Trial Outcomes & Findings for Study to Evaluate Efficacy and Safety of Mepolizumab for Frequently Exacerbating Chronic Obstructive Pulmonary Disease (COPD) Patients (NCT NCT02105948)

Last Updated: 2018-08-31

Results Overview

Moderate exacerbations are defined as clinically significant exacerbations that require treatment with oral/systemic corticosteroids and/or antibiotics. Severe exacerbations are defined as clinically significant exacerbations that require in-patient hospitalization ( \>= 24 hours) or result in death. Moderate and severe exacerbations occurring from the start of investigational product (IP) up to the Week 52 visit, including exacerbations reported after early discontinuation from investigational product by subjects who remained in the study, were included in the analysis. The analysis was performed on the mITT high stratum (mITT-H) Population which comprised of participants in the mITT Population (all randomized participants who received at least one dose of study treatment) with blood eosinophil counts \>=150 cells/µL at Screening or \>=300 cells/ µL in the 12 months prior.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

837 participants

Primary outcome timeframe

From randomization to Week 52

Results posted on

2018-08-31

Participant Flow

Participants with chronic obstructive pulmonary disease (COPD) with frequent exacerbations and on high dose inhaled corticosteroid (ICS)-based triple inhaled maintenance therapy were included in this study. Participants were randomized to receive mepolizumab 100 milligrams (mg) or placebo by subcutaneous (SC) injection every 4 weeks for 52 weeks.

A total of 836 participants were randomized and received at least one dose of study treatment and were included in the modified intent to treat (mITT) population. One participant randomized to the placebo group was withdrawn without receiving study treatment.

Participant milestones

Participant milestones
Measure	Placebo - High Stratum Participants with blood eosinophil counts \>=150 cells per microliter (cells/µL) at Screening or \>=300 cells/µL in the 12 months prior were assigned to the high stratum group. These participants were randomized to and received placebo by SC injection every 4 weeks for up to 52 weeks in addition to their standard of care (SoC) therapy. Salbutamol metered dose inhaler (MDI) was issued for use as rescue medication throughout the study.	Mepolizumab 100 mg - High Stratum Participants with blood eosinophil counts \>=150 cells/µL at Screening or \>=300 cells/ µL in the 12 months prior were assigned to the high stratum group. These participants were randomized to and received mepolizumab 100 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.	Placebo - Low Stratum Participants with blood eosinophil counts \<150 cells/µL at Screening and no evidence of blood eosinophil counts \>=300 cells/µL in the 12 months prior were assigned to the low stratum group. These participants were randomized to and received placebo by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.	Mepolizumab 100 mg - Low Stratum Participants with blood eosinophil counts \<150 cells/µL at Screening and no evidence of blood eosinophil counts \>=300 cells/µL in the 12 months prior were assigned to the low stratum group. These participants were randomized to and received mepolizumab 100 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.
Overall Study STARTED	229	233	190	184
Overall Study Completed Investigational Product (IP)	185	203	148	149
Overall Study Not Completed IP	44	30	42	35
Overall Study Withdrew IP Due to: Adverse Event	20	16	15	13
Overall Study Withdrew IP Due to: Lack of Efficacy	5	2	8	2
Overall Study Withdrew IP Due to: Protocol Deviation	1	3	3	0
Overall Study Withdrew IP Due to: Lost to Follow-up	0	0	1	2
Overall Study Withdrew IP Due to: Withdrawal by Subj.	16	8	11	15
Overall Study Withdrew IP Due to: Physician Decision	2	1	4	2
Overall Study Withdrew IP Due to: Stopping Criteria	0	0	0	1
Overall Study COMPLETED	202	213	162	157
Overall Study NOT COMPLETED	27	20	28	27

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo - High Stratum Participants with blood eosinophil counts \>=150 cells per microliter (cells/µL) at Screening or \>=300 cells/µL in the 12 months prior were assigned to the high stratum group. These participants were randomized to and received placebo by SC injection every 4 weeks for up to 52 weeks in addition to their standard of care (SoC) therapy. Salbutamol metered dose inhaler (MDI) was issued for use as rescue medication throughout the study.	Mepolizumab 100 mg - High Stratum Participants with blood eosinophil counts \>=150 cells/µL at Screening or \>=300 cells/ µL in the 12 months prior were assigned to the high stratum group. These participants were randomized to and received mepolizumab 100 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.	Placebo - Low Stratum Participants with blood eosinophil counts \<150 cells/µL at Screening and no evidence of blood eosinophil counts \>=300 cells/µL in the 12 months prior were assigned to the low stratum group. These participants were randomized to and received placebo by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.	Mepolizumab 100 mg - Low Stratum Participants with blood eosinophil counts \<150 cells/µL at Screening and no evidence of blood eosinophil counts \>=300 cells/µL in the 12 months prior were assigned to the low stratum group. These participants were randomized to and received mepolizumab 100 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.
Overall Study Adverse Event	10	7	11	11
Overall Study Lack of Efficacy	0	1	3	2
Overall Study Lost to Follow-up	0	0	2	1
Overall Study Physician Decision	2	2	2	2
Overall Study Withdrawal by Subject	15	10	10	11

