Efficacy and Safety Study of Mepolizumab Adjunctive Therapy in Participants With Severe Eosinophilic Asthma on Markers of Asthma Control

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02281318
• Collaborator: (none)
• Enrollment: 556
• Locations: 144
• Arms: 2
• Actual Duration (Months): 18
• Patients Per Site: 3.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a multi-centre, placebo-controlled, double-blind, parallel-group study to evaluate the efficacy and safety of mepolizumab adjunctive therapy in participants with severe eosinophilic asthma on markers of asthma control. The overall intent of the current study is to more fully explore the impact of mepolizumab on health-related quality of life (HR-QoL) and other measures of asthma control, including lung function.

Participants who meet the predefined criteria will be randomised to receive either mepolizumab or placebo in addition to standard of care asthma treatment. Approximately 780 participants with severe eosinophilic asthma will be screened to ensure the randomisation of 544 participants (272 participants per treatment group) into the study.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 556 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomised, Double-blind, Placebo-controlled, Parallel-group, Multi-centre 24-week Study to Evaluate the Efficacy and Safety of Mepolizumab Adjunctive Therapy in Subjects With Severe Eosinophilic Asthma on Markers of Asthma Control
• Actual Study Start Date: Dec 11, 2014
• Actual Primary Completion Date: Jun 10, 2016
• Actual Study Completion Date: Jun 10, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mepolizumab SC Participants will receive Mepolizumab 100 mg subcutaneously (SC) into the upper arm or thigh every 4 weeks for a period of 24 weeks (total of 6 doses) along with their respective standard care of treatment	Biological: Mepolizumab; Humanised Immunoglobulin G (IgG) antibody (IgG1, kappa) with human heavy and light chain frameworks, provided as a lyophilised cake in sterile vial. Vial to be reconstituted with sterile water for injection, just prior to use; Drug: SOC; Standard of Care (SOC) will differ by participants, however it will include high dose ICS with at least one other controller, e.g. LABA, with or without maintenance OCS
Placebo Comparator: Placebo SC Participants will receive placebo (0.9% sodium chloride) subcutaneously into the upper arm or thigh every 4 weeks for a period of 24 weeks (total of 6 doses) along with their respective standard care of treatment	Drug: Placebo; Sterile 0.9% sodium chloride solution; Drug: SOC; Standard of Care (SOC) will differ by participants, however it will include high dose ICS with at least one other controller, e.g. LABA, with or without maintenance OCS

Outcome Measures

Primary Outcome Measures

1. Mean Change From Baseline (BL) in St. George's Respiratory Questionnaire (SGRQ) Score at Week 24 [Baseline and Week 24]

   SGRQ consisted of 50 questions (scored from 0 to 100 where 0 indicates best and 100 indicates worst health) designed to measure Quality of Life in par. with diseases of airway obstruction, measuring symptoms, impact, and activity. Questions were completed by the par. with a recall over the past 4 weeks. SGRQ Total Score was calculated by summing the pre-assigned weights of answers, dividing by the sum of the maximum weights for items in SGRQ and multiplying by 100 to get a %. Change from BL in SGRQ was calculated as value at Week 24 minus value at BL for each par. and was analyzed using mixed model repeated measures allowing for covariates of BL value, region, BL maintenance oral corticosteroid (OCS) therapy, exacerbations in the year prior to the study (as an ordinal variable), BL % predicted FEV1 and visit, plus interaction terms for visit by BL and visit by treatment group. Modified Intent-to-Treat (mITT) Population consisted of all randomized par. who received >= 1 dose of drug.

Secondary Outcome Measures

1. Mean Change From Baseline in Clinic Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Week 24 [Baseline and Week 24]

   FEV1 is the volume of air that can be forced out in one second after taking a deep breath. The change from Baseline in pre-bronchodilator FEV1 was calculated as the value at Week 24 minus the value at Baseline for each subject and was analyzed using a mixed model repeated measures adjusting for Baseline absolute pre-bronchodilator FEV1, region, Baseline maintenance OCS therapy, exacerbations in the year prior to the study and visit, plus interaction terms for visit by Baseline and visit by treatment group.

2. Percentage of Participants Achieving a 4 Point or Greater Reduction From Baseline in SGRQ Score at Week 24 [Baseline (Visit 2-latest pre-dose assessment) and Week 24]

   The percentage of participants achieving a 4 point or greater reduction from Baseline in SGRQ (scored from 0-100 with lower scores indicating better outcome) at Week 24 was compared between treatment groups using a logistic regression model with covariates of Baseline value, region, Baseline maintenance OCS therapy, exacerbations in the year prior to the study (as an ordinal variable) and Baseline % predicted FEV1.

