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

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02135692
• Collaborator: (none)
• Enrollment: 339
• Locations: 114
• Arm: 1
• Actual Duration (Months): 40.2
• Patients Per Site: 3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a multi-center, open-label, long-term study of subcutaneously (SC) administered mepolizumab 100mg in addition to standard of care (SOC), in subjects with severe eosinophilic asthma. This study will enroll a subset of subjects from Study MEA115661 who have demonstrated clear benefit from therapy and who without continuation of mepolizumab therapy are individuals at greatest risk of serious deterioration of their health status. In order to target individuals at greatest risk for serious deterioration of their health status, only subjects from the MEA115661 study with a history of life-threatening or seriously debilitating asthma, will be allowed to participate. Subjects meeting all of the eligibility criteria for the study will be offered the opportunity to consent for this study of up to 128 weeks in length (including the Follow-Up Visit). This study will give opportunity to extend the collection of clinical data for long-term use and further assess the sustainability of efficacy in a population likely to experience significant loss of asthma control and the need for higher doses of systemic steroids if returned to SOC only.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Biological: Mepolizumab; Drug: SOC	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 339 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi-Centre, Open-Label, Study of Mepolizumab in a Subset of Subjects With a History of Life Threatening/Seriously Debilitating Asthma Who Participated in the MEA115661 Trial
• Actual Study Start Date: May 29, 2014
• Actual Primary Completion Date: Oct 5, 2017
• Actual Study Completion Date: Oct 5, 2017

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Mepolizumab 100 mg All subjects will receive mepolizumab 100mg administered SC into the upper arm or thigh approximately every 4 weeks.

Biological: Mepolizumab; Mepolizumab is a fully humanised IgG antibody (IgG1, kappa) with human heavy and light chain frameworks. Mepolizumab will be supplied as a lyophilised cake in sterile vials for individual use.; Drug: SOC; Standard of Care (SOC) will differ by participant, however it will generally include oral corticosteroids and an inhaled controller medicine (an inhaled corticosteroid plus a long acting beta agonist) and/or short acting beta agonists

Outcome Measures

Primary Outcome Measures

1. Annualized Rate of On-treatment Exacerbations Per Year [Baseline (Week 0) to Week 172]

   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.

2. Number of Participants With Any On-treatment Adverse Event (AE) or On-treatment Serious AE (SAE) [Baseline (Week 0) to Week 172]

   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.

Secondary Outcome Measures

1. Mean Change From Baseline in Asthma Control Questionnaire (ACQ)-5 On-treatment Score [Baseline (Week 0) to Week 168]

   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.

2. Mean Change From Baseline in On-treatment Clinic Pre-bronchodilator FEV1 [Baseline (Week 0) to Week 168]

   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.

3. Number of Participants Withdrawn From the Study Due to Lack of Efficacy and Adverse Events [Baseline (Week 0) to Week 172]

   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.

4. Number of Participants Hospitalized Due to Adverse Events Including Asthma Exacerbations [Baseline (Week 0) to Week 172]

   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.

5. Number of Participants With AEs Including Both Systemic (Allergic and Non-allergic) and Local Site Reactions [Baseline (Week 0) to Week 172]

   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.

6. 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) [Baseline (Week 0) to Week 172]

   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)..

7. Number of Participants With Maximum Change From Baseline in QTcB and QTcF Interval for ECG Assessed at Any Time Post Baseline [Baseline (Week 0) to Week 172]

   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.

8. Change From Baseline in Systolic Blood Pressure and Diastolic Blood Pressure [Baseline (Week 0) to Week 168]

   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.

9. Change From Baseline in Pulse Rate [Baseline (Week 0) to Week 168]

   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.

10. Number of Participants With Positive Anti-mepolizumab Binding Antibodies (ADA) and Neutralizing Antibodies (NAb) [Baseline (Week 0) to Week 172]

    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).

11. 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 [Baseline (Week 0) to Week 172]

    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).

12. 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 [Baseline (Week 0) to Week 172]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Informed Consent: Prior to commencing any study related activities, subjects must be able and willing to provide written informed consent.

• Male or Eligible Female Subjects: To be eligible for the study, females of child-bearing potential must commit to consistent and correct use of an acceptable method of birth control and for 4 months after the last study drug administration. A urine pregnancy test is required of all females of childbearing potential at the initial Baseline Visit (Visit 1).

• French Subjects Only: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.

• MEA115661 Participation: Subjects must have completed Visit 14 of MEA115661.

• Current Anti-Asthma Therapy: The subject's asthma has been treated with an ICS controller medication for the last 8 months with fluticasone propionate (FP) >=500 mcg/day (or equivalent).

