MEA112997 Open-label Long Term Extension Safety Study of Mepolizumab in Asthmatic Subjects

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01691859
• Collaborator: (none)
• Enrollment: 347
• Locations: 67
• Arm: 1
• Actual Duration (Months): 56
• Patients Per Site: 5.2
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This is a multi-centre, open-label long term safety study of 100 milligrams (mg) mepolizumab administered subcutaneously (SC) in addition to standard of care in subjects who participated in the MEA112997 study. At each clinic visit, adverse events will be assessed and exacerbations will also be reviewed.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 347 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: MEA115666: A Multi-centre, Open-label, Long Term Safety Study of Mepolizumab in Asthmatic Subjects Who Participated in the MEA112997 Trial
• Actual Study Start Date: Sep 28, 2012
• Actual Primary Completion Date: May 31, 2017
• Actual Study Completion Date: May 31, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mepolizumab Subjects will receive 100 mg of mepolizumab (in 1ml polypropylene syringe) injected subcutaneously (SC) approximately every 4 weeks.	Drug: Mepolizumab; 100 mg of mepolizumab will be injected subcutaneously (SC) once every 4 weeks

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Experienced On-treatment Adverse Events (AE) and On-treatment Serious Adverse Events (SAE) [Baseline (Week 0) to Week 240]

   AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with use of a medicinal product (MP), whether or not considered related to MP. AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with use of MP. 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. As Treated (AT) Population consisted of participants who received at least one dose of open label mepolizumab. 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 of mepolizumab + 28 days.

Secondary Outcome Measures

1. Number of Participants Who Experienced On-treatment Systemic (i.e., Allergic/Immunoglobulin E [IgE]-Mediated and Non-allergic) and On-treatment Local Site Reactions [Baseline (Week 0) to Week 240]

   Systemic and local site reactions following mepolizumab dosing as identified by the investigator and the number of participants who experienced systemic and/or local site reactions are presented. 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 of mepolizumab + 28 days.

2. Mean Change From Baseline in QT Interval Corrected by Bazett's Method (QTc[B]) [Baseline (Week 0) to Week 240]

   Twelve-lead ECGs were performed at Screening and every 24 weeks during the treatment period. ECG measurements were made after the participant had rested in the supine position for 5 minutes. Collection shortly after a meal or during sleep was avoided as QT prolongation can occur at these times. Baseline was the last available ECG prior to mepolizumab dosing. Change from Baseline was post-Baseline values minus Baseline values. Only those participants available at the specified time points were analyzed represented by n=X in the category titles.

3. Mean Change From Baseline in QT Interval Corrected by Fridericia's Method (QTc[F]) [Baseline (Week 0) to Week 240]

   Twelve-lead ECGs were performed at Screening and every 24 weeks during the treatment period. ECG measurements were made after the participant had rested in the supine position for 5 minutes. Collection shortly after a meal or during sleep was avoided as QT prolongation can occur at these times. Baseline was the last available ECG prior to mepolizumab dosing. Change from Baseline was post-Baseline values minus Baseline values. Only those participants available at the specified time points were analyzed represented by n=X in the category titles.

4. Number of Participants With a Maximum Change From Baseline for QTc(F) and QTc(B) [Baseline (Week 0) to Week 240]

   Twelve-lead ECGs were performed at Screening and every 24 weeks during the treatment period. ECG measurements were made after the participant had rested in the supine position for 5 minutes. Collection shortly after a meal or during sleep was avoided as QT prolongation can occur at these times. Baseline was the last available ECG prior to mepolizumab dosing. Change from Baseline was post-Baseline values minus Baseline values. Number of participants with a maximum change from Baseline for QTc(F) and QTc(B) at any time post Baseline are presented. Only those participants who provided ECG data at baseline and post-baseline were analyzed.

5. Number of Participants With Clinical Chemistry Data of Potential Clinical Concern [Baseline (Week 0) to Week 240]

   Clinical chemistry analytes with laboratory ranges defining values of potential clinical concern included sodium, potassium, calcium, phosphate, serum glucose and alanine aminotransferase. Number of participants with clinical chemistry abnormalities of potential clinical concern anytime post baseline are presented. Only those participants who provided lab data post-baseline were analyzed represented by n=X in the category titles.

6. Number of Participants With Hematology Data of Potential Clinical Concern [Baseline (Week 0) to Week 240]

   Hematology parameters with laboratory ranges defining values of potential clinical concern included hemoglobin, hematocrit, platelet count, white blood cell count. Number of participants with clinical hematology abnormalities of potential clinical concern anytime post baseline are presented, which only included participants with low hemoglobin values. Only those participants who provided lab data post-baseline were analyzed.

7. Mean Change From Baseline in Vital Signs-Sitting Diastolic Blood Pressure and Sitting Systolic Blood Pressure [Baseline (Week 0) to Week 240]

   Vital signs included sitting pulse rate and sitting blood pressure (diastolic and systolic). Measurements were done pre injection with the participant sitting, having rested in this position for at least 5 minutes before each reading. Baseline was Week 0. Change from Baseline was post-Baseline values minus Baseline values. Only those participants available at the specified time points were analyzed represented by n=X in the category titles.

8. Mean Change From Baseline in Vital Signs-Sitting Pulse Rate [Baseline (Week 0) to Week 240]

   Vital signs included sitting pulse rate and blood pressure (diastolic and systolic). Measurements were done pre injection with the participant sitting, having rested in this position for at least 5 minutes before each reading. Baseline was Week 0. Change from Baseline was post-Baseline values minus Baseline values. Only those participants available at the specified time points were analyzed represented by n=X in the category titles.

9. Annualized Rate of On-treatment Exacerbations [Baseline (Week 0) to Week 240]

   Exacerbations were defined as worsening of asthma which required use of systemic corticosteroids and/or hospitalization and/or Emergency Department visits. Data is presented as mean which is exacerbation rate/year. Exacerbation data are performed using a negative binomial model with covariates of region, annualized rate of exacerbations in the interval between MEA112997 and MEA115666 (as an ordinal variable) and baseline % predicted FEV1, and with logarithm of time on treatment as an offset variable.

10. Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score [Baseline (Week 0) to Week 240]

    The ACQ-5 is a five-item questionnaire, which was developed as a measure of participant' asthma control that was completed by the participant. The five questions enquire about the frequency and/or severity of symptoms (nocturnal awakening on waking in the morning, activity limitation, and shortness of breath, wheeze). The ACQ consists of 5 questions that are scored on a 7 point scale from 0 (totally controlled) to 6 (severely uncontrolled). The ACQ score was derived as mean of five questions: ACQ score = Question 1 (Q1)+Q2+Q3+Q4+Q5 divided by 5 where Q1, Q2,... Q5 are the scores of Q1, Q2, ..., Q5, respectively. The total score ranged from zero (no impairment/limitation) which indicated best condition to six (total impairment/ limitation) which indicated worst asthma. Baseline was Week 0. Change from Baseline was post-Baseline values minus Baseline values. Only those participants available at the specified time points were analyzed represented by n=X in the category titles.

11. Mean Change From Baseline in Clinic Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) [Baseline (Week 0) to Week 240]

    FEV1 is forced expiratory volume in the first second. The volume of air that can be forced out in one second after taking a deep breath, an important measure of pulmonary function. Forced expiratory volume (FEV) measures how much air a person can exhale during a forced breath. FEV1 was measured by clinic spirometry. Baseline was Week 0. Change from Baseline was post-Baseline values minus Baseline values. Only those participants available at the specified time points were analyzed represented by n=X in the category titles.

