Clincosm LogoSign in Get a demo

DREAM: Dose Ranging Efficacy And Safety With Mepolizumab in Severe Asthma

Sponsor
GlaxoSmithKline (Industry)
Overall Status
Completed
CT.gov ID
NCT01000506
Collaborator
(none)
621
Enrollment
95
Locations
4
Arms
28.7
Duration (Months)
6.5
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to show whether mepolizumab given every 4 weeks intravenously (i.v.) can reduce the frequency of asthma exacerbations in subjects with severe asthma despite receiving high doses of standard asthma medications. The study will look at different doses of mepolizumab in comparison to a placebo.

Condition or Disease Intervention/Treatment Phase
  • Biological: Mepolizumab 750
  • Biological: Mepolizumab 250
  • Biological: Mepolizumab 75
  • Drug: Placebo saline
 Phase 2

Detailed Description

A double-blind, placebo-controlled study to evaluate the efficacy, safety and pharmacodynamics of three doses (75 mg, 250 mg and 750 mg) of mepolizumab intravenous (i.v.) administered every 4 weeks compared with placebo over a 52-week treatment period in subjects with severe uncontrolled refractory asthma. Efficacy will be measured by the frequency of asthma exacerbations. In addition lung function, rescue medication usage, daily symptoms, asthma control score, asthma quality of life score and withdrawals due to asthma exacerbations will be assessed. Safety will be assessed by adverse events, clinical laboratory evaluations, ECGs, immunogenicity and vital signs. Pharmacodynamics will be assessed by eosinophil levels in blood, serum IL-5 and eosinophil levels in induced sputum.

Study Design

Study Type:
Interventional
Actual Enrollment :
621 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group, Dose Ranging Study to Determine the Effect of Mepolizumab on Exacerbation Rates in Subjects With Severe Uncontrolled Refractory Asthma
Study Start Date :
Nov 1, 2009
Actual Primary Completion Date :
Mar 23, 2012
Actual Study Completion Date :
Mar 23, 2012

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Mepolizumab 750mg

Mepolizumab 750mcg i.v. every 4 weeks

Biological: Mepolizumab 750
Mepolizumab 750mg every four weeks by i.v.
Active Comparator: Mepolizumab 250mg

Mepolizumab 250mcg i.v. every 4 weeks

Biological: Mepolizumab 250
Mepolizumab 250mg every four weeks by i.v.
Active Comparator: Mepolizumab 75mg

Mepolizumab 75mcg i.v. every 4 weeks

Biological: Mepolizumab 75
Mepolizumab 75mg every four weeks by i.v.
Placebo Comparator: Placebo

Placebo saline every 4 weeks i.v.

Drug: Placebo saline
Placebo saline every four weeks by i.v.

Outcome Measures

Primary Outcome Measures

  1. Number of Clinically Significant Exacerbations of Asthma Per Year [From randomization (Week 0) to Week 52 or early withdrawal (EW)]

    Clinically significant exacerbations of asthma are defined as worsening of asthma which required use of oral/systemic corticosteroids (for participants on maintenance oral corticosteroids [OCS], an exacerbation requiring OCS is defined as the use of oral/systemic corticosteroids at least double the existing maintenance dose for at least 3 days) and/or hospitalization and/or emergency department (ED) visit. The frequency of clinically significant exacerbations of asthma over the 52-week treatment period is expressed as exacerbation rate per year. Analysis of the number of exacerbations was performed using a negative binomial regression model with covariates of treatment group, Baseline (BL) maintenance OCS therapy (OCS vs. no OCS), region, exacerbations in the year prior to the study (as an ordinal variable) and BL percent (%) predicted forced expiratory volume in 1 second (FEV1), and with logarithm of time on treatment as an offset variable

Secondary Outcome Measures

  1. Time to First Clinically Significant Exacerbation Requiring Oral or Systemic Corticosteroid, Hospitalization and/ or ED Visit [From randomization (Week 0) to Week 52 or EW]

    Clinically significant exacerbations of asthma are defined as worsening of asthma which required use of oral/systemic corticosteroids (for participants on maintenance OCS, an exacerbation requiring OCS is defined as the use of oral/systemic corticosteroids at least double the existing maintenance dose for at least 3 days) and/or hospitalization and/or ED visit. Kaplan-Meier estimates of the probability of an exacerbation is expressed as percentage of participants with an exacerbation over time (by Week 16, Week 32 and Week 52).

  2. Number of Exacerbations Requiring Hospitalization (Including Intubation and Admittance to an Intensive Care Unit [ICU]) or ED Visit Per Year [From randomization (Week 0) to Week 52 or EW]

    The frequency of exacerbations of asthma requiring hospitalization (including intubation and admittance to an intensive care unit [ICU]) or ED visit over the 52-week treatment period is expressed as exacerbation rate per year. Analysis of the number of exacerbations was performed using a negative binomial regression model with covariates of treatment group, Baseline (BL) maintenance OCS therapy (OCS vs. no OCS), region, exacerbations in the year prior to the study (as an ordinal variable) and BL percent (%) predicted forced expiratory volume in 1 second (FEV1), and with logarithm of time on treatment as an offset variable.

  3. Time to First Exacerbation Requiring Hospitalization or ED Visit [From randomization (Week 0) to Week 52 or EW]

    Exacerbations of asthma requiring hospitalization or ED visit were assessed. Kaplan-Meier estimates of the probability of an exacerbation is expressed as percentage of participants with an exacerbation over time (by Week 16, Week 32 and Week 52).

  4. Number of All Recorded Exacerbations Per Year [From randomization (Week 0) to Week 52 or EW]

    Clinically significant exacerbations (ex) of asthma are defined as worsening of asthma which required use of oral/systemic corticosteroids (for par. on maintenance OCS, an ex requiring OCS is defined as the use of oral/systemic corticosteroids at least double the existing maintenance dose for at least 3 days) and/or hospitalization and/or ED visit. In the case, an event described as an ex was not associated with a deterioration in >=1 of the objectives of eDiary parameters, the investigator (inv) provided an explanation to support the decision for defining the event as an ex. All recorded ex were defined as those recorded by inv, regardless of the outcome of the ex review process. Analysis was performed using Negative Binomial regression model with covariates of treatment group, BL maintenance OCS therapy (OCS vs. no OCS), region, ex in the year prior to the study (as an ordinal variable) and BL % predicted FEV1, and with logarithm of time on treatment as an offset variable.

  5. Time to First All Recorded Exacerbation [From randomization (Week 0) to Week 52 or EW]

    All recorded exacerbations are defined as those recorded by investigators, regardless of the outcome of the exacerbation review process. In the case, an event described as an exacerbation was not associated with a deterioration in at least one of the objectives of eDiary parameters, the investigator provided an explanation to support the decision for defining the event as an exacerbation. Kaplan-Meier estimates of the probability of an exacerbation is expressed as percentage of participants with an exacerbation over time (by week 16, week 32 and week 52).