Baseline Characteristics

Study to Evaluate Efficacy and Safety of Mepolizumab for Frequently Exacerbating Chronic Obstructive Pulmonary Disease (COPD) Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo - High Stratum n=229 Participants Participants with blood eosinophil counts \>=150 cells/µL at Screening or \>=300 cells/µL in the 12 months prior were assigned to the high stratum group. These participants were randomized to and received placebo by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.	Mepolizumab 100 mg - High Stratum n=233 Participants Participants with blood eosinophil counts \>=150 cells/µL at Screening or \>=300 cells/ µL in the 12 months prior were assigned to the high stratum group. These participants were randomized to and received mepolizumab 100 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.	Placebo - Low Stratum n=190 Participants Participants with blood eosinophil counts \<150 cells/µL at Screening and no evidence of blood eosinophil counts \>=300 cells/µL in the 12 months prior were assigned to the low stratum group. These participants were randomized to and received placebo by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.	Mepolizumab 100 mg - Low Stratum n=184 Participants Participants with blood eosinophil counts \<150 cells/µL at Screening and no evidence of blood eosinophil counts \>=300 cells/µL in the 12 months prior were assigned to the low stratum group. These participants were randomized to and received mepolizumab 100 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.	Total n=836 Participants Total of all reporting groups
Age, Continuous	65.3 Years STANDARD_DEVIATION 8.53 • n=5 Participants	65.2 Years STANDARD_DEVIATION 8.36 • n=7 Participants	65.2 Years STANDARD_DEVIATION 8.62 • n=5 Participants	66.1 Years STANDARD_DEVIATION 9.14 • n=4 Participants	65.4 Years STANDARD_DEVIATION 8.64 • n=21 Participants
Sex: Female, Male Female	79 Participants n=5 Participants	84 Participants n=7 Participants	77 Participants n=5 Participants	76 Participants n=4 Participants	316 Participants n=21 Participants
Sex: Female, Male Male	150 Participants n=5 Participants	149 Participants n=7 Participants	113 Participants n=5 Participants	108 Participants n=4 Participants	520 Participants n=21 Participants
Race/Ethnicity, Customized Race customized · American Indian/ Alaska native Heritage	14 Participants n=5 Participants	19 Participants n=7 Participants	22 Participants n=5 Participants	14 Participants n=4 Participants	69 Participants n=21 Participants
Race/Ethnicity, Customized Race customized · Asian- East Asian Heritage	0 Participants n=5 Participants	2 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	2 Participants n=21 Participants
Race/Ethnicity, Customized Race customized · Asian- Japanese Heritage	3 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants	5 Participants n=21 Participants
Race/Ethnicity, Customized Race customized · Black/ African American Heritage	4 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants	2 Participants n=4 Participants	11 Participants n=21 Participants
Race/Ethnicity, Customized Race customized · White- Arabic/ North African Heritage	2 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants	4 Participants n=21 Participants
Race/Ethnicity, Customized Race customized · White- White/ Caucasian/ European Heritage	190 Participants n=5 Participants	198 Participants n=7 Participants	145 Participants n=5 Participants	143 Participants n=4 Participants	676 Participants n=21 Participants
Race/Ethnicity, Customized Race customized · Multiple - American Indian/Alaska Native and White	16 Participants n=5 Participants	11 Participants n=7 Participants	19 Participants n=5 Participants	23 Participants n=4 Participants	69 Participants n=21 Participants