12. Number of Participants With Positive Anti-mepolizumab Binding Antibodies (ADA) and Neutralizing Antibodies (NAb) [Baseline (Week 0) to Week 240]

    Immunogenicity testing included two types of assays: a binding antibody assay (anti-drug antibody; ADA) and a neutralizing antibody (NAb) assay for participants who were tested positive in the ADA assay. Blood samples were collected for the determination of anti-mepolizumab antibodies, just prior to administration of mepolizumab. Samples that test positive for anti-mepolizumab antibodies were further tested for the presence of neutralizing antibody. Number of participants with positive highest value post-Baseline have been presented. Only those participants available at the specified time points were analyzed represented by n=X in the category titles.

13. Number of Participants Who Withdrew Due to Lack of Efficacy [Baseline (Week 0) to Week 240]

    Lack of efficacy referred to failure of expected pharmacological action of Mepolizumab. Number of participants who withdrew due to lack of efficacy are presented.

14. Number of Participants Requiring Hospitalizations Due to Adverse Events Including Asthma Exacerbations [Baseline (Week 0) to Week 240]

    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. 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 open-label mepolizumab date and before/on last dose of mepolizumab + 28 days.

15. Number of Participants Who Withdrew Due to AE [Baseline (Week 0) to Week 240]

    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. 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. 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 who withdrew due to AE are presented.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Informed Consent.

• MEA112997 Study Participation: Received at least 2 doses of double-blind investigational product during the MEA112997 trial.

• MEA112997 Treatment Assignment: If the subject received mepolizumab, they must have had a positive risk: benefit ratio.

• Currently being treated with a controller medication and the subject has been on a controller medication for the past 12 weeks.

• Male or Eligible Female Subjects. To be eligible for entry into the study, females of childbearing potential must commit to consistent and correct use of an acceptable method of birth control for the duration of the trial and for 4 months after the last study drug administration.

Exclusion Criteria:

• Hypersensitivity related to mepolizumab.

• Clinically significant change in health status since completing participation in the MEA112997 trial.

• A current malignancy or previous history of cancer in remission for less than 12 months prior to screening.

• For those subjects who had a SAE in MEA112997 that was assessed as possibly related to mepolizumab by the investigator.

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

• Screening ECG which has a clinically significant abnormality.

• Received Xolair (omalizumab) within the past 130 days.

• Participated in a clinical trial within the past 30 days or have received investigational medication within five terminal half-lives of Screen Visit, whichever is longer.

• Current smokers.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Long Beach	California	United States	90808
2	GSK Investigational Site	Riverside	California	United States	92506
3	GSK Investigational Site	Denver	Colorado	United States	80206
4	GSK Investigational Site	New Haven	Connecticut	United States	06520
5	GSK Investigational Site	Albany	Georgia	United States	31707
6	GSK Investigational Site	Lexington	Kentucky	United States	40508
7	GSK Investigational Site	Winston-Salem	North Carolina	United States	27103
8	GSK Investigational Site	Cleveland	Ohio	United States	44195
9	GSK Investigational Site	Hershey	Pennsylvania	United States	17033
10	GSK Investigational Site	Pittsburgh	Pennsylvania	United States	15213
11	GSK Investigational Site	Charleston	South Carolina	United States	29407
12	GSK Investigational Site	Nashville	Tennessee	United States	37212
13	GSK Investigational Site	Mar del Plata	Buenos Aires	Argentina	B7600FZN
14	GSK Investigational Site	Ciudad Autónoma de Buenos Aires		Argentina	C1121ABE
15	GSK Investigational Site	Ciudad Autónoma de Buenos Aires		Argentina	C1426ABP
16	GSK Investigational Site	Mendoza		Argentina	M5500CCG
17	GSK Investigational Site	New Lambton	New South Wales	Australia	2305
18	GSK Investigational Site	Adelaide	South Australia	Australia	5000
19	GSK Investigational Site	Clayton	Victoria	Australia	3168
20	GSK Investigational Site	Melbourne	Victoria	Australia	3004
21	GSK Investigational Site	Nedlands	Western Australia	Australia	6009
22	GSK Investigational Site	Calgary	Alberta	Canada	T2N 4Z6
23	GSK Investigational Site	Vancouver	British Columbia	Canada	V5Z 1M9
24	GSK Investigational Site	Mississauga	Ontario	Canada	L5A 3V4
25	GSK Investigational Site	Quebec City	Quebec	Canada	G1V 4G5
26	GSK Investigational Site	Puente Alto - Santiago	Región Metro De Santiago	Chile	8207257
27	GSK Investigational Site	Valparaiso	Valparaíso	Chile	2341131
28	GSK Investigational Site	Santiago		Chile	8380453
29	GSK Investigational Site	Talcahuano		Chile	4270918
30	GSK Investigational Site	Le Kremlin-Bicêtre Cedex		France	94275
31	GSK Investigational Site	Marseille cedex 20		France	13915
32	GSK Investigational Site	Montpellier cedex 5		France	34295
33	GSK Investigational Site	Saint Pierre cedex		France	97448
34	GSK Investigational Site	Ruedersdorf	Brandenburg	Germany	15562
35	GSK Investigational Site	Frankfurt am Main	Hessen	Germany	60596
36	GSK Investigational Site	Frankfurt	Hessen	Germany	60596
37	GSK Investigational Site	Mainz	Rheinland-Pfalz	Germany	55131
38	GSK Investigational Site	Luebeck	Schleswig-Holstein	Germany	23552
39	GSK Investigational Site	Berlin		Germany	10367
40	GSK Investigational Site	Berlin		Germany	10717
41	GSK Investigational Site	Magdeburg		Germany	39120
42	GSK Investigational Site	Cheongju, Chungcheongbuk-do		Korea, Republic of	361-711
43	GSK Investigational Site	Suwon, Kyonggi-do		Korea, Republic of	443-721
44	GSK Investigational Site	Lodz		Poland	90-153
45	GSK Investigational Site	Wroclaw		Poland	54-239
46	GSK Investigational Site	Bucharest		Romania	011461
47	GSK Investigational Site	Bucharest		Romania	050159
48	GSK Investigational Site	Bucuresti		Romania	010457
49	GSK Investigational Site	Iasi		Romania	700115
50	GSK Investigational Site	Targu Mures		Romania	540143
51	GSK Investigational Site	Barnaul		Russian Federation	656 045
52	GSK Investigational Site	Chelyabinsk		Russian Federation	454106
53	GSK Investigational Site	Kazan		Russian Federation	420008
54	GSK Investigational Site	Moscow		Russian Federation	105 077
55	GSK Investigational Site	Moscow		Russian Federation	123182
56	GSK Investigational Site	Saint-Petersburg		Russian Federation	194354
57	GSK Investigational Site	St'Petersburg		Russian Federation	191015
58	GSK Investigational Site	Dnipropetrovsk		Ukraine	49051
59	GSK Investigational Site	Donetsk		Ukraine	83099
60	GSK Investigational Site	Kharkiv		Ukraine	61035
61	GSK Investigational Site	Kiev		Ukraine	03680
62	GSK Investigational Site	Kyiv		Ukraine	03038
63	GSK Investigational Site	Leicester	Leicestershire	United Kingdom	LE3 9QP
64	GSK Investigational Site	London		United Kingdom	EC1M 6BQ
65	GSK Investigational Site	London		United Kingdom	SW3 6HP
66	GSK Investigational Site	Manchester		United Kingdom	M23 9LT
67	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 - Jun 19, 2015
• Statistical Analysis Plan - Apr 6, 2017

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT01691859
• Other Study ID Numbers: 115666
• First Posted: Sep 25, 2012
• Last Update Posted: May 22, 2018
• Last Verified: Jan 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by GlaxoSmithKline: extension study; Severe refractory asthma; safety; SB-240563; mepolizumab; eosinophils
• Additional relevant MeSH terms: Asthma

Study Results

Participant Flow

Recruitment Details	This was a multi-center, open-label, long term safety study of mepolizumab in 347 asthmatic participants who participated in the MEA112997 trial and were found eligible for this study after screening and run in phase. The study was conducted at 65 centers in 13 countries from 28 Sep 2012 to 31 May 2017.
Pre-assignment Detail	A total of 362 participants were screened; 4 participants were screen failures (did not meet the inclusion/exclusion criteria); 11 participants were withdrawn during the run-in period (4 did not meet the continuation criteria, 4 withdrawal by participant and 3 following physician decision).