• Disease Severity: Subjects must be assessed as having life-threatening /serious debilitating asthma in order to enroll, as defined by the following: Subjects enrolled in MEA115588 must meet one of the following criteria: a) Subject has a history of at least one intubation during their lifetime; b) >=3 asthma exacerbations in the 12 months prior to screening for MEA115588; c) >=1 or more hospitalization for asthma exacerbation in the 12 months prior to screening for MEA115588. Subjects enrolled in MEA115575 must meet one of the following criteria: d) Subject has a history of at least one intubation during their lifetime; e) Their optimized dose at randomization in MEA115575 was >=10mg of prednisone; f) >=1 or more hospitalization for asthma exacerbation in the 12 months prior to screening for MEA115575.

• Clinical Benefit: Subjects must have experienced documented clinical benefit to enroll. Subjects must meet the following criteria demonstrating clinical benefit: Subjects enrolled in MEA115588 who received mepolizumab must meet all of the following criteria: a) Subject must have had a reduction in their exacerbation frequency by

=50% during MEA115588. The baseline for comparison is the total number of exacerbations reported in the 12 months prior to screening for MEA115588. b) The investigator response on the "Clinician-Rated Response to Therapy" questionnaire at Visit 10 was either: mildly improved, moderately improved or significantly improved. Subjects enrolled in MEA115588 who received placebo must meet all of the following criteria: c) Subject must have had a reduction in their exacerbation frequency by =50% during the first 8 months of MEA115661. The baseline for comparison is the total number of exacerbations reported in the 12 months prior to screening for MEA115588; d) The investigator confirms that the subject demonstrated improvement during MEA115661. Subjects enrolled in MEA115575 who received mepolizumab must meet all of the following criteria: e) Subject must have reduced their oral corticosteroid dose by >=50% during MEA115575. The baseline for comparison is the subject's optimized oral corticosteroid (OCS) dose at randomization in MEA115575; f) The investigator response on the "Clinician-Rated Response to Therapy" questionnaire at Visit 9 was either: mildly improved, moderately improved or significantly improved. Subjects enrolled in MEA115575 who received placebo must meet all of the following criteria: g) Subject must have reduced their oral corticosteroid dose at randomization by >=50% in the first 6 months of MEA115661. The baseline for comparison is the subject's optimized OCS dose at randomization in MEA115575; h) The investigator confirms that the subject demonstrated improvement during MEA115661.

Exclusion Criteria

• Health Status: Clinically significant change in health status during MEA115661 which in the opinion of the investigator would make the subject unsuitable for participation in this long-term study.

• Pregnancy: Subjects who are pregnant or breastfeeding. Subjects should not be enrolled if they plan to become pregnanDeart during the time of study participation.

• Exacerbation History: Subjects who received placebo in MEA115588 and had NO exacerbations during the study.

• Oral Corticosteroid Use: Subjects who received placebo in MEA115575 and were able to discontinue oral corticosteroid therapy by the end of the study.

• Smoking Status: Current smokers

• Previous Significant Protocol Deviation: Subjects who were excluded from the per protocol analysis due to significant protocol deviations in either study MEA115575 or MEA115588.

