Mepolizumab Steroid-Sparing Study in Subjects With Severe Refractory Asthma

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01691508
• Collaborator: (none)
• Enrollment: 135
• Locations: 47
• Arms: 2
• Duration (Months): 14
• Patients Per Site: 2.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

This is a randomised, double-blind, placebo-controlled, parallel-group, multicenter study of mepolizumab in comparison with placebo in reducing Oral Corticosteroid (OCS) use in subjects with severe refractory asthma. The study consists of four phases, OCS Optimisation Phase (Week -8 to Week 0), and the double-blind treatment period divided into an Induction Phase (Week 0 to Week 4), OCS Reduction Phase (Week 5 upto Week 20) followed by Maintenance Phase (Week 20 to Week 24). During the Optimisation Phase the investigator will adjust the OCS (prednisone/prednisolone) dose according to the Optimisation titration schedule based on a review of Asthma Control Questionnaire (ACQ)-5 score and exacerbation. In the Induction Phase subjects will be randomized 1:1 (approximately 60 per arm) to receive either mepolizumab (100 mg) administered subcutaneously (SC) or placebo every 4 weeks in addition to their existing maintenance asthma therapy with the lowest dose of OCS from Optimisation Phase. The Induction Phase will allow sufficient time for those subjects randomised to the mepolizumab arm to achieve a decrease in the eosinophilic inflammation prior to the reduction in OCS. During the Reduction Phase, subjects will continue receiving 100 mg mepolizumab/placebo every 4 weeks and the OCS dose reduction will be done every 4 weeks using the reduction titration schedule based on a review of eDiary parameters recorded by the subject, the subjects' exacerbation history, and a review of the signs and symptoms of adrenal insufficiency. In the Maintenance Phase subjects will be maintained without any further OCS dose adjustment. Subjects who complete the 24 week double-blind period and meet the eligibility criteria, will be offered the opportunity to participate in an open label extension (OLE) study otherwise they will return for a Follow-up Visit 12 weeks after their last dose of double blind study treatment. At each clinic visit, adverse events, safety labs, spirometery parameters and exacerbations will be assessed. The pharmacokinetic samples will be collected in the beginning of the treatment, prior to last dose, at the end of study (exit visit) and the follow up.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: Mepolizumab; Drug: Placebo; Drug: OCS (prednisone/prednisolone)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 135 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: MEA115575: A Randomised, Double-Blind, Placebo-Controlled, Parallel-Group, Multicenter Study of Mepolizumab Adjunctive Therapy to Reduce Steroid Use in Subjects With Severe Refractory Asthma
• Study Start Date: Oct 1, 2012
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Mepolizumab Mepolizumab 100 mg subcutaneous once every 4 weeks upto Week 20	Drug: Mepolizumab; Mepolizumab is a fully humanised Immunoglobulin G antibody (IgG1, kappa) with human heavy and light chain frameworks.; Drug: OCS (prednisone/prednisolone); Oral Corticosteroid (prednisone/prednisolone)
Experimental: Placebo Placebo subcutaneous once every 4 weeks upto Week 20	Drug: Placebo; Will be available as an equivalent volume of 0.9% sodium chloride.; Drug: OCS (prednisone/prednisolone); Oral Corticosteroid (prednisone/prednisolone)

Outcome Measures

Primary Outcome Measures

1. Number of Participants With the Indicated Percent Reduction From Baseline in Oral Corticosteroid (OCS) Dose During Weeks 20 to 24 While Maintaining Asthma Control [Baseline; Weeks 20 to 24]

   Baseline (BL) dose was the prescribed optimized prednisone/prednisolone dose following the OCS Optimization Phase. Maintenance (MN) dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). The percent reduction of OCS dose during weeks 20 to 24 compared to BL dose was calculated as: 100 x (BL dose minus MN dose)/BL dose. Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. The percent reduction of OCS was categorized as: 90 to 100%; 75 to <90%; 50 to <75%; >0 to <50%; no decrease in prednisone dose, or lack of asthma control, or withdrawal (WD) from treatment. Analysis was performed using a proportional odds model with terms for treatment group, region, duration of OCS use at BL (<5 years vs. >=5 years) and BL OCS dose.

