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A Phase 3a, Repeat Dose, Open-label, Long-term Safety Study of Mepolizumab in Asthmatic Subjects

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ClinicalTrials.gov Identifier: NCT02135692
Recruitment Status : Completed
First Posted : May 12, 2014
Results First Posted : May 2, 2018
Last Update Posted : December 3, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Asthma
Interventions Biological: Mepolizumab
Drug: SOC
Enrollment 339
Recruitment Details This was an open-label, long-term study of mepolizumab 100 milligram (mg) administered subcutaneously (SC), in addition to standard of care (SOC), in eligible participants with severe eosinophilic asthma, who completed the MEA115661 Exit Visit (Visit 14). The study enrolled participants across 18 countries.
Pre-assignment Details A total of 340 participants were screened for the study, of which one participant was screening failure, and 339 participants received the study treatment.
Arm/Group Title Mepolizumab 100 mg SC
Hide Arm/Group Description Participants received mepolizumab 100 mg administered via SC injection into the upper arm or thigh approximately every 4 weeks for 172 weeks. Participants remained on standard of care asthma therapy which could be adjusted during the study at the discretion of the physician.
Period Title: Overall Study
Started 339
Completed 0
Not Completed 339
Reason Not Completed
Adverse Event             3
Lack of Efficacy             2
Protocol Violation             2
Subject met Liver Stopping Criteria             1
Product commercially available             159
Study closed/terminated             153
Lost to Follow-up             4
Withdrawal by Subject             15
Arm/Group Title Mepolizumab 100 mg SC
Hide Arm/Group Description Participants received mepolizumab 100 mg administered via SC injection into the upper arm or thigh approximately every 4 weeks for 172 weeks. Participants remained on standard of care asthma therapy which could be adjusted during the study at the discretion of the physician.
Overall Number of Baseline Participants 339
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 339 participants
52.9  (13.08)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 339 participants
Female
178
  52.5%
Male
161
  47.5%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Race/ Ethnicity Number Analyzed 339 participants
Asian-Central/South Asian Heritage
2
   0.6%
Asian-East Asian Heritage
19
   5.6%
Asian-Japanese Heritage
26
   7.7%
Asian-South East Asian Heritage
4
   1.2%
Black or African American
4
   1.2%
White-Arabic/North African Heritage
7
   2.1%
White-White/Caucasian/European Heritage
277
  81.7%
1.Primary Outcome
Title Annualized Rate of On-treatment Exacerbations Per Year
Hide Description Exacerbations are defined as the worsening of asthma which requires use of systemic corticosteroids intravenous (IV) or oral steroid like prednisone, for at least 3 days or a single intramuscular (IM) corticosteroid (CS) dose is required. For maintenance systemic corticosteroids, at least double the existing maintenance dose for at least 3 days was required) and/or hospitalization and/or emergency department (ED) visit. On-Treatment data between first dose date and earliest of Withdrawal date/last dose + 28 days was considered for analysis. Analysis of the number of exacerbations was performed using a negative binomial generalized linear model.
Time Frame Baseline (Week 0) to Week 172
Hide Outcome Measure Data
Hide Analysis Population Description
As Treated (AT) Population. AT Population included all participants who received at least one dose of mepolizumab within study 201312.
Arm/Group Title Mepolizumab 100 mg SC
Hide Arm/Group Description:
Participants received mepolizumab 100 mg administered via SC injection into the upper arm or thigh approximately every 4 weeks for 172 weeks. Participants remained on standard of care asthma therapy which could be adjusted during the study at the discretion of the physician.
Overall Number of Participants Analyzed 339
Mean (95% Confidence Interval)
Unit of Measure: Exacerbations per year
0.93
(0.81 to 1.06)
2.Primary Outcome
Title Number of Participants With Any On-treatment Adverse Event (AE) or On-treatment Serious AE (SAE)
Hide Description An AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention or event associated with liver injury and impaired liver function were categorized as SAE. On-treatment AEs and on-treatment SAEs are the events occurring on/after the first dose of open-label mepolizumab date and before/on last dose+28 days.
Time Frame Baseline (Week 0) to Week 172
Hide Outcome Measure Data
Hide Analysis Population Description
AT Population
Arm/Group Title Mepolizumab 100 mg SC
Hide Arm/Group Description:
Participants received mepolizumab 100 mg administered via SC injection into the upper arm or thigh approximately every 4 weeks for 172 weeks. Participants remained on standard of care asthma therapy which could be adjusted during the study at the discretion of the physician.
Overall Number of Participants Analyzed 339
Measure Type: Count of Participants
Unit of Measure: Participants
Any AE
315
  92.9%
Any SAE
84
  24.8%
3.Secondary Outcome
Title Mean Change From Baseline in Asthma Control Questionnaire (ACQ)-5 On-treatment Score
Hide Description The ACQ-5 is a five-item questionnaire developed as a measure of participants asthma control. The five questions enquire about the frequency and/or severity of symptoms (nocturnal awakening on waking in the morning, activity limitation, shortness of breath, wheeze). 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 5 questions and therefore ranges between 0 (totally controlled) and 6 (severely uncontrolled). Baseline was considered as the latest assessment prior to first dose of mepolizumab in this study. The change from Baseline is defined as the difference between the value of the endpoint at the time point of interest and Baseline value.
Time Frame Baseline (Week 0) to Week 168
Hide Outcome Measure Data
Hide Analysis Population Description
AT Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Arm/Group Title Mepolizumab 100 mg SC
Hide Arm/Group Description:
Participants received mepolizumab 100 mg administered via SC injection into the upper arm or thigh approximately every 4 weeks for 172 weeks. Participants remained on standard of care asthma therapy which could be adjusted during the study at the discretion of the physician.