  6. Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period [From Baseline up to Week 52 or EW]

    FEV1 is defined as the volume of air forcefully expelled from the lungs in 1 second. Pre-bronchodilator FEV1 measurements were taken by spirometry at each clinic visit. The change from Baseline is defined as the difference between the value of the endpoint at the time point of interest and the Baseline value. Analysis was performed using mixed model repeated measures with covariates of Baseline, region, Baseline maintenance OCS therapy (OCS vs. no OCS), exacerbations in the year prior to the study (as an ordinal variable), treatment and visit, plus interaction terms for visit by Baseline and visit by treatment group.

  7. Mean Change From Baseline in Clinic Post-bronchodilator FEV1 Over the 52-week Treatment Period [From Baseline up to Week 52 or EW]

    FEV1 is defined as the volume of air forcefully expelled from the lungs in 1 second. Post-bronchodilator FEV1 measurements were taken by spirometry at Baseline, Week 16, Week 32 and Week 52. Post bronchodilator values were recorded following reversibility testing, using the maximum post bronchodilator method. Participants unable to achieve >=12% reversibility and 200 mL change at Visit 1, reversibility test was repeated at Visit 2. These procedures to achieve the maximum post-bronchodilator are generated by the Asthma Clinical Research Network. The change from Baseline is defined as the difference between the value of the endpoint at the time point of interest and the Baseline value. Analysis was performed using mixed model repeated measures with covariates of Baseline, region, Baseline maintenance OCS therapy (OCS vs. no OCS), exacerbations in the year prior to the study (as an ordinal variable), treatment and visit, plus interaction terms for visit by Baseline and visit by treatment

  8. Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period [From Baseline up to Week 52 or EW]

    The ACQ-6 is a six-item questionnaire. The six questions enquire about the frequency and/or severity of symptoms (nocturnal awakening on waking in the morning, activity limitation, shortness of breath, wheeze) and use of short-acting bronchodilator over the previous week. The response options for all these questions consist of a 0 (no impairment/limitation) to 6 (total impairment/ limitation) scale. The overall ACQ score is calculated as the mean of the 6 questions and therefore ranges between 0 (totally controlled) and 6 (severely uncontrolled). Change from BL is defined as the difference between the value of the endpoint at the time point of interest and BL value. Analysis was performed using mixed model repeated measures with covariates of BL, region, BL maintenance OCS therapy (OCS vs. no OCS), exacerbations in the year prior to the study (as an ordinal variable), BL % predicted FEV1, treatment and visit, plus interaction terms for visit by BL and visit by treatment group.

Eligibility Criteria

Criteria

Ages Eligible for Study:
12 Years to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • Male or female

  • Aged 12 to 65 years inclusive

  • Minimum weight 45kg

  • Clinical features of severe refractory asthma

  • Well documented requirement for high dose inhaled corticosteroids (ICS) [i.e. >= 880mcg/day fluticasone propionate or equivalent daily] for at least 12 months

  • Using additional controller medication in addition to high dose ICS for at least 12 months

  • Persistent airflow obstruction indicated by a pre-bronchodilator FEV1<80% predicted at visit 1 or 2 or peak flow diurnal variability of >20% on 3 or more days during the run-in

  • Airway inflammation which is likely to be eosinophilic in nature demonstrated by either raised peripheral blood eosinophils (>=300/microL), sputum eosinophils (>=3%), exhaled nitric oxide (>=50ppb) or prompt deterioration of asthma control following a <=25% reduction in regular maintenance dose of inhaled or oral corticosteroids (OCS)

  • History of 2 or more exacerbations requiring systemic corticosteroids in the previous 12 months

  • Evidence of asthma documented by airway reversibility, airway hyperresponsiveness or airflow variability

  • ECG assessment demonstrating QTc<450msec or QTc<480msec for patients with bundle branch block

  • Liver function tests demonstrating ALT<2xUpper Limit of Normal (ULN), AST<2xULN, Alk Phos <=1.5xULN, bilirubin <=1.5xULN

  • Female of non-child-bearing potential or child-bearing potential with a negative pregnancy test at screening and prepared to agree to an acceptable method of contraception

  • Able to give written informed consent

  • Able to read, comprehend and write at a sufficient level to complete study materials

Exclusion Criteria:

  • Current smokers or smoking history of >=10 pack years

  • Clinically important lung condition other than asthma

  • Diagnosis of malignancy or in the process of investigation

  • Unstable liver disease

  • Churg-Strauss syndrome

  • Using methotrexate, troleandomycin, oral gold, cyclosporine, azathioprine or any experimental anti-inflammatory therapy within 3 months of screening

  • Omalizumab (Xolair) or any other biological for the treatment of inflammatory disease within 6 months of Visit 1

  • Regular use of oral or systemic corticosteroids for diseases other than asthma within 12 months or any intra-articular, short-acting intramuscular corticosteroid within 1 month or intramuscular, long-acting depot corticosteroid within 3 months

  • Allergy/intolerance to the excipients in the mepolizumab formulation

  • Any investigational drug within 30 days or 5 terminal half-lives, whichever is longer

  • Pregnant or breastfeeding or planning to become pregnant

  • Clinically significant disease which is uncontrolled with standard treatment

  • History of alcohol misuse or substance abuse

  • Parasitic infestation within previous 6 months

  • Known immunodeficiency

  • Unable to follow instructions, use the electronic diary or peak flow meter

  • Known evidence of lack of adherence to controller medications and/or follow physician's recommendations

  • Previous participation in a study of mepolizumab and received study medication within 90 days