Secondary Outcome Measures

1. Number of Participants Who Achieved a Reduction of >=50% in Their Daily Oral Corticosteroid (OCS) Dose Compared With Baseline Dose, During Weeks 20 to 24 While Maintaining Asthma Control [Baseline; Weeks 20 to 24]

   Baseline (BL) dose was the prescribed optimized prednisone/prednisolone dose following the OCS Optimization Phase. Maintenance (MN) dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). The percent reduction of OCS dose during weeks 20 to 24 compared to BL dose was calculated as: 100 x (BL dose minus MN dose)/BL dose. Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. Analysis was performed using a binary logistic regression model with terms for treatment group, region, duration of OCS use at BL (<5 years vs. >=5 years) and BL OCS dose.

2. Number of Participants Who Achieved a Reduction of Their Daily OCS Dose to <=5.0 mg During Weeks 20 to 24 While Maintaining Asthma Control [Weeks 20 to 24]

   Maintenance (MN) dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. Number of participants who achieved a reduction of their daily OCS dose to <=5.0 mg was based on the value of the MN dose. Analysis was performed using a binary logistic regression model with terms for treatment group, region, duration of OCS use at BL (<5 years vs. >=5 years) and BL OCS dose.

3. Number of Participants Who Achieved a Total Reduction of OCS Dose During Weeks 20 to 24 While Maintaining Asthma Control [Weeks 20 to 24]

   MN dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. The number of participants who achieved a total reduction of OCS dose was based on the value of the MN dose. Total reduction implied no OCS use during the entire MN phase. Analysis was performed using a binary logistic regression model with terms for treatment group, region, duration of OCS use at BL (<5 years vs. >=5 years) and BL OCS dose.

4. Median Percentage Change From Baseline in Daily OCS Dose During Weeks 20 to 24 While Maintaining Asthma Control [Baseline; Weeks 20 to 24]

   BL dose was the prescribed optimized prednisone/prednisolone dose following the OCS Optimization Phase. MN dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). The percent change of OCS dose during weeks 20 to 24 compared to BL dose was calculated as: 100 x (MN dose minus BL dose)/BL dose. Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. For participants who withdrew from the study prior to the Maintenance Phase, and for participants with a lack of asthma control during the Maintenance Phase, a value equal to the minimum percent reduction in OCS use across all subjects was imputed for the analysis.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Informed Consent and Study Compliance: Subjects must be able to give written informed consent prior to participation in the study, which will include the ability to comply with the requirements and restrictions listed in the consent form.

• Systemic Corticosteroids: Requirement for regular treatment with maintenance systemic corticosteroids in the 6 months prior to Visit 1 and using a stable oral corticosteroid dose for 4 weeks prior to Visit 1. Subjects must be taking 5.0 to 35 mg/day of prednisone or equivalent at Visit 1 and must agree to switch to study required prednisone/prednisolone as their oral corticosteroid and use it per protocol for the duration of the study.

• Inhaled Corticosteroids: Requirement for regular treatment with high dose inhaled corticosteroid in the 6 months prior to Visit 1. For 18 years of age and older: inhaled corticosteroid (ICS) dose must be >=880 microgram (µg)/day fluticasone propionate (FP) (ex-actuator) or equivalent daily. For ICS/ long acting beta2 agonist (LABA) combination preparations, the highest approved maintenance dose in the local country will meet this ICS criterion. For ages 12 to 17: ICS dose must be >=440 μg/day FP (ex-actuator) or equivalent daily.

• Controller Medication: Current treatment with an additional controller medication for at least 3 months OR documentation of having used and failed an additional controller medication for at least 3 successive months during the prior 12 months [e.g., LABA, leukotriene receptor antagonist (LTRA), or theophylline].

• Eosinophilic Asthma: Prior documentation of eosinophilic asthma or high likelihood of eosinophilic asthma.

• FEV1: Persistent airflow obstruction as indicated by a pre-bronchodilator FEV1 <80% predicted.

• Asthma: Evidence of asthma indicated by airway reversibility, hyperresponsiveness or airway variability.

Exclusion Criteria:

• Smoking history: Current smokers or former smokers with a smoking history of >=10 pack years.

• Concurrent Respiratory Disease: Presence of a clinically important lung condition other than asthma.

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

• Liver Disease: Unstable liver disease

• Cardiovascular: Subjects who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment.

• Other Concurrent Medical Conditions: Subjects 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: Subjects with other conditions that could lead to elevated eosinophils such as Hypereosiniophilic Syndromes, including Churg-Strauss Syndrome, or Eosinophilic Esophaghitis. Subjects with a known, pre-existing parasitic infestation within 6 months prior to Visit 1 are also to be excluded.