Arm/Group Title	Mepolizumab 100 mg
Arm/Group Description	Participants received 100 milligram (mg) of mepolizumab injected subcutaneously (SC) once every 4 weeks until participant withdrawal or mepolizumab becomes commercially available in the relevant participating country. Participants remained on standard of care asthma therapy, which was adjusted during the study, at the discretion of their physician.
Period Title: Overall Study
STARTED	347
COMPLETED	0
NOT COMPLETED	347

Baseline Characteristics

Arm/Group Title	Mepolizumab 100 mg
Arm/Group Description	Participants received 100 mg of mepolizumab injected SC once every 4 weeks until participant withdrawal or mepolizumab becomes commercially available in the relevant participating country. Participants remained on standard of care asthma therapy, which was adjusted during the study, at the discretion of their physician.
Overall Participants	347
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	52.2 (10.73)
Sex: Female, Male (Count of Participants)
Female	224 64.6%
Male	123 35.4%
Race/Ethnicity, Customized (Count of Participants)
African American/African Heritage	8 2.3%
American Indian or Alaskan Native	2 0.6%
Asian - Central/South Asian Heritage	4 1.2%
Asian - East Asian Heritage	14 4%
White - Arabic/North African Heritage	7 2%
White - White/Caucasian/European Heritage	311 89.6%
Asian & Native Hawaiian or Other Pacific Islander	1 0.3%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Experienced On-treatment Adverse Events (AE) and On-treatment Serious Adverse Events (SAE)
Description	AE is any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with use of a medicinal product (MP), whether or not considered related to MP. AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with use of MP. 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. As Treated (AT) Population consisted of participants who received at least one dose of open label mepolizumab. 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 of mepolizumab + 28 days.
Time Frame	Baseline (Week 0) to Week 240

Outcome Measure Data

Analysis Population Description

AT Population.

Arm/Group Title	Mepolizumab 100 mg
Arm/Group Description	Participants received 100 mg of mepolizumab injected SC once every 4 weeks until participant withdrawal or mepolizumab becomes commercially available in the relevant participating country. Participants remained on standard of care asthma therapy, which was adjusted during the study, at the discretion of their physician.
Measure Participants	347
AE	326 93.9%
SAE	79 22.8%

2. Secondary Outcome

Title	Number of Participants Who Experienced On-treatment Systemic (i.e., Allergic/Immunoglobulin E [IgE]-Mediated and Non-allergic) and On-treatment Local Site Reactions
Description	Systemic and local site reactions following mepolizumab dosing as identified by the investigator and the number of participants who experienced systemic and/or local site reactions are presented. 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 of mepolizumab + 28 days.
Time Frame	Baseline (Week 0) to Week 240

Outcome Measure Data

Analysis Population Description

AT Population.

Arm/Group Title	Mepolizumab 100 mg
Arm/Group Description	Participants received 100 mg of mepolizumab injected SC once every 4 weeks until participant withdrawal or mepolizumab becomes commercially available in the relevant participating country. Participants remained on standard of care asthma therapy, which was adjusted during the study, at the discretion of their physician.
Measure Participants	347
Systemic reactions	9 2.6%
Local site reactions	42 12.1%

3. Secondary Outcome

Title	Mean Change From Baseline in QT Interval Corrected by Bazett's Method (QTc[B])
Description	Twelve-lead ECGs were performed at Screening and every 24 weeks during the treatment period. ECG measurements were made after the participant had rested in the supine position for 5 minutes. Collection shortly after a meal or during sleep was avoided as QT prolongation can occur at these times. Baseline was the last available ECG prior to mepolizumab dosing. Change from Baseline was post-Baseline values minus Baseline values. Only those participants available at the specified time points were analyzed represented by n=X in the category titles.
Time Frame	Baseline (Week 0) to Week 240

Outcome Measure Data

Analysis Population Description

AT Population.

Arm/Group Title	Mepolizumab 100 mg
Arm/Group Description	Participants received 100 mg of mepolizumab injected SC once every 4 weeks until participant withdrawal or mepolizumab becomes commercially available in the relevant participating country. Participants remained on standard of care asthma therapy, which was adjusted during the study, at the discretion of their physician.
Measure Participants	347
Week 24, n=330	4.2 (18.57)
Week 48, n=319	3.2 (17.19)
Week 72, n=307	-0.5 (16.76)
Week 96, n=293	1.3 (17.92)
Week 124, n=292	1.5 (19.69)
Week 148, n=275	1.6 (17.84)
Week 176, n=201	0.6 (18.02)
Week 200, n=149	3.3 (17.02)
Week 228, n=32	1.5 (20.95)
Follow up, n=270	2.5 (18.71)

4. Secondary Outcome

Title	Mean Change From Baseline in QT Interval Corrected by Fridericia's Method (QTc[F])
Description	Twelve-lead ECGs were performed at Screening and every 24 weeks during the treatment period. ECG measurements were made after the participant had rested in the supine position for 5 minutes. Collection shortly after a meal or during sleep was avoided as QT prolongation can occur at these times. Baseline was the last available ECG prior to mepolizumab dosing. Change from Baseline was post-Baseline values minus Baseline values. Only those participants available at the specified time points were analyzed represented by n=X in the category titles.
Time Frame	Baseline (Week 0) to Week 240

Outcome Measure Data

Analysis Population Description

AT Population.

Arm/Group Title	Mepolizumab 100 mg
Arm/Group Description	Participants received 100 mg of mepolizumab injected SC once every 4 weeks until participant withdrawal or mepolizumab becomes commercially available in the relevant participating country. Participants remained on standard of care asthma therapy, which was adjusted during the study, at the discretion of their physician.
Measure Participants	347
Week 24, n=330	5.1 (17.00)
Week 48, n=319	4.1 (15.72)
Week 72, n=307	0.2 (15.11)
Week 96, n=293	2.2 (15.37)
Week 124, n=292	3.2 (16.77)
Week 148, n=275	2.9 (15.49)
Week 176, n=201	2.0 (15.97)
Week 200, n=149	4.3 (14.52)
Week 228, n=32	0.4 (15.81)
Follow up, n=270	3.9 (16.39)

5. Secondary Outcome

Title	Number of Participants With a Maximum Change From Baseline for QTc(F) and QTc(B)
Description	Twelve-lead ECGs were performed at Screening and every 24 weeks during the treatment period. ECG measurements were made after the participant had rested in the supine position for 5 minutes. Collection shortly after a meal or during sleep was avoided as QT prolongation can occur at these times. Baseline was the last available ECG prior to mepolizumab dosing. Change from Baseline was post-Baseline values minus Baseline values. Number of participants with a maximum change from Baseline for QTc(F) and QTc(B) at any time post Baseline are presented. Only those participants who provided ECG data at baseline and post-baseline were analyzed.
Time Frame	Baseline (Week 0) to Week 240

Outcome Measure Data

Analysis Population Description

AT Population.

