participants received Mepolizumab 300mg injection via SC route once every 4 weeks along with SOC drugs up to Week 48.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/68 (0%)		1/68 (1.5%)
Serious Adverse Events
	Placebo		Mepolizumab 300mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	18/68 (26.5%)		12/68 (17.6%)
Cardiac disorders
Cardiac arrest	0/68 (0%)		1/68 (1.5%)
Coronary artery disease	1/68 (1.5%)		0/68 (0%)
Stress cardiomyopathy	1/68 (1.5%)		0/68 (0%)
Gastrointestinal disorders
Abdominal pain	0/68 (0%)		1/68 (1.5%)
General disorders
Hernia	0/68 (0%)		1/68 (1.5%)
Pyrexia	1/68 (1.5%)		0/68 (0%)
Immune system disorders
Allergic granulomatous angiitis	1/68 (1.5%)		0/68 (0%)
Hypersensitivity	0/68 (0%)		1/68 (1.5%)
Infections and infestations
Influenza	2/68 (2.9%)		0/68 (0%)
Pneumonia	2/68 (2.9%)		0/68 (0%)
Appendicitis	1/68 (1.5%)		0/68 (0%)
Bronchitis	1/68 (1.5%)		0/68 (0%)
Cellulitis	1/68 (1.5%)		0/68 (0%)
Corona virus infection	1/68 (1.5%)		0/68 (0%)
Enterococcal infection	0/68 (0%)		1/68 (1.5%)
Gastroenteritis	1/68 (1.5%)		0/68 (0%)
Herpes zoster	1/68 (1.5%)		0/68 (0%)
Lower respiratory infection	2/68 (2.9%)		0/68 (0%)
Parainfluenzae virus infection	0/68 (0%)		1/68 (1.5%)
Perirectal abscess	0/68 (0%)		1/68 (1.5%)
Pneumonia bacterial	1/68 (1.5%)		0/68 (0%)
Respiratory tract infection	0/68 (0%)		1/68 (1.5%)
Urinary tract infection	0/68 (0%)		1/68 (1.5%)
Injury, poisoning and procedural complications
Road traffic accident	1/68 (1.5%)		0/68 (0%)
Spinal fracture	1/68 (1.5%)		0/68 (0%)
Musculoskeletal and connective tissue disorders
Back pain	0/68 (0%)		1/68 (1.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Testis cancer	1/68 (1.5%)		0/68 (0%)
Nervous system disorders
Cerebellar ischaemia	0/68 (0%)		1/68 (1.5%)
Dizziness	0/68 (0%)		1/68 (1.5%)
Facial paralysis	1/68 (1.5%)		0/68 (0%)
Facial paresis	0/68 (0%)		1/68 (1.5%)
Lacunar infarction	0/68 (0%)		1/68 (1.5%)
Nystagmus	0/68 (0%)		1/68 (1.5%)
Pachymeningitis	0/68 (0%)		1/68 (1.5%)
Toxic encephalopathy	1/68 (1.5%)		0/68 (0%)
Psychiatric disorders
Mental status changes	1/68 (1.5%)		0/68 (0%)
Renal and urinary disorders
Acute kidney injury	1/68 (1.5%)		0/68 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	4/68 (5.9%)		2/68 (2.9%)
Acute respiratory failure	2/68 (2.9%)		0/68 (0%)
Lung infiltration	1/68 (1.5%)		0/68 (0%)
Pneumonia aspiration	1/68 (1.5%)		0/68 (0%)
Respiratory failure	1/68 (1.5%)		0/68 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Mepolizumab 300mg
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	61/68 (89.7%)		65/68 (95.6%)
Ear and labyrinth disorders
Vertigo	1/68 (1.5%)		5/68 (7.4%)
Ear discomfort	4/68 (5.9%)		1/68 (1.5%)
Endocrine disorders
Adrenal insufficiency	0/68 (0%)		3/68 (4.4%)
Eye disorders
Vision blurred	2/68 (2.9%)		4/68 (5.9%)
Cataract	2/68 (2.9%)		3/68 (4.4%)
Eye pruritus	0/68 (0%)		3/68 (4.4%)
Gastrointestinal disorders
Nausea	13/68 (19.1%)		11/68 (16.2%)
Diarrhoea	8/68 (11.8%)		12/68 (17.6%)
Vomiting	4/68 (5.9%)		11/68 (16.2%)
Abdominal pain upper	5/68 (7.4%)		5/68 (7.4%)
Abdominal pain	4/68 (5.9%)		2/68 (2.9%)
Gastrooesophageal reflux disease	4/68 (5.9%)		1/68 (1.5%)
Dyspepsia	3/68 (4.4%)		1/68 (1.5%)
General disorders
Fatigue	10/68 (14.7%)		10/68 (14.7%)
Injection site reaction	7/68 (10.3%)		9/68 (13.2%)
Pyrexia	7/68 (10.3%)		7/68 (10.3%)
Asthenia	3/68 (4.4%)		5/68 (7.4%)
Chest pain	5/68 (7.4%)		1/68 (1.5%)
Injection site pain	3/68 (4.4%)		2/68 (2.9%)
Oedema peripheral	1/68 (1.5%)		3/68 (4.4%)
Influenza like illness	0/68 (0%)		3/68 (4.4%)
Infections and infestations
Nasopharyngitis	16/68 (23.5%)		12/68 (17.6%)
Sinusitis	11/68 (16.2%)		14/68 (20.6%)