3. Mean Change From Baseline in Asthma Control Questionnaire (ACQ-5) Score at Week 24 [Baseline and Week 24]

   The ACQ-5 is a five-item questionnaire, designed to be self-completed by the participants. ACQ-5 score is the mean score of 5 questions, each assessed on a 0-6 point scale to give a mean ranging between 0-6 with lower scores indicating better outcome. The five questions inquired about the frequency and/or severity of symptoms over the previous week. The response options for all these questions consisted of a zero (no impairment/limitation) to six (total impairment/limitation) scale. The mean change from Baseline was calculated as the value at Week 24 minus the Baseline value for each participant and analyzed using a mixed model repeated measures allowing for covariates of Baseline value, region, Baseline maintenance OCS therapy, exacerbations in the year prior to the study (as an ordinal variable), Baseline % predicted FEV1 and visit, plus interaction terms for visit by Baseline and visit by treatment group.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Age: At least 12 years of age at the time of signing the informed consent/assent (For those countries where local regulations permit enrolment of adults only, participant recruitment will be restricted to those who are >=18 years of age)

• Inhaled Corticosteroid: A well-documented requirement for regular treatment with high dose inhaled corticosteroid (ICS) in the 12 months prior to Visit 1 with or without maintenance oral corticosteroids (OCS). For participants >=18 years old: ICS dose must be >=880 micrograms (mcg)/day fluticasone propionate (FP) (exactuator) or equivalent daily. For ICS/long-acting beta-2-agonist (LABA) combination preparations, the highest approved maintenance dose in the local country will meet this ICS criterion. For participants >=12 to <=17 years old: ICS dose must be >=440 mcg/day FP (ex-actuator) or equivalent daily. For ICS/LABA combination preparations, the mid-strength approved maintenance dose in the local country will meet this ICS criterion

• Controller Medication: Current treatment with an additional controller medication, besides ICS, for at least 3 months or a documented failure in the past 12 months of an additional controller medication for at least 3 successive months (e.g. LABA, leukotriene receptor antagonist [LTRA], or theophylline)

• Eosinophilic asthma: Prior documentation of eosinophilic asthma or high likelihood of eosinophilic asthma as per Randomisation Criteria 1 and 2

• FEV1: Persistent airflow obstruction as indicated by : For participants >=18 years of age at visit 1, a pre-bronchodilator FEV1 <80% predicted (National Health and Nutrition Examination Survey [NHANES III]) recorded at Visit 1. For participants 12-17 years of age at Visit 1: A pre-bronchodilator FEV1 <90% predicted (NHANES III) recorded at Visit 1 OR FEV1:FVC ratio <0.8 recorded at Visit 1

• Exacerbation history: Previously confirmed history of two or more exacerbations requiring treatment with systemic Corticosteroid (CS) (intramuscular, intravenous, or oral), in the 12 months prior to visit 1, despite the use of high-dose inhaled corticosteroids (ICS). For participants receiving maintenance CS, the CS treatment for the exacerbations must have been a two-fold dose increase or greater.

• Gender: Male or Eligible Female. 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 listed in the protocol for the duration of the trial and for 4 months after the last study drug administration.

• Informed Consent/Assent: Able to give written informed consent/assent prior to participation in the core study, which will include the ability to comply with the requirements and restrictions listed in the consent/assent form and in this protocol. Participants must be able to read, comprehend, and write at a level sufficient to complete study related materials. Written informed consent must be obtained from ALL patients/legally authorized representative(s); for patients 12-17 years old, written informed assent must be obtained in addition to the legally authorized representative(s)' consent.

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

Exclusion Criteria:

• Smoking history: Current smokers or former smokers with a smoking history of >=10 pack years (number of pack years = (number of cigarettes per day/20) x number of years smoked). A former smoker is defined as a participant who quit smoking at least 6 months prior to Visit 1.

• Concurrent Respiratory Disease: Presence of a known pre-existing, clinically important lung condition other than asthma. This includes current infection, bronchiectasis, pulmonary fibrosis, bronchopulmonary aspergillosis, or diagnoses of emphysema or chronic bronchitis (chronic obstructive pulmonary disease other than asthma) or a history of lung cancer.

• Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior to screening (Participants that had localized carcinoma of the skin which was resected for cure will not be excluded).

• Liver Disease: Known, pre-existing, unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices or persistent jaundice), cirrhosis, and known biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones).

• Cardiovascular: Participants who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment. Including but not limited to: (a) known ejection fraction of <30% OR (b) severe heart failure meeting New York Heart Association Class IV classification OR (c) hospitalised in the 12 months prior to Visit 1 for severe heart failure meeting New York Heart Association Class III OR (d) angina diagnosed less than 3 months prior to Visit 1 or at Visit 1.