Overall Number of Participants Analyzed 339
Mean (Standard Deviation)
Unit of Measure: Scores on a scale
Week 12, n=333 Number Analyzed 333 participants
-0.16  (1.096)
Week 24, n=333 Number Analyzed 333 participants
-0.15  (1.131)
Week 36, n=326 Number Analyzed 326 participants
-0.21  (1.089)
Week 48, n=328 Number Analyzed 328 participants
-0.17  (0.965)
Week 60, n=307 Number Analyzed 307 participants
-0.18  (1.066)
Week 72, n=282 Number Analyzed 282 participants
-0.08  (1.145)
Week 84, n=254 Number Analyzed 254 participants
-0.03  (1.151)
Week 96, n=212 Number Analyzed 212 participants
-0.12  (0.976)
Week 108, n=190 Number Analyzed 190 participants
-0.06  (1.057)
Week 120, n=164 Number Analyzed 164 participants
-0.01  (1.244)
Week 132, n=135 Number Analyzed 135 participants
-0.09  (1.089)
Week 144, n=73 Number Analyzed 73 participants
0.34  (1.220)
Week 156, n=23 Number Analyzed 23 participants
0.07  (0.962)
Week 168, n=6 Number Analyzed 6 participants
-0.33  (0.935)
4.Secondary Outcome
Title Mean Change From Baseline in On-treatment Clinic Pre-bronchodilator FEV1
Hide 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 Baseline and Weeks 24, 48, 72, 96, 120, 144 and 168. Spirometry was performed within 1 hour of the Baseline assessment. Baseline was considered as the latest assessment prior to first dose of mepolizumab in this study. The change from Baseline is defined as the difference between the value of the endpoint at the time point of interest and Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles). Data between first dose date and earliest of Withdrawal date/last dose + 28 days considered on-treatment.
Time Frame Baseline (Week 0) to Week 168
Hide Outcome Measure Data
Hide Analysis Population Description
AT Population
Arm/Group Title Mepolizumab 100 mg SC
Hide Arm/Group Description:
Participants received mepolizumab 100 mg administered via SC injection into the upper arm or thigh approximately every 4 weeks for 172 weeks. Participants remained on standard of care asthma therapy which could be adjusted during the study at the discretion of the physician.
Overall Number of Participants Analyzed 339
Mean (Standard Deviation)
Unit of Measure: Milliliter
Week 24, n=332 Number Analyzed 332 participants
67  (382.9)
Week 48, n=325 Number Analyzed 325 participants
27  (404.6)
Week 72, n=289 Number Analyzed 289 participants
30  (406.0)
Week 96, n=223 Number Analyzed 223 participants
47  (433.7)
Week 120, n=169 Number Analyzed 169 participants
34  (369.9)
Week 144, n=88 Number Analyzed 88 participants
14  (374.9)
Week 168, n=15 Number Analyzed 15 participants
78  (302.9)
5.Secondary Outcome
Title Number of Participants Withdrawn From the Study Due to Lack of Efficacy and Adverse Events
Hide Description AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. Number of participants withdrawn due to lack of efficacy and adverse events from the study have been presented.
Time Frame Baseline (Week 0) to Week 172
Hide Outcome Measure Data
Hide Analysis Population Description
AT Population
Arm/Group Title Mepolizumab 100 mg SC
Hide Arm/Group Description:
Participants received mepolizumab 100 mg administered via SC injection into the upper arm or thigh approximately every 4 weeks for 172 weeks. Participants remained on standard of care asthma therapy which could be adjusted during the study at the discretion of the physician.
Overall Number of Participants Analyzed 339
Measure Type: Count of Participants
Unit of Measure: Participants
Withdrawals due to lack of efficacy
2
   0.6%
Withdrawals due to adverse events
3
   0.9%
6.Secondary Outcome
Title Number of Participants Hospitalized Due to Adverse Events Including Asthma Exacerbations
Hide Description AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect or is medically significant or all events of possible drug induced liver injury with hyperbilirubinemia. Number of participants requiring hospitalization due to an on-treatment serious adverse event including asthma exacerbations are presented. On-treatment SAEs are the events occurring on/after the first dose of mepolizumab date and before/on last dose of mepolizumab + 28 days.
Time Frame Baseline (Week 0) to Week 172
Hide Outcome Measure Data
Hide Analysis Population Description
AT Population
Arm/Group Title Mepolizumab 100 mg SC
Hide Arm/Group Description:
Participants received mepolizumab 100 mg administered via SC injection into the upper arm or thigh approximately every 4 weeks for 172 weeks. Participants remained on standard of care asthma therapy which could be adjusted during the study at the discretion of the physician.
Overall Number of Participants Analyzed 339
Measure Type: Count of Participants
Unit of Measure: Participants
78
  23.0%
7.Secondary Outcome
Title Number of Participants With AEs Including Both Systemic (Allergic and Non-allergic) and Local Site Reactions
Hide Description AEs were collected from the Baseline visit until the follow-up visit (Week 172). Participants were monitored to evaluate the AEs of systemic and local site reaction. AE is defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. On treatment AEs were defined as events occurring from the first dose until 28 days after the last dose of mepolizumab. Number of participants with AEs including both systemic (i.e. allergic/immunoglobulin (Ig)E-mediated and non-allergic) and local site reactions have been presented.
Time Frame Baseline (Week 0) to Week 172
Hide Outcome Measure Data
Hide Analysis Population Description
AT Population
Arm/Group Title Mepolizumab 100 mg SC
Hide Arm/Group Description:
Participants received mepolizumab 100 mg administered via SC injection into the upper arm or thigh approximately every 4 weeks for 172 weeks. Participants remained on standard of care asthma therapy which could be adjusted during the study at the discretion of the physician.