Arm/Group Title	Mepolizumab 100 mg
Arm/Group Description	Participants received 100 mg of mepolizumab injected SC once every 4 weeks until participant withdrawal or mepolizumab becomes commercially available in the relevant participating country. Participants remained on standard of care asthma therapy, which was adjusted during the study, at the discretion of their physician.
Measure Participants	342
QTc(F): < -60	0 0%
QTc(F): >= -60 - < -30	1 0.3%
QTc(F): >= -30 - < 0	31 8.9%
QTc(F): >= 0 - < 30	252 72.6%
QTc(F): >= 30 - < 60	55 15.9%
QTc(F): >= 60	3 0.9%
QTc(B): < -60	0 0%
QTc(B): >= -60 - < -30	1 0.3%
QTc(B): >= -30 - < 0	36 10.4%
QTc(B): >= 0 - < 30	228 65.7%
QTc(B): >= 30 - < 60	69 19.9%
QTc(B): >= 60	8 2.3%

6. Secondary Outcome

Title	Number of Participants With Clinical Chemistry Data of Potential Clinical Concern
Description	Clinical chemistry analytes with laboratory ranges defining values of potential clinical concern included sodium, potassium, calcium, phosphate, serum glucose and alanine aminotransferase. Number of participants with clinical chemistry abnormalities of potential clinical concern anytime post baseline are presented. Only those participants who provided lab data post-baseline were analyzed represented by n=X in the category titles.
Time Frame	Baseline (Week 0) to Week 240

Outcome Measure Data

Analysis Population Description

AT Population.

Arm/Group Title	Mepolizumab 100 mg
Arm/Group Description	Participants received 100 mg of mepolizumab injected SC once every 4 weeks until participant withdrawal or mepolizumab becomes commercially available in the relevant participating country. Participants remained on standard of care asthma therapy, which was adjusted during the study, at the discretion of their physician.
Measure Participants	346
Potassium high, n=346	1 0.3%
Serum glucose high, n=346	1 0.3%
Serum glucose low, n=346	7 2%

7. Secondary Outcome

Title	Number of Participants With Hematology Data of Potential Clinical Concern
Description	Hematology parameters with laboratory ranges defining values of potential clinical concern included hemoglobin, hematocrit, platelet count, white blood cell count. Number of participants with clinical hematology abnormalities of potential clinical concern anytime post baseline are presented, which only included participants with low hemoglobin values. Only those participants who provided lab data post-baseline were analyzed.
Time Frame	Baseline (Week 0) to Week 240

Outcome Measure Data

Analysis Population Description

AT Population.

Arm/Group Title	Mepolizumab 100 mg
Arm/Group Description	Participants received 100 mg of mepolizumab injected SC once every 4 weeks until participant withdrawal or mepolizumab becomes commercially available in the relevant participating country. Participants remained on standard of care asthma therapy, which was adjusted during the study, at the discretion of their physician.
Measure Participants	346
Number [Participants]	1 0.3%

8. Secondary Outcome

Title	Mean Change From Baseline in Vital Signs-Sitting Diastolic Blood Pressure and Sitting Systolic Blood Pressure
Description	Vital signs included sitting pulse rate and sitting blood pressure (diastolic and systolic). Measurements were done pre injection with the participant sitting, having rested in this position for at least 5 minutes before each reading. Baseline was Week 0. Change from Baseline was post-Baseline values minus Baseline values. Only those participants available at the specified time points were analyzed represented by n=X in the category titles.
Time Frame	Baseline (Week 0) to Week 240

Outcome Measure Data

Analysis Population Description

AT Population.