• Other Concurrent Medical Conditions: Participants who have known, pre-existing, clinically significant endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, haematological or any other system abnormalities that are uncontrolled with standard treatment.

• Eosinophilic Diseases: Participants with other conditions that could lead to elevated eosinophils such as Hypereosinophilic Syndromes, including Churg-Strauss Syndrome (Eosinophilic Granulomatosis with Polyangiitis [EGPA]), or Eosinophilic Esophagitis. Participants with a known, pre-existing parasitic infestation within 6 months prior to Visit 1 are also to be excluded.

• Electrocardiogram (ECG) Assessment: QT interval corrected for heart rate by Fridericia's formula (QTc(F)) >=450 milliseconds (msec) or QTc(F) >=480 msec for participants with Bundle Branch Block at Visit 1.

• Alcohol/Substance Abuse: A history (or suspected history) of alcohol misuse or substance abuse within 2 years prior to Visit 1.

• Immunodeficiency: A known immunodeficiency (e.g. human immunodeficiency virus [HIV]), other than that explained by the use of corticosteroids taken as therapy for asthma.

• Xolair: Participants who have received omalizumab (Xolair) within 130 days of Visit 1.

• Other Monoclonal Antibodies: Participants who have received any monoclonal antibody (other than Xolair) to treat inflammatory disease within 5 half-lives of Visit 1.

• Investigational Medications: Participants who have received treatment with an investigational drug within the past 30 days or five terminal phase half-lives of the drug whichever is longer, prior to Visit 1 (this also includes investigational formulations of marketed products).

• Hypersensitivity: Participants with allergy/intolerance to a monoclonal antibody or biologic.

• Pregnancy: Participants who are pregnant or breastfeeding. Patients should not be enrolled if they plan to become pregnant during the time of study participation. A urine pregnancy test is required of all women of child bearing potential. This test will be performed at the time points specified in the Time and Events Schedule in protocol.

• Adherence: Participants who have known evidence of lack of adherence to controller medications and/or ability to follow physician's recommendations.