Overall Number of Participants Analyzed 339
Measure Type: Count of Participants
Unit of Measure: Participants
Any systemic events
2
   0.6%
Any local site reactions
14
   4.1%
8.Secondary Outcome
Title Mean Change From Baseline in QT Interval Corrected by Bazett's Method (QTcB) and QT Interval Corrected by Fridericia's Method (QTcF) Values for 12-lead Electrocardiogram (ECG)
Hide Description Twelve-lead ECG measurements were recorded after the participant has rested in the supine position for 5 minutes. The ECG was obtained before lung function testing followed by other study procedures. Baseline was considered as the latest assessment prior to first dose of mepolizumab in this study. The change from Baseline is defined as the difference between the value of the endpoint at the time point of interest and Baseline value. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles)..
Time Frame Baseline (Week 0) to Week 172
Hide Outcome Measure Data
Hide Analysis Population Description
AT Population
Arm/Group Title Mepolizumab 100 mg SC
Hide Arm/Group Description:
Participants received mepolizumab 100 mg administered via SC injection into the upper arm or thigh approximately every 4 weeks for 172 weeks. Participants remained on standard of care asthma therapy which could be adjusted during the study at the discretion of the physician.
Overall Number of Participants Analyzed 339
Mean (Standard Deviation)
Unit of Measure: Milliseconds
QTcB, Week 24, n=301 Number Analyzed 301 participants
0.1  (16.90)
QTcB, Week 48, n=294 Number Analyzed 294 participants
-0.9  (17.27)
QTcB, Week 72, n=269 Number Analyzed 269 participants
-2.9  (18.13)
QTcB, Week 96, n=221 Number Analyzed 221 participants
-0.6  (17.96)
QTcB, Week 144, n=131 Number Analyzed 131 participants
0.5  (21.07)
QTcB, Week 172, n=16 Number Analyzed 16 participants
1.8  (22.08)
QTcF, Week 24, n=301 Number Analyzed 301 participants
-1.1  (14.61)
QTcF, Week 48, n=294 Number Analyzed 294 participants
-1.3  (14.08)
QTcF, Week 72, n=269 Number Analyzed 269 participants
-3.7  (15.68)
QTcF, Week 96, n=221 Number Analyzed 221 participants
-0.8  (16.18)
QTcF, Week 144, n=131 Number Analyzed 131 participants
-0.0  (17.88)
QTcF, Week 172, n=16 Number Analyzed 16 participants
1.7  (17.06)
9.Secondary Outcome
Title Number of Participants With Maximum Change From Baseline in QTcB and QTcF Interval for ECG Assessed at Any Time Post Baseline
Hide Description Twelve-lead ECG measurements were recorded after the participant has rested in the supine position for 5 minutes. The ECG was obtained before lung function testing followed by other study procedures. Baseline was considered as the latest assessment prior to first dose of mepolizumab in this study. The change from Baseline is defined as the difference between the value of the endpoint at the time point of interest and Baseline value. Participants with maximum change from Baseline were summarised at any time post Baseline for the following categories <-60, >=-60 to <-30, >=-30 to <0, >=0 to <30, >=30 to <60 and >=60. QTc intervals shown at any time post Baseline are the maximum seen in each participant over the course of the trial.
Time Frame Baseline (Week 0) to Week 172
Hide Outcome Measure Data
Hide Analysis Population Description
AT Population
Arm/Group Title Mepolizumab 100 mg SC
Hide Arm/Group Description:
Participants received mepolizumab 100 mg administered via SC injection into the upper arm or thigh approximately every 4 weeks for 172 weeks. Participants remained on standard of care asthma therapy which could be adjusted during the study at the discretion of the physician.
Overall Number of Participants Analyzed 305
Measure Type: Count of Participants
Unit of Measure: Participants
QTcB, <-60
0
   0.0%
QTcB, >=-60 to <-30
1
   0.3%
QTcB, >=-30 to < 0
70
  23.0%
QTcB, >= 0 to < 30
196
  64.3%
QTcB, >= 30 to < 60
35
  11.5%
QTcB, >=60
3
   1.0%
QTcF, <-60
0
   0.0%
QTcF, >=-60 to <-30
1
   0.3%
QTcF, >=-30 to < 0
77
  25.2%
QTcF, >= 0 to < 30
199
  65.2%
QTcF, >= 30 to < 60
28
   9.2%
QTcF, >=60
0
   0.0%
10.Secondary Outcome
Title Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure
Hide Description Vital sign measurements including systolic blood pressure (SBP) and diastolic blood pressure (DBP) were done pre-injection with the participants sitting, having rested in this position for at least 5 minutes before each reading. They were taken before measurement of any clinic lung function tests or ECGs at the specified time point. Baseline was considered as the latest assessment prior to first dose of mepolizumab in this study. The change from Baseline is defined as the difference between the value of the endpoint at the time point of interest and Baseline value.
Time Frame Baseline (Week 0) to Week 168
Hide Outcome Measure Data
Hide Analysis Population Description
AT Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Arm/Group Title Mepolizumab 100 mg SC
Hide Arm/Group Description:
Participants received mepolizumab 100 mg administered via SC injection into the upper arm or thigh approximately every 4 weeks for 172 weeks. Participants remained on standard of care asthma therapy which could be adjusted during the study at the discretion of the physician.