• Electrocardiogram (ECG) Assessment: A clinically significant ECG abnormality at the exit visit of MEA115661, as determined by the investigator.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Newport Beach	California	United States	92663
2	GSK Investigational Site	Riverside	California	United States	92506-0174
3	GSK Investigational Site	Rolling Hills Estates	California	United States	90274
4	GSK Investigational Site	Denver	Colorado	United States	80206
5	GSK Investigational Site	New Haven	Connecticut	United States	06510
6	GSK Investigational Site	Albany	Georgia	United States	31707
7	GSK Investigational Site	Baltimore	Maryland	United States	21224
8	GSK Investigational Site	Rochester	Minnesota	United States	55905
9	GSK Investigational Site	New York	New York	United States	10029
10	GSK Investigational Site	Rochester	New York	United States	14642
11	GSK Investigational Site	Durham	North Carolina	United States	27705
12	GSK Investigational Site	Winston-Salem	North Carolina	United States	27103
13	GSK Investigational Site	Cleveland	Ohio	United States	44195
14	GSK Investigational Site	Hershey	Pennsylvania	United States	17033
15	GSK Investigational Site	Pittsburgh	Pennsylvania	United States	15213
16	GSK Investigational Site	Salt Lake City	Utah	United States	84112
17	GSK Investigational Site	Mar del Plata	Buenos Aires	Argentina	7600
18	GSK Investigational Site	San Rafael	Mendoza	Argentina
19	GSK Investigational Site	Rosario	Santa Fe	Argentina	S2000DBS
20	GSK Investigational Site	Buenos Aires		Argentina	C1424BSF
21	GSK Investigational Site	Mendoza		Argentina	5500
22	GSK Investigational Site	New Lambton	New South Wales	Australia	2305
23	GSK Investigational Site	Bedford Park	South Australia	Australia	5042
24	GSK Investigational Site	Clayton	Victoria	Australia	3168
25	GSK Investigational Site	Nedlands	Western Australia	Australia	6009
26	GSK Investigational Site	Bruxelles		Belgium	1020
27	GSK Investigational Site	Gent		Belgium	9000
28	GSK Investigational Site	Leuven		Belgium	3000
29	GSK Investigational Site	Liège		Belgium	4000
30	GSK Investigational Site	Calgary	Alberta	Canada	T2N 4Z6
31	GSK Investigational Site	Edmonton	Alberta	Canada	T6G 2G3
32	GSK Investigational Site	Vancouver	British Columbia	Canada	V5Z 1M9
33	GSK Investigational Site	Winnipeg	Manitoba	Canada	R2H 2A6
34	GSK Investigational Site	St-Charles-Borromée	Ontario	Canada	J6E 2B4
35	GSK Investigational Site	Montreal	Quebec	Canada	H2W 1T8
36	GSK Investigational Site	Montreal	Quebec	Canada	H2X 2P2
37	GSK Investigational Site	Montreal	Quebec	Canada	H4J 1C5
38	GSK Investigational Site	Sainte-Foy	Quebec	Canada	G1V 4G5
39	GSK Investigational Site	Rancagua	Reg Del Libert Bern Ohiggins	Chile	2843099
40	GSK Investigational Site	Santiago		Chile	8380453
41	GSK Investigational Site	Talcahuano		Chile	4270918
42	GSK Investigational Site	Brno		Czechia	625 00
43	GSK Investigational Site	Olomouc		Czechia	775 20
44	GSK Investigational Site	Praha 4		Czechia	140 59
45	GSK Investigational Site	Praha 8		Czechia	180 01
46	GSK Investigational Site	Gières		France	38610
47	GSK Investigational Site	Kremlin-Bicêtre		France	94270
48	GSK Investigational Site	Lille cedex		France	59037
49	GSK Investigational Site	Lyon cedex 04		France	69317
50	GSK Investigational Site	Marseille cedex 20		France	13915
51	GSK Investigational Site	Montpellier cedex 5		France	34295
52	GSK Investigational Site	Nantes cedex 1		France	44093
53	GSK Investigational Site	Paris Cedex 18		France	75877
54	GSK Investigational Site	Perpignan		France	66000
55	GSK Investigational Site	Strasbourg		France	67091
56	GSK Investigational Site	Aschaffenburg	Bayern	Germany	63739
57	GSK Investigational Site	Ruedersdorf	Brandenburg	Germany	15562
58	GSK Investigational Site	Frankfurt	Hessen	Germany	60389
59	GSK Investigational Site	Frankfurt	Hessen	Germany	60596
60	GSK Investigational Site	Gelnhausen	Hessen	Germany	63571
61	GSK Investigational Site	Neu-Isenburg	Hessen	Germany	63263
62	GSK Investigational Site	Hannover	Niedersachsen	Germany	30173
63	GSK Investigational Site	Mainz	Rheinland-Pfalz	Germany	55131
64	GSK Investigational Site	Luebeck	Schleswig-Holstein	Germany	23552
65	GSK Investigational Site	Berlin		Germany	10367
66	GSK Investigational Site	Hamburg		Germany	22299
67	GSK Investigational Site	Magdeburg		Germany	39120
68	GSK Investigational Site	Napoli	Campania	Italy	80131
69	GSK Investigational Site	Parma	Emilia-Romagna	Italy	43125
70	GSK Investigational Site	Genova	Liguria	Italy	16132
71	GSK Investigational Site	Pietra Ligure (SV)	Liguria	Italy	17027
72	GSK Investigational Site	Foggia	Puglia	Italy	71100
73	GSK Investigational Site	Perugia	Umbria	Italy	06156
74	GSK Investigational Site	Cittadella PD	Veneto	Italy	35013
75	GSK Investigational Site	Chiba		Japan	296-8602
76	GSK Investigational Site	Fukuoka		Japan	802-0052
77	GSK Investigational Site	Fukuoka		Japan	811-1394
78	GSK Investigational Site	Gunma		Japan	370-0615
79	GSK Investigational Site	Hokkaido		Japan	070-8644
80	GSK Investigational Site	Ibaraki		Japan	319-1113
81	GSK Investigational Site	Kanagawa		Japan	252-0392
82	GSK Investigational Site	Okinawa		Japan	904-2293
83	GSK Investigational Site	Osaka		Japan	596-8501
84	GSK Investigational Site	Tokyo		Japan	102-0083
85	GSK Investigational Site	Tokyo		Japan	103-0027
86	GSK Investigational Site	Tokyo		Japan	187-0024
87	GSK Investigational Site	Anyang-Si Gyeonggi-do		Korea, Republic of	431-070
88	GSK Investigational Site	Bucheon city, Gyenggi-do		Korea, Republic of	420-767
89	GSK Investigational Site	Cheongju, Chungcheongbuk-do		Korea, Republic of	361-711
90	GSK Investigational Site	Donggu Gwangju		Korea, Republic of	501757
91	GSK Investigational Site	Seoul		Korea, Republic of	120-752
92	GSK Investigational Site	Seoul		Korea, Republic of	156-755
93	GSK Investigational Site	Suwon-si, Gyeonggi-do		Korea, Republic of	443-380
94	GSK Investigational Site	Amsterdam		Netherlands	1105 AZ
95	GSK Investigational Site	Leeuwarden		Netherlands	8934 AD
96	GSK Investigational Site	Bialystok		Poland	15-044
97	GSK Investigational Site	Krakow		Poland	31-024
98	GSK Investigational Site	Chelyabinsk		Russian Federation	454106
99	GSK Investigational Site	Moscow		Russian Federation	123182
100	GSK Investigational Site	Saint-Petersburg		Russian Federation	194354
101	GSK Investigational Site	St. Petersburg		Russian Federation	194356
102	GSK Investigational Site	Alicante		Spain	03004
103	GSK Investigational Site	Barcelona		Spain	08036
104	GSK Investigational Site	Barcelona		Spain	08041
105	GSK Investigational Site	Barcelona		Spain	08208
106	GSK Investigational Site	Pozuelo De Alarcón/Madrid		Spain	28223
107	GSK Investigational Site	Kharkiv		Ukraine	61124
108	GSK Investigational Site	Kiev		Ukraine	03680
109	GSK Investigational Site	Mykolaiv		Ukraine	54003
110	GSK Investigational Site	Vinnytsia		Ukraine	21018
111	GSK Investigational Site	Leicester	Leicestershire	United Kingdom	LE3 9QP
112	GSK Investigational Site	Bradford		United Kingdom	BD9 6RJ
113	GSK Investigational Site	Plymouth		United Kingdom	PL6 8DH
114	GSK Investigational Site	Southampton		United Kingdom	SO16 6YD