Contacts and Locations

Locations

Site City State Country Postal Code
1 GSK Investigational Site Long Beach California United States 90808
2 GSK Investigational Site Los Angeles California United States 90095
3 GSK Investigational Site Riverside California United States 92506
4 GSK Investigational Site San Diego California United States 92103-8415
5 GSK Investigational Site Denver Colorado United States 80206
6 GSK Investigational Site New Haven Connecticut United States 06510
7 GSK Investigational Site Albany Georgia United States 31707
8 GSK Investigational Site Columbus Georgia United States 31904
9 GSK Investigational Site Lexington Kentucky United States 40508
10 GSK Investigational Site Saint Louis Missouri United States 63110
11 GSK Investigational Site Winston-Salem North Carolina United States 27103
12 GSK Investigational Site Canton Ohio United States 44718
13 GSK Investigational Site Cleveland Ohio United States 44195
14 GSK Investigational Site Oklahoma City Oklahoma United States 73103
15 GSK Investigational Site Hershey Pennsylvania United States 17033
16 GSK Investigational Site Pittsburgh Pennsylvania United States PA 15213
17 GSK Investigational Site Charleston South Carolina United States 29406
18 GSK Investigational Site Nashville Tennessee United States 37203
19 GSK Investigational Site Boerne Texas United States 78006
20 GSK Investigational Site Houston Texas United States 77054
21 GSK Investigational Site Madison Wisconsin United States 53792
22 GSK Investigational Site Mar del Plata Buenos Aires Argentina B7600FZN
23 GSK Investigational Site Buenos Aires Argentina 1425
24 GSK Investigational Site Ciudad Autónoma de Buenos Aires Argentina C1426ABP
25 GSK Investigational Site Mendoza Argentina M5500CCG
26 GSK Investigational Site Tucuman Argentina 4000
27 GSK Investigational Site New Lambton New South Wales Australia 2305
28 GSK Investigational Site Adelaide South Australia Australia 5000
29 GSK Investigational Site Clayton Victoria Australia 3168
30 GSK Investigational Site Melbourne Victoria Australia 3004
31 GSK Investigational Site Nedlands Western Australia Australia 6009
32 GSK Investigational Site Calgary Alberta Canada T2N 4Z6
33 GSK Investigational Site Vancouver British Columbia Canada V5Z 1M9
34 GSK Investigational Site Mississauga Ontario Canada L5A 3V4
35 GSK Investigational Site Mississauga Ontario Canada L5M 2V8
36 GSK Investigational Site Quebec City Quebec Canada G1V 4G5
37 GSK Investigational Site Puente Alto - Santiago Región Metro De Santiago Chile 8207257
38 GSK Investigational Site Valparaiso Valparaíso Chile 2341131
39 GSK Investigational Site Santiago Chile 8380453
40 GSK Investigational Site Talcahuano Chile 4270918
41 GSK Investigational Site Clamart France 92140
42 GSK Investigational Site Marseille cedex 20 France 13915
43 GSK Investigational Site Montpellier France 34295
44 GSK Investigational Site Nantes France 44093
45 GSK Investigational Site Saint Pierre cedex France 97448
46 GSK Investigational Site Ruedersdorf Brandenburg Germany 15562
47 GSK Investigational Site Frankfurt am Main Hessen Germany 60596
48 GSK Investigational Site Frankfurt Hessen Germany 60596
49 GSK Investigational Site Mainz Rheinland-Pfalz Germany 55131
50 GSK Investigational Site Magdeburg Sachsen-Anhalt Germany 39112
51 GSK Investigational Site Luebeck Schleswig-Holstein Germany 23552
52 GSK Investigational Site Berlin Germany 10367
53 GSK Investigational Site Berlin Germany 10717
54 GSK Investigational Site Berlin Germany 12203
55 GSK Investigational Site Berlin Germany 14050
56 GSK Investigational Site Bucheon-si, Korea, Republic of 420-767
57 GSK Investigational Site Cheongju, Chungcheongbuk-do Korea, Republic of 361-711
58 GSK Investigational Site Seoul Korea, Republic of 133--792
59 GSK Investigational Site Seoul Korea, Republic of 152-703
60 GSK Investigational Site Suwon, Kyonggi-do Korea, Republic of 443-721
61 GSK Investigational Site Bialystok Poland 15-276
62 GSK Investigational Site Lodz Poland 90-153
63 GSK Investigational Site Warszawa Poland 01-138
64 GSK Investigational Site Wroclaw Poland 54-239
65 GSK Investigational Site Zawadzkie Poland 47-120
66 GSK Investigational Site Zgierz Poland 95-100
67 GSK Investigational Site Bucharest Romania 050159
68 GSK Investigational Site Bucuresti Romania 70000
69 GSK Investigational Site Iasi Romania 700115
70 GSK Investigational Site Targu Mures Romania 540143
71 GSK Investigational Site Barnaul Russian Federation 656 045
72 GSK Investigational Site Chelyabinsk Russian Federation 454106
73 GSK Investigational Site Kazan Russian Federation 420015
74 GSK Investigational Site Moscow Russian Federation 105 077
75 GSK Investigational Site Moscow Russian Federation 115478
76 GSK Investigational Site Moscow Russian Federation 123 182
77 GSK Investigational Site Saint-Petersburg Russian Federation 194354
78 GSK Investigational Site St. Petersburg Russian Federation 198216
79 GSK Investigational Site Tomsk Russian Federation 634001
80 GSK Investigational Site Cherkassy Ukraine 18009
81 GSK Investigational Site Dnipropetrovsk Ukraine 49006
82 GSK Investigational Site Dnipropetrovsk Ukraine 49027
83 GSK Investigational Site Dnipropetrovsk Ukraine 49051
84 GSK Investigational Site Donetsk Ukraine 83003
85 GSK Investigational Site Donetsk Ukraine 83099
86 GSK Investigational Site Kharkiv Ukraine 61035
87 GSK Investigational Site Kiev Ukraine 03680
88 GSK Investigational Site Kyiv Ukraine 03038
89 GSK Investigational Site Kyiv Ukraine 03115
90 GSK Investigational Site Mykolayiv Ukraine 54003
91 GSK Investigational Site Leicester Leicestershire United Kingdom LE3 9QP
92 GSK Investigational Site London United Kingdom E1 2AT
93 GSK Investigational Site London United Kingdom SW3 6HP
94 GSK Investigational Site Manchester United Kingdom M23 9LT
95 GSK Investigational Site Southampton United Kingdom SO16 6YD

Sponsors and Collaborators

  • GlaxoSmithKline

Investigators

  • Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01000506
Other Study ID Numbers:
  • 112997
First Posted:
Oct 23, 2009
Last Update Posted:
Jan 24, 2018
Last Verified:
Jan 1, 2018
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by GlaxoSmithKline
Dose-ranging
Safety
Pharmacodynamics
eosinophils
SB-240563
Efficacy
Severe refractory asthma
mepolizumab
Placebo
Additional relevant MeSH terms:
Asthma

Study Results

Participant Flow

Recruitment Details Participants (par.) who met the eligibility criteria at screening, entered the two week Run-in phase and par. who met the randomization eligibility criteria at the end of the Run-in phase entered into the 52-week Double-blind treatment period followed by a 4-week Follow-up phase. The total duration of participation in the study was 58 Weeks.
Pre-assignment Detail A total of 888 par. were enrolled, of these, 168 were screen failures and 720 entered the run-in phase. 99 participants were run-in failures and 621 completed the run-in phase and were randomized. Of these, 616 participants were randomized and received treatment and were included within the Intent-to-Treat (ITT) Population.
Arm/Group Title Placebo IV Mepolizumab 75 mg IV Mepolizumab 250 mg IV Mepolizumab 750 mg IV
Arm/Group Description Participants received placebo intravenous (IV) infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 75 milligrams (mg) IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 250 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 750 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product).
Period Title: Overall Study
STARTED 155 153 152 156
COMPLETED 127 129 131 133
NOT COMPLETED 28 24 21 23