Overall Number of Participants Analyzed 339
Mean (Standard Deviation)
Unit of Measure: Millimeter of mercury
SBP, Week 4, n=333 Number Analyzed 333 participants
1.8  (11.26)
SBP, Week 8, n=334 Number Analyzed 334 participants
0.6  (11.75)
SBP, Week 12, n=337 Number Analyzed 337 participants
1.5  (12.48)
SBP, Week 16, n=334 Number Analyzed 334 participants
2.0  (12.35)
SBP, Week 20, n=327 Number Analyzed 327 participants
1.2  (13.69)
SBP, Week 24, n=333 Number Analyzed 333 participants
1.8  (13.35)
SBP, Week 28, n=330 Number Analyzed 330 participants
1.4  (13.56)
SBP, Week 32, n=324 Number Analyzed 324 participants
1.0  (13.43)
SBP, Week 36, n=330 Number Analyzed 330 participants
0.8  (13.00)
SBP, Week 40, n=327 Number Analyzed 327 participants
1.6  (13.44)
SBP, Week 44, n=327 Number Analyzed 327 participants
1.2  (12.75)
SBP, Week 48, n=329 Number Analyzed 329 participants
1.8  (13.22)
SBP, Week 52, n=325 Number Analyzed 325 participants
1.5  (13.31)
SBP, Week 56, n=324 Number Analyzed 324 participants
2.0  (13.52)
SBP, Week 60, n=315 Number Analyzed 315 participants
2.0  (13.17)
SBP, Week 64, n=307 Number Analyzed 307 participants
2.5  (13.37)
SBP, Week 68, n=286 Number Analyzed 286 participants
2.5  (13.46)
SBP, Week 72, n=281 Number Analyzed 281 participants
2.3  (13.35)
SBP, Week 76, n=274 Number Analyzed 274 participants
2.3  (12.31)
SBP, Week 80, n=265 Number Analyzed 265 participants
3.5  (13.58)
SBP, Week 84, n=255 Number Analyzed 255 participants
2.7  (14.01)
SBP, Week 88, n=245 Number Analyzed 245 participants
1.5  (13.70)
SBP, Week 92, n=218 Number Analyzed 218 participants
0.7  (13.24)
SBP, Week 96, n=208 Number Analyzed 208 participants
1.2  (13.39)
SBP, Week 100, n=199 Number Analyzed 199 participants
1.0  (12.43)
SBP, Week 104, n=197 Number Analyzed 197 participants
2.4  (13.38)
SBP, Week 108, n=192 Number Analyzed 192 participants
1.7  (12.76)
SBP, Week 112, n=182 Number Analyzed 182 participants
1.8  (14.12)
SBP, Week 116, n=177 Number Analyzed 177 participants
1.9  (14.66)
SBP, Week 120, n=167 Number Analyzed 167 participants
1.9  (13.63)
SBP, Week 124, n=152 Number Analyzed 152 participants
2.5  (14.88)
SBP, Week 128, n=151 Number Analyzed 151 participants
2.6  (14.15)
SBP, Week 132, n=139 Number Analyzed 139 participants
1.0  (14.37)
SBP, Week 136, n=112 Number Analyzed 112 participants
2.3  (14.94)
SBP, Week 140, n=91 Number Analyzed 91 participants
-0.9  (16.53)
SBP, Week 144, n=77 Number Analyzed 77 participants
2.3  (14.13)
SBP, Week 148, n=62 Number Analyzed 62 participants
0.6  (13.02)
SBP, Week 152, n=35 Number Analyzed 35 participants
0.6  (11.33)
SBP, Week 156, n=32 Number Analyzed 32 participants
1.5  (15.73)
SBP, Week 160, n=14 Number Analyzed 14 participants
4.4  (9.48)
SBP, Week 164, n=8 Number Analyzed 8 participants
7.0  (15.07)
SBP, Week 168, n=1 Number Analyzed 1 participants
-4.0 [1]   (NA)
DBP, Week 4, n=333 Number Analyzed 333 participants
0.1  (8.41)
DBP, Week 8, n=334 Number Analyzed 334 participants
-0.8  (8.81)
DBP, Week 12, n=337 Number Analyzed 337 participants
0.2  (9.25)
DBP, Week 16, n=334 Number Analyzed 334 participants
0.5  (9.30)
DBP, Week 20, n=327 Number Analyzed 327 participants
-0.7  (10.35)
DBP, Week 24, n=333 Number Analyzed 333 participants
-0.2  (9.40)
DBP, Week 28, n=330 Number Analyzed 330 participants
0.1  (8.88)
DBP, Week 32, n=324 Number Analyzed 324 participants
-0.1  (10.44)
DBP, Week 36, n=330 Number Analyzed 330 participants
-0.4  (10.12)
DBP, Week 40, n=327 Number Analyzed 327 participants
-0.6  (9.24)
DBP, Week 44, n=327 Number Analyzed 327 participants
0.1  (9.39)
DBP, Week 48, n=329 Number Analyzed 329 participants
0.2  (9.71)
DBP, Week 52, n=325 Number Analyzed 325 participants
-0.1  (9.83)
DBP, Week 56, n=324 Number Analyzed 324 participants
0.7  (9.77)
DBP, Week 60, n=315 Number Analyzed 315 participants
-0.5  (10.40)
DBP, Week 64, n=307 Number Analyzed 307 participants
-0.4  (9.92)
DBP, Week 68, n=286 Number Analyzed 286 participants
-0.1  (10.04)
DBP, Week 72, n=281 Number Analyzed 281 participants
-0.3  (10.13)
DBP, Week 76, n=274 Number Analyzed 274 participants
-0.2  (9.92)
DBP, Week 80, n=265 Number Analyzed 265 participants
0.7  (9.83)
DBP, Week 84, n=255 Number Analyzed 255 participants
-0.6  (10.05)
DBP, Week 88, n=245 Number Analyzed 245 participants
-0.3  (9.22)
DBP, Week 92, n=218 Number Analyzed 218 participants
-0.9  (9.10)
DBP, Week 96, n=208 Number Analyzed 208 participants
-0.2  (9.17)
DBP, Week 100, n=199 Number Analyzed 199 participants
-0.7  (10.04)
DBP, Week 104, n=197 Number Analyzed 197 participants
0.1  (10.21)
DBP, Week 108, n=192 Number Analyzed 192 participants
0.1  (9.89)
DBP, Week 112, n=182 Number Analyzed 182 participants
0.0  (10.17)
DBP, Week 116, n=177 Number Analyzed 177 participants
-0.1  (10.31)
DBP, Week 120, n=167 Number Analyzed 167 participants
0.4  (9.74)
DBP, Week 124, n=152 Number Analyzed 152 participants
-0.3  (11.11)
DBP, Week 128, n=151 Number Analyzed 151 participants
0.6  (9.58)
DBP, Week 132, n=139 Number Analyzed 139 participants
-0.5  (10.10)
DBP, Week 136, n=112 Number Analyzed 112 participants
0.1  (9.89)