Arm/Group Title	Mepolizumab 100 mg
Arm/Group Description	Participants received 100 mg of mepolizumab injected SC once every 4 weeks until participant withdrawal or mepolizumab becomes commercially available in the relevant participating country. Participants remained on standard of care asthma therapy, which was adjusted during the study, at the discretion of their physician.
Measure Participants	347
Sitting Diastolic Blood Pressure: Week 4, n=346	-1.0 (8.71)
Sitting Diastolic Blood Pressure: Week 8, n=345	-1.5 (8.85)
Sitting Diastolic Blood Pressure: Week 12, n=342	-0.7 (9.67)
Sitting Diastolic Blood Pressure: Week 16, n=341	-1.6 (9.27)
Sitting Diastolic Blood Pressure: Week 20, n=338	-1.6 (9.17)
Sitting Diastolic Blood Pressure: Week 24, n=336	-0.7 (9.27)
Sitting Diastolic Blood Pressure: Week 28, n=332	-1.3 (8.90)
Sitting Diastolic Blood Pressure: Week 32, n=333	-1.0 (9.62)
Sitting Diastolic Blood Pressure: Week 36, n=329	-1.8 (8.95)
Sitting Diastolic Blood Pressure: Week 40, n=329	-1.2 (9.33)
Sitting Diastolic Blood Pressure: Week 44, n=326	-1.1 (10.00)
Sitting Diastolic Blood Pressure: Week 48, n=325	-0.7 (9.67)
Sitting Diastolic Blood Pressure: Week 52, n=322	-1.1 (9.85)
Sitting Diastolic Blood Pressure: Week 56, n=320	-1.3 (9.67)
Sitting Diastolic Blood Pressure: Week 60, n=318	-0.9 (9.56)
Sitting Diastolic Blood Pressure: Week 64, n=318	-1.0 (9.29)
Sitting Diastolic Blood Pressure: Week 68, n=317	-1.1 (9.94)
Sitting Diastolic Blood Pressure: Week 72, n=312	-1.5 (9.67)
Sitting Diastolic Blood Pressure: Week 76, n=313	-1.1 (10.06)
Sitting Diastolic Blood Pressure: Week 80, n=311	-1.6 (10.23)
Sitting Diastolic Blood Pressure: Week 84, n=310	-1.7 (10.51)
Sitting Diastolic Blood Pressure: Week 88, n=310	-1.4 (10.45)
Sitting Diastolic Blood Pressure: Week 92, n=311	-1.0 (9.89)
Sitting Diastolic Blood Pressure: Week 96, n=303	-1.2 (9.81)
Sitting Diastolic Blood Pressure: Week 100, n=300	-0.3 (9.40)
Sitting Diastolic Blood Pressure: Week 104, n=301	-1.0 (9.69)
Sitting Diastolic Blood Pressure: Week 108, n=300	-0.9 (10.28)
Sitting Diastolic Blood Pressure: Week 112, n=299	-0.9 (9.78)
Sitting Diastolic Blood Pressure: Week 116, n=297	-0.7 (9.56)
Sitting Diastolic Blood Pressure: Week 120, n=295	-0.8 (9.41)
Sitting Diastolic Blood Pressure: Week 124, n=294	-1.3 (10.52)
Sitting Diastolic Blood Pressure: Week 128, n=293	-1.2 (10.08)
Sitting Diastolic Blood Pressure: Week 132, n=289	-1.0 (10.48)
Sitting Diastolic Blood Pressure: Week 136, n=288	-0.7 (10.42)
Sitting Diastolic Blood Pressure: Week 140, n=287	-0.6 (9.90)
Sitting Diastolic Blood Pressure: Week 144, n=290	-0.9 (9.83)
Sitting Diastolic Blood Pressure: Week 148, n=287	0.1 (10.22)
Sitting Diastolic Blood Pressure: Week 152, n=284	-0.9 (10.17)
Sitting Diastolic Blood Pressure: Week 156, n=275	-0.4 (10.44)
Sitting Diastolic Blood Pressure: Week 160, n=265	-0.6 (9.93)
Sitting Diastolic Blood Pressure: Week 164, n=242	-1.7 (10.83)
Sitting Diastolic Blood Pressure: Week 168, n=232	-1.3 (10.46)
Sitting Diastolic Blood Pressure: Week 172, n=226	-1.2 (10.18)
Sitting Diastolic Blood Pressure: Week 176, n=212	-1.6 (9.84)
Sitting Diastolic Blood Pressure: Week 180, n=200	-1.6 (10.42)
Sitting Diastolic Blood Pressure: Week 184, n=184	-1.3 (9.94)
Sitting Diastolic Blood Pressure: Week 188, n=180	-1.4 (9.81)
Sitting Diastolic Blood Pressure: Week 192, n=176	-1.1 (10.25)
Sitting Diastolic Blood Pressure: Week 196, n=175	-1.5 (10.18)
Sitting Diastolic Blood Pressure: Week 200, n=172	-0.4 (10.07)
Sitting Diastolic Blood Pressure: Week 204, n=169	-1.1 (10.25)
Sitting Diastolic Blood Pressure: Week 208, n=157	-1.8 (9.48)
Sitting Diastolic Blood Pressure: Week 212, n=146	-1.3 (9.53)
Sitting Diastolic Blood Pressure: Week 216, n=130	-0.2 (9.55)
Sitting Diastolic Blood Pressure: Week 220, n=67	-1.6 (10.85)
Sitting Diastolic Blood Pressure: Week 224, n=54	-1.9 (11.97)
Sitting Diastolic Blood Pressure: Week 228, n=37	-0.2 (9.60)
Sitting Diastolic Blood Pressure: Week 232, n=5	4.6 (5.86)
Sitting Diastolic Blood Pressure: Follow-up, n=306	-0.7 (10.03)
Sitting Systolic Blood Pressure: Week 4, n=346	0.2 (10.79)
Sitting Systolic Blood Pressure: Week 8, n=345	-0.7 (12.57)
Sitting Systolic Blood Pressure: Week 12, n=342	-0.3 (12.59)
Sitting Systolic Blood Pressure: Week 16, n=341	-0.5 (13.60)
Sitting Systolic Blood Pressure: Week 20, n=338	-1.8 (13.31)
Sitting Systolic Blood Pressure: Week 24, n=336	-0.8 (13.93)
Sitting Systolic Blood Pressure: Week 28, n=332	-0.6 (13.61)
Sitting Systolic Blood Pressure: Week 32, n=333	-1.0 (14.24)
Sitting Systolic Blood Pressure: Week 36, n=329	-0.7 (14.19)
Sitting Systolic Blood Pressure: Week 40, n=329	-0.6 (14.11)
Sitting Systolic Blood Pressure: Week 44, n=326	-0.9 (14.87)
Sitting Systolic Blood Pressure: Week 48, n=325	-0.1 (13.59)
Sitting Systolic Blood Pressure: Week 52, n=322	-0.3 (13.63)
Sitting Systolic Blood Pressure: Week 56, n=320	-0.3 (14.33)
Sitting Systolic Blood Pressure: Week 60, n=318	-0.0 (14.21)
Sitting Systolic Blood Pressure: Week 64, n=318	-0.2 (13.99)
Sitting Systolic Blood Pressure: Week 68, n=317	-1.1 (14.83)
Sitting Systolic Blood Pressure: Week 72, n=312	-1.8 (13.16)
Sitting Systolic Blood Pressure: Week 76, n=313	-0.8 (14.44)
Sitting Systolic Blood Pressure: Week 80, n=311	-1.1 (14.49)
Sitting Systolic Blood Pressure: Week 84, n=310	-1.9 (14.47)
Sitting Systolic Blood Pressure: Week 88, n=310	-1.7 (14.94)
Sitting Systolic Blood Pressure: Week 92, n=311	-0.3 (15.16)
Sitting Systolic Blood Pressure: Week 96, n=303	0.1 (14.32)
Sitting Systolic Blood Pressure: Week 100, n=300	0.7 (14.71)
Sitting Systolic Blood Pressure: Week 104, n=301	0.3 (14.81)
Sitting Systolic Blood Pressure: Week 108, n=300	0.5 (15.15)
Sitting Systolic Blood Pressure: Week 112, n=299	-0.4 (14.83)
Sitting Systolic Blood Pressure: Week 116, n=297	0.4 (14.31)
Sitting Systolic Blood Pressure: Week 120, n=295	0.5 (14.37)
Sitting Systolic Blood Pressure: Week 124, n=294	0.7 (14.80)
Sitting Systolic Blood Pressure: Week 128, n=293	0.7 (14.68)
Sitting Systolic Blood Pressure: Week 132, n=289	0.7 (14.51)
Sitting Systolic Blood Pressure: Week 136, n=288	0.9 (16.81)
Sitting Systolic Blood Pressure: Week 140, n=287	0.3 (15.48)
Sitting Systolic Blood Pressure: Week 144, n=290	1.1 (15.79)
Sitting Systolic Blood Pressure: Week 148, n=287	1.8 (13.59)
Sitting Systolic Blood Pressure: Week 152, n=284	0.2 (15.53)
Sitting Systolic Blood Pressure: Week 156, n=275	0.8 (14.56)
Sitting Systolic Blood Pressure: Week 160, n=265	1.1 (15.34)
Sitting Systolic Blood Pressure: Week 164, n=242	0.6 (15.51)
Sitting Systolic Blood Pressure: Week 168, n=232	0.1 (14.87)
Sitting Systolic Blood Pressure: Week 172, n=226	-0.8 (15.67)
Sitting Systolic Blood Pressure: Week 176, n=212	0.4 (13.78)
Sitting Systolic Blood Pressure: Week 180, n=200	0.6 (15.32)
Sitting Systolic Blood Pressure: Week 184, n=184	-0.5 (16.36)
Sitting Systolic Blood Pressure: Week 188, n=180	-1.0 (15.54)
Sitting Systolic Blood Pressure: Week 192, n=176	-1.2 (16.60)
Sitting Systolic Blood Pressure: Week 196, n=175	-0.8 (14.76)
Sitting Systolic Blood Pressure: Week 200, n=172	-0.1 (15.28)
Sitting Systolic Blood Pressure: Week 204, n=169	-0.4 (15.64)
Sitting Systolic Blood Pressure: Week 208, n=157	-1.0 (16.92)
Sitting Systolic Blood Pressure: Week 212, n=146	0.5 (14.98)
Sitting Systolic Blood Pressure: Week 216, n=130	0.4 (15.52)
Sitting Systolic Blood Pressure: Week 220, n=67	-4.2 (20.86)
Sitting Systolic Blood Pressure: Week 224, n=54	-3.8 (17.87)
Sitting Systolic Blood Pressure: Week 228, n=37	-3.6 (15.15)
Sitting Systolic Blood Pressure: Week 232, n=5	-0.8 (6.30)
Sitting Systolic Blood Pressure: Follow-up, n=306	-0.0 (14.92)

9. Secondary Outcome

Title	Mean Change From Baseline in Vital Signs-Sitting Pulse Rate
Description	Vital signs included sitting pulse rate and blood pressure (diastolic and systolic). Measurements were done pre injection with the participant sitting, having rested in this position for at least 5 minutes before each reading. Baseline was Week 0. Change from Baseline was post-Baseline values minus Baseline values. Only those participants available at the specified time points were analyzed represented by n=X in the category titles.
Time Frame	Baseline (Week 0) to Week 240

Outcome Measure Data

Analysis Population Description

AT Population.