• Previous participation: Previously participated in any study with mepolizumab and received investigational product (including placebo)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Birmingham	Alabama	United States	35243
2	GSK Investigational Site	Birmingham	Alabama	United States	35294
3	GSK Investigational Site	Fresno	California	United States	93720
4	GSK Investigational Site	Long Beach	California	United States	90808
5	GSK Investigational Site	Newport Beach	California	United States	92663
6	GSK Investigational Site	Riverside	California	United States	92506
7	GSK Investigational Site	Rolling Hills Estates	California	United States	90274
8	GSK Investigational Site	Upland	California	United States	91786
9	GSK Investigational Site	Denver	Colorado	United States	80206
10	GSK Investigational Site	New Haven	Connecticut	United States	06520
11	GSK Investigational Site	Aventura	Florida	United States	33180
12	GSK Investigational Site	Orlando	Florida	United States	32825
13	GSK Investigational Site	Baltimore	Maryland	United States	21236
14	GSK Investigational Site	Rochester	Minnesota	United States	55905
15	GSK Investigational Site	Rochester	New York	United States	14642
16	GSK Investigational Site	Durham	North Carolina	United States	27705
17	GSK Investigational Site	Gastonia	North Carolina	United States	28054
18	GSK Investigational Site	Cincinnati	Ohio	United States	45231
19	GSK Investigational Site	Upland	Pennsylvania	United States	19013
20	GSK Investigational Site	Orangeburg	South Carolina	United States	29118
21	GSK Investigational Site	Rapid City	South Dakota	United States	57702
22	GSK Investigational Site	Salt Lake City	Utah	United States	84132
23	GSK Investigational Site	Richmond	Virginia	United States	23229
24	GSK Investigational Site	Williamsburg	Virginia	United States	23188
25	GSK Investigational Site	La Plata	Buenos Aires	Argentina	1900
26	GSK Investigational Site	Mar del Plata	Buenos Aires	Argentina	7600
27	GSK Investigational Site	Concepcion del Uruguay	Entre Ríos	Argentina	3260
28	GSK Investigational Site	San Rafael	Mendoza	Argentina	5600
29	GSK Investigational Site	Rosario	Santa Fe	Argentina	2000
30	GSK Investigational Site	Buenos Aires		Argentina	C1425BEN
31	GSK Investigational Site	Ciudad Autónoma de Buenos Aires		Argentina	C1121ABE
32	GSK Investigational Site	Mendoza		Argentina	5500
33	GSK Investigational Site	Brussels		Belgium	1000
34	GSK Investigational Site	Erpent		Belgium	5101
35	GSK Investigational Site	Gent		Belgium	9000
36	GSK Investigational Site	Leuven		Belgium	3000
37	GSK Investigational Site	Liège		Belgium	4000
38	GSK Investigational Site	Pleven		Bulgaria	5800
39	GSK Investigational Site	Sofia		Bulgaria	1431
40	GSK Investigational Site	Calgary	Alberta	Canada	T2N 4Z6
41	GSK Investigational Site	Vancouver	British Columbia	Canada	V5Z 1M9
42	GSK Investigational Site	Winnipeg	Manitoba	Canada	R2H 2A6
43	GSK Investigational Site	Burlington	Ontario	Canada	L7N 3V2
44	GSK Investigational Site	St-Charles-Borromée	Ontario	Canada	J6E 2B4
45	GSK Investigational Site	Toronto	Ontario	Canada	M5T 3A9
46	GSK Investigational Site	Windsor	Ontario	Canada	N8X 5A6
47	GSK Investigational Site	Montreal	Quebec	Canada	H4J 1C5
48	GSK Investigational Site	Sainte-Foy	Quebec	Canada	G1V 4G5
49	GSK Investigational Site	Trois-Rivieres	Quebec	Canada	G8T 7A1
50	GSK Investigational Site	Brno		Czechia	625 00
51	GSK Investigational Site	Hlucin		Czechia	748 01
52	GSK Investigational Site	Hradec Kralove		Czechia	500 05
53	GSK Investigational Site	Kralupy nad Vltavou		Czechia	278 01
54	GSK Investigational Site	Olomouc		Czechia	775 20
55	GSK Investigational Site	Plzen		Czechia	305 99
56	GSK Investigational Site	Praha 4		Czechia	140 59
57	GSK Investigational Site	Tallinn		Estonia	13419
58	GSK Investigational Site	Tallinn		Estonia	13619
59	GSK Investigational Site	Tartu		Estonia	51014
60	GSK Investigational Site	Brest Cedex		France	29609
61	GSK Investigational Site	Dijon Cedex		France	21079
62	GSK Investigational Site	Lille cedex		France	59037
63	GSK Investigational Site	Lyon cedex 04		France	69317
64	GSK Investigational Site	Marseille cedex 20		France	13915
65	GSK Investigational Site	Montpellier cedex 5		France	34295
66	GSK Investigational Site	Nantes cedex 1		France	44093
67	GSK Investigational Site	Paris Cedex 18		France	75877
68	GSK Investigational Site	Pessac cedex		France	33604