Baseline Characteristics

Arm/Group Title Placebo IV Mepolizumab 75 mg IV Mepolizumab 250 mg IV Mepolizumab 750 mg IV Total
Arm/Group Description Participants received placebo intravenous (IV) infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 75 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 250 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 750 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Total of all reporting groups
Overall Participants 155 153 152 156 616
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
46.4
(11.33)
50.2
(10.84)
49.4
(11.63)
48.6
(11.06)
48.6
(11.28)
Sex: Female, Male (Count of Participants)
Female
97
62.6%
104
68%
93
61.2%
93
59.6%
387
62.8%
Male
58
37.4%
49
32%
59
38.8%
63
40.4%
229
37.2%
Race/Ethnicity, Customized (Number) [Number]
African American/African Heritage
6
3.9%
5
3.3%
8
5.3%
5
3.2%
24
3.9%
American Indian or Alaska Native
0
0%
0
0%
0
0%
1
0.6%
1
0.2%
Asian - Central/South Asian Heritage
1
0.6%
2
1.3%
0
0%
2
1.3%
5
0.8%
Asian - East Asian Heritage
7
4.5%
6
3.9%
7
4.6%
6
3.8%
26
4.2%
Asian - South East Asian Heritage
0
0%
1
0.7%
0
0%
2
1.3%
3
0.5%
Native Hawaiian or other Pacific Islander
1
0.6%
0
0%
0
0%
0
0%
1
0.2%
White - Arabic/North African Heritage
3
1.9%
1
0.7%
2
1.3%
1
0.6%
7
1.1%
White - White/Caucasian/European Heritage
137
88.4%
138
90.2%
133
87.5%
139
89.1%
547
88.8%
Mixed Race
0
0%
0
0%
2
1.3%
0
0%
2
0.3%

Outcome Measures

1. Primary Outcome
Title Number of Clinically Significant Exacerbations of Asthma Per Year
Description Clinically significant exacerbations of asthma are defined as worsening of asthma which required use of oral/systemic corticosteroids (for participants on maintenance oral corticosteroids [OCS], an exacerbation requiring OCS is defined as the use of oral/systemic corticosteroids at least double the existing maintenance dose for at least 3 days) and/or hospitalization and/or emergency department (ED) visit. The frequency of clinically significant exacerbations of asthma over the 52-week treatment period is expressed as exacerbation rate per year. Analysis of the number of exacerbations was performed using a negative binomial regression model with covariates of treatment group, Baseline (BL) maintenance OCS therapy (OCS vs. no OCS), region, exacerbations in the year prior to the study (as an ordinal variable) and BL percent (%) predicted forced expiratory volume in 1 second (FEV1), and with logarithm of time on treatment as an offset variable
Time Frame From randomization (Week 0) to Week 52 or early withdrawal (EW)

Outcome Measure Data

Analysis Population Description
Intent-to-Treat (ITT) Population: all participants who were randomized and who received at least one dose of study medication.
Arm/Group Title Placebo IV Mepolizumab 75 mg IV Mepolizumab 250 mg IV Mepolizumab 750 mg IV
Arm/Group Description Participants received placebo intravenous (IV) infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 75 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 250 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 750 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product).
Measure Participants 155 153 152 156
Number [Exacerbations per year]
2.40
1.24
1.46
1.15
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo IV, Mepolizumab 75 mg IV
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments Hochberg testing procedure with a one-sided alpha of 2.5% used for controlling multiplicity
Method Negative Binomial regression model
Comments
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.52
Confidence Interval (2-Sided) 95%
0.39 to 0.69
Parameter Dispersion Type:
Value:
Estimation Comments Number of exacerbations per year in the mepolizumab 75mg IV arm divided by the number of exacerbations per year in the placebo arm.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo IV, Mepolizumab 250 mg IV
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments Hochberg testing procedure with a one-sided alpha of 2.5% used for controlling multiplicity
Method Negative Binomial regression model
Comments
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.61
Confidence Interval (2-Sided) 95%
0.46 to 0.81
Parameter Dispersion Type:
Value:
Estimation Comments Number of exacerbations per year in the mepolizumab 250 mg IV arm divided by the number of exacerbations per year in the placebo arm.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Placebo IV, Mepolizumab 750 mg IV
Comments
Type of Statistical Test Superiority or Other
Comments
Statistical Test of Hypothesis p-Value <0.001
Comments Hochberg testing procedure with a one-sided alpha of 2.5% used for controlling multiplicity
Method Negative Binomial regression model
Comments
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.48
Confidence Interval (2-Sided) 95%
0.36 to 0.64
Parameter Dispersion Type:
Value:
Estimation Comments Number of exacerbations per year in the mepolizumab 750 mg IV arm divided by the number of exacerbations per year in the placebo arm.
2. Secondary Outcome
Title Time to First Clinically Significant Exacerbation Requiring Oral or Systemic Corticosteroid, Hospitalization and/ or ED Visit
Description Clinically significant exacerbations of asthma are defined as worsening of asthma which required use of oral/systemic corticosteroids (for participants on maintenance OCS, an exacerbation requiring OCS is defined as the use of oral/systemic corticosteroids at least double the existing maintenance dose for at least 3 days) and/or hospitalization and/or ED visit. Kaplan-Meier estimates of the probability of an exacerbation is expressed as percentage of participants with an exacerbation over time (by Week 16, Week 32 and Week 52).
Time Frame From randomization (Week 0) to Week 52 or EW

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo IV Mepolizumab 75 mg IV Mepolizumab 250 mg IV Mepolizumab 750 mg IV
Arm/Group Description Participants received placebo intravenous (IV) infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 75 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 250 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 750 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product).
Measure Participants 155 153 152 156
Week 16
45.2
29.2%
22.8
14.9%
26.8
17.6%
18.9
12.1%
Week 32
60.4
39%
38.2
25%
45.5
29.9%
39.9
25.6%
Week 52
69.7
45%
48.5
31.7%
58.3
38.4%
50.1
32.1%
3. Secondary Outcome
Title Number of Exacerbations Requiring Hospitalization (Including Intubation and Admittance to an Intensive Care Unit [ICU]) or ED Visit Per Year
Description The frequency of exacerbations of asthma requiring hospitalization (including intubation and admittance to an intensive care unit [ICU]) or ED visit over the 52-week treatment period is expressed as exacerbation rate per year. Analysis of the number of exacerbations was performed using a negative binomial regression model with covariates of treatment group, Baseline (BL) maintenance OCS therapy (OCS vs. no OCS), region, exacerbations in the year prior to the study (as an ordinal variable) and BL percent (%) predicted forced expiratory volume in 1 second (FEV1), and with logarithm of time on treatment as an offset variable.
Time Frame From randomization (Week 0) to Week 52 or EW

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo IV Mepolizumab 75 mg IV Mepolizumab 250 mg IV Mepolizumab 750 mg IV
Arm/Group Description Participants received placebo intravenous (IV) infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 75 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 250 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 750 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product).
Measure Participants 155 153 152 156
Number [Exacerbations per year]
0.43
0.17
0.25
0.22
4. Secondary Outcome
Title Time to First Exacerbation Requiring Hospitalization or ED Visit
Description Exacerbations of asthma requiring hospitalization or ED visit were assessed. Kaplan-Meier estimates of the probability of an exacerbation is expressed as percentage of participants with an exacerbation over time (by Week 16, Week 32 and Week 52).
Time Frame From randomization (Week 0) to Week 52 or EW