Arm/Group Title	Mepolizumab 100 mg
Arm/Group Description	Participants received 100 mg of mepolizumab injected SC once every 4 weeks until participant withdrawal or mepolizumab becomes commercially available in the relevant participating country. Participants remained on standard of care asthma therapy, which was adjusted during the study, at the discretion of their physician.
Measure Participants	347
Sitting Pulse Rate: Week 4, n=346	-0.3 (8.94)
Sitting Pulse Rate: Week 8, n=345	1.0 (9.98)
Sitting Pulse Rate: Week 12, n=342	0.0 (9.52)
Sitting Pulse Rate: Week 16, n=341	-0.1 (10.08)
Sitting Pulse Rate: Week 20, n=338	-0.3 (9.44)
Sitting Pulse Rate: Week 24, n=337	-1.6 (9.83)
Sitting Pulse Rate: Week 28, n=332	-0.2 (9.58)
Sitting Pulse Rate: Week 32, n=333	-0.2 (9.74)
Sitting Pulse Rate: Week 36, n=329	-0.6 (9.60)
Sitting Pulse Rate: Week 40, n=329	-0.2 (9.56)
Sitting Pulse Rate: Week 44, n=327	-0.4 (9.80)
Sitting Pulse Rate: Week 48, n=325	-1.6 (9.65)
Sitting Pulse Rate: Week 52, n=322	0.1 (9.56)
Sitting Pulse Rate: Week 56, n=320	-0.3 (9.79)
Sitting Pulse Rate: Week 60, n=318	-0.8 (9.54)
Sitting Pulse Rate: Week 64, n=318	-0.9 (9.63)
Sitting Pulse Rate: Week 68, n=317	-1.2 (9.51)
Sitting Pulse Rate: Week 72, n=312	-1.8 (10.07)
Sitting Pulse Rate: Week 76, n=313	-1.2 (9.65)
Sitting Pulse Rate: Week 80, n=311	-0.5 (10.08)
Sitting Pulse Rate: Week 84, n=310	-1.2 (9.80)
Sitting Pulse Rate: Week 88, n=310	-0.6 (10.12)
Sitting Pulse Rate: Week 92, n=311	-0.6 (9.36)
Sitting Pulse Rate: Week 96, n=303	-1.7 (10.61)
Sitting Pulse Rate: Week 100, n=300	-0.5 (9.81)
Sitting Pulse Rate: Week 104, n=301	-0.9 (10.45)
Sitting Pulse Rate: Week 108, n=300	-0.8 (10.04)
Sitting Pulse Rate: Week 112, n=299	-0.5 (9.60)
Sitting Pulse Rate: Week 116, n=297	-1.5 (9.33)
Sitting Pulse Rate: Week 120, n=294	-1.2 (10.27)
Sitting Pulse Rate: Week 124, n=294	-2.5 (10.27)
Sitting Pulse Rate: Week 128, n=293	-1.2 (10.00)
Sitting Pulse Rate: Week 132, n=289	-0.7 (9.20)
Sitting Pulse Rate: Week 136, n=288	-0.6 (10.55)
Sitting Pulse Rate: Week 140, n=287	-0.6 (9.71)
Sitting Pulse Rate: Week 144, n=290	-0.7 (9.72)
Sitting Pulse Rate: Week 148, n=287	-1.8 (9.82)
Sitting Pulse Rate: Week 152, n=284	-0.9 (10.45)
Sitting Pulse Rate: Week 156, n=275	-0.8 (9.83)
Sitting Pulse Rate: Week 160, n=265	-0.5 (10.42)
Sitting Pulse Rate: Week 164, n=242	-1.1 (11.07)
Sitting Pulse Rate: Week 168, n=232	-0.5 (11.25)
Sitting Pulse Rate: Week 172, n=226	-1.0 (9.80)
Sitting Pulse Rate: Week 176, n=212	-2.9 (9.57)
Sitting Pulse Rate: Week 180, n=200	-0.5 (10.01)
Sitting Pulse Rate: Week 184, n=184	-1.3 (9.89)
Sitting Pulse Rate: Week 188, n=180	-1.3 (10.38)
Sitting Pulse Rate: Week 192, n=176	-1.6 (10.37)
Sitting Pulse Rate: Week 196, n=175	-1.2 (9.79)
Sitting Pulse Rate: Week 200, n=172	-2.3 (11.03)
Sitting Pulse Rate: Week 204, n=169	-1.9 (10.67)
Sitting Pulse Rate: Week 208, n=157	-0.6 (10.64)
Sitting Pulse Rate: Week 212, n=146	-0.4 (10.09)
Sitting Pulse Rate: Week 216, n=130	-1.4 (10.49)
Sitting Pulse Rate: Week 220, n=67	-0.0 (11.13)
Sitting Pulse Rate: Week 224, n=54	-1.4 (13.19)
Sitting Pulse Rate: Week 228, n=37	-2.4 (10.57)
Sitting Pulse Rate: Week 232, n=5	-2.0 (16.63)
Sitting Pulse Rate: Follow-up, n=306	-1.5 (10.72)

10. Secondary Outcome

Title	Annualized Rate of On-treatment Exacerbations
Description	Exacerbations were defined as worsening of asthma which required use of systemic corticosteroids and/or hospitalization and/or Emergency Department visits. Data is presented as mean which is exacerbation rate/year. Exacerbation data are performed using a negative binomial model with covariates of region, annualized rate of exacerbations in the interval between MEA112997 and MEA115666 (as an ordinal variable) and baseline % predicted FEV1, and with logarithm of time on treatment as an offset variable.
Time Frame	Baseline (Week 0) to Week 240

Outcome Measure Data

Analysis Population Description

AT Population.

Arm/Group Title	Mepolizumab 100 mg
Arm/Group Description	Participants received 100 mg of mepolizumab injected SC once every 4 weeks until participant withdrawal or mepolizumab becomes commercially available in the relevant participating country. Participants remained on standard of care asthma therapy, which was adjusted during the study, at the discretion of their physician.
Measure Participants	347
Mean (95% Confidence Interval) [Exacerbations per year]	0.68

11. Secondary Outcome

Title	Mean Change From Baseline in Asthma Control Questionnaire (ACQ) Score
Description	The ACQ-5 is a five-item questionnaire, which was developed as a measure of participant' asthma control that was completed by the participant. The five questions enquire about the frequency and/or severity of symptoms (nocturnal awakening on waking in the morning, activity limitation, and shortness of breath, wheeze). The ACQ consists of 5 questions that are scored on a 7 point scale from 0 (totally controlled) to 6 (severely uncontrolled). The ACQ score was derived as mean of five questions: ACQ score = Question 1 (Q1)+Q2+Q3+Q4+Q5 divided by 5 where Q1, Q2,... Q5 are the scores of Q1, Q2, ..., Q5, respectively. The total score ranged from zero (no impairment/limitation) which indicated best condition to six (total impairment/ limitation) which indicated worst asthma. Baseline was Week 0. Change from Baseline was post-Baseline values minus Baseline values. Only those participants available at the specified time points were analyzed represented by n=X in the category titles.
Time Frame	Baseline (Week 0) to Week 240

Outcome Measure Data

Analysis Population Description

AT Population.