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

• Study Protocol - Jul 6, 2015
• Statistical Analysis Plan - Oct 25, 2017

More Information

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
• First Posted: May 12, 2014
• Last Update Posted: Dec 3, 2019
• Last Verified: Nov 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by GlaxoSmithKline: Severe eosinophilic asthma; Extension study; Expanded access; Safety; Mepolizumab; Eosinophils
• Additional relevant MeSH terms: Asthma

Study Results

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 Detail	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

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 Participants	339
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	52.9 (13.08)
Sex: Female, Male (Count of Participants)
Female	178 52.5%
Male	161 47.5%
Race/Ethnicity, Customized (Count of 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.
Measure Participants	339
Mean (95% Confidence Interval) [Exacerbations per year]	0.93

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.
Measure Participants	339
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.
Measure Participants	339
Week 12, n=333	-0.16 (1.096)
Week 24, n=333	-0.15 (1.131)
Week 36, n=326	-0.21 (1.089)
Week 48, n=328	-0.17 (0.965)
Week 60, n=307	-0.18 (1.066)
Week 72, n=282	-0.08 (1.145)
Week 84, n=254	-0.03 (1.151)
Week 96, n=212	-0.12 (0.976)
Week 108, n=190	-0.06 (1.057)
Week 120, n=164	-0.01 (1.244)
Week 132, n=135	-0.09 (1.089)
Week 144, n=73	0.34 (1.220)
Week 156, n=23	0.07 (0.962)
Week 168, n=6	-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.
Measure Participants	339
Week 24, n=332	67 (382.9)
Week 48, n=325	27 (404.6)
Week 72, n=289	30 (406.0)
Week 96, n=223	47 (433.7)
Week 120, n=169	34 (369.9)
Week 144, n=88	14 (374.9)
Week 168, n=15	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.
Measure Participants	339
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.
Measure Participants	339
Count of Participants [Participants]	78 23%

