Cessation Versus Continuation of Long-term Mepolizumab in Severe Eosinophilic Asthma Patients

• ClinicalTrials.gov Identifier: NCT02555371
• Recruitment Status: Completed
• First Posted: September 21, 2015
• Results First Posted: February 5, 2020
• Last Update Posted: February 5, 2020
• Sponsor: GlaxoSmithKline
• Information provided by (Responsible Party): GlaxoSmithKline

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Asthma
• Interventions: Biological: Mepolizumab 100mg; Drug: Placebo
• Enrollment: 306

Participant Flow

Recruitment Details	A multi-center, randomized, double-blind, placebo controlled, parallel group study to compare cessation versus continuation of long-term mepolizumab treatment. Participants (par.) who completed the Follow Up/Exit Visit or Early Withdrawal Visit from study MEA115666 (NCT01691859) or 201312 (NCT02135692) were eligible to participate in this study.
Pre-assignment Details	This is a 3 period study including variable open-label (OL) run-in, double-blind (DB) treatment period and open-label treatment switch period. The study was conducted in 75 centers across 14 countries from 07-Jan-2016 to 24-Jul-2019.

Arm/Group Title	Part A/B: Mepolizumab 100mg SC	Part C: Placebo	Part C: Mepolizumab 100mg SC	Part D: Mepolizumab 100mg SC (Previous Placebo)	Part D: Mepolizumab 100mg SC (Previous Mepolizumab)
Arm/Group Description	Participants with less than 3 years of mepolizumab treatment entered variable open-label run-in period-Part A in order to reach 3 years of exposure and received 100 mg of mepolizumab injected subcutaneously (SC) once every 4 weeks (W) up to 132 weeks. Upon achieving 3 years exposure, participants entered Part B. Participants with at least 3 years of mepolizumab treatment directly entered fixed open-label run-in period-Part B and received 100 mg of mepolizumab injected SC once every 4 weeks up to 8 weeks.	Upon completion of the fixed run-in period, participants entered a double-blind study treatment and received placebo SC every 4 weeks up to 52 weeks. Participants who experienced a clinically significant asthma exacerbation were assessed by the investigator to determine if they could continue double-blind treatment or should instead enter OL mepolizumab 100 mg SC every 4 weeks for the remainder of the treatment period (up to 52 weeks post-randomization).	Upon completion of the fixed run-in period, participants entered a double-blind study treatment and received continued mepolizumab 100 mg SC every 4 weeks up to 52 weeks. Participants who experienced a clinically significant asthma exacerbation were assessed by the investigator to determine if they could continue double-blind treatment or should instead enter OL mepolizumab 100 mg SC every 4 weeks for the remainder of the treatment period (up to 52 weeks post-randomization).	Participants who experienced a clinically significant asthma exacerbation were assessed by the investigator to determine if they could continue double-blind treatment or should instead enter OL mepolizumab 100 mg SC every 4 weeks for the remainder of the treatment period (up to 52 weeks post-randomization in Part C).	Participants who experienced a clinically significant asthma exacerbation were assessed by the investigator to determine if they could continue double-blind treatment or should instead enter OL mepolizumab 100 mg SC every 4 weeks for the remainder of the treatment period (up to 52 weeks post-randomization in Part C ).
Period Title: PartA(Upto 132W)+PartB(Upto 8W)
Started [1]	306	0	0	0	0
Completed	295	0	0	0	0
Not Completed	11	0	0	0	0
Reason Not Completed
Adverse Event	1	0	0	0	0
Failure to meet continuation criteria	2	0	0	0	0
Withdrawal by Subject	5	0	0	0	0
Physician Decision	1	0	0	0	0
Lack of Efficacy	2	0	0	0	0
[1] Variable & fixed run-in periods have been combined since all par. received OL mepolizumab 100 mg SC
Period Title: Part C (DB Period: Up to 52W)
Started [1]	0	151	144	0	0
Completed	0	62	96	0	0
Not Completed	0	89	48	0	0
Reason Not Completed
Switched to Part D treatment	0	84	45	0	0
Withdrawal by Subject	0	2	2	0	0
Lack of Efficacy	0	1	0	0	0
Adverse Event	0	2	1	0	0
[1] Double-blind Treatment Period
Period Title: PartD(OL: 52W Post-randomization PartC)
Started	0	0	0	84	45
Completed	0	0	0	80	42
Not Completed	0	0	0	4	3
Reason Not Completed
Withdrawal by Subject	0	0	0	1	0
Physician Decision	0	0	0	2	0
Lost to Follow-up	0	0	0	0	2
Lack of Efficacy	0	0	0	0	1
Adverse Event	0	0	0	1	0