PRIMARY outcome

Timeframe: From randomization to Week 52

Population: mITT-H Population

Outcome measures

Outcome measures
Measure	Placebo - High Stratum n=229 Participants Participants with blood eosinophil counts \>=150 cells/µL at Screening or \>=300 cells/µL in the 12 months prior were assigned to the high stratum group. These participants were randomized to and received placebo by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.	Mepolizumab 100 mg - High Stratum n=233 Participants Participants with blood eosinophil counts \>=150 cells/µL at Screening or \>=300 cells/ µL in the 12 months prior were assigned to the high stratum group. These participants were randomized to and received mepolizumab 100 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.
Rate of Moderate or Severe Exacerbations in Participants in the High Stratum	1.71 Moderate/severe exacerbations per year Interval 1.51 to 1.94	1.40 Moderate/severe exacerbations per year Interval 1.23 to 1.6

PRIMARY outcome

Timeframe: From randomization to Week 52

Population: mITT Population

Moderate and severe exacerbations occurring from the start of IP up to the Week 52 visit, including exacerbations reported after early discontinuation from IP by participants who remained in the study, were included in the analysis. The analysis was performed on the mITT Population which comprised of all randomized participants who received at least one dose of trial medication. The strata were combined as pre-specified in the protocol and reporting and analysis plan (RAP).

Outcome measures

Outcome measures
Measure	Placebo - High Stratum n=419 Participants Participants with blood eosinophil counts \>=150 cells/µL at Screening or \>=300 cells/µL in the 12 months prior were assigned to the high stratum group. These participants were randomized to and received placebo by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.	Mepolizumab 100 mg - High Stratum n=417 Participants Participants with blood eosinophil counts \>=150 cells/µL at Screening or \>=300 cells/ µL in the 12 months prior were assigned to the high stratum group. These participants were randomized to and received mepolizumab 100 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.
Rate of Moderate or Severe Exacerbations in the mITT Population	1.52 Moderate/severe exacerbations per year Interval 1.38 to 1.68	1.49 Moderate/severe exacerbations per year Interval 1.35 to 1.64

SECONDARY outcome

Timeframe: From randomization to Week 52

Population: mITT-H Population

Kaplan Meier estimates of the probability of a moderate or severe exacerbation are expressed as the percentage of participants with an exacerbation over time (by Week 8, 16, 24, 32, 40, 48, 52). Analysis was performed on the mITT-H Population and included exacerbations reported on-treatment and those reported after early discontinuation from IP by participants who remained in the study.

Outcome measures

Outcome measures
Measure	Placebo - High Stratum n=229 Participants Participants with blood eosinophil counts \>=150 cells/µL at Screening or \>=300 cells/µL in the 12 months prior were assigned to the high stratum group. These participants were randomized to and received placebo by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.	Mepolizumab 100 mg - High Stratum n=233 Participants Participants with blood eosinophil counts \>=150 cells/µL at Screening or \>=300 cells/ µL in the 12 months prior were assigned to the high stratum group. These participants were randomized to and received mepolizumab 100 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.
Time to First Moderate/Severe Exacerbation in Participants in the High Stratum Week 8	28.1 Percentage of participants Interval 22.7 to 34.4	20.2 Percentage of participants Interval 15.6 to 26.0
Time to First Moderate/Severe Exacerbation in Participants in the High Stratum Week 16	45.5 Percentage of participants Interval 39.3 to 52.3	34.9 Percentage of participants Interval 29.2 to 41.5
Time to First Moderate/Severe Exacerbation in Participants in the High Stratum Week 24	53.4 Percentage of participants Interval 47.0 to 60.1	45.8 Percentage of participants Interval 39.6 to 52.4
Time to First Moderate/Severe Exacerbation in Participants in the High Stratum Week 32	60.9 Percentage of participants Interval 54.5 to 67.4	55.3 Percentage of participants Interval 49.0 to 61.8
Time to First Moderate/Severe Exacerbation in Participants in the High Stratum Week 40	68.5 Percentage of participants Interval 62.2 to 74.5	59.3 Percentage of participants Interval 53.0 to 65.7
Time to First Moderate/Severe Exacerbation in Participants in the High Stratum Week 48	71.8 Percentage of participants Interval 65.7 to 77.6	62.0 Percentage of participants Interval 55.8 to 68.3
Time to First Moderate/Severe Exacerbation in Participants in the High Stratum Week 52	75.2 Percentage of participants Interval 69.3 to 80.8	64.6 Percentage of participants Interval 58.3 to 70.8

SECONDARY outcome

Timeframe: From randomization to Week 52

Population: mITT-H Population

COPD exacerbations requiring an ED visit and/or hosp. occurring from the start of IP up to the Week 52 visit, including exacerbations reported after early discontinuation from IP by participants who remained in the study, were included in the analysis. The analysis was performed on mITT-H Population.