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo IV Mepolizumab 75 mg IV Mepolizumab 250 mg IV Mepolizumab 750 mg IV
Arm/Group Description Participants received placebo intravenous (IV) infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 75 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 250 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 750 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product).
Measure Participants 155 153 152 156
Week 16
8.6
5.5%
3.4
2.2%
6.7
4.4%
3.9
2.5%
Week 32
14.8
9.5%
8.3
5.4%
15.1
9.9%
8.0
5.1%
Week 52
18.5
11.9%
10.4
6.8%
15.9
10.5%
12.4
7.9%
5. Secondary Outcome
Title Number of All Recorded Exacerbations Per Year
Description Clinically significant exacerbations (ex) of asthma are defined as worsening of asthma which required use of oral/systemic corticosteroids (for par. on maintenance OCS, an ex requiring OCS is defined as the use of oral/systemic corticosteroids at least double the existing maintenance dose for at least 3 days) and/or hospitalization and/or ED visit. In the case, an event described as an ex was not associated with a deterioration in >=1 of the objectives of eDiary parameters, the investigator (inv) provided an explanation to support the decision for defining the event as an ex. All recorded ex were defined as those recorded by inv, regardless of the outcome of the ex review process. Analysis was performed using Negative Binomial regression model with covariates of treatment group, BL maintenance OCS therapy (OCS vs. no OCS), region, ex in the year prior to the study (as an ordinal variable) and BL % predicted FEV1, and with logarithm of time on treatment as an offset variable.
Time Frame From randomization (Week 0) to Week 52 or EW

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo IV Mepolizumab 75 mg IV Mepolizumab 250 mg IV Mepolizumab 750 mg IV
Arm/Group Description Participants received placebo intravenous (IV) infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 75 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 250 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 750 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product).
Measure Participants 155 153 152 156
Number [Exacerbations per year]
2.46
1.34
1.49
1.20
6. Secondary Outcome
Title Time to First All Recorded Exacerbation
Description All recorded exacerbations are defined as those recorded by investigators, regardless of the outcome of the exacerbation review process. In the case, an event described as an exacerbation was not associated with a deterioration in at least one of the objectives of eDiary parameters, the investigator provided an explanation to support the decision for defining the event as an exacerbation. Kaplan-Meier estimates of the probability of an exacerbation is expressed as percentage of participants with an exacerbation over time (by week 16, week 32 and week 52).
Time Frame From randomization (Week 0) to Week 52 or EW

Outcome Measure Data

Analysis Population Description
ITT Population
Arm/Group Title Placebo IV Mepolizumab 75 mg IV Mepolizumab 250 mg IV Mepolizumab 750 mg IV
Arm/Group Description Participants received placebo intravenous (IV) infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 75 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 250 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 750 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product).
Measure Participants 155 153 152 156
Week 16
45.9
29.6%
26.1
17.1%
27.5
18.1%
19.6
12.6%
Week 32
60.9
39.3%
41.5
27.1%
45.5
29.9%
40.5
26%
Week 52
70.1
45.2%
52.2
34.1%
58.3
38.4%
50.8
32.6%
7. Secondary Outcome
Title Mean Change From Baseline in Clinic Pre-bronchodilator FEV1 Over the 52-week Treatment Period
Description FEV1 is defined as the volume of air forcefully expelled from the lungs in 1 second. Pre-bronchodilator FEV1 measurements were taken by spirometry at each clinic visit. The change from Baseline is defined as the difference between the value of the endpoint at the time point of interest and the Baseline value. Analysis was performed using mixed model repeated measures with covariates of Baseline, region, Baseline maintenance OCS therapy (OCS vs. no OCS), exacerbations in the year prior to the study (as an ordinal variable), treatment and visit, plus interaction terms for visit by Baseline and visit by treatment group.
Time Frame From Baseline up to Week 52 or EW

Outcome Measure Data

Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed for each treatment and represented as n=X, X, X, X respectively.
Arm/Group Title Placebo IV Mepolizumab 75 mg IV Mepolizumab 250 mg IV Mepolizumab 750 mg IV
Arm/Group Description Participants received placebo intravenous (IV) infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 75 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 250 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 750 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product).
Measure Participants 155 153 152 156
Week 4, n=154, 151, 151, 155
149
(35.3)
163
(35.6)
137
(35.3)
112
(34.9)
Week 8, n=152, 149, 149, 154
154
(36.0)
165
(36.3)
133
(36.1)
142
(35.6)
Week 12, n=150, 147, 148, 151
118
(36.5)
129
(36.9)
115
(36.5)
136
(36.1)
Week 16, n=143, 147, 144, 150
135
(37.4)
137
(37.4)
97
(37.3)
94
(36.7)
Week 20, n=141, 144, 142, 147
131
(37.3)
155
(37.3)
89
(37.1)
124
(36.6)
Week 24, n=136, 138, 141, 141
148
(38.7)
153
(38.7)
148
(38.3)
123
(38.0)
Week 28, n=135, 136, 139, 141
125
(37.9)
176
(37.9)
89
(37.5)
95
(37.1)
Week 32, n=134, 136, 139, 137
139
(37.6)
142
(37.6)
134
(37.2)
43
(37.0)
Week 36, n=132, 136, 137, 135
88
(36.7)
138
(36.6)
133
(36.3)
119
(36.1)
Week 40, n=129, 133, 135, 135
125
(38.9)
180
(38.8)
140
(38.4)
87
(38.1)
Week 44, n=127, 133, 134, 134
125
(37.4)
153
(37.1)
93
(36.8)
111
(36.6)
Week 48, n=128, 132, 133, 133
91
(36.7)
140
(36.5)
123
(36.2)
112
(36.0)
Week 52, n=127, 129, 129, 132
60
(37.7)
121
(37.6)
140
(37.3)
115
(36.9)
8. Secondary Outcome
Title Mean Change From Baseline in Clinic Post-bronchodilator FEV1 Over the 52-week Treatment Period
Description FEV1 is defined as the volume of air forcefully expelled from the lungs in 1 second. Post-bronchodilator FEV1 measurements were taken by spirometry at Baseline, Week 16, Week 32 and Week 52. Post bronchodilator values were recorded following reversibility testing, using the maximum post bronchodilator method. Participants unable to achieve >=12% reversibility and 200 mL change at Visit 1, reversibility test was repeated at Visit 2. These procedures to achieve the maximum post-bronchodilator are generated by the Asthma Clinical Research Network. The change from Baseline is defined as the difference between the value of the endpoint at the time point of interest and the Baseline value. Analysis was performed using mixed model repeated measures with covariates of Baseline, region, Baseline maintenance OCS therapy (OCS vs. no OCS), exacerbations in the year prior to the study (as an ordinal variable), treatment and visit, plus interaction terms for visit by Baseline and visit by treatment
Time Frame From Baseline up to Week 52 or EW