Baseline Characteristics

Arm/Group Title		Parts A/B: Mepolizumab 100mg SC
Arm/Group Description		Participants with less than 3 years of mepolizumab treatment entered variable open-label run-in period-Part A in order to reach 3 years of exposure and received 100 mg of mepolizumab injected subcutaneously (SC) once every 4 weeks up to 132 weeks. Upon achieving 3 years exposure, participants entered Part B. Participants with at least 3 years of mepolizumab treatment directly entered fixed open-label run-in period-Part B and received 100 mg of mepolizumab injected SC once every 4 weeks up to 8 weeks.
Overall Number of Baseline Participants		306
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	306 participants
		55.6 (11.74)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	306 participants
	Female	180 58.8%
	Male	126 41.2%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	306 participants
ASIAN - CENTRAL/SOUTH ASIAN HERITAGE		1 0.3%
ASIAN - EAST ASIAN HERITAGE		28 9.2%
ASIAN - JAPANESE HERITAGE		21 6.9%
BLACK OR AFRICAN AMERICAN		8 2.6%
WHITE - ARABIC/NORTH AFRICAN HERITAGE		3 1.0%
WHITE - WHITE/CAUCASIAN/EUROPEAN HERITAGE		245 80.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With First Clinically Significant Exacerbation in Part C
Description	Clinically significant exacerbation was defined as worsening of asthma which requires use of systemic corticosteroids (e.g., prednisone) for at least 3 days or a single intramuscular (IM) corticosteroid dose and/or hospitalization and/or emergency department (ED) visits. For participants on maintenance systemic corticosteroids, at least double the existing maintenance dose for at least 3 days is required. Percentage of participants with clinically significant exacerbation over time during the on-treatment period of Part C and 95% confidence interval were estimated using Kaplan-Meier estimates. Intent-to-Treat Population includes all randomized participants who received at least one dose of double-blind study medication within Part C.
Time Frame	Weeks 12, 24, 36 and 52

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population.

Arm/Group Title	Part C: Placebo	Part C: Mepolizumab 100mg SC
Arm/Group Description:	Upon completion of the fixed run-in period, participants entered a double-blind study treatment and received placebo SC every 4 weeks up to 52 weeks. Participants who experienced a clinically significant asthma exacerbation were assessed by the investigator to determine if they could continue double-blind treatment or should instead enter OL mepolizumab 100 mg SC every 4 weeks for the remainder of the treatment period (up to 52 weeks post-randomization).	Upon completion of the fixed run-in period, participants entered a double-blind study treatment and received continued mepolizumab 100 mg SC every 4 weeks up to 52 weeks. Participants who experienced a clinically significant asthma exacerbation were assessed by the investigator to determine if they could continue double-blind treatment or should instead enter OL mepolizumab 100 mg SC every 4 weeks for the remainder of the treatment period (up to 52 weeks post-randomization).
Overall Number of Participants Analyzed	151	144
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Week 12	31.8; (25.0 to 39.9)	20.2; (14.5 to 27.7)
Week 24	49.3; (41.5 to 57.6)	32.3; (25.3 to 40.7)
Week 36	56.0; (48.1 to 64.2)	40.3; (32.8 to 48.9)
Weeks 52	60.7; (52.7 to 68.8)	47.1; (39.2 to 55.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part C: Placebo, Part C: Mepolizumab 100mg SC
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.004
	Comments	[Not Specified]
	Method	Cox Proportional Hazards Model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.62
	Confidence Interval	(2-Sided) 95%; 0.45 to 0.86
	Estimation Comments	Treatment comparison between mepolizumab 100 mg SC and placebo using hazards ratio and 95% confidence interval has been presented.