69	GSK Investigational Site	Reims Cedex		France	51092
70	GSK Investigational Site	Bamberg	Bayern	Germany	96049
71	GSK Investigational Site	Muenchen	Bayern	Germany	80539
72	GSK Investigational Site	Witten	Nordrhein-Westfalen	Germany	58452
73	GSK Investigational Site	Koblenz	Rheinland-Pfalz	Germany	56068
74	GSK Investigational Site	Leipzig	Sachsen	Germany	04103
75	GSK Investigational Site	Leipzig	Sachsen	Germany	04357
76	GSK Investigational Site	Schleswig	Schleswig-Holstein	Germany	24837
77	GSK Investigational Site	Berlin		Germany	10717
78	GSK Investigational Site	Berlin		Germany	12157
79	GSK Investigational Site	Berlin		Germany	12203
80	GSK Investigational Site	Hamburg		Germany	20354
81	GSK Investigational Site	Hamburg		Germany	22299
82	GSK Investigational Site	Athens		Greece	106 76
83	GSK Investigational Site	Athens		Greece	11527
84	GSK Investigational Site	Haidari / Athens		Greece	124 62
85	GSK Investigational Site	Rethymnon, Crete		Greece	74100
86	GSK Investigational Site	Thessaloniki		Greece	56403
87	GSK Investigational Site	Thessaloniki		Greece	56429
88	GSK Investigational Site	Thessaloniki		Greece	57010
89	GSK Investigational Site	Chieti	Abruzzo	Italy	66100
90	GSK Investigational Site	Parma	Emilia-Romagna	Italy	43100
91	GSK Investigational Site	Reggio Emilia	Emilia-Romagna	Italy	42100
92	GSK Investigational Site	Bari	Puglia	Italy	70124
93	GSK Investigational Site	Foggia	Puglia	Italy	71100
94	GSK Investigational Site	Firenze	Toscana	Italy	50134
95	GSK Investigational Site	Pisa	Toscana	Italy	56124
96	GSK Investigational Site	Amsterdam		Netherlands	1105 AZ
97	GSK Investigational Site	Breda		Netherlands	4818 CK
98	GSK Investigational Site	Leeuwarden		Netherlands	8934 AD
99	GSK Investigational Site	Leiden		Netherlands	2333 ZA
100	GSK Investigational Site	Rotterdam		Netherlands	3045 PM
101	GSK Investigational Site	Bergen		Norway	5021
102	GSK Investigational Site	Oslo		Norway	0405
103	GSK Investigational Site	Stavanger		Norway	4011
104	GSK Investigational Site	Trondheim		Norway	7006
105	GSK Investigational Site	Lima 27	Lima	Peru	Lima 27
106	GSK Investigational Site	San Martin de Porres	Lima	Peru	Lima 31
107	GSK Investigational Site	San Miguel	Lima	Peru	Lima 32
108	GSK Investigational Site	Lima		Peru	Lima 1
109	GSK Investigational Site	Lima		Peru	Lima 32
110	GSK Investigational Site	Ekaterinburg		Russian Federation	620109
111	GSK Investigational Site	Irkutsk		Russian Federation	664043
112	GSK Investigational Site	Moscow		Russian Federation	115211
113	GSK Investigational Site	Novosibirsk		Russian Federation	630102
114	GSK Investigational Site	Saint Petesburg		Russian Federation	195030
115	GSK Investigational Site	Sestroretsk		Russian Federation	197706
116	GSK Investigational Site	St. Petersburg		Russian Federation	198216
117	GSK Investigational Site	Stavropol		Russian Federation	355030
118	GSK Investigational Site	Voronezh		Russian Federation	394066
119	GSK Investigational Site	Bojnice		Slovakia	972 01
120	GSK Investigational Site	Sala		Slovakia	927 01
121	GSK Investigational Site	Spisska Nova Ves		Slovakia	052 01
122	GSK Investigational Site	Vrable		Slovakia	952 01
123	GSK Investigational Site	Alcorcón (Madrid)		Spain	28922
124	GSK Investigational Site	Alicante		Spain	03004
125	GSK Investigational Site	Barcelona		Spain	08041
126	GSK Investigational Site	Madrid		Spain	28041
127	GSK Investigational Site	Pozuelo De Alarcón/Madrid		Spain	28223
128	GSK Investigational Site	Santander		Spain	39008
129	GSK Investigational Site	Santiago de Compostela		Spain	15706
130	GSK Investigational Site	Valencia		Spain	46026
131	GSK Investigational Site	Dnepropetrovsk		Ukraine	49074
132	GSK Investigational Site	Kharkiv		Ukraine	61093
133	GSK Investigational Site	Kharkiv		Ukraine	61124
134	GSK Investigational Site	Kyiv		Ukraine	03038
135	GSK Investigational Site	Kyiv		Ukraine	03049
136	GSK Investigational Site	Kyiv		Ukraine	03680
137	GSK Investigational Site	Odesa		Ukraine	65025
138	GSK Investigational Site	Vinnytsia		Ukraine	21018
139	GSK Investigational Site	Vinnytsia		Ukraine	21029
140	GSK Investigational Site	Zaporizhia		Ukraine	69076
141	GSK Investigational Site	Bradford		United Kingdom	BD9 6RJ
142	GSK Investigational Site	Oxford		United Kingdom	OX3 7LE
143	GSK Investigational Site	Plymouth		United Kingdom	PL6 8DH
144	GSK Investigational Site	Swansea		United Kingdom	SA2 8PP