Arm/Group Title	Mepolizumab 100 mg
Arm/Group Description	Participants received 100 mg of mepolizumab injected SC once every 4 weeks until participant withdrawal or mepolizumab becomes commercially available in the relevant participating country. Participants remained on standard of care asthma therapy, which was adjusted during the study, at the discretion of their physician.
Measure Participants	347
Week 12, n=341	-0.47 (0.991)
Week 24, n=335	-0.55 (1.037)
Week 36, n=327	-0.56 (1.088)
Week 48, n=324	-0.55 (1.098)
Week 60, n=317	-0.58 (1.126)
Week 72, n=311	-0.51 (1.054)
Week 84, n=308	-0.54 (1.090)
Week 96, n=301	-0.44 (1.171)
Week 112, n=297	-0.51 (1.228)
Week 124, n=293	-0.66 (1.216)
Week 136, n=287	-0.58 (1.215)
Week 148, n=286	-0.54 (1.070)
Week 164, n=240	-0.59 (1.221)
Week 176, n=211	-0.49 (1.179)
Week 188, n=178	-0.40 (1.310)
Week 200, n=171	-0.45 (1.119)
Week 216, n=130	-0.42 (1.161)
Week 228, n=37	-0.47 (1.502)
Follow-up, n=301	-0.53 (1.193)

12. Secondary Outcome

Title	Mean Change From Baseline in Clinic Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1)
Description	FEV1 is forced expiratory volume in the first second. The volume of air that can be forced out in one second after taking a deep breath, an important measure of pulmonary function. Forced expiratory volume (FEV) measures how much air a person can exhale during a forced breath. FEV1 was measured by clinic spirometry. Baseline was Week 0. Change from Baseline was post-Baseline values minus Baseline values. Only those participants available at the specified time points were analyzed represented by n=X in the category titles.
Time Frame	Baseline (Week 0) to Week 240

Outcome Measure Data

Analysis Population Description

AT Population.

Arm/Group Title	Mepolizumab 100 mg
Arm/Group Description	Participants received 100 mg of mepolizumab injected SC once every 4 weeks until participant withdrawal or mepolizumab becomes commercially available in the relevant participating country. Participants remained on standard of care asthma therapy, which was adjusted during the study, at the discretion of their physician.
Measure Participants	347
Week 12, n=340	124 (346.9)
Week 24, n=334	144 (335.0)
Week 48, n=325	98 (395.2)
Week 72, n=312	91 (405.5)
Week 96, n=301	51 (385.8)
Week 124, n=292	85 (395.5)
Week 148, n=281	17 (370.2)
Week 176, n=210	45 (352.2)
Week 200, n=171	8 (375.7)
Week 228, n=37	-23 (331.9)

13. Secondary Outcome

Title	Number of Participants With Positive Anti-mepolizumab Binding Antibodies (ADA) and Neutralizing Antibodies (NAb)
Description	Immunogenicity testing included two types of assays: a binding antibody assay (anti-drug antibody; ADA) and a neutralizing antibody (NAb) assay for participants who were tested positive in the ADA assay. Blood samples were collected for the determination of anti-mepolizumab antibodies, just prior to administration of mepolizumab. Samples that test positive for anti-mepolizumab antibodies were further tested for the presence of neutralizing antibody. Number of participants with positive highest value post-Baseline have been presented. Only those participants available at the specified time points were analyzed represented by n=X in the category titles.
Time Frame	Baseline (Week 0) to Week 240

Outcome Measure Data

Analysis Population Description

AT Population.

Arm/Group Title	Mepolizumab 100 mg
Arm/Group Description	Participants received 100 mg of mepolizumab injected SC once every 4 weeks until participant withdrawal or mepolizumab becomes commercially available in the relevant participating country. Participants remained on standard of care asthma therapy, which was adjusted during the study, at the discretion of their physician.
Measure Participants	347
Positive ADA result, n=346	27 7.8%
Positive NAb result, n=27	0 0%

14. Secondary Outcome

Title	Number of Participants Who Withdrew Due to Lack of Efficacy
Description	Lack of efficacy referred to failure of expected pharmacological action of Mepolizumab. Number of participants who withdrew due to lack of efficacy are presented.
Time Frame	Baseline (Week 0) to Week 240

Outcome Measure Data

Analysis Population Description

AT Population.

Arm/Group Title	Mepolizumab 100 mg
Arm/Group Description	Participants received 100 mg of mepolizumab injected SC once every 4 weeks until participant withdrawal or mepolizumab becomes commercially available in the relevant participating country. Participants remained on standard of care asthma therapy, which was adjusted during the study, at the discretion of their physician.
Measure Participants	347
Number [Participants]	11 3.2%

15. Secondary Outcome

Title	Number of Participants Requiring Hospitalizations Due to Adverse Events Including Asthma Exacerbations
Description	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. 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 open-label mepolizumab date and before/on last dose of mepolizumab + 28 days.
Time Frame	Baseline (Week 0) to Week 240

Outcome Measure Data

Analysis Population Description

AT Population.

Arm/Group Title	Mepolizumab 100 mg
Arm/Group Description	Participants received 100 mg of mepolizumab injected SC once every 4 weeks until participant withdrawal or mepolizumab becomes commercially available in the relevant participating country. Participants remained on standard of care asthma therapy, which was adjusted during the study, at the discretion of their physician.
Measure Participants	347
Number [Participants]	71 20.5%

16. Secondary Outcome

Title	Number of Participants Who Withdrew Due to AE
Description	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. 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. 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 who withdrew due to AE are presented.
Time Frame	Baseline (Week 0) to Week 240

Outcome Measure Data

Analysis Population Description

AT Population.

Arm/Group Title	Mepolizumab 100 mg
Arm/Group Description	Participants received 100 mg of mepolizumab injected SC once every 4 weeks until participant withdrawal or mepolizumab becomes commercially available in the relevant participating country. Participants remained on standard of care asthma therapy, which was adjusted during the study, at the discretion of their physician.
Measure Participants	347
Number [Participants]	19 5.5%