2. Secondary Outcome

Title	Ratio to Baseline in Blood Eosinophil Count in Part C
Description	Blood samples were collected at specific time points to measure blood eosinophils level. Baseline was defined as the latest available assessment prior to first dose of double-blind treatment within Part C. Ratio to Baseline is defined as visit value divided by Baseline value and was analyzed using Mixed Model Repeated Measures with covariates of Baseline, region, exacerbations in the year prior to randomization (as an ordinal variable), Baseline maintenance oral corticosteroids (OCS) therapy (OCS versus no OCS), treatment and visit, plus interaction terms for visit by Baseline and visit by treatment group. The log transformation was applied to blood eosinophil counts prior to analysis. If a blood eosinophil count of zero was reported, a small value was added prior to log transforming the data. The dispersion measure used was log standard error.
Time Frame	Baseline and Weeks 12, 24, 36 and 52

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population. Only those participants available at the specified time points were analyzed for each treatment and represented as n=X in category titles

Arm/Group Title		Part C: Placebo	Part C: Mepolizumab 100mg SC
Arm/Group Description:		Upon completion of the fixed run-in period, participants entered a double-blind study treatment and received placebo SC every 4 weeks up to 52 weeks. Participants who experienced a clinically significant asthma exacerbation were assessed by the investigator to determine if they could continue double-blind treatment or should instead enter OL mepolizumab 100 mg SC every 4 weeks for the remainder of the treatment period (up to 52 weeks post-randomization).	Upon completion of the fixed run-in period, participants entered a double-blind study treatment and received continued mepolizumab 100 mg SC every 4 weeks up to 52 weeks. Participants who experienced a clinically significant asthma exacerbation were assessed by the investigator to determine if they could continue double-blind treatment or should instead enter OL mepolizumab 100 mg SC every 4 weeks for the remainder of the treatment period (up to 52 weeks post-randomization).
Overall Number of Participants Analyzed		121	120
Least Squares Mean (Standard Error); Unit of Measure: Ratio
Week 12, n=121, 120	Number Analyzed	121 participants	120 participants
		6.03 (0.077)	1.16 (0.078)
Week 24, n= 79, 106	Number Analyzed	79 participants	106 participants
		6.58 (0.095)	1.03 (0.084)
Week 36, n= 65, 99	Number Analyzed	65 participants	99 participants
		6.48 (0.093)	1.20 (0.079)
Week 52, n=60, 92	Number Analyzed	60 participants	92 participants
		6.17 (0.091)	1.00 (0.077)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part C: Placebo, Part C: Mepolizumab 100mg SC
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Mixed model repeated measures
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.19
	Confidence Interval	(2-Sided) 95%; 0.15 to 0.24
	Estimation Comments	Treatment comparison between mepolizumab 100 mg SC and placebo using ratio of mepolizumab to placebo and its 95% confidence interval at Week 12 has been presented.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part C: Placebo, Part C: Mepolizumab 100mg SC
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Mixed model repeated measures
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.16
	Confidence Interval	(2-Sided) 95%; 0.12 to 0.20
	Estimation Comments	Treatment comparison between mepolizumab 100 mg SC and placebo using ratio of mepolizumab to placebo and its 95% confidence interval at Week 24 has been presented.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Part C: Placebo, Part C: Mepolizumab 100mg SC
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Mixed model repeated measures
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.19
	Confidence Interval	(2-Sided) 95%; 0.15 to 0.24
	Estimation Comments	Treatment comparison between mepolizumab 100 mg SC and placebo using ratio of mepolizumab to placebo and its 95% confidence interval at Week 36 has been presented.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Part C: Placebo, Part C: Mepolizumab 100mg SC
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Mixed model repeated measures
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Ratio
	Estimated Value	0.16
	Confidence Interval	(2-Sided) 95%; 0.13 to 0.20
	Estimation Comments	Treatment comparison between mepolizumab 100 mg SC and placebo using ratio of mepolizumab to placebo and its 95% confidence interval at Week 52 has been presented.

3. Secondary Outcome

Title	Percentage of Participants With 0.5 Point or More Increase in Asthma Control Questionnaire (ACQ)-5 Score From Baseline in Part C
Description	The ACQ-5 is a five-item, self-completed questionnaire. Five questions (concerning nocturnal awakening, waking in the morning, activity limitation, shortness of breath and wheeze) enquire about the frequency and/or severity of symptoms over the previous week. The response ranges from zero (no impairment/limitation) to six (total impairment/ limitation) scale. Increase in score of >= 0.5 units from Baseline indicates decrease in asthma control. Baseline is the latest available assessment prior to first dose of double-blind treatment within Part C. Percentage of participants with a 0.5 point or more increase in ACQ-5 score from Baseline over time during the on-treatment period of Part C and its 95% confidence interval were estimated using Kaplan-Meier estimates.
Time Frame	Baseline and Weeks 12, 24, 36 and 52

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population.