Outcome Measure Data

Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed for each treatment and represented as n=X, X, X, X respectively.
Arm/Group Title Placebo IV Mepolizumab 75 mg IV Mepolizumab 250 mg IV Mepolizumab 750 mg IV
Arm/Group Description Participants received placebo intravenous (IV) infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 75 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 250 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 750 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product).
Measure Participants 155 153 152 156
Week 16, n=142, 140, 141, 147
59
(37.6)
77
(37.5)
50
(37.3)
87
(36.3)
Week 32, n=130, 132, 133, 132
40
(37.8)
49
(37.5)
72
(37.2)
17
(36.8)
Week 52, n=126, 128, 129, 130
-9
(36.7)
36
(36.4)
80
(36.1)
69
(35.6)
9. Secondary Outcome
Title Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score Over the 52-week Treatment Period
Description The ACQ-6 is a six-item questionnaire. The six questions enquire about the frequency and/or severity of symptoms (nocturnal awakening on waking in the morning, activity limitation, shortness of breath, wheeze) and use of short-acting bronchodilator over the previous week. The response options for all these questions consist of a 0 (no impairment/limitation) to 6 (total impairment/ limitation) scale. The overall ACQ score is calculated as the mean of the 6 questions and therefore ranges between 0 (totally controlled) and 6 (severely uncontrolled). Change from BL is defined as the difference between the value of the endpoint at the time point of interest and BL value. Analysis was performed using mixed model repeated measures with covariates of BL, region, BL maintenance OCS therapy (OCS vs. no OCS), exacerbations in the year prior to the study (as an ordinal variable), BL % predicted FEV1, treatment and visit, plus interaction terms for visit by BL and visit by treatment group.
Time Frame From Baseline up to Week 52 or EW

Outcome Measure Data

Analysis Population Description
ITT Population. Only those participants available at the specified time points were analyzed for each treatment and represented as n=X, X, X, X respectively.
Arm/Group Title Placebo IV Mepolizumab 75 mg IV Mepolizumab 250 mg IV Mepolizumab 750 mg IV
Arm/Group Description Participants received placebo intravenous (IV) infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 75 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 250 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 750 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product).
Measure Participants 155 153 152 156
Week 4, n=146, 139, 148, 150
-0.45
(0.076)
-0.61
(0.077)
-0.50
(0.075)
-0.56
(0.075)
Week 8, n=147, 140, 142, 145
-0.50
(0.080)
-0.73
(0.081)
-0.60
(0.080)
-0.65
(0.079)
Week 12, n=148, 142, 144, 147
-0.63
(0.080)
-0.79
(0.081)
-0.65
(0.080)
-0.72
(0.079)
Week 16, n=138, 143, 143, 146
-0.59
(0.085)
-0.80
(0.085)
-0.52
(0.084)
-0.76
(0.083)
Week 20, n=138, 140, 137, 139
-0.59
(0.081)
-0.82
(0.081)
-0.61
(0.080)
-0.72
(0.080)
Week 24, n=135, 133, 138, 137
-0.66
(0.080)
-0.85
(0.080)
-0.70
(0.079)
-0.79
(0.079)
Week 28, n=131, 135, 135, 136
-0.70
(0.082)
-0.81
(0.081)
-0.66
(0.080)
-0.73
(0.080)
Week 32, n=130, 133, 136, 136
-0.62
(0.084)
-0.74
(0.084)
-0.76
(0.083)
-0.74
(0.083)
Week 36, n=129, 133, 133, 134
-0.60
(0.082)
-0.78
(0.082)
-0.75
(0.081)
-0.76
(0.081)
Week 40, n=126, 128, 129, 131
-0.64
(0.090)
-0.76
(0.090)
-0.73
(0.089)
-0.67
(0.089)
Week 44, n=123, 125, 129, 129
-0.62
(0.089)
-0.75
(0.089)
-0.77
(0.087)
-0.69
(0.087)
Week 48, n=122, 130, 130, 129
-0.63
(0.085)
-0.72
(0.084)
-0.74
(0.083)
-0.68
(0.084)
Week 52, n=121, 127, 126, 129
-0.59
(0.087)
-0.75
(0.087)
-0.87
(0.086)
-0.80
(0.086)