• ECG: ECG assessment QTcF >=450 milliseconds (msec) or QTcF >= 480 msec for subjects with Bundle Branch Block.

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

• Omalizumab Use: Subjects who have received omalizumab [Xolair] within 130 days of Visit 1.

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

• Investigational Medications: Subjects 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: Subjects with a known allergy or intolerance to a monoclonal antibody or biologic.

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

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

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

• Previous participation: Subjects who have previously any study of mepolizumab and received Investigational Product.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Long Beach	California	United States	90808
2	GSK Investigational Site	Denver	Colorado	United States	80206
3	GSK Investigational Site	New Haven	Connecticut	United States	06520
4	GSK Investigational Site	Rochester	Minnesota	United States	55905
5	GSK Investigational Site	St. Louis	Missouri	United States	63110
6	GSK Investigational Site	Cincinnati	Ohio	United States	45229
7	GSK Investigational Site	Pittsburg	Pennsylvania	United States	PA 15213
8	GSK Investigational Site	Spartanburg	South Carolina	United States	29303
9	GSK Investigational Site	New Lambton	New South Wales	Australia	2305
10	GSK Investigational Site	Bedford Park	South Australia	Australia	5042
11	GSK Investigational Site	Parkville	Victoria	Australia	3050
12	GSK Investigational Site	Nedlands	Western Australia	Australia	6009
13	GSK Investigational Site	Hamilton	Ontario	Canada	L8N 4A6
14	GSK Investigational Site	Montreal	Quebec	Canada	H2X 2P4
15	GSK Investigational Site	Montreal	Quebec	Canada	H4J 1C5
16	GSK Investigational Site	Quebec City	Quebec	Canada	G1V 4G5
17	GSK Investigational Site	Brno		Czech Republic	625 00
18	GSK Investigational Site	Olomouc		Czech Republic	775 20
19	GSK Investigational Site	Praha 4		Czech Republic	140 59
20	GSK Investigational Site	Praha 8		Czech Republic	180 01
21	GSK Investigational Site	Gières		France	38610
22	GSK Investigational Site	Montpellier cedex 5		France	34295
23	GSK Investigational Site	Nantes cedex 1		France	44093
24	GSK Investigational Site	Paris Cedex 18		France	75877
25	GSK Investigational Site	Strasbourg		France	67091
26	GSK Investigational Site	Aschaffenburg	Bayern	Germany	63739
27	GSK Investigational Site	Potsdam	Brandenburg	Germany	14478
28	GSK Investigational Site	Ruedersdorf	Brandenburg	Germany	15562
29	GSK Investigational Site	Frankfurt	Hessen	Germany	60596
30	GSK Investigational Site	Gelnhausen	Hessen	Germany	63571
31	GSK Investigational Site	Neu isenburg	Hessen	Germany	63263
32	GSK Investigational Site	Hannover	Niedersachsen	Germany	30173
33	GSK Investigational Site	Mainz	Rheinland-Pfalz	Germany	55131
34	GSK Investigational Site	Luebeck	Schleswig-Holstein	Germany	23552
35	GSK Investigational Site	Guadalajara	Jalisco	Mexico	44100
36	GSK Investigational Site	Zapopan	Jalisco	Mexico	45040
37	GSK Investigational Site	Amsterdam		Netherlands	1105 AZ
38	GSK Investigational Site	Leeuwarden		Netherlands	8934 AD
39	GSK Investigational Site	Rotterdam		Netherlands	3045 PM
40	GSK Investigational Site	Bialystok		Poland	15-010
41	GSK Investigational Site	Bialystok		Poland	15-044
42	GSK Investigational Site	Krakow		Poland	31-024
43	GSK Investigational Site	Lodz		Poland	90-153
44	GSK Investigational Site	Leicester	Leicestershire	United Kingdom	LE3 9QP
45	GSK Investigational Site	Liverpool		United Kingdom	L9 7AL
46	GSK Investigational Site	Newcastle upon Tyne		United Kingdom	NE1 4LP
47	GSK Investigational Site	Southampton		United Kingdom	SO16 6YD

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: NCT01691508
• Other Study ID Numbers: 115575
• First Posted: Sep 24, 2012
• Last Update Posted: Mar 23, 2017
• Last Verified: Mar 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Safety; Steroid Reduction; Efficacy; SB-240563; Eosinophils; Quality of Life; Mepolizumab; Severe Refractory Asthma
• Additional relevant MeSH terms: Asthma; Prednisone; Prednisolone

Study Results

Participant Flow

Recruitment Details	The study consisted 4 phases: oral corticosteroids (OCS) Optimization (Run-in); Induction; OCS Reduction and Maintenance. Participants (par.) who completed the 4 phases and met the eligibility criteria were offered the opportunity to participate in an open label extension (OLE) study. Par. not entering the OLE study completed the Follow-up Visit.
Pre-assignment Detail	A total of 185 par. were screened; 3 par. were Screen failures; 47 par. were Run-in failures; 135 par. were randomized and received >=1 dose of study drug.