DBP, Week 140, n=91 Number Analyzed 91 participants
-1.8  (9.68)
DBP, Week 144, n=77 Number Analyzed 77 participants
-0.6  (10.92)
DBP, Week 148, n=62 Number Analyzed 62 participants
-0.7  (11.03)
DBP, Week 152, n=35 Number Analyzed 35 participants
-1.0  (8.97)
DBP, Week 156, n=32 Number Analyzed 32 participants
-2.0  (10.42)
DBP, Week 160, n=14 Number Analyzed 14 participants
2.9  (7.92)
DBP, Week 164, n=8 Number Analyzed 8 participants
1.9  (8.06)
DBP, Week 168, n=1 Number Analyzed 1 participants
5.0 [1]   (NA)
[1]
NA indicates that data were not available as n=1 at this timepoint and standard deviation could not be calculated.
11.Secondary Outcome
Title Change From Baseline in Pulse Rate
Hide Description Vital sign measurements including pulse rate was done pre-injection with the participants sitting, having rested in this position for at least 5 minutes before each reading. They were taken before measurement of any clinic lung function tests or ECGs at the specified time point. Baseline was considered as the latest assessment prior to first dose of mepolizumab in this study. The change from Baseline is defined as the difference between the value of the endpoint at the time point of interest and Baseline value.
Time Frame Baseline (Week 0) to Week 168
Hide Outcome Measure Data
Hide Analysis Population Description
AT Population. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Arm/Group Title Mepolizumab 100 mg SC
Hide Arm/Group Description:
Participants received mepolizumab 100 mg administered via SC injection into the upper arm or thigh approximately every 4 weeks for 172 weeks. Participants remained on standard of care asthma therapy which could be adjusted during the study at the discretion of the physician.
Overall Number of Participants Analyzed 339
Mean (Standard Deviation)
Unit of Measure: Beats per minute
Pulse rate, Week 4, n=334 Number Analyzed 334 participants
2.1  (9.98)
Pulse rate, Week 8, n=333 Number Analyzed 333 participants
2.3  (10.65)
Pulse rate, Week 12, n=337 Number Analyzed 337 participants
2.6  (11.05)
Pulse rate, Week 16, n=334 Number Analyzed 334 participants
2.1  (11.03)
Pulse rate, Week 20, n=327 Number Analyzed 327 participants
2.7  (11.10)
Pulse rate, Week 24, n=333 Number Analyzed 333 participants
1.2  (11.22)
Pulse rate, Week 28, n=330 Number Analyzed 330 participants
2.8  (10.43)
Pulse rate, Week 32, n=324 Number Analyzed 324 participants
2.7  (11.44)
Pulse rate, Week 36, n=330 Number Analyzed 330 participants
2.6  (11.02)
Pulse rate, Week 40, n=327 Number Analyzed 327 participants
2.7  (11.09)
Pulse rate, Week 44, n=327 Number Analyzed 327 participants
2.7  (12.05)
Pulse rate, Week 48, n=329 Number Analyzed 329 participants
0.4  (10.63)
Pulse rate, Week 52, n=325 Number Analyzed 325 participants
1.7  (10.48)
Pulse rate, Week 56, n=324 Number Analyzed 324 participants
2.1  (11.36)
Pulse rate, Week 60, n=315 Number Analyzed 315 participants
2.1  (10.97)
Pulse rate, Week 64, n=307 Number Analyzed 307 participants
2.7  (10.96)
Pulse rate, Week 68, n=286 Number Analyzed 286 participants
2.9  (11.32)
Pulse rate, Week 72, n=281 Number Analyzed 281 participants
2.0  (11.15)
Pulse rate, Week 76, n=274 Number Analyzed 274 participants
2.8  (11.15)
Pulse rate, Week 80, n=265 Number Analyzed 265 participants
3.3  (11.45)
Pulse rate, Week 84, n=255 Number Analyzed 255 participants
3.2  (12.21)
Pulse rate, Week 88, n=245 Number Analyzed 245 participants
2.4  (11.98)
Pulse rate, Week 92, n=218 Number Analyzed 218 participants
2.4  (12.42)
Pulse rate, Week 96, n=208 Number Analyzed 208 participants
0.0  (11.16)
Pulse rate, Week 100, n=199 Number Analyzed 199 participants
1.8  (12.30)
Pulse rate, Week 104, n=197 Number Analyzed 197 participants
2.3  (12.29)
Pulse rate, Week 108, n=192 Number Analyzed 192 participants
2.2  (11.34)
Pulse rate, Week 112, n=182 Number Analyzed 182 participants
2.3  (12.35)
Pulse rate, Week 116, n=177 Number Analyzed 177 participants
2.0  (12.06)
Pulse rate, Week 120, n=167 Number Analyzed 167 participants
1.2  (12.19)
Pulse rate, Week 124, n=152 Number Analyzed 152 participants
2.3  (12.56)
Pulse rate, Week 128, n=151 Number Analyzed 151 participants
1.5  (11.69)
Pulse rate, Week 132, n=139 Number Analyzed 139 participants
2.2  (12.46)
Pulse rate, Week 136, n=112 Number Analyzed 112 participants
2.0  (11.68)
Pulse rate, Week 140, n=92 Number Analyzed 92 participants
0.7  (11.45)
Pulse rate, Week 144, n=77 Number Analyzed 77 participants
-1.5  (11.92)
Pulse rate, Week 148, n=62 Number Analyzed 62 participants
-0.5  (11.68)
Pulse rate, Week 152, n=35 Number Analyzed 35 participants
-0.6  (13.80)
Pulse rate, Week 156, n=32 Number Analyzed 32 participants
-0.4  (12.94)
Pulse rate, Week 160, n=14 Number Analyzed 14 participants
1.5  (13.24)
Pulse rate, Week 164, n=8 Number Analyzed 8 participants
1.4  (21.23)
Pulse rate, Week 168, n=1 Number Analyzed 1 participants
36.0 [1]   (NA)
[1]
NA indicates that data were not available as n=1 at this timepoint
12.Secondary Outcome
Title Number of Participants With Positive Anti-mepolizumab Binding Antibodies (ADA) and Neutralizing Antibodies (NAb)