Adverse Events

Time Frame On-treatment serious adverse events (SAEs) and non-serious AEs were defined as events occurring from the first dose of investigational product until 4 weeks after the last dose of investigational product, up to 52 weeks.
Adverse Event Reporting Description SAEs and Non-serious AEs were collected for participants of safety population identical to the ITT population, comprised of all participants who were randomized to treatment and who received at least one dose of study medication.
Arm/Group Title Placebo IV Mepolizumab 75 mg IV Mepolizumab 250 mg IV Mepolizumab 750 mg IV
Arm/Group Description Participants received placebo intravenous (IV) infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 75 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 250 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product). Participants received mepolizumab 750 mg IV infusion every 4 weeks for 48 weeks (giving 52 weeks of exposure to investigational product).
All Cause Mortality
Placebo IV Mepolizumab 75 mg IV Mepolizumab 250 mg IV Mepolizumab 750 mg IV
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN) / (NaN) / (NaN)
Serious Adverse Events
Placebo IV Mepolizumab 75 mg IV Mepolizumab 250 mg IV Mepolizumab 750 mg IV
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 25/155 (16.1%) 20/153 (13.1%) 24/152 (15.8%) 19/156 (12.2%)
Blood and lymphatic system disorders
Leukopenia 0/155 (0%) 0/153 (0%) 1/152 (0.7%) 0/156 (0%)
Cardiac disorders
Myocardial ischaemia 0/155 (0%) 1/153 (0.7%) 0/152 (0%) 1/156 (0.6%)
Acute myocardial infarction 0/155 (0%) 1/153 (0.7%) 0/152 (0%) 0/156 (0%)
Atrial fibrillation 0/155 (0%) 0/153 (0%) 0/152 (0%) 1/156 (0.6%)
Atrial flutter 1/155 (0.6%) 0/153 (0%) 0/152 (0%) 0/156 (0%)
Coronary artery thrombosis 0/155 (0%) 1/153 (0.7%) 0/152 (0%) 0/156 (0%)
Coronary artery insufficiency 0/155 (0%) 0/153 (0%) 1/152 (0.7%) 0/156 (0%)
Myocardial infarction 0/155 (0%) 0/153 (0%) 0/152 (0%) 1/156 (0.6%)
Supraventricular tachycardia 0/155 (0%) 0/153 (0%) 0/152 (0%) 1/156 (0.6%)
Gastrointestinal disorders
Abdominal pain lower 0/155 (0%) 0/153 (0%) 1/152 (0.7%) 0/156 (0%)
Colitis 0/155 (0%) 0/153 (0%) 0/152 (0%) 1/156 (0.6%)
Pancreatitis acute 0/155 (0%) 0/153 (0%) 1/152 (0.7%) 0/156 (0%)
Peritoneal haemorrhage 1/155 (0.6%) 0/153 (0%) 0/152 (0%) 0/156 (0%)
Thrombosis mesenteric vessel 0/155 (0%) 0/153 (0%) 1/152 (0.7%) 0/156 (0%)
General disorders
Chest pain 0/155 (0%) 1/153 (0.7%) 0/152 (0%) 0/156 (0%)
Microlithiasis 0/155 (0%) 0/153 (0%) 1/152 (0.7%) 0/156 (0%)
Hepatobiliary disorders
Cholecystitis acute 0/155 (0%) 1/153 (0.7%) 0/152 (0%) 0/156 (0%)
Immune system disorders
Anaphylactic reaction 0/155 (0%) 1/153 (0.7%) 0/152 (0%) 0/156 (0%)
Infections and infestations
Lobar pneumonia 1/155 (0.6%) 2/153 (1.3%) 0/152 (0%) 0/156 (0%)
Pneumonia 0/155 (0%) 1/153 (0.7%) 0/152 (0%) 2/156 (1.3%)
Bacteraemia 0/155 (0%) 1/153 (0.7%) 0/152 (0%) 0/156 (0%)
Bronchitis 0/155 (0%) 1/153 (0.7%) 0/152 (0%) 0/156 (0%)
Cholecystitis infective 0/155 (0%) 1/153 (0.7%) 0/152 (0%) 0/156 (0%)
Haematoma infection 1/155 (0.6%) 0/153 (0%) 0/152 (0%) 0/156 (0%)
Herpes zoster ophthalmic 0/155 (0%) 0/153 (0%) 0/152 (0%) 1/156 (0.6%)
Infected skin ulcer 0/155 (0%) 1/153 (0.7%) 0/152 (0%) 0/156 (0%)
Infection 1/155 (0.6%) 0/153 (0%) 0/152 (0%) 0/156 (0%)
Lung infection pseudomonal 0/155 (0%) 0/153 (0%) 0/152 (0%) 1/156 (0.6%)
Meningitis viral 0/155 (0%) 0/153 (0%) 1/152 (0.7%) 0/156 (0%)
Post procedural infection 1/155 (0.6%) 0/153 (0%) 0/152 (0%) 0/156 (0%)
Sinusitis 0/155 (0%) 0/153 (0%) 1/152 (0.7%) 0/156 (0%)
Staphylococcal infection 0/155 (0%) 0/153 (0%) 1/152 (0.7%) 0/156 (0%)
Streptococcal bacteraemia 0/155 (0%) 0/153 (0%) 0/152 (0%) 1/156 (0.6%)
Tonsillitis 0/155 (0%) 0/153 (0%) 0/152 (0%) 1/156 (0.6%)
Upper respiratory tract infection 0/155 (0%) 0/153 (0%) 1/152 (0.7%) 0/156 (0%)
Viral upper respiratory tract infection 1/155 (0.6%) 0/153 (0%) 0/152 (0%) 0/156 (0%)
Injury, poisoning and procedural complications
Tendon rupture 1/155 (0.6%) 0/153 (0%) 0/152 (0%) 1/156 (0.6%)
Concussion 0/155 (0%) 0/153 (0%) 1/152 (0.7%) 0/156 (0%)
Overdose 1/155 (0.6%) 0/153 (0%) 0/152 (0%) 0/156 (0%)
Post procedural haemorrhage 0/155 (0%) 1/153 (0.7%) 0/152 (0%) 0/156 (0%)
Spinal compression fracture 0/155 (0%) 0/153 (0%) 1/152 (0.7%) 0/156 (0%)
Investigations
Liver function test abnormal 1/155 (0.6%) 0/153 (0%) 0/152 (0%) 0/156 (0%)
Reticulocyte count decreased 0/155 (0%) 0/153 (0%) 1/152 (0.7%) 0/156 (0%)
Metabolism and nutrition disorders
Diabetes mellitus inadequate control 0/155 (0%) 1/153 (0.7%) 0/152 (0%) 0/156 (0%)
Diabetic ketoacidosis 0/155 (0%) 1/153 (0.7%) 0/152 (0%) 0/156 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine cancer 0/155 (0%) 0/153 (0%) 1/152 (0.7%) 0/156 (0%)
Nervous system disorders
Cerebrovascular accident 2/155 (1.3%) 0/153 (0%) 0/152 (0%) 0/156 (0%)
Cervicobrachial syndrome 1/155 (0.6%) 0/153 (0%) 0/152 (0%) 0/156 (0%)
Cranial nerve disorder 0/155 (0%) 0/153 (0%) 0/152 (0%) 1/156 (0.6%)
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous 0/155 (0%) 1/153 (0.7%) 0/152 (0%) 0/156 (0%)
Renal and urinary disorders
Nephrolithiasis 2/155 (1.3%) 0/153 (0%) 0/152 (0%) 0/156 (0%)
Haematuria 1/155 (0.6%) 0/153 (0%) 0/152 (0%) 0/156 (0%)
Urinary retention 0/155 (0%) 0/153 (0%) 1/152 (0.7%) 0/156 (0%)
Urinary tract obstruction 0/155 (0%) 0/153 (0%) 1/152 (0.7%) 0/156 (0%)
Reproductive system and breast disorders