Adverse Events

Time Frame	The on-treatment AEs and on-treatment SAEs are the events which happened on/after the first dose of open label mepolizumab date and before/on last dose of mepolizumab date + 28 days (up to 240 weeks)
Adverse Event Reporting Description	AE and SAE were collected for all participants within the As Treated Population which comprised of all participants who received at least one dose of open label mepolizumab.
Arm/Group Title	Mepolizumab
Arm/Group Description	Subjects will receive 100 mg of mepolizumab (in 1ml polypropylene syringe) injected subcutaneously (SC) approximately every 4 weeks.
All Cause Mortality
	Mepolizumab
	Affected / at Risk (%)	# Events
Total	6/347 (1.7%)
Serious Adverse Events
	Mepolizumab
	Affected / at Risk (%)	# Events
Total	79/347 (22.8%)
Blood and lymphatic system disorders
Lymphocytosis	1/347 (0.3%)
Cardiac disorders
Acute myocardial infarction	1/347 (0.3%)
Angina unstable	1/347 (0.3%)
Atrial fibrillation	1/347 (0.3%)
Atrial flutter	1/347 (0.3%)
Atrial tachycardia	1/347 (0.3%)
Cardiac failure acute	1/347 (0.3%)
Myocardial infarction	1/347 (0.3%)
Endocrine disorders
Basedow's disease	1/347 (0.3%)
Thyroid mass	1/347 (0.3%)
Gastrointestinal disorders
Abdominal pain	1/347 (0.3%)
Abdominal pain upper	1/347 (0.3%)
Chronic gastritis	1/347 (0.3%)
Colitis	1/347 (0.3%)
Constipation	1/347 (0.3%)
Diverticulum intestinal	1/347 (0.3%)
Faecaloma	1/347 (0.3%)
Gastric polyps	1/347 (0.3%)
Incarcerated inguinal hernia	1/347 (0.3%)
Inguinal hernia	1/347 (0.3%)
Large intestinal obstruction	1/347 (0.3%)
Umbilical hernia	1/347 (0.3%)
General disorders
Chills	1/347 (0.3%)
Non-cardiac chest pain	1/347 (0.3%)
Sudden death	1/347 (0.3%)
Hepatobiliary disorders
Cholelithiasis	2/347 (0.6%)
Cholestasis	1/347 (0.3%)
Hepatocellular injury	1/347 (0.3%)
Immune system disorders
Anaphylactic reaction	1/347 (0.3%)
Anaphylactic shock	1/347 (0.3%)
Infections and infestations
Pneumonia	6/347 (1.7%)
Cellulitis	2/347 (0.6%)
Respiratory tract infection	2/347 (0.6%)
Abscess limb	1/347 (0.3%)
Anal abscess	1/347 (0.3%)
Gastroenteritis	1/347 (0.3%)
Herpes zoster	1/347 (0.3%)
Influenza	1/347 (0.3%)
Lower respiratory tract infection	1/347 (0.3%)
Myelitis	1/347 (0.3%)
Postoperative wound infection	1/347 (0.3%)
Pyelonephritis	1/347 (0.3%)
Staphylococcal infection	1/347 (0.3%)
Streptococcal infection	1/347 (0.3%)
Urinary tract infection	1/347 (0.3%)
Injury, poisoning and procedural complications
Comminuted fracture	1/347 (0.3%)
Femur fracture	1/347 (0.3%)
Joint dislocation	1/347 (0.3%)
Ligament rupture	1/347 (0.3%)
Ligament sprain	1/347 (0.3%)
Subarachnoid haemorrhage	1/347 (0.3%)
Tendon rupture	1/347 (0.3%)
Investigations
Blood glucose increased	1/347 (0.3%)
Hepatic enzyme increased	1/347 (0.3%)
Metabolism and nutrition disorders
Obesity	1/347 (0.3%)
Musculoskeletal and connective tissue disorders
Bursitis	2/347 (0.6%)
Intervertebral disc protrusion	2/347 (0.6%)
Back pain	1/347 (0.3%)
Lumbar spinal stenosis	1/347 (0.3%)
Neuropathic arthropathy	1/347 (0.3%)
Osteoarthritis	1/347 (0.3%)
Rheumatoid arthritis	1/347 (0.3%)
Rotator cuff syndrome	1/347 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer	2/347 (0.6%)
Basal cell carcinoma	1/347 (0.3%)
Bladder papilloma	1/347 (0.3%)
Breast cancer	1/347 (0.3%)
Nervous system disorders
Epilepsy	2/347 (0.6%)
Sciatica	2/347 (0.6%)
Cerebral haemorrhage	1/347 (0.3%)
Dizziness	1/347 (0.3%)
Peroneal nerve palsy	1/347 (0.3%)
Spinal claudication	1/347 (0.3%)
Syncope	1/347 (0.3%)
Renal and urinary disorders
Bladder prolapse	1/347 (0.3%)
Renal colic	1/347 (0.3%)
Urinary incontinence	1/347 (0.3%)
Reproductive system and breast disorders
Cervical polyp	1/347 (0.3%)
Rectocele	1/347 (0.3%)
Respiratory, thoracic and mediastinal disorders
Asthma	33/347 (9.5%)
Pneumonia aspiration	1/347 (0.3%)
Respiratory arrest	1/347 (0.3%)
Sleep apnoea syndrome	1/347 (0.3%)
Status asthmaticus	1/347 (0.3%)
Vascular disorders
Hypertension	1/347 (0.3%)
Hypertensive crisis	1/347 (0.3%)
Thrombophlebitis superficial	1/347 (0.3%)
Other (Not Including Serious) Adverse Events
	Mepolizumab
	Affected / at Risk (%)	# Events
Total	314/347 (90.5%)
Eye disorders
Cataract	14/347 (4%)
Gastrointestinal disorders
Diarrhoea	26/347 (7.5%)
Toothache	22/347 (6.3%)
Abdominal pain	17/347 (4.9%)
Nausea	17/347 (4.9%)
Abdominal pain upper	15/347 (4.3%)
Gastrooesophageal reflux disease	14/347 (4%)
Dyspepsia	12/347 (3.5%)
Vomiting	11/347 (3.2%)
General disorders
Injection site reaction	42/347 (12.1%)
Fatigue	12/347 (3.5%)
Immune system disorders
Hypersensitivity	13/347 (3.7%)
Infections and infestations
Viral upper respiratory tract infection	169/347 (48.7%)
Upper respiratory tract infection	81/347 (23.3%)
Bronchitis	73/347 (21%)
Sinusitis	57/347 (16.4%)
Influenza	43/347 (12.4%)
Respiratory tract infection	38/347 (11%)
Lower respiratory tract infection	31/347 (8.9%)
Gastroenteritis	27/347 (7.8%)
Pharyngitis	24/347 (6.9%)
Urinary tract infection	24/347 (6.9%)
Rhinitis	23/347 (6.6%)
Respiratory tract infection viral	20/347 (5.8%)
Viral infection	18/347 (5.2%)
Ear infection	15/347 (4.3%)
Acute sinusitis	14/347 (4%)
Cystitis	13/347 (3.7%)
Nasopharyngitis	13/347 (3.7%)
Oral candidiasis	13/347 (3.7%)
Injury, poisoning and procedural complications
Laceration	15/347 (4.3%)
Contusion	13/347 (3.7%)
Ligament sprain	11/347 (3.2%)
Metabolism and nutrition disorders
Hypercholesterolaemia	11/347 (3.2%)
Musculoskeletal and connective tissue disorders
Back pain	63/347 (18.2%)
Arthralgia	58/347 (16.7%)
Pain in extremity	40/347 (11.5%)
Osteoarthritis	20/347 (5.8%)
Myalgia	18/347 (5.2%)
Musculoskeletal pain	14/347 (4%)
Nervous system disorders
Headache	99/347 (28.5%)
Dizziness	23/347 (6.6%)
Sciatica	16/347 (4.6%)
Respiratory, thoracic and mediastinal disorders
Asthma	69/347 (19.9%)
Rhinitis allergic	36/347 (10.4%)
Oropharyngeal pain	27/347 (7.8%)
Cough	22/347 (6.3%)
Productive cough	12/347 (3.5%)
Rhinorrhoea	12/347 (3.5%)
Dysphonia	11/347 (3.2%)
Dyspnoea	11/347 (3.2%)
Skin and subcutaneous tissue disorders
Rash	12/347 (3.5%)
Vascular disorders
Hypertension	32/347 (9.2%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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