Upper respiratory tract infection	11/68 (16.2%)		14/68 (20.6%)
Bronchitis	8/68 (11.8%)		7/68 (10.3%)
Influenza	6/68 (8.8%)		7/68 (10.3%)
Respiratory tract infection	8/68 (11.8%)		5/68 (7.4%)
Urinary tract infection	4/68 (5.9%)		5/68 (7.4%)
Acute sinusitis	2/68 (2.9%)		6/68 (8.8%)
Conjunctivitis	4/68 (5.9%)		4/68 (5.9%)
Rhinitis	3/68 (4.4%)		5/68 (7.4%)
Ear infection	6/68 (8.8%)		1/68 (1.5%)
Fungal skin infection	3/68 (4.4%)		4/68 (5.9%)
Oral herpes	3/68 (4.4%)		4/68 (5.9%)
Gastroenteritis	1/68 (1.5%)		5/68 (7.4%)
Otitis media	1/68 (1.5%)		3/68 (4.4%)
Viral infection	1/68 (1.5%)		3/68 (4.4%)
Injury, poisoning and procedural complications
Laceration	2/68 (2.9%)		3/68 (4.4%)
Ligament sprain	1/68 (1.5%)		4/68 (5.9%)
Contusion	1/68 (1.5%)		3/68 (4.4%)
Investigations
Alanine aminotransferase increased	0/68 (0%)		5/68 (7.4%)
Weight increased	1/68 (1.5%)		4/68 (5.9%)
Aspartate aminotransferase increased	0/68 (0%)		3/68 (4.4%)
Gamma-glutamyltransferase increased	0/68 (0%)		3/68 (4.4%)
Musculoskeletal and connective tissue disorders
Arthralgia	12/68 (17.6%)		15/68 (22.1%)
Myalgia	9/68 (13.2%)		6/68 (8.8%)
Back pain	6/68 (8.8%)		8/68 (11.8%)
Pain in extremity	6/68 (8.8%)		5/68 (7.4%)
Neck pain	2/68 (2.9%)		8/68 (11.8%)
Musculoskeletal pain	2/68 (2.9%)		6/68 (8.8%)
Joint swelling	3/68 (4.4%)		2/68 (2.9%)
Muscle spasms	2/68 (2.9%)		3/68 (4.4%)
Nervous system disorders
Headache	12/68 (17.6%)		22/68 (32.4%)
Dizziness	5/68 (7.4%)		3/68 (4.4%)
Paraesthesia	3/68 (4.4%)		4/68 (5.9%)
Sinus headache	3/68 (4.4%)		2/68 (2.9%)
Migraine	1/68 (1.5%)		3/68 (4.4%)
Psychiatric disorders
Insomnia	4/68 (5.9%)		2/68 (2.9%)
Respiratory, thoracic and mediastinal disorders
Asthma	7/68 (10.3%)		10/68 (14.7%)
Cough	8/68 (11.8%)		5/68 (7.4%)
Oropharyngeal pain	5/68 (7.4%)		8/68 (11.8%)
Productive cough	7/68 (10.3%)		6/68 (8.8%)
Sinus congestion	6/68 (8.8%)		6/68 (8.8%)
Wheezing	6/68 (8.8%)		5/68 (7.4%)
Nasal congestion	5/68 (7.4%)		4/68 (5.9%)
Upper-airway cough syndrome	6/68 (8.8%)		2/68 (2.9%)
Dyspnoea	4/68 (5.9%)		1/68 (1.5%)
Epistaxis	2/68 (2.9%)		3/68 (4.4%)
Sneezing	1/68 (1.5%)		3/68 (4.4%)
Skin and subcutaneous tissue disorders
Rash	6/68 (8.8%)		9/68 (13.2%)
Pruritus	1/68 (1.5%)		6/68 (8.8%)
Urticaria	1/68 (1.5%)		4/68 (5.9%)
Skin lesion	0/68 (0%)		3/68 (4.4%)
Vascular disorders
Hot flush	0/68 (0%)		3/68 (4.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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

Results Point of Contact

Name/Title	GSK Response Center
Organization	GlaxoSmithKline
Phone	866-435-7343
Email

Responsible Party:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT02020889

Other Study ID Numbers:

115921

First Posted:

Dec 25, 2013

Last Update Posted:

Jan 31, 2018

Last Verified:

Jan 1, 2018

A Study to Investigate Mepolizumab in the Treatment of Eosinophilic Granulomatosis With Polyangiitis

Study Details

Study Description

Brief Summary

Study Design

Arms and Interventions

Outcome Measures

Primary Outcome Measures

Secondary Outcome Measures

Eligibility Criteria

Criteria

Inclusion Criteria:

Exclusion Criteria:

Contacts and Locations

Locations

Sponsors and Collaborators

Investigators

Study Documents (Full-Text)

More Information

Publications

Study Results

Participant Flow

Baseline Characteristics

Outcome Measures

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Statistical Analysis 1

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Outcome Measure Data

Adverse Events

All Cause Mortality

Serious Adverse Events

Other (Not Including Serious) Adverse Events

Limitations/Caveats

More Information

Certain Agreements

Results Point of Contact