Arm/Group Title	Placebo	Mepolizumab 100mg SC
Arm/Group Description	Participants received placebo subcutaneously (SC) every 4 weeks (for a total of 6 doses),with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.	Participants received mepolizumab 100 mg SC every 4 weeks (for a total of 6 doses), with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.
Period Title: Overall Study
STARTED	66	69
COMPLETED	62	66
NOT COMPLETED	4	3

Baseline Characteristics

Arm/Group Title	Placebo	Mepolizumab 100 mg SC	Total
Arm/Group Description	Participants received placebo subcutaneously (SC) every 4 weeks (for a total of 6 doses),with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.	Participants received mepolizumab 100 mg SC every 4 weeks (for a total of 6 doses), with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.	Total of all reporting groups
Overall Participants	66	69	135
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	49.9 (10.30)	49.8 (14.10)	49.9 (12.34)
Sex: Female, Male (Count of Participants)
Female	30 45.5%	44 63.8%	74 54.8%
Male	36 54.5%	25 36.2%	61 45.2%
Race/Ethnicity, Customized (Number) [Number]
American Indian or Alaskan Native	1 1.5%	0 0%	1 0.7%
Asian - Central/South Asian Heritage	1 1.5%	0 0%	1 0.7%
Asian - East Asian Heritage	0 0%	1 1.4%	1 0.7%
Asian - South East Asian Heritage	1 1.5%	0 0%	1 0.7%
Native Hawaiian or Other Pacific Islander	1 1.5%	0 0%	1 0.7%
White - Arabic/North African Heritage	1 1.5%	2 2.9%	3 2.2%
White - White/Caucasian/European Heritage	60 90.9%	65 94.2%	125 92.6%
Mixed Race	1 1.5%	1 1.4%	2 1.5%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With the Indicated Percent Reduction From Baseline in Oral Corticosteroid (OCS) Dose During Weeks 20 to 24 While Maintaining Asthma Control
Description	Baseline (BL) dose was the prescribed optimized prednisone/prednisolone dose following the OCS Optimization Phase. Maintenance (MN) dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). The percent reduction of OCS dose during weeks 20 to 24 compared to BL dose was calculated as: 100 x (BL dose minus MN dose)/BL dose. Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. The percent reduction of OCS was categorized as: 90 to 100%; 75 to <90%; 50 to <75%; >0 to <50%; no decrease in prednisone dose, or lack of asthma control, or withdrawal (WD) from treatment. Analysis was performed using a proportional odds model with terms for treatment group, region, duration of OCS use at BL (<5 years vs. >=5 years) and BL OCS dose.
Time Frame	Baseline; Weeks 20 to 24

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT) Population: all participants who were randomized and who received at least one dose of study medication.

Arm/Group Title	Placebo	Mepolizumab 100 mg SC
Arm/Group Description	Participants received placebo subcutaneously (SC) every 4 weeks (for a total of 6 doses),with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.	Participants received mepolizumab 100 mg SC every 4 weeks (for a total of 6 doses), with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.
Measure Participants	66	69
90 to 100%	7 10.6%	16 23.2%
75 to <90%	5 7.6%	12 17.4%
50 to <75%	10 15.2%	9 13%
>0 to <50%	7 10.6%	7 10.1%
No decrease /lack of asthma control/early WD	37 56.1%	25 36.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Mepolizumab 100 mg SC
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.008
	Comments
	Method	Proportional odds model
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	2.39
	Confidence Interval	(2-Sided) 95%; 1.25 to 4.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Participants Who Achieved a Reduction of >=50% in Their Daily Oral Corticosteroid (OCS) Dose Compared With Baseline Dose, During Weeks 20 to 24 While Maintaining Asthma Control
Description	Baseline (BL) dose was the prescribed optimized prednisone/prednisolone dose following the OCS Optimization Phase. Maintenance (MN) dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). The percent reduction of OCS dose during weeks 20 to 24 compared to BL dose was calculated as: 100 x (BL dose minus MN dose)/BL dose. Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. Analysis was performed using a binary logistic regression model with terms for treatment group, region, duration of OCS use at BL (<5 years vs. >=5 years) and BL OCS dose.
Time Frame	Baseline; Weeks 20 to 24