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.
Measure Participants	339
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.
Measure Participants	339
QTcB, Week 24, n=301	0.1 (16.90)
QTcB, Week 48, n=294	-0.9 (17.27)
QTcB, Week 72, n=269	-2.9 (18.13)
QTcB, Week 96, n=221	-0.6 (17.96)
QTcB, Week 144, n=131	0.5 (21.07)
QTcB, Week 172, n=16	1.8 (22.08)
QTcF, Week 24, n=301	-1.1 (14.61)
QTcF, Week 48, n=294	-1.3 (14.08)
QTcF, Week 72, n=269	-3.7 (15.68)
QTcF, Week 96, n=221	-0.8 (16.18)
QTcF, Week 144, n=131	-0.0 (17.88)
QTcF, Week 172, n=16	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.
Measure Participants	305
QTcB, <-60	0 0%
QTcB, >=-60 to <-30	1 0.3%
QTcB, >=-30 to < 0	70 20.6%
QTcB, >= 0 to < 30	196 57.8%
QTcB, >= 30 to < 60	35 10.3%
QTcB, >=60	3 0.9%
QTcF, <-60	0 0%
QTcF, >=-60 to <-30	1 0.3%
QTcF, >=-30 to < 0	77 22.7%
QTcF, >= 0 to < 30	199 58.7%
QTcF, >= 30 to < 60	28 8.3%
QTcF, >=60	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.
Measure Participants	339
SBP, Week 4, n=333	1.8 (11.26)
SBP, Week 8, n=334	0.6 (11.75)
SBP, Week 12, n=337	1.5 (12.48)
SBP, Week 16, n=334	2.0 (12.35)
SBP, Week 20, n=327	1.2 (13.69)
SBP, Week 24, n=333	1.8 (13.35)
SBP, Week 28, n=330	1.4 (13.56)
SBP, Week 32, n=324	1.0 (13.43)
SBP, Week 36, n=330	0.8 (13.00)
SBP, Week 40, n=327	1.6 (13.44)
SBP, Week 44, n=327	1.2 (12.75)
SBP, Week 48, n=329	1.8 (13.22)
SBP, Week 52, n=325	1.5 (13.31)
SBP, Week 56, n=324	2.0 (13.52)
SBP, Week 60, n=315	2.0 (13.17)
SBP, Week 64, n=307	2.5 (13.37)
SBP, Week 68, n=286	2.5 (13.46)
SBP, Week 72, n=281	2.3 (13.35)
SBP, Week 76, n=274	2.3 (12.31)
SBP, Week 80, n=265	3.5 (13.58)
SBP, Week 84, n=255	2.7 (14.01)
SBP, Week 88, n=245	1.5 (13.70)
SBP, Week 92, n=218	0.7 (13.24)
SBP, Week 96, n=208	1.2 (13.39)
SBP, Week 100, n=199	1.0 (12.43)
SBP, Week 104, n=197	2.4 (13.38)
SBP, Week 108, n=192	1.7 (12.76)
SBP, Week 112, n=182	1.8 (14.12)
SBP, Week 116, n=177	1.9 (14.66)
SBP, Week 120, n=167	1.9 (13.63)
SBP, Week 124, n=152	2.5 (14.88)
SBP, Week 128, n=151	2.6 (14.15)
SBP, Week 132, n=139	1.0 (14.37)
SBP, Week 136, n=112	2.3 (14.94)
SBP, Week 140, n=91	-0.9 (16.53)
SBP, Week 144, n=77	2.3 (14.13)
SBP, Week 148, n=62	0.6 (13.02)
SBP, Week 152, n=35	0.6 (11.33)
SBP, Week 156, n=32	1.5 (15.73)
SBP, Week 160, n=14	4.4 (9.48)
SBP, Week 164, n=8	7.0 (15.07)
SBP, Week 168, n=1	-4.0 (NA)
DBP, Week 4, n=333	0.1 (8.41)
DBP, Week 8, n=334	-0.8 (8.81)
DBP, Week 12, n=337	0.2 (9.25)
DBP, Week 16, n=334	0.5 (9.30)
DBP, Week 20, n=327	-0.7 (10.35)
DBP, Week 24, n=333	-0.2 (9.40)
DBP, Week 28, n=330	0.1 (8.88)
DBP, Week 32, n=324	-0.1 (10.44)
DBP, Week 36, n=330	-0.4 (10.12)
DBP, Week 40, n=327	-0.6 (9.24)
DBP, Week 44, n=327	0.1 (9.39)
DBP, Week 48, n=329	0.2 (9.71)
DBP, Week 52, n=325	-0.1 (9.83)
DBP, Week 56, n=324	0.7 (9.77)
DBP, Week 60, n=315	-0.5 (10.40)
DBP, Week 64, n=307	-0.4 (9.92)
DBP, Week 68, n=286	-0.1 (10.04)
DBP, Week 72, n=281	-0.3 (10.13)
DBP, Week 76, n=274	-0.2 (9.92)
DBP, Week 80, n=265	0.7 (9.83)
DBP, Week 84, n=255	-0.6 (10.05)
DBP, Week 88, n=245	-0.3 (9.22)
DBP, Week 92, n=218	-0.9 (9.10)
DBP, Week 96, n=208	-0.2 (9.17)
DBP, Week 100, n=199	-0.7 (10.04)
DBP, Week 104, n=197	0.1 (10.21)
DBP, Week 108, n=192	0.1 (9.89)
DBP, Week 112, n=182	0.0 (10.17)
DBP, Week 116, n=177	-0.1 (10.31)
DBP, Week 120, n=167	0.4 (9.74)
DBP, Week 124, n=152	-0.3 (11.11)
DBP, Week 128, n=151	0.6 (9.58)
DBP, Week 132, n=139	-0.5 (10.10)
DBP, Week 136, n=112	0.1 (9.89)
DBP, Week 140, n=91	-1.8 (9.68)
DBP, Week 144, n=77	-0.6 (10.92)
DBP, Week 148, n=62	-0.7 (11.03)
DBP, Week 152, n=35	-1.0 (8.97)
DBP, Week 156, n=32	-2.0 (10.42)
DBP, Week 160, n=14	2.9 (7.92)
DBP, Week 164, n=8	1.9 (8.06)
DBP, Week 168, n=1	5.0 (NA)