Hide Description Blood samples were collected for the determination of ADA just prior to administration of mepolizumab. Samples that tested positive for anti-mepolizumab antibodies were further tested for the presence of NAb. The highest value post-Baseline visit are based on each participant's highest post-Baseline titer. NAb assay result was only presented for participants with positive ADA assay. Highest value post-Baseline would be positive for a participant who had both negative and positive post-Baseline results. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame Baseline (Week 0) to Week 172
Hide Outcome Measure Data
Hide Analysis Population Description
AT Population
Arm/Group Title Mepolizumab 100 mg SC
Hide Arm/Group Description:
Participants received mepolizumab 100 mg administered via SC injection into the upper arm or thigh approximately every 4 weeks for 172 weeks. Participants remained on standard of care asthma therapy which could be adjusted during the study at the discretion of the physician.
Overall Number of Participants Analyzed 339
Measure Type: Count of Participants
Unit of Measure: Participants
Highest value post-Baseline, ADA, positive, n=335 Number Analyzed 335 participants
6
   1.8%
Highest value post-Baseline, ADA, Negative, n=335 Number Analyzed 335 participants
329
  98.2%
Highest value post-Baseline, NAb, positive, n=6 Number Analyzed 6 participants
0
   0.0%
Highest value post-Baseline, NAb, Negative, n=6 Number Analyzed 6 participants
6
 100.0%
13.Secondary Outcome
Title Number of Participants With Potential Clinical Importance Values for Change From Baseline Relative to the Reference Range for Clinical Chemistry Parameters at Any Time Post-Baseline
Hide Description Blood samples were collected to assess clinical chemistry laboratory parameters. Number of participants with Potential Clinical Importance values for change from Baseline relative to the reference range at any time post-Baseline are presented. Any time post Baseline = all visits (including scheduled and unscheduled) post-Baseline. Participants are counted in the category that their value changes to (low, normal or high), unless there was no change in their category. If lab value category was unchanged, participants were recorded in the "To Normal or No Change" category. Alanine Aminotransferase=ALT. Only those participants with data available at the specified time points were analyzed (represented by n=X in the category titles).
Time Frame Baseline (Week 0) to Week 172
Hide Outcome Measure Data
Hide Analysis Population Description
AT Population
Arm/Group Title Mepolizumab 100 mg SC
Hide Arm/Group Description:
Participants received mepolizumab 100 mg administered via SC injection into the upper arm or thigh approximately every 4 weeks for 172 weeks. Participants remained on standard of care asthma therapy which could be adjusted during the study at the discretion of the physician.
Overall Number of Participants Analyzed 339
Measure Type: Count of Participants
Unit of Measure: Participants
Glucose, To low, n=336 Number Analyzed 336 participants
1
   0.3%
Glucose, To Normal or No Change, n=336 Number Analyzed 336 participants
334
  99.4%
Glucose, To high, n=336 Number Analyzed 336 participants
1
   0.3%
ALT, To low, n=337 Number Analyzed 337 participants
0
   0.0%
ALT, To Normal or No Change, n=337 Number Analyzed 337 participants
337
 100.0%
ALT, To high, n=337 Number Analyzed 337 participants
0
   0.0%
Calcium, To low, n=336 Number Analyzed 336 participants
0
   0.0%
Calcium, To Normal or No Change, n=336 Number Analyzed 336 participants
336
 100.0%
Calcium, To high, n=336 Number Analyzed 336 participants
0
   0.0%
Phosphate, To low, n=336 Number Analyzed 336 participants
0
   0.0%
Phosphate, To Normal or No Change, n=336 Number Analyzed 336 participants
336
 100.0%
Phosphate, To high, n=336 Number Analyzed 336 participants
0
   0.0%
Potassium, To low, n=336 Number Analyzed 336 participants
0
   0.0%
Potassium, To Normal or No Change, n=336 Number Analyzed 336 participants
336
 100.0%
Potassium, To high, n=336 Number Analyzed 336 participants
0
   0.0%
Sodium, To low, n=336 Number Analyzed 336 participants
1
   0.3%
Sodium, To Normal or No Change, n=336 Number Analyzed 336 participants
335
  99.7%
Sodium, To high, n=336 Number Analyzed 336 participants
0
   0.0%
14.Secondary Outcome
Title Number of Participants With Potential Clinical Importance Values for Change From Baseline Relative to the Reference Range for Hematology Parameters at Any Time Post-Baseline
Hide Description Blood samples were collected to assess hematology laboratory parameters. Number of participants with Potential Clinical Importance values for change from Baseline relative to the reference range at any time post-Baseline are presented. Any time post Baseline = all visits (including scheduled and unscheduled) post-Baseline. Participants are counted in the category that their value changes to (low, normal or high), unless there was no change in their category. If lab value category was unchanged, participants were recorded in the "To Normal or No Change" category.