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT02281318
• Other Study ID Numbers: 200862
• First Posted: Nov 2, 2014
• Last Update Posted: Aug 6, 2018
• Last Verified: Aug 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Asthma control; Lung function; Health-related quality of life; Mepolizumab; Severe Eosinophilic asthma
• Additional relevant MeSH terms: Asthma; Pulmonary Eosinophilia

Study Results

Participant Flow

Pre-assignment Detail	A total of 830 participants (par.) were screened (Visit 1) and entered into the run-in period, of which 556 participants were randomized and 551 participants received either mepolizumab 100 milligrams (mg) or placebo in addition to standard of care asthma treatment.

Arm/Group Title	Placebo	Mepolizumab 100 mg
Arm/Group Description	Participants received placebo subcutaneously in upper arm or thigh following randomization at Visit 2 (Week 0) and every 4 weeks thereafter (last dose at Week 20) along with their standard of care asthma treatment up to 24 weeks.	Participants received mepolizumab 100 mg subcutaneously in upper arm or thigh following randomization at Visit 2 (Week 0) and every 4 weeks thereafter (last dose at Week 20) along with their standard of care asthma treatment up to 24 weeks.
Period Title: Overall Study
STARTED	277	274
COMPLETED	263	269
NOT COMPLETED	14	5

Baseline Characteristics

Arm/Group Title	Placebo	Mepolizumab 100 mg	Total
Arm/Group Description	Participants received placebo subcutaneously in upper arm or thigh following randomization at Visit 2 (Week 0) and every 4 weeks thereafter (last dose at Week 20) along with their standard of care asthma treatment up to 24 weeks.	Participants received mepolizumab 100 mg subcutaneously in upper arm or thigh following randomization at Visit 2 (Week 0) and every 4 weeks thereafter (last dose at Week 20) along with their standard of care asthma treatment up to 24 weeks.	Total of all reporting groups
Overall Participants	277	274	551
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	52.1 (12.94)	49.8 (14.01)	51.0 (13.52)
Sex: Female, Male (Count of Participants)
Female	176 63.5%	149 54.4%	325 59%
Male	101 36.5%	125 45.6%	226 41%
Race/Ethnicity, Customized (Number) [Number]
American Indian or Alaska Native	10 3.6%	9 3.3%	19 3.4%
Asian-Central/South Asian Heritage	0 0%	1 0.4%	1 0.2%
Asian-East Asian Heritage	0 0%	2 0.7%	2 0.4%
Asian-South East Asian Heritage	0 0%	1 0.4%	1 0.2%
Black or African American	7 2.5%	8 2.9%	15 2.7%
Native Hawaiian or Other Pacific Islander	1 0.4%	1 0.4%	2 0.4%
White-Arabic/North African Heritage	8 2.9%	1 0.4%	9 1.6%
White-White/Caucasian/European Heritage	251 90.6%	251 91.6%	502 91.1%

Outcome Measures

1. Primary Outcome

Title	Mean Change From Baseline (BL) in St. George's Respiratory Questionnaire (SGRQ) Score at Week 24
Description	SGRQ consisted of 50 questions (scored from 0 to 100 where 0 indicates best and 100 indicates worst health) designed to measure Quality of Life in par. with diseases of airway obstruction, measuring symptoms, impact, and activity. Questions were completed by the par. with a recall over the past 4 weeks. SGRQ Total Score was calculated by summing the pre-assigned weights of answers, dividing by the sum of the maximum weights for items in SGRQ and multiplying by 100 to get a %. Change from BL in SGRQ was calculated as value at Week 24 minus value at BL for each par. and was analyzed using mixed model repeated measures allowing for covariates of BL value, region, BL maintenance oral corticosteroid (OCS) therapy, exacerbations in the year prior to the study (as an ordinal variable), BL % predicted FEV1 and visit, plus interaction terms for visit by BL and visit by treatment group. Modified Intent-to-Treat (mITT) Population consisted of all randomized par. who received >= 1 dose of drug.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

mITT Population. Participants with a missing Baseline covariate value or with no observed change from Baseline at any time point were excluded from the analysis model.

Arm/Group Title	Placebo	Mepolizumab 100 mg
Arm/Group Description	Participants received placebo subcutaneously in upper arm or thigh following randomization at Visit 2 (Week 0) and every 4 weeks thereafter (last dose at Week 20) along with their standard of care asthma treatment up to 24 weeks.	Participants received mepolizumab 100 mg subcutaneously in upper arm or thigh following randomization at Visit 2 (Week 0) and every 4 weeks thereafter (last dose at Week 20) along with their standard of care asthma treatment up to 24 weeks.
Measure Participants	260	265
Least Squares Mean (Standard Error) [Scores on a scale]	-7.9 (1.01)	-15.6 (1.00)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mepolizumab 100 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed model repeated measures analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-7.7
	Confidence Interval	(2-Sided) 95%; -10.5 to -4.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Mean Change From Baseline in Clinic Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) at Week 24
Description	FEV1 is the volume of air that can be forced out in one second after taking a deep breath. The change from Baseline in pre-bronchodilator FEV1 was calculated as the value at Week 24 minus the value at Baseline for each subject and was analyzed using a mixed model repeated measures adjusting for Baseline absolute pre-bronchodilator FEV1, region, Baseline maintenance OCS therapy, exacerbations in the year prior to the study and visit, plus interaction terms for visit by Baseline and visit by treatment group.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

mITT Population. Participants with a missing Baseline covariate value or with no observed change from Baseline at any time point were excluded from the analysis model.