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.
Measure Participants	339
Pulse rate, Week 4, n=334	2.1 (9.98)
Pulse rate, Week 8, n=333	2.3 (10.65)
Pulse rate, Week 12, n=337	2.6 (11.05)
Pulse rate, Week 16, n=334	2.1 (11.03)
Pulse rate, Week 20, n=327	2.7 (11.10)
Pulse rate, Week 24, n=333	1.2 (11.22)
Pulse rate, Week 28, n=330	2.8 (10.43)
Pulse rate, Week 32, n=324	2.7 (11.44)
Pulse rate, Week 36, n=330	2.6 (11.02)
Pulse rate, Week 40, n=327	2.7 (11.09)
Pulse rate, Week 44, n=327	2.7 (12.05)
Pulse rate, Week 48, n=329	0.4 (10.63)
Pulse rate, Week 52, n=325	1.7 (10.48)
Pulse rate, Week 56, n=324	2.1 (11.36)
Pulse rate, Week 60, n=315	2.1 (10.97)
Pulse rate, Week 64, n=307	2.7 (10.96)
Pulse rate, Week 68, n=286	2.9 (11.32)
Pulse rate, Week 72, n=281	2.0 (11.15)
Pulse rate, Week 76, n=274	2.8 (11.15)
Pulse rate, Week 80, n=265	3.3 (11.45)
Pulse rate, Week 84, n=255	3.2 (12.21)
Pulse rate, Week 88, n=245	2.4 (11.98)
Pulse rate, Week 92, n=218	2.4 (12.42)
Pulse rate, Week 96, n=208	0.0 (11.16)
Pulse rate, Week 100, n=199	1.8 (12.30)
Pulse rate, Week 104, n=197	2.3 (12.29)
Pulse rate, Week 108, n=192	2.2 (11.34)
Pulse rate, Week 112, n=182	2.3 (12.35)
Pulse rate, Week 116, n=177	2.0 (12.06)
Pulse rate, Week 120, n=167	1.2 (12.19)
Pulse rate, Week 124, n=152	2.3 (12.56)
Pulse rate, Week 128, n=151	1.5 (11.69)
Pulse rate, Week 132, n=139	2.2 (12.46)
Pulse rate, Week 136, n=112	2.0 (11.68)
Pulse rate, Week 140, n=92	0.7 (11.45)
Pulse rate, Week 144, n=77	-1.5 (11.92)
Pulse rate, Week 148, n=62	-0.5 (11.68)
Pulse rate, Week 152, n=35	-0.6 (13.80)
Pulse rate, Week 156, n=32	-0.4 (12.94)
Pulse rate, Week 160, n=14	1.5 (13.24)
Pulse rate, Week 164, n=8	1.4 (21.23)
Pulse rate, Week 168, n=1	36.0 (NA)

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.
Measure Participants	339
Highest value post-Baseline, ADA, positive, n=335	6 1.8%
Highest value post-Baseline, ADA, Negative, n=335	329 97.1%
Highest value post-Baseline, NAb, positive, n=6	0 0%
Highest value post-Baseline, NAb, Negative, n=6	6 1.8%