Endometrial hyperplasia 0/155 (0%) 0/153 (0%) 1/152 (0.7%) 0/156 (0%)
Ovarian cyst 0/155 (0%) 0/153 (0%) 0/152 (0%) 1/156 (0.6%)
Respiratory, thoracic and mediastinal disorders
Asthma 17/155 (11%) 11/153 (7.2%) 16/152 (10.5%) 9/156 (5.8%)
Asphyxia 0/155 (0%) 0/153 (0%) 0/152 (0%) 1/156 (0.6%)
Nasal septum deviation 0/155 (0%) 1/153 (0.7%) 0/152 (0%) 0/156 (0%)
Pleuritic pain 1/155 (0.6%) 0/153 (0%) 0/152 (0%) 0/156 (0%)
Skin and subcutaneous tissue disorders
Decubitus ulcer 0/155 (0%) 0/153 (0%) 1/152 (0.7%) 0/156 (0%)
Vascular disorders
Hypertension 0/155 (0%) 1/153 (0.7%) 0/152 (0%) 1/156 (0.6%)
Distributive shock 0/155 (0%) 0/153 (0%) 1/152 (0.7%) 0/156 (0%)
Malignant hypertension 0/155 (0%) 1/153 (0.7%) 0/152 (0%) 0/156 (0%)
Venous thrombosis limb 0/155 (0%) 1/153 (0.7%) 0/152 (0%) 0/156 (0%)
Other (Not Including Serious) Adverse Events
Placebo IV Mepolizumab 75 mg IV Mepolizumab 250 mg IV Mepolizumab 750 mg IV
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 106/155 (68.4%) 113/153 (73.9%) 113/152 (74.3%) 112/156 (71.8%)
Gastrointestinal disorders
Diarrhoea 6/155 (3.9%) 2/153 (1.3%) 2/152 (1.3%) 8/156 (5.1%)
Nausea 3/155 (1.9%) 4/153 (2.6%) 5/152 (3.3%) 4/156 (2.6%)
Vomiting 2/155 (1.3%) 4/153 (2.6%) 7/152 (4.6%) 3/156 (1.9%)
Abdominal pain upper 3/155 (1.9%) 3/153 (2%) 3/152 (2%) 4/156 (2.6%)
Toothache 0/155 (0%) 5/153 (3.3%) 2/152 (1.3%) 5/156 (3.2%)
Abdominal pain 2/155 (1.3%) 5/153 (3.3%) 2/152 (1.3%) 2/156 (1.3%)
Dyspepsia 2/155 (1.3%) 2/153 (1.3%) 1/152 (0.7%) 5/156 (3.2%)
Gastrooesophageal reflux disease 5/155 (3.2%) 0/153 (0%) 3/152 (2%) 2/156 (1.3%)
General disorders
Oedema peripheral 7/155 (4.5%) 5/153 (3.3%) 6/152 (3.9%) 3/156 (1.9%)
Fatigue 4/155 (2.6%) 6/153 (3.9%) 7/152 (4.6%) 2/156 (1.3%)
Chest pain 4/155 (2.6%) 1/153 (0.7%) 7/152 (4.6%) 3/156 (1.9%)
Injection site reaction 5/155 (3.2%) 5/153 (3.3%) 0/152 (0%) 0/156 (0%)
Pyrexia 0/155 (0%) 4/153 (2.6%) 4/152 (2.6%) 2/156 (1.3%)
Asthenia 0/155 (0%) 4/153 (2.6%) 3/152 (2%) 0/156 (0%)
Immune system disorders
Hypersensitivity 4/155 (2.6%) 2/153 (1.3%) 3/152 (2%) 3/156 (1.9%)
Infections and infestations
Nasopharyngitis 24/155 (15.5%) 34/153 (22.2%) 33/152 (21.7%) 29/156 (18.6%)
Upper respiratory tract infection 15/155 (9.7%) 10/153 (6.5%) 17/152 (11.2%) 19/156 (12.2%)
Bronchitis 15/155 (9.7%) 16/153 (10.5%) 13/152 (8.6%) 13/156 (8.3%)
Sinusitis 16/155 (10.3%) 10/153 (6.5%) 10/152 (6.6%) 12/156 (7.7%)
Influenza 8/155 (5.2%) 6/153 (3.9%) 5/152 (3.3%) 9/156 (5.8%)
Urinary tract infection 4/155 (2.6%) 8/153 (5.2%) 8/152 (5.3%) 1/156 (0.6%)
Respiratory tract infection 4/155 (2.6%) 4/153 (2.6%) 6/152 (3.9%) 6/156 (3.8%)
Rhinitis 7/155 (4.5%) 4/153 (2.6%) 5/152 (3.3%) 3/156 (1.9%)
Lower respiratory tract infection 4/155 (2.6%) 6/153 (3.9%) 4/152 (2.6%) 4/156 (2.6%)
Pharyngitis 4/155 (2.6%) 8/153 (5.2%) 2/152 (1.3%) 3/156 (1.9%)
Viral infection 3/155 (1.9%) 5/153 (3.3%) 3/152 (2%) 6/156 (3.8%)
Respiratory tract infection viral 3/155 (1.9%) 4/153 (2.6%) 4/152 (2.6%) 4/156 (2.6%)
Ear infection 3/155 (1.9%) 6/153 (3.9%) 2/152 (1.3%) 2/156 (1.3%)
Acute sinusitis 4/155 (2.6%) 5/153 (3.3%) 1/152 (0.7%) 2/156 (1.3%)
Gastroenteritis 3/155 (1.9%) 4/153 (2.6%) 0/152 (0%) 4/156 (2.6%)
Cystitis 2/155 (1.3%) 4/153 (2.6%) 3/152 (2%) 1/156 (0.6%)
Viral upper respiratory tract infection 4/155 (2.6%) 1/153 (0.7%) 4/152 (2.6%) 1/156 (0.6%)
Tonsillitis 4/155 (2.6%) 1/153 (0.7%) 1/152 (0.7%) 0/156 (0%)
Tooth infection 0/155 (0%) 0/153 (0%) 0/152 (0%) 4/156 (2.6%)
Injury, poisoning and procedural complications
Infusion related reaction 10/155 (6.5%) 8/153 (5.2%) 12/152 (7.9%) 19/156 (12.2%)
Ligament sprain 6/155 (3.9%) 1/153 (0.7%) 1/152 (0.7%) 3/156 (1.9%)
Investigations
Blood creatine phosphokinase increased 2/155 (1.3%) 2/153 (1.3%) 0/152 (0%) 5/156 (3.2%)
Musculoskeletal and connective tissue disorders
Back pain 11/155 (7.1%) 11/153 (7.2%) 7/152 (4.6%) 15/156 (9.6%)
Arthralgia 10/155 (6.5%) 6/153 (3.9%) 9/152 (5.9%) 9/156 (5.8%)
Pain in extremity 5/155 (3.2%) 5/153 (3.3%) 4/152 (2.6%) 8/156 (5.1%)
Myalgia 5/155 (3.2%) 2/153 (1.3%) 4/152 (2.6%) 5/156 (3.2%)
Musculoskeletal chest pain 4/155 (2.6%) 3/153 (2%) 0/152 (0%) 2/156 (1.3%)
Musculoskeletal pain 1/155 (0.6%) 5/153 (3.3%) 1/152 (0.7%) 2/156 (1.3%)
Tendonitis 0/155 (0%) 3/153 (2%) 4/152 (2.6%) 2/156 (1.3%)
Nervous system disorders
Headache 27/155 (17.4%) 32/153 (20.9%) 32/152 (21.1%) 32/156 (20.5%)
Dizziness 2/155 (1.3%) 4/153 (2.6%) 3/152 (2%) 6/156 (3.8%)
Migraine 1/155 (0.6%) 0/153 (0%) 2/152 (1.3%) 4/156 (2.6%)
Respiratory, thoracic and mediastinal disorders
Cough 11/155 (7.1%) 8/153 (5.2%) 11/152 (7.2%) 9/156 (5.8%)
Asthma 10/155 (6.5%) 5/153 (3.3%) 10/152 (6.6%) 8/156 (5.1%)
Oropharyngeal pain 7/155 (4.5%) 4/153 (2.6%) 12/152 (7.9%) 6/156 (3.8%)
Dyspnoea 3/155 (1.9%) 5/153 (3.3%) 7/152 (4.6%) 7/156 (4.5%)
Rhinitis allergic 2/155 (1.3%) 6/153 (3.9%) 6/152 (3.9%) 6/156 (3.8%)
Nasal congestion 2/155 (1.3%) 5/153 (3.3%) 1/152 (0.7%) 6/156 (3.8%)
Sinus congestion 0/155 (0%) 1/153 (0.7%) 0/152 (0%) 5/156 (3.2%)
Skin and subcutaneous tissue disorders
Rash 2/155 (1.3%) 4/153 (2.6%) 4/152 (2.6%) 3/156 (1.9%)
Eczema 0/155 (0%) 3/153 (2%) 4/152 (2.6%) 3/156 (1.9%)
Pruritus 0/155 (0%) 4/153 (2.6%) 5/152 (3.3%) 1/156 (0.6%)
Vascular disorders
Hypertension 7/155 (4.5%) 6/153 (3.9%) 6/152 (3.9%) 4/156 (2.6%)

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:
NCT01000506
Other Study ID Numbers:
  • 112997
First Posted:
Oct 23, 2009
Last Update Posted:
Jan 24, 2018
Last Verified:
Jan 1, 2018