Time Frame Baseline (Week 0) to Week 172
Hide Outcome Measure Data
Hide Analysis Population Description
AT Population
Arm/Group Title Mepolizumab 100 mg SC
Hide Arm/Group Description:
Participants received mepolizumab 100 mg administered via SC injection into the upper arm or thigh approximately every 4 weeks for 172 weeks. Participants remained on standard of care asthma therapy which could be adjusted during the study at the discretion of the physician.
Overall Number of Participants Analyzed 336
Measure Type: Count of Participants
Unit of Measure: Participants
Hematocrit, To low
1
   0.3%
Hematocrit, To Normal or No Change
335
  99.7%
Hematocrit, To high
0
   0.0%
Hemoglobin, To low
1
   0.3%
Hemoglobin, To Normal or No Change
335
  99.7%
Hemoglobin, To high
0
   0.0%
Leukocytes, To low
1
   0.3%
Leukocytes, To Normal or No Change
335
  99.7%
Leukocytes, To high
0
   0.0%
Platelets, To low
1
   0.3%
Platelets, To Normal or No Change
335
  99.7%
Platelets, To high
0
   0.0%
Time Frame The on-treatment AEs and on-treatment SAEs are the events which happened on/after the first dose of mepolizumab date and before/on last dose of mepolizumab date + 28 days (up to 172 weeks)
Adverse Event Reporting Description AEs and SAEs were collected for all participants within the As Treated Population which comprised of all participants who received at least one dose of mepolizumab.
 
Arm/Group Title Mepolizumab 100 mg SC
Hide Arm/Group Description Participants received mepolizumab 100 mg administered via SC injection into the upper arm or thigh approximately every 4 weeks for 172 weeks. Participants remained on standard of care asthma therapy which could be adjusted during the study at the discretion of the physician.
All-Cause Mortality
Mepolizumab 100 mg SC
Affected / at Risk (%)
Total   2/339 (0.59%)    
Hide Serious Adverse Events
Mepolizumab 100 mg SC
Affected / at Risk (%) # Events
Total   84/339 (24.78%)    
Cardiac disorders   
Acute myocardial infarction † 1  1/339 (0.29%)  1
Aortic valve stenosis † 1  1/339 (0.29%)  1
Arrhythmia † 1  1/339 (0.29%)  1
Atrioventricular block complete † 1  1/339 (0.29%)  1
Coronary artery disease † 1  1/339 (0.29%)  1
Myocardial infarction † 1  1/339 (0.29%)  1
Congenital, familial and genetic disorders   
Congenital anomaly † 1  1/339 (0.29%)  1
Eye disorders   
Glaucoma † 1  1/339 (0.29%)  1
Gastrointestinal disorders   
Gastrooesophageal reflux disease † 1  2/339 (0.59%)  2
Abdominal adhesions † 1  1/339 (0.29%)  1
Dental cyst † 1  1/339 (0.29%)  1
Diarrhoea † 1  1/339 (0.29%)  1
Inguinal hernia † 1  1/339 (0.29%)  1
Large intestine perforation † 1  1/339 (0.29%)  1
Pancreatitis acute † 1  1/339 (0.29%)  1
General disorders   
Cyst † 1  1/339 (0.29%)  1
Immune system disorders   
Anaphylactic reaction † 1  1/339 (0.29%)  1
Anaphylactic shock † 1  1/339 (0.29%)  1
Food allergy † 1  1/339 (0.29%)  1
Infections and infestations   
Pneumonia † 1  6/339 (1.77%)  7
Lower respiratory tract infection † 1  3/339 (0.88%)  3
Respiratory tract infection † 1  3/339 (0.88%)  5
Diverticulitis † 1  2/339 (0.59%)  2
Influenza † 1  2/339 (0.59%)  2
Bronchitis † 1  1/339 (0.29%)  1
Enteritis infectious † 1  1/339 (0.29%)  1
Gastroenteritis † 1  1/339 (0.29%)  1
Gastroenteritis viral † 1  1/339 (0.29%)  1
Osteomyelitis † 1  1/339 (0.29%)  1
Pneumonia haemophilus † 1  1/339 (0.29%)  1
Pneumonia pneumococcal † 1  1/339 (0.29%)  1
Pneumonia staphylococcal † 1  1/339 (0.29%)  1
Pyelonephritis acute † 1  1/339 (0.29%)  1
Sepsis † 1  1/339 (0.29%)  1
Sinusitis † 1  1/339 (0.29%)  1
Staphylococcal sepsis † 1  1/339 (0.29%)  1
Urinary tract infection † 1  1/339 (0.29%)  1
Injury, poisoning and procedural complications   
Foot fracture † 1  3/339 (0.88%)  3
Fracture † 1  2/339 (0.59%)  2
Joint injury † 1  1/339 (0.29%)  1
Ligament rupture † 1  1/339 (0.29%)  1
Lumbar vertebral fracture † 1  1/339 (0.29%)  1
Rib fracture † 1  1/339 (0.29%)  1
Spinal fracture † 1  1/339 (0.29%)  1
Tendon injury † 1  1/339 (0.29%)  1
Tendon rupture † 1  1/339 (0.29%)  1
Wrist fracture † 1  1/339 (0.29%)  1
Investigations   
Alanine aminotransferase increased † 1  1/339 (0.29%)  1
Liver function test increased † 1  1/339 (0.29%)  1
Metabolism and nutrition disorders   