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.
Measure Participants	339
Glucose, To low, n=336	1 0.3%
Glucose, To Normal or No Change, n=336	334 98.5%
Glucose, To high, n=336	1 0.3%
ALT, To low, n=337	0 0%
ALT, To Normal or No Change, n=337	337 99.4%
ALT, To high, n=337	0 0%
Calcium, To low, n=336	0 0%
Calcium, To Normal or No Change, n=336	336 99.1%
Calcium, To high, n=336	0 0%
Phosphate, To low, n=336	0 0%
Phosphate, To Normal or No Change, n=336	336 99.1%
Phosphate, To high, n=336	0 0%
Potassium, To low, n=336	0 0%
Potassium, To Normal or No Change, n=336	336 99.1%
Potassium, To high, n=336	0 0%
Sodium, To low, n=336	1 0.3%
Sodium, To Normal or No Change, n=336	335 98.8%
Sodium, To high, n=336	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.
Measure Participants	336
Hematocrit, To low	1 0.3%
Hematocrit, To Normal or No Change	335 98.8%
Hematocrit, To high	0 0%
Hemoglobin, To low	1 0.3%
Hemoglobin, To Normal or No Change	335 98.8%
Hemoglobin, To high	0 0%
Leukocytes, To low	1 0.3%
Leukocytes, To Normal or No Change	335 98.8%
Leukocytes, To high	0 0%
Platelets, To low	1 0.3%
Platelets, To Normal or No Change	335 98.8%
Platelets, To high	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 (%)	# Events
Total	2/339 (0.6%)
Serious Adverse Events
	Mepolizumab 100 mg SC
	Affected / at Risk (%)	# Events
Total	84/339 (24.8%)
Cardiac disorders
Acute myocardial infarction	1/339 (0.3%)	1
Aortic valve stenosis	1/339 (0.3%)	1
Arrhythmia	1/339 (0.3%)	1
Atrioventricular block complete	1/339 (0.3%)	1
Coronary artery disease	1/339 (0.3%)	1
Myocardial infarction	1/339 (0.3%)	1
Congenital, familial and genetic disorders
Congenital anomaly	1/339 (0.3%)	1
Eye disorders
Glaucoma	1/339 (0.3%)	1
Gastrointestinal disorders
Gastrooesophageal reflux disease	2/339 (0.6%)	2
Abdominal adhesions	1/339 (0.3%)	1
Dental cyst	1/339 (0.3%)	1
Diarrhoea	1/339 (0.3%)	1
Inguinal hernia	1/339 (0.3%)	1
Large intestine perforation	1/339 (0.3%)	1
Pancreatitis acute	1/339 (0.3%)	1
General disorders
Cyst	1/339 (0.3%)	1
Immune system disorders
Anaphylactic reaction	1/339 (0.3%)	1
Anaphylactic shock	1/339 (0.3%)	1
Food allergy	1/339 (0.3%)	1
Infections and infestations
Pneumonia	6/339 (1.8%)	7
Lower respiratory tract infection	3/339 (0.9%)	3
Respiratory tract infection	3/339 (0.9%)	5
Diverticulitis	2/339 (0.6%)	2
Influenza	2/339 (0.6%)	2
Bronchitis	1/339 (0.3%)	1
Enteritis infectious	1/339 (0.3%)	1
Gastroenteritis	1/339 (0.3%)	1
Gastroenteritis viral	1/339 (0.3%)	1
Osteomyelitis	1/339 (0.3%)	1
Pneumonia haemophilus	1/339 (0.3%)	1
Pneumonia pneumococcal	1/339 (0.3%)	1
Pneumonia staphylococcal	1/339 (0.3%)	1
Pyelonephritis acute	1/339 (0.3%)	1
Sepsis	1/339 (0.3%)	1
Sinusitis	1/339 (0.3%)	1
Staphylococcal sepsis	1/339 (0.3%)	1
Urinary tract infection	1/339 (0.3%)	1
Injury, poisoning and procedural complications
Foot fracture	3/339 (0.9%)	3
Fracture	2/339 (0.6%)	2
Joint injury	1/339 (0.3%)	1
Ligament rupture	1/339 (0.3%)	1
Lumbar vertebral fracture	1/339 (0.3%)	1
Rib fracture	1/339 (0.3%)	1
Spinal fracture	1/339 (0.3%)	1
Tendon injury	1/339 (0.3%)	1
Tendon rupture	1/339 (0.3%)	1
Wrist fracture	1/339 (0.3%)	1
Investigations
Alanine aminotransferase increased	1/339 (0.3%)	1