Arm/Group Title	Part C: Placebo	Part C: Mepolizumab 100mg SC
Arm/Group Description:	Upon completion of the fixed run-in period, participants entered a double-blind study treatment and received placebo SC every 4 weeks up to 52 weeks. Participants who experienced a clinically significant asthma exacerbation were assessed by the investigator to determine if they could continue double-blind treatment or should instead enter OL mepolizumab 100 mg SC every 4 weeks for the remainder of the treatment period (up to 52 weeks post-randomization).	Upon completion of the fixed run-in period, participants entered a double-blind study treatment and received continued mepolizumab 100 mg SC every 4 weeks up to 52 weeks. Participants who experienced a clinically significant asthma exacerbation were assessed by the investigator to determine if they could continue double-blind treatment or should instead enter OL mepolizumab 100 mg SC every 4 weeks for the remainder of the treatment period (up to 52 weeks post-randomization).
Overall Number of Participants Analyzed	151	144
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Week 12	44.5; (36.9 to 52.8)	39.3; (31.8 to 47.8)
Week 24	69.5; (61.6 to 77.1)	49.3; (41.3 to 57.9)
Week 36	74.9; (67.1 to 82.1)	56.0; (47.8 to 64.6)
Weeks 52	79.0; (71.3 to 85.7)	63.1; (54.8 to 71.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part C: Placebo, Part C: Mepolizumab 100mg SC
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.005
	Comments	[Not Specified]
	Method	Cox Proportional Hazards Model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.66
	Confidence Interval	(2-Sided) 95%; 0.49 to 0.88
	Estimation Comments	Treatment comparison between mepolizumab 100 mg SC and placebo using hazards ratio and 95% confidence interval has been presented.

4. Secondary Outcome

Title	Percentage of Participants With Time to First Exacerbation Requiring Hospitalization or ED Visit in Part C
Description	Exacerbations of asthma requiring hospitalization or ED visit were assessed. The analysis was performed from Cox Proportional Hazards Model with covariates of treatment group, region, exacerbations in the year prior to randomization (as an ordinal variable) and Baseline maintenance OCS therapy (OCS versus no OCS). Percentage of participants with an exacerbation over time and its 95% confidence intervals were estimated using Kaplan-Meier estimates
Time Frame	Weeks 12, 24, 36 and 52

Outcome Measure Data

Analysis Population Description

Intent-to-Treat Population.

Arm/Group Title	Part C: Placebo	Part C: Mepolizumab 100mg SC
Arm/Group Description:	Upon completion of the fixed run-in period, participants entered a double-blind study treatment and received placebo SC every 4 weeks up to 52 weeks. Participants who experienced a clinically significant asthma exacerbation were assessed by the investigator to determine if they could continue double-blind treatment or should instead enter OL mepolizumab 100 mg SC every 4 weeks for the remainder of the treatment period (up to 52 weeks post-randomization).	Upon completion of the fixed run-in period, participants entered a double-blind study treatment and received continued mepolizumab 100 mg SC every 4 weeks up to 52 weeks. Participants who experienced a clinically significant asthma exacerbation were assessed by the investigator to determine if they could continue double-blind treatment or should instead enter OL mepolizumab 100 mg SC every 4 weeks for the remainder of the treatment period (up to 52 weeks post-randomization).
Overall Number of Participants Analyzed	151	144
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
Week 12	2.9; (1.1 to 7.5)	2.8; (1.1 to 7.2)
Week 24	5.7; (2.7 to 11.8)	5.1; (2.4 to 10.3)
Week 36	5.7; (2.7 to 11.8)	5.9; (3.0 to 11.6)
Weeks 52	5.7; (2.7 to 11.8)	7.9; (4.3 to 14.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part C: Placebo, Part C: Mepolizumab 100mg SC
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.570
	Comments	[Not Specified]
	Method	Cox Proportional Hazards Model
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.33
	Confidence Interval	(2-Sided) 95%; 0.50 to 3.51
	Estimation Comments	Treatment comparison between mepolizumab 100 mg SC and placebo using hazards ratio and 95% confidence interval has been presented.