Arm/Group Title	Placebo	Mepolizumab 100 mg
Arm/Group Description	Participants received placebo subcutaneously in upper arm or thigh following randomization at Visit 2 (Week 0) and every 4 weeks thereafter (last dose at Week 20) along with their standard of care asthma treatment up to 24 weeks.	Participants received mepolizumab 100 mg subcutaneously in upper arm or thigh following randomization at Visit 2 (Week 0) and every 4 weeks thereafter (last dose at Week 20) along with their standard of care asthma treatment up to 24 weeks.
Measure Participants	259	264
Least Squares Mean (Standard Error) [Milliliters (mL)]	56 (26.2)	176 (26.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mepolizumab 100 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Mixed model repeated measures analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	120
	Confidence Interval	(2-Sided) 95%; 47 to 192
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants Achieving a 4 Point or Greater Reduction From Baseline in SGRQ Score at Week 24
Description	The percentage of participants achieving a 4 point or greater reduction from Baseline in SGRQ (scored from 0-100 with lower scores indicating better outcome) at Week 24 was compared between treatment groups using a logistic regression model with covariates of Baseline value, region, Baseline maintenance OCS therapy, exacerbations in the year prior to the study (as an ordinal variable) and Baseline % predicted FEV1.
Time Frame	Baseline (Visit 2-latest pre-dose assessment) and Week 24

Outcome Measure Data

Analysis Population Description

mITT Population. Participants with a missing Baseline covariate value were excluded from the analysis model.

Arm/Group Title	Placebo	Mepolizumab 100 mg
Arm/Group Description	Participants received placebo subcutaneously in upper arm or thigh following randomization at Visit 2 (Week 0) and every 4 weeks thereafter (last dose at Week 20) along with their standard of care asthma treatment up to 24 weeks.	Participants received mepolizumab 100 mg subcutaneously in upper arm or thigh following randomization at Visit 2 (Week 0) and every 4 weeks thereafter (last dose at Week 20) along with their standard of care asthma treatment up to 24 weeks.
Measure Participants	275	273
Number [Percentage of participants]	55 19.9%	73 26.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mepolizumab 100 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.23
	Confidence Interval	(2-Sided) 95%; 1.55 to 3.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Mean Change From Baseline in Asthma Control Questionnaire (ACQ-5) Score at Week 24
Description	The ACQ-5 is a five-item questionnaire, designed to be self-completed by the participants. ACQ-5 score is the mean score of 5 questions, each assessed on a 0-6 point scale to give a mean ranging between 0-6 with lower scores indicating better outcome. The five questions inquired about the frequency and/or severity of symptoms over the previous week. The response options for all these questions consisted of a zero (no impairment/limitation) to six (total impairment/limitation) scale. The mean change from Baseline was calculated as the value at Week 24 minus the Baseline value for each participant and analyzed using a mixed model repeated measures allowing for covariates of Baseline value, region, Baseline maintenance OCS therapy, exacerbations in the year prior to the study (as an ordinal variable), Baseline % predicted FEV1 and visit, plus interaction terms for visit by Baseline and visit by treatment group.
Time Frame	Baseline and Week 24

Outcome Measure Data

Analysis Population Description

mITT Population. Participants with a missing Baseline covariate value or with no observed change from Baseline at any time point were excluded from the analysis model.