Liver function test increased	1/339 (0.3%)	1
Metabolism and nutrition disorders
Hyponatraemia	2/339 (0.6%)	2
Hypokalaemia	1/339 (0.3%)	2
Musculoskeletal and connective tissue disorders
Osteonecrosis	2/339 (0.6%)	3
Arthritis	1/339 (0.3%)	1
Back pain	1/339 (0.3%)	2
Intervertebral disc protrusion	1/339 (0.3%)	1
Musculoskeletal chest pain	1/339 (0.3%)	1
Osteoarthritis	1/339 (0.3%)	1
Pain in extremity	1/339 (0.3%)	1
Polyarthritis	1/339 (0.3%)	1
Rotator cuff syndrome	1/339 (0.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma of colon	1/339 (0.3%)	1
Colon neoplasm	1/339 (0.3%)	1
Invasive lobular breast carcinoma	1/339 (0.3%)	1
Prostate cancer	1/339 (0.3%)	1
Superficial spreading melanoma stage unspecified	1/339 (0.3%)	1
Nervous system disorders
Dizziness	1/339 (0.3%)	1
Hemiparesis	1/339 (0.3%)	1
IIIrd nerve paralysis	1/339 (0.3%)	1
Psychiatric disorders
Anxiety disorder	1/339 (0.3%)	1
Renal and urinary disorders
Nephrolithiasis	1/339 (0.3%)	1
Urinary incontinence	1/339 (0.3%)	1
Reproductive system and breast disorders
Endometrial hyperplasia	1/339 (0.3%)	1
Respiratory, thoracic and mediastinal disorders
Asthma	34/339 (10%)	51
Nasal polyps	4/339 (1.2%)	4
Dyspnoea	1/339 (0.3%)	1
Haemoptysis	1/339 (0.3%)	1
Pleural effusion	1/339 (0.3%)	1
Pneumothorax	1/339 (0.3%)	1
Status asthmaticus	1/339 (0.3%)	1
Skin and subcutaneous tissue disorders
Neurodermatitis	1/339 (0.3%)	1
Vascular disorders
Hypertension	1/339 (0.3%)	1
Other (Not Including Serious) Adverse Events
	Mepolizumab 100 mg SC
	Affected / at Risk (%)	# Events
Total	288/339 (85%)
Gastrointestinal disorders
Diarrhoea	16/339 (4.7%)	17
Nausea	15/339 (4.4%)	16
Vomiting	14/339 (4.1%)	32
Gastrooesophageal reflux disease	11/339 (3.2%)	13
General disorders
Fatigue	16/339 (4.7%)	23
Influenza like illness	15/339 (4.4%)	17
Injection site reaction	15/339 (4.4%)	48
Infections and infestations
Nasopharyngitis	143/339 (42.2%)	270
Bronchitis	64/339 (18.9%)	106
Upper respiratory tract infection	64/339 (18.9%)	110
Sinusitis	62/339 (18.3%)	115
Influenza	42/339 (12.4%)	52
Respiratory tract infection	20/339 (5.9%)	23
Gastroenteritis	19/339 (5.6%)	20
Lower respiratory tract infection	18/339 (5.3%)	28
Rhinitis	18/339 (5.3%)	31
Urinary tract infection	17/339 (5%)	19
Pharyngitis	15/339 (4.4%)	22
Ear infection	12/339 (3.5%)	15
Viral upper respiratory tract infection	12/339 (3.5%)	14
Pneumonia	11/339 (3.2%)	11
Musculoskeletal and connective tissue disorders
Back pain	41/339 (12.1%)	51
Arthralgia	32/339 (9.4%)	48
Pain in extremity	15/339 (4.4%)	16
Musculoskeletal pain	14/339 (4.1%)	16
Myalgia	11/339 (3.2%)	11
Nervous system disorders
Headache	57/339 (16.8%)	160
Dizziness	15/339 (4.4%)	19
Psychiatric disorders
Insomnia	17/339 (5%)	18
Respiratory, thoracic and mediastinal disorders
Asthma	52/339 (15.3%)	78
Oropharyngeal pain	25/339 (7.4%)	31
Cough	22/339 (6.5%)	27
Dyspnoea	13/339 (3.8%)	14
Skin and subcutaneous tissue disorders
Eczema	14/339 (4.1%)	17
Rash	14/339 (4.1%)	18
Pruritus	13/339 (3.8%)	17
Vascular disorders
Hypertension	14/339 (4.1%)	15

Limitations/Caveats

[Not Specified]

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Certain Agreements

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

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