Adverse Events

Time Frame	Adverse Events (AEs) & Serious Adverse Events (SAEs) were collected for Part A/B: from first dose of OL mepolizumab in Parts A/B until the last dose of mepolizumab in Parts A/B (upto 132 weeks for Part A & upto 8 weeks for Part B); for Part C: from start of double blind treatment until the last dose of double-blind treatment (upto 52 weeks) & for Part D: from start of first dose of OL treatment in Part D until the last dose of OL treatment in Part D (upto 52 weeks post-randomization in Part C)
Adverse Event Reporting Description	AEs and SAEs were collected for As Treated Population which comprised of all participants who received at least one dose of open label mepolizumab for Parts A/B and Part D. Intent-to-Treat (ITT) Population was used for Part C which comprised of all randomized participants who received at least one dose of double-blind study medication. Combined data for parts A and B are presented since all par. received OL mepolizumab 100 mg SC.
Arm/Group Title	Part A/B: Mepolizumab 100mg SC		Part C: Placebo		Part C: Mepolizumab 100mg		Part D: Mepolizumab 100mg SC (Previous Placebo)		Part D: Mepolizumab 100mg SC (Previous Mepolizumab)
Arm/Group Description	Participants with less than 3 years of mepolizumab treatment entered variable open-label run-in period-Part A in order to reach 3 years of exposure and received 100 mg of mepolizumab injected subcutaneously (SC) once every 4 weeks (W) up to 132 weeks. Upon achieving 3 years exposure, participants entered Part B. Participants with at least 3 years of mepolizumab treatment directly entered fixed open-label run-in period-Part B and received 100 mg of mepolizumab injected SC once every 4 weeks up to 8 weeks.		Upon completion of the fixed run-in period, participants entered a double-blind study treatment and received placebo SC every 4 weeks up to 52 weeks. Participants who experienced a clinically significant asthma exacerbation were assessed by the investigator to determine if they could continue double-blind treatment or should instead enter OL mepolizumab 100 mg SC every 4 weeks for the remainder of the treatment period (up to 52 weeks post-randomization).		Upon completion of the fixed run-in period, participants entered a double-blind study treatment and received continued mepolizumab 100 mg SC every 4 weeks up to 52 weeks. Participants who experienced a clinically significant asthma exacerbation were assessed by the investigator to determine if they could continue double-blind treatment or should instead enter OL mepolizumab 100 mg SC every 4 weeks for the remainder of the treatment period (up to 52 weeks post-randomization).		Participants who experienced a clinically significant asthma exacerbation were assessed by the investigator to determine if they could continue double-blind treatment or should instead enter OL mepolizumab 100 mg SC every 4 weeks for the remainder of the treatment period (up to 52 weeks post-randomization in Part C).		Participants who experienced a clinically significant asthma exacerbation were assessed by the investigator to determine if they could continue double-blind treatment or should instead enter OL mepolizumab 100 mg SC every 4 weeks for the remainder of the treatment period (up to 52 weeks post-randomization in Part C).