Arm/Group Title	Placebo	Mepolizumab 100 mg
Arm/Group Description	Participants received placebo subcutaneously in upper arm or thigh following randomization at Visit 2 (Week 0) and every 4 weeks thereafter (last dose at Week 20) along with their standard of care asthma treatment up to 24 weeks.	Participants received mepolizumab 100 mg subcutaneously in upper arm or thigh following randomization at Visit 2 (Week 0) and every 4 weeks thereafter (last dose at Week 20) along with their standard of care asthma treatment up to 24 weeks.
Measure Participants	261	266
Least Squares Mean (Standard Error) [Scores on a scale]	-0.40 (0.064)	-0.80 (0.064)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mepolizumab 100 mg
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Mixed model repeated measures analysis
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.40
	Confidence Interval	(2-Sided) 95%; -0.58 to -0.22
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	All serious adverse events (SAEs) and on-treatment non-serious adverse events (AEs) were collected from the start of investigational product and until 28 days after the IP stop date (on-treatment) and to the end of the study for SAEs (Week 24).
Adverse Event Reporting Description	The Safety Population consisted of all randomized participants who received at least one dose of trial medication. Subjects were analysed according to treatment actually received.
Arm/Group Title	Placebo		Mepolizumab 100 mg SC
Arm/Group Description	Participants received placebo subcutaneously in upper arm or thigh following randomization at Visit 2 (Week 0) and every 4 weeks thereafter (last dose at Week 20) along with their standard of care asthma treatment up to 24 weeks.		Participants received mepolizumab 100 mg subcutaneously in upper arm or thigh following randomization at Visit 2 (Week 0) and every 4 weeks thereafter (last dose at Week 20) along with their standard of care asthma treatment up to 24 weeks.
All Cause Mortality
	Placebo		Mepolizumab 100 mg SC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Placebo		Mepolizumab 100 mg SC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/278 (8.3%)		15/273 (5.5%)
Blood and lymphatic system disorders
Anemia	1/278 (0.4%)		0/273 (0%)
Cardiac disorders
Myocardial ischemia	1/278 (0.4%)		0/273 (0%)
Palpitations	0/278 (0%)		1/273 (0.4%)
Endocrine disorders
Adrenal insufficiency	1/278 (0.4%)		0/273 (0%)
Gastrointestinal disorders
Hiatus hernia	0/278 (0%)		1/273 (0.4%)
General disorders
Non-cardiac chest pain	1/278 (0.4%)		0/273 (0%)
Pyrexia	1/278 (0.4%)		0/273 (0%)
Immune system disorders
Allergic granulomatous angiitis	0/278 (0%)		1/273 (0.4%)
Hypersensitivity	1/278 (0.4%)		0/273 (0%)
Infections and infestations
Appendicitis	0/278 (0%)		1/273 (0.4%)
Bronchitis bacterial	1/278 (0.4%)		0/273 (0%)
Catheter site infection	0/278 (0%)		1/273 (0.4%)
Cellulitis	1/278 (0.4%)		0/273 (0%)
Gastroenteritis rotavirus	1/278 (0.4%)		0/273 (0%)
Hemophilus infection	1/278 (0.4%)		0/273 (0%)
Laryngitis	0/278 (0%)		1/273 (0.4%)
Localized infection	1/278 (0.4%)		0/273 (0%)
Lung infection	1/278 (0.4%)		0/273 (0%)
Sinusitis	1/278 (0.4%)		0/273 (0%)
Staphylococcal bacteremia	0/278 (0%)		1/273 (0.4%)
Staphylococcal infection	0/278 (0%)		1/273 (0.4%)
Injury, poisoning and procedural complications
Post procedural complication	2/278 (0.7%)		0/273 (0%)
Clavicle fracture	0/278 (0%)		1/273 (0.4%)
Fibula fracture	1/278 (0.4%)		0/273 (0%)
Meniscus injury	0/278 (0%)		1/273 (0.4%)
Tibia fracture	1/278 (0.4%)		0/273 (0%)
Investigations
Blood glucose increased	0/278 (0%)		1/273 (0.4%)
Metabolism and nutrition disorders
Dehydration	1/278 (0.4%)		0/273 (0%)
Musculoskeletal and connective tissue disorders
Rheumatic disorder	1/278 (0.4%)		0/273 (0%)
Nervous system disorders
Dizziness	0/278 (0%)		1/273 (0.4%)
Renal and urinary disorders
Urethral stenosis	0/278 (0%)		1/273 (0.4%)
Respiratory, thoracic and mediastinal disorders
Asthma	9/278 (3.2%)		3/273 (1.1%)
Acute respiratory failure	1/278 (0.4%)		0/273 (0%)
Nasal polyps	0/278 (0%)		1/273 (0.4%)
Skin and subcutaneous tissue disorders
Angioedema	1/278 (0.4%)		0/273 (0%)
Dermatitis atopic	1/278 (0.4%)		0/273 (0%)
Vascular disorders
Hypertension	1/278 (0.4%)		0/273 (0%)
Hypotension	1/278 (0.4%)		0/273 (0%)
Subclavian vein thrombosis	0/278 (0%)		1/273 (0.4%)
Vasculitis	1/278 (0.4%)		0/273 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Mepolizumab 100 mg SC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	140/278 (50.4%)		124/273 (45.4%)
Gastrointestinal disorders
Nausea	7/278 (2.5%)		10/273 (3.7%)
General disorders
Fatigue	11/278 (4%)		7/273 (2.6%)
Infections and infestations
Nasopharyngitis	46/278 (16.5%)		31/273 (11.4%)
Upper respiratory tract infection	14/278 (5%)		17/273 (6.2%)
Sinusitis	12/278 (4.3%)		11/273 (4%)
Bronchitis	11/278 (4%)		6/273 (2.2%)
Rhinitis	7/278 (2.5%)		10/273 (3.7%)
Musculoskeletal and connective tissue disorders
Back pain	18/278 (6.5%)		13/273 (4.8%)
Arthralgia	18/278 (6.5%)		9/273 (3.3%)
Muscle spasms	10/278 (3.6%)		3/273 (1.1%)
Nervous system disorders
Headache	59/278 (21.2%)		45/273 (16.5%)
Respiratory, thoracic and mediastinal disorders
Nasal congestion	14/278 (5%)		4/273 (1.5%)
Oropharyngeal pain	8/278 (2.9%)		11/273 (4%)

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.