Hyponatraemia † 1  2/339 (0.59%)  2
Hypokalaemia † 1  1/339 (0.29%)  2
Musculoskeletal and connective tissue disorders   
Osteonecrosis † 1  2/339 (0.59%)  3
Arthritis † 1  1/339 (0.29%)  1
Back pain † 1  1/339 (0.29%)  2
Intervertebral disc protrusion † 1  1/339 (0.29%)  1
Musculoskeletal chest pain † 1  1/339 (0.29%)  1
Osteoarthritis † 1  1/339 (0.29%)  1
Pain in extremity † 1  1/339 (0.29%)  1
Polyarthritis † 1  1/339 (0.29%)  1
Rotator cuff syndrome † 1  1/339 (0.29%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Adenocarcinoma of colon † 1  1/339 (0.29%)  1
Colon neoplasm † 1  1/339 (0.29%)  1
Invasive lobular breast carcinoma † 1  1/339 (0.29%)  1
Prostate cancer † 1  1/339 (0.29%)  1
Superficial spreading melanoma stage unspecified † 1  1/339 (0.29%)  1
Nervous system disorders   
Dizziness † 1  1/339 (0.29%)  1
Hemiparesis † 1  1/339 (0.29%)  1
IIIrd nerve paralysis † 1  1/339 (0.29%)  1
Psychiatric disorders   
Anxiety disorder † 1  1/339 (0.29%)  1
Renal and urinary disorders   
Nephrolithiasis † 1  1/339 (0.29%)  1
Urinary incontinence † 1  1/339 (0.29%)  1
Reproductive system and breast disorders   
Endometrial hyperplasia † 1  1/339 (0.29%)  1
Respiratory, thoracic and mediastinal disorders   
Asthma † 1  34/339 (10.03%)  51
Nasal polyps † 1  4/339 (1.18%)  4
Dyspnoea † 1  1/339 (0.29%)  1
Haemoptysis † 1  1/339 (0.29%)  1
Pleural effusion † 1  1/339 (0.29%)  1
Pneumothorax † 1  1/339 (0.29%)  1
Status asthmaticus † 1  1/339 (0.29%)  1
Skin and subcutaneous tissue disorders   
Neurodermatitis † 1  1/339 (0.29%)  1
Vascular disorders   
Hypertension † 1  1/339 (0.29%)  1
1
Term from vocabulary, MedDRA 20.1
†
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 3%
Mepolizumab 100 mg SC
Affected / at Risk (%) # Events
Total   288/339 (84.96%)    
Gastrointestinal disorders   
Diarrhoea † 1  16/339 (4.72%)  17
Nausea † 1  15/339 (4.42%)  16
Vomiting † 1  14/339 (4.13%)  32
Gastrooesophageal reflux disease † 1  11/339 (3.24%)  13
General disorders   
Fatigue † 1  16/339 (4.72%)  23
Influenza like illness † 1  15/339 (4.42%)  17
Injection site reaction † 1  15/339 (4.42%)  48
Infections and infestations   
Nasopharyngitis † 1  143/339 (42.18%)  270
Bronchitis † 1  64/339 (18.88%)  106
Upper respiratory tract infection † 1  64/339 (18.88%)  110
Sinusitis † 1  62/339 (18.29%)  115
Influenza † 1  42/339 (12.39%)  52
Respiratory tract infection † 1  20/339 (5.90%)  23
Gastroenteritis † 1  19/339 (5.60%)  20
Lower respiratory tract infection † 1  18/339 (5.31%)  28
Rhinitis † 1  18/339 (5.31%)  31
Urinary tract infection † 1  17/339 (5.01%)  19
Pharyngitis † 1  15/339 (4.42%)  22
Ear infection † 1  12/339 (3.54%)  15
Viral upper respiratory tract infection † 1  12/339 (3.54%)  14
Pneumonia † 1  11/339 (3.24%)  11
Musculoskeletal and connective tissue disorders   
Back pain † 1  41/339 (12.09%)  51
Arthralgia † 1  32/339 (9.44%)  48
Pain in extremity † 1  15/339 (4.42%)  16
Musculoskeletal pain † 1  14/339 (4.13%)  16
Myalgia † 1  11/339 (3.24%)  11
Nervous system disorders   
Headache † 1  57/339 (16.81%)  160
Dizziness † 1  15/339 (4.42%)  19
Psychiatric disorders   
Insomnia † 1  17/339 (5.01%)  18
Respiratory, thoracic and mediastinal disorders   
Asthma † 1  52/339 (15.34%)  78
Oropharyngeal pain † 1  25/339 (7.37%)  31
Cough † 1  22/339 (6.49%)  27
Dyspnoea † 1  13/339 (3.83%)  14
Skin and subcutaneous tissue disorders   
Eczema † 1  14/339 (4.13%)  17
Rash † 1  14/339 (4.13%)  18
Pruritus † 1  13/339 (3.83%)  17
Vascular disorders   
Hypertension † 1  14/339 (4.13%)  15
1
Term from vocabulary, MedDRA 20.1
†
Indicates events were collected by systematic assessment
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Layout table for Results Point of Contact information
Name/Title: GSK Response Center
Organization: GlaxoSmithKline
Phone: 866-435-7343
EMail: GSKClinicalSupportHD@gsk.com
Publications:
Layout table for additonal information
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT02135692    
Other Study ID Numbers: 201312
2014-000314-54 ( EudraCT Number )
First Submitted: May 8, 2014
First Posted: May 12, 2014
Results First Submitted: March 29, 2018
Results First Posted: May 2, 2018
Last Update Posted: December 3, 2019