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	Mepolizumab 100 mg SC
Arm/Group Description	Participants received placebo subcutaneously (SC) every 4 weeks (for a total of 6 doses),with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.	Participants received mepolizumab 100 mg SC every 4 weeks (for a total of 6 doses), with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.
Measure Participants	66	69
50 to 100%	22 33.3%	37 53.6%
<50% or no decrease/lack of asthma control/WD	44 66.7%	32 46.4%

3. Secondary Outcome

Title	Number of Participants Who Achieved a Reduction of Their Daily OCS Dose to <=5.0 mg During Weeks 20 to 24 While Maintaining Asthma Control
Description	Maintenance (MN) dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. Number of participants who achieved a reduction of their daily OCS dose to <=5.0 mg was based on the value of the MN dose. Analysis was performed using a binary logistic regression model with terms for treatment group, region, duration of OCS use at BL (<5 years vs. >=5 years) and BL OCS dose.
Time Frame	Weeks 20 to 24

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	Mepolizumab 100 mg SC
Arm/Group Description	Participants received placebo subcutaneously (SC) every 4 weeks (for a total of 6 doses),with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.	Participants received mepolizumab 100 mg SC every 4 weeks (for a total of 6 doses), with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.
Measure Participants	66	69
<=5 mg/day	21 31.8%	37 53.6%
>5 mg/day or lack of asthma control or WD	45 68.2%	32 46.4%

4. Secondary Outcome

Title	Number of Participants Who Achieved a Total Reduction of OCS Dose During Weeks 20 to 24 While Maintaining Asthma Control
Description	MN dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. The number of participants who achieved a total reduction of OCS dose was based on the value of the MN dose. Total reduction implied no OCS use during the entire MN phase. Analysis was performed using a binary logistic regression model with terms for treatment group, region, duration of OCS use at BL (<5 years vs. >=5 years) and BL OCS dose.
Time Frame	Weeks 20 to 24

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	Mepolizumab 100 mg SC
Arm/Group Description	Participants received placebo subcutaneously (SC) every 4 weeks (for a total of 6 doses),with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.	Participants received mepolizumab 100 mg SC every 4 weeks (for a total of 6 doses), with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.
Measure Participants	66	69
0 mg/day	5 7.6%	10 14.5%
OCS taken or lack of asthma control or WD	61 92.4%	59 85.5%

5. Secondary Outcome

Title	Median Percentage Change From Baseline in Daily OCS Dose During Weeks 20 to 24 While Maintaining Asthma Control
Description	BL dose was the prescribed optimized prednisone/prednisolone dose following the OCS Optimization Phase. MN dose was the mean of all daily prednisone/prednisolone doses during the MN Phase (weeks 20 to 24). The percent change of OCS dose during weeks 20 to 24 compared to BL dose was calculated as: 100 x (MN dose minus BL dose)/BL dose. Asthma control between weeks 20 and 24 was defined as no clinically significant exacerbation (worsening of asthma that required use of systemic corticosteroids or hospitalization and/or emergency department visits) during this period. For participants who withdrew from the study prior to the Maintenance Phase, and for participants with a lack of asthma control during the Maintenance Phase, a value equal to the minimum percent reduction in OCS use across all subjects was imputed for the analysis.
Time Frame	Baseline; Weeks 20 to 24

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	Placebo	Mepolizumab 100 mg SC
Arm/Group Description	Participants received placebo subcutaneously (SC) every 4 weeks (for a total of 6 doses),with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.	Participants received mepolizumab 100 mg SC every 4 weeks (for a total of 6 doses), with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.
Measure Participants	66	69
Median (95% Confidence Interval) [Percentage reduction in OCS dose]	0.0	-50.0