All-Cause Mortality
	Part A/B: Mepolizumab 100mg SC		Part C: Placebo		Part C: Mepolizumab 100mg		Part D: Mepolizumab 100mg SC (Previous Placebo)		Part D: Mepolizumab 100mg SC (Previous Mepolizumab)
	Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/306 (0.00%)		0/151 (0.00%)		0/144 (0.00%)		1/84 (1.19%)		0/45 (0.00%)
Serious Adverse Events
	Part A/B: Mepolizumab 100mg SC		Part C: Placebo		Part C: Mepolizumab 100mg		Part D: Mepolizumab 100mg SC (Previous Placebo)		Part D: Mepolizumab 100mg SC (Previous Mepolizumab)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/306 (2.29%)		10/151 (6.62%)		9/144 (6.25%)		10/84 (11.90%)		4/45 (8.89%)
Gastrointestinal disorders
Abdominal hernia † 1	1/306 (0.33%)	1	0/151 (0.00%)	0	0/144 (0.00%)	0	0/84 (0.00%)	0	0/45 (0.00%)	0
Diarrhoea † 1	0/306 (0.00%)	0	0/151 (0.00%)	0	1/144 (0.69%)	1	0/84 (0.00%)	0	0/45 (0.00%)	0
Inguinal hernia † 1	0/306 (0.00%)	0	0/151 (0.00%)	0	0/144 (0.00%)	0	1/84 (1.19%)	1	0/45 (0.00%)	0
Salivary gland calculus † 1	0/306 (0.00%)	0	0/151 (0.00%)	0	0/144 (0.00%)	0	0/84 (0.00%)	0	1/45 (2.22%)	1
General disorders
Device related thrombosis † 1	0/306 (0.00%)	0	1/151 (0.66%)	1	0/144 (0.00%)	0	0/84 (0.00%)	0	0/45 (0.00%)	0
Non-cardiac chest pain † 1	0/306 (0.00%)	0	0/151 (0.00%)	0	1/144 (0.69%)	1	0/84 (0.00%)	0	0/45 (0.00%)	0
Hepatobiliary disorders
Cholelithiasis † 1	0/306 (0.00%)	0	1/151 (0.66%)	1	0/144 (0.00%)	0	0/84 (0.00%)	0	0/45 (0.00%)	0
Infections and infestations
Cytomegalovirus infection † 1	1/306 (0.33%)	1	0/151 (0.00%)	0	0/144 (0.00%)	0	0/84 (0.00%)	0	0/45 (0.00%)	0
Influenza † 1	1/306 (0.33%)	1	0/151 (0.00%)	0	0/144 (0.00%)	0	0/84 (0.00%)	0	0/45 (0.00%)	0
Pharyngeal abscess † 1	1/306 (0.33%)	1	0/151 (0.00%)	0	0/144 (0.00%)	0	0/84 (0.00%)	0	0/45 (0.00%)	0
Urinary tract infection † 1	1/306 (0.33%)	1	0/151 (0.00%)	0	0/144 (0.00%)	0	0/84 (0.00%)	0	0/45 (0.00%)	0
Appendicitis † 1	0/306 (0.00%)	0	0/151 (0.00%)	0	1/144 (0.69%)	1	0/84 (0.00%)	0	0/45 (0.00%)	0
Bronchitis † 1	0/306 (0.00%)	0	1/151 (0.66%)	1	0/144 (0.00%)	0	0/84 (0.00%)	0	0/45 (0.00%)	0
Diverticulitis † 1	0/306 (0.00%)	0	0/151 (0.00%)	0	1/144 (0.69%)	1	0/84 (0.00%)	0	0/45 (0.00%)	0
Escherichia pyelonephritis † 1	0/306 (0.00%)	0	1/151 (0.66%)	1	0/144 (0.00%)	0	0/84 (0.00%)	0	0/45 (0.00%)	0
Atypical pneumonia † 1	0/306 (0.00%)	0	0/151 (0.00%)	0	0/144 (0.00%)	0	1/84 (1.19%)	1	0/45 (0.00%)	0
Sinusitis fungal † 1	0/306 (0.00%)	0	0/151 (0.00%)	0	0/144 (0.00%)	0	1/84 (1.19%)	1	0/45 (0.00%)	0
Injury, poisoning and procedural complications
