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

• 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: GlaxoSmithKline
• 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

Participant Flow

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
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

Baseline Characteristics

Arm/Group Title		Mepolizumab 100 mg SC
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
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%

Outcome Measures

1. Primary Outcome

Title	Annualized Rate of On-treatment Exacerbations Per Year
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

Outcome Measure Data

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
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)
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

Outcome Measure Data

Analysis Population Description

AT Population

Arm/Group Title	Mepolizumab 100 mg SC
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
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

Outcome Measure Data

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
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
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

Outcome Measure Data

Analysis Population Description

AT Population

Arm/Group Title		Mepolizumab 100 mg SC
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
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

Outcome Measure Data

Analysis Population Description

AT Population

Arm/Group Title	Mepolizumab 100 mg SC
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
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

Outcome Measure Data

Analysis Population Description

AT Population

Arm/Group Title	Mepolizumab 100 mg SC
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
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

Outcome Measure Data

Analysis Population Description

AT Population

Arm/Group Title	Mepolizumab 100 mg SC
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)
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

Outcome Measure Data

Analysis Population Description

AT Population

Arm/Group Title		Mepolizumab 100 mg SC
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
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

Outcome Measure Data

Analysis Population Description

AT Population

Arm/Group Title	Mepolizumab 100 mg SC
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
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

Outcome Measure Data

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
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
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

Outcome Measure Data

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
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)
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

Outcome Measure Data

Analysis Population Description

AT Population

Arm/Group Title		Mepolizumab 100 mg SC
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
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

Outcome Measure Data

Analysis Population Description

AT Population

Arm/Group Title		Mepolizumab 100 mg SC
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
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

Outcome Measure Data

Analysis Population Description

AT Population

Arm/Group Title	Mepolizumab 100 mg SC
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%

Adverse Events

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
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%)
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
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

Limitations and Caveats

[Not Specified]

More Information

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

• Name/Title: GSK Response Center
• Organization: GlaxoSmithKline
• Phone: 866-435-7343
• EMail: GSKClinicalSupportHD@gsk.com

Publications:

Khurana S, Brusselle GG, Bel EH, FitzGerald JM, Masoli M, Korn S, Kato M, Albers FC, Bradford ES, Gilson MJ, Price RG, Humbert M. Long-term Safety and Clinical Benefit of Mepolizumab in Patients With the Most Severe Eosinophilic Asthma: The COSMEX Study. Clin Ther. 2019 Oct;41(10):2041-2056.e5. doi: 10.1016/j.clinthera.2019.07.007. Epub 2019 Aug 22.

• 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