Adverse Events

Time Frame	On-treatment serious adverse events (SAEs) and non-serious AEs were defined as events occurring from the first dose of investigational product until 28 days after the last dose of investigational product, up to 24 weeks.
Adverse Event Reporting Description	SAEs and Non-serious AEs were collected in members of Intent-to-Treat (ITT) Population, comprised of all participants who were randomized and who received at least one dose of study medication.
Arm/Group Title	Placebo		Mepolizumab 100 mg SC
Arm/Group Description	Participants received placebo subcutaneously (SC) every 4 weeks (for a total of 6 doses),with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.		Participants received mepolizumab 100 mg SC every 4 weeks (for a total of 6 doses), with the last dose at Week 20. A topical anaesthetic was permitted at the injection site to minimize discomfort, as needed. Rescue personnel and rescue medications (salbutamol/albuterol) /equipment were available throughout the study.
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	12/66 (18.2%)		1/69 (1.4%)
Infections and infestations
Pneumonia	3/66 (4.5%)		0/69 (0%)
Chronic sinusitis	0/66 (0%)		1/69 (1.4%)
Urinary tract infection	1/66 (1.5%)		0/69 (0%)
Injury, poisoning and procedural complications
Post gastric surgery syndrome	1/66 (1.5%)		0/69 (0%)
Metabolism and nutrition disorders
Hypokalaemia	0/66 (0%)		1/69 (1.4%)
Musculoskeletal and connective tissue disorders
Fistula	0/66 (0%)		1/69 (1.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basosquamous carcinoma	1/66 (1.5%)		0/69 (0%)
Prostate cancer	1/66 (1.5%)		0/69 (0%)
Reproductive system and breast disorders
Prostatitis	1/66 (1.5%)		0/69 (0%)
Respiratory, thoracic and mediastinal disorders
Asthma	7/66 (10.6%)		0/69 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Mepolizumab 100 mg SC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	53/66 (80.3%)		47/69 (68.1%)
Cardiac disorders
Palpitations	2/66 (3%)		0/69 (0%)
Endocrine disorders
Adrenal insufficiency	4/66 (6.1%)		3/69 (4.3%)
Eye disorders
Eye pruritus	2/66 (3%)		0/69 (0%)
Gastrointestinal disorders
Nausea	6/66 (9.1%)		4/69 (5.8%)
Toothache	3/66 (4.5%)		1/69 (1.4%)
Diarrhoea	2/66 (3%)		0/69 (0%)
General disorders
Fatigue	4/66 (6.1%)		7/69 (10.1%)
Pyrexia	4/66 (6.1%)		3/69 (4.3%)
Injection site reaction	2/66 (3%)		4/69 (5.8%)
Oedema peripheral	2/66 (3%)		4/69 (5.8%)
Immune system disorders
Hypersensitivity	3/66 (4.5%)		1/69 (1.4%)
Infections and infestations
Nasopharyngitis	10/66 (15.2%)		10/69 (14.5%)
Bronchitis	6/66 (9.1%)		7/69 (10.1%)
Sinusitis	6/66 (9.1%)		7/69 (10.1%)
Upper respiratory tract infection	5/66 (7.6%)		3/69 (4.3%)
Rhinitis	1/66 (1.5%)		5/69 (7.2%)
Lower respiratory tract infection	2/66 (3%)		3/69 (4.3%)
Influenza	1/66 (1.5%)		3/69 (4.3%)
Urinary tract infection	2/66 (3%)		2/69 (2.9%)
Cystitis	2/66 (3%)		1/69 (1.4%)
Otitis media	2/66 (3%)		1/69 (1.4%)
Oral candidiasis	2/66 (3%)		0/69 (0%)
Tooth infection	2/66 (3%)		0/69 (0%)
Injury, poisoning and procedural complications
Injection related reaction	2/66 (3%)		2/69 (2.9%)
Musculoskeletal and connective tissue disorders
Arthralgia	4/66 (6.1%)		5/69 (7.2%)
Pain in extremity	1/66 (1.5%)		4/69 (5.8%)
Back pain	2/66 (3%)		2/69 (2.9%)
Muscle spasms	0/66 (0%)		4/69 (5.8%)
Musculoskeletal chest pain	2/66 (3%)		0/69 (0%)
Nervous system disorders
Headache	14/66 (21.2%)		14/69 (20.3%)
Dizziness	3/66 (4.5%)		2/69 (2.9%)
Sinus headache	2/66 (3%)		1/69 (1.4%)
Psychiatric disorders
Insomnia	1/66 (1.5%)		3/69 (4.3%)
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain	5/66 (7.6%)		4/69 (5.8%)
Skin and subcutaneous tissue disorders
Pruritus	2/66 (3%)		2/69 (2.9%)
Urticaria	2/66 (3%)		1/69 (1.4%)
Rash	2/66 (3%)		0/69 (0%)
Vascular disorders
Haematoma	2/66 (3%)		0/69 (0%)

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.