Hip fracture † 1	0/306 (0.00%)	0	1/151 (0.66%)	1	0/144 (0.00%)	0	0/84 (0.00%)	0	0/45 (0.00%)	0
Spinal fracture † 1	0/306 (0.00%)	0	0/151 (0.00%)	0	1/144 (0.69%)	1	0/84 (0.00%)	0	0/45 (0.00%)	0
Meniscus injury † 1	0/306 (0.00%)	0	0/151 (0.00%)	0	0/144 (0.00%)	0	1/84 (1.19%)	1	0/45 (0.00%)	0
Rib fracture † 1	0/306 (0.00%)	0	0/151 (0.00%)	0	0/144 (0.00%)	0	1/84 (1.19%)	1	0/45 (0.00%)	0
Traumatic haemothorax † 1	0/306 (0.00%)	0	0/151 (0.00%)	0	0/144 (0.00%)	0	1/84 (1.19%)	1	0/45 (0.00%)	0
Metabolism and nutrition disorders
Decreased appetite † 1	1/306 (0.33%)	1	0/151 (0.00%)	0	0/144 (0.00%)	0	0/84 (0.00%)	0	0/45 (0.00%)	0
Hypoglycaemia † 1	0/306 (0.00%)	0	0/151 (0.00%)	0	0/144 (0.00%)	0	1/84 (1.19%)	1	0/45 (0.00%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant polyp † 1	1/306 (0.33%)	1	0/151 (0.00%)	0	0/144 (0.00%)	0	0/84 (0.00%)	0	0/45 (0.00%)	0
Benign ovarian tumour † 1	0/306 (0.00%)	0	1/151 (0.66%)	1	0/144 (0.00%)	0	0/84 (0.00%)	0	0/45 (0.00%)	0
Colon cancer stage 0 † 1	0/306 (0.00%)	0	0/151 (0.00%)	0	1/144 (0.69%)	1	0/84 (0.00%)	0	0/45 (0.00%)	0
Intraductal papillary mucinous neoplasm † 1	0/306 (0.00%)	0	0/151 (0.00%)	0	1/144 (0.69%)	1	0/84 (0.00%)	0	0/45 (0.00%)	0
Prostate cancer † 1	0/306 (0.00%)	0	0/151 (0.00%)	0	1/144 (0.69%)	1	0/84 (0.00%)	0	0/45 (0.00%)	0
Uterine leiomyoma † 1	0/306 (0.00%)	0	1/151 (0.66%)	1	0/144 (0.00%)	0	0/84 (0.00%)	0	0/45 (0.00%)	0
Nervous system disorders
Myasthenia gravis † 1	0/306 (0.00%)	0	0/151 (0.00%)	0	1/144 (0.69%)	1	0/84 (0.00%)	0	0/45 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Asthma † 1	3/306 (0.98%)	4	6/151 (3.97%)	6	2/144 (1.39%)	2	4/84 (4.76%)	4	4/45 (8.89%)	6
Acute respiratory failure † 1	0/306 (0.00%)	0	0/151 (0.00%)	0	0/144 (0.00%)	0	1/84 (1.19%)	1	0/45 (0.00%)	0
Paranasal cyst † 1	0/306 (0.00%)	0	0/151 (0.00%)	0	0/144 (0.00%)	0	1/84 (1.19%)	1	0/45 (0.00%)	0
Pneumonia aspiration † 1	0/306 (0.00%)	0	0/151 (0.00%)	0	0/144 (0.00%)	0	1/84 (1.19%)	1	0/45 (0.00%)	0
1 Term from vocabulary, MedDRA 22.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	3%
	Part A/B: Mepolizumab 100mg SC		Part C: Placebo		Part C: Mepolizumab 100mg		Part D: Mepolizumab 100mg SC (Previous Placebo)		Part D: Mepolizumab 100mg SC (Previous Mepolizumab)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	14/306 (4.58%)		69/151 (45.70%)		82/144 (56.94%)		44/84 (52.38%)		32/45 (71.11%)
Gastrointestinal disorders
Abdominal pain † 1	0/306 (0.00%)	0	0/151 (0.00%)	0	0/144 (0.00%)	0	1/84 (1.19%)	1	2/45 (4.44%)	2
Diarrhoea † 1	0/306 (0.00%)	0	0/151 (0.00%)	0	0/144 (0.00%)	0	3/84 (3.57%)	3	0/45 (0.00%)	0
Large intestine polyp † 1	0/306 (0.00%)	0	0/151 (0.00%)	0	0/144 (0.00%)	0	0/84 (0.00%)	0	2/45 (4.44%)	2
Infections and infestations
Nasopharyngitis † 1	14/306 (4.58%)	23	26/151 (17.22%)	44	27/144 (18.75%)	36	16/84 (19.05%)	22	9/45 (20.00%)	12
Upper respiratory tract infection † 1	0/306 (0.00%)	0	14/151 (9.27%)	18	12/144 (8.33%)	14	5/84 (5.95%)	5	3/45 (6.67%)	3
Sinusitis † 1	0/306 (0.00%)	0	9/151 (5.96%)	10	13/144 (9.03%)	14	7/84 (8.33%)	11	5/45 (11.11%)	8
Bronchitis † 1	0/306 (0.00%)	0	5/151 (3.31%)	5	14/144 (9.72%)	14	7/84 (8.33%)	8	8/45 (17.78%)	13
Respiratory tract infection viral † 1	0/306 (0.00%)	0	2/151 (1.32%)	2	6/144 (4.17%)	11	0/84 (0.00%)	0	0/45 (0.00%)	0
Viral upper respiratory tract infection † 1	0/306 (0.00%)	0	5/151 (3.31%)	7	3/144 (2.08%)	3	0/84 (0.00%)	0	0/45 (0.00%)	0
Influenza † 1	0/306 (0.00%)	0	1/151 (0.66%)	1	5/144 (3.47%)	5	1/84 (1.19%)	1	2/45 (4.44%)	2
Urinary tract infection † 1	0/306 (0.00%)	0	0/151 (0.00%)	0	0/144 (0.00%)	0	4/84 (4.76%)	6	0/45 (0.00%)	0
Chronic sinusitis † 1	0/306 (0.00%)	0	0/151 (0.00%)	0	0/144 (0.00%)	0	1/84 (1.19%)	1	2/45 (4.44%)	4
Pneumonia † 1	0/306 (0.00%)	0	0/151 (0.00%)	0	0/144 (0.00%)	0	3/84 (3.57%)	3	0/45 (0.00%)	0
Oral candidiasis † 1	0/306 (0.00%)	0	0/151 (0.00%)	0	0/144 (0.00%)	0	0/84 (0.00%)	0	2/45 (4.44%)	2
Tooth infection † 1	0/306 (0.00%)	0	0/151 (0.00%)	0	0/144 (0.00%)	0	0/84 (0.00%)	0	2/45 (4.44%)	2
Metabolism and nutrition disorders
Hyperglycaemia † 1	0/306 (0.00%)	0	0/151 (0.00%)	0	0/144 (0.00%)	0	1/84 (1.19%)	1	2/45 (4.44%)	2
Musculoskeletal and connective tissue disorders
Back pain † 1	0/306 (0.00%)	0	6/151 (3.97%)	12	6/144 (4.17%)	8	3/84 (3.57%)	4	2/45 (4.44%)	2
Arthralgia † 1	0/306 (0.00%)	0	3/151 (1.99%)	3	6/144 (4.17%)	6	0/84 (0.00%)	0	0/45 (0.00%)	0
Neck pain † 1	0/306 (0.00%)	0	0/151 (0.00%)	0	0/144 (0.00%)	0	2/84 (2.38%)	2	2/45 (4.44%)	2
Nervous system disorders
Headache † 1	0/306 (0.00%)	0	9/151 (5.96%)	11	9/144 (6.25%)	12	6/84 (7.14%)	7	4/45 (8.89%)	7
Respiratory, thoracic and mediastinal disorders
Asthma † 1	0/306 (0.00%)	0	14/151 (9.27%)	16	10/144 (6.94%)	14	7/84 (8.33%)	7	4/45 (8.89%)	12
Cough † 1	0/306 (0.00%)	0	6/151 (3.97%)	7	1/144 (0.69%)	1	0/84 (0.00%)	0	0/45 (0.00%)	0
Oropharyngeal pain † 1	0/306 (0.00%)	0	0/151 (0.00%)	0	0/144 (0.00%)	0	3/84 (3.57%)	3	1/45 (2.22%)	1
Vascular disorders
Hypertension † 1	0/306 (0.00%)	0	1/151 (0.66%)	1	5/144 (3.47%)	6	0/84 (0.00%)	0	0/45 (0.00%)	0
1 Term from vocabulary, MedDRA 22.0; † 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 automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Moore WC, Kornmann O, Humbert M, Poirier C, Bel EH, Kaneko N, Smith SG, Martin N, Gilson MJ, Price RG, Bradford ES, Liu MC. Stopping versus continuing long-term mepolizumab treatment in severe eosinophilic asthma (COMET study). Eur Respir J. 2022 Jan 6;59(1). pii: 2100396. doi: 10.1183/13993003.00396-2021. Print 2022 Jan.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT02555371
• Other Study ID Numbers: 201810; 2015-002361-32 ( EudraCT Number )
• First Submitted: September 17, 2015
• First Posted: September 21, 2015
• Results First Submitted: January 23, 2020
• Results First Posted: February 5, 2020
• Last Update Posted: February 5, 2020