Outcome measures

Outcome measures
Measure	Placebo - High Stratum n=229 Participants Participants with blood eosinophil counts \>=150 cells/µL at Screening or \>=300 cells/µL in the 12 months prior were assigned to the high stratum group. These participants were randomized to and received placebo by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.	Mepolizumab 100 mg - High Stratum n=233 Participants Participants with blood eosinophil counts \>=150 cells/µL at Screening or \>=300 cells/ µL in the 12 months prior were assigned to the high stratum group. These participants were randomized to and received mepolizumab 100 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.
Rate of COPD Exacerbations Requiring an Emergency Department (ED) Visit and/or Hospitalization (Hosp.) in Participants in the High Stratum	0.26 Exacerbations requiring ED/hosp per year Interval 0.19 to 0.36	0.30 Exacerbations requiring ED/hosp per year Interval 0.22 to 0.4

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: mITT-H Population. Participants analyzed represents those with a Baseline and at least one post-Baseline assessment, and with no missing covariates.

The SGRQ for COPD is a 40-item questionnaire derived from the original SGRQ, designed to measure health impairment by addressing the frequency of respiratory symptoms and current state of the participant. SGRQ Total Scores ranges from 0 to 100 with higher scores indicating worse health-related quality of life and reductions indicating improvement. The Baseline value will be the last measurement collected prior to the first dose of investigational product. Change from Baseline is calculated as the post-dose visit value minus the Baseline value. Mean change from Baseline in SGRQ score at Week 52 has been presented.

Outcome measures

Outcome measures
Measure	Placebo - High Stratum n=214 Participants Participants with blood eosinophil counts \>=150 cells/µL at Screening or \>=300 cells/µL in the 12 months prior were assigned to the high stratum group. These participants were randomized to and received placebo by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.	Mepolizumab 100 mg - High Stratum n=226 Participants Participants with blood eosinophil counts \>=150 cells/µL at Screening or \>=300 cells/ µL in the 12 months prior were assigned to the high stratum group. These participants were randomized to and received mepolizumab 100 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.
Change From Baseline in Mean Total St. George's Respiratory Questionnaire (SGRQ) Score in Participants in the High Stratum	-3.0 Score on SGRQ scale Standard Error 1.11	-2.8 Score on SGRQ scale Standard Error 1.06

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: mITT-H Population. Participants analyzed represents those with a Baseline and at least one post-Baseline assessment, and with no missing covariates.

The CAT is an 8-item questionnaire developed for use in routine clinical practice to measure the health status of participants with COPD. Each question is assessed on a 6-point scale ranging from 0 (no impairment) to 5 (maximum impairment) with the CAT score ranging from 0-40. Higher scores indicate greater disease impact with reductions indicating improvement. The Baseline value will be the last measurement collected prior to the first dose of investigational product. Change from Baseline is calculated as the post-dose visit value minus the Baseline value. Mean change from Baseline in CAT score at Week 52 has been presented.

Outcome measures

Outcome measures
Measure	Placebo - High Stratum n=212 Participants Participants with blood eosinophil counts \>=150 cells/µL at Screening or \>=300 cells/µL in the 12 months prior were assigned to the high stratum group. These participants were randomized to and received placebo by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.	Mepolizumab 100 mg - High Stratum n=224 Participants Participants with blood eosinophil counts \>=150 cells/µL at Screening or \>=300 cells/ µL in the 12 months prior were assigned to the high stratum group. These participants were randomized to and received mepolizumab 100 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.
Change From Baseline in Mean COPD Assessment Test (CAT) Score in Participants in the High Stratum	0.0 Score on CAT scale Standard Error 0.47	-0.8 Score on CAT scale Standard Error 0.45

SECONDARY outcome

Timeframe: From randomization to Week 52

Population: mITT Population

Kaplan Meier estimates of the probability of a moderate/severe exacerbation are expressed as the percentage of participants with an exacerbation over time (by Week 8, 16, 24, 32, 40, 48, 52). The analysis was performed on the mITT population and included exacerbations reported on-treatment and those reported after early discontinuation from IP by participants who remained in the study. The strata were combined as pre-specified in the protocol and reporting and analysis plan (RAP).

Outcome measures

Outcome measures
Measure	Placebo - High Stratum n=419 Participants Participants with blood eosinophil counts \>=150 cells/µL at Screening or \>=300 cells/µL in the 12 months prior were assigned to the high stratum group. These participants were randomized to and received placebo by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.	Mepolizumab 100 mg - High Stratum n=417 Participants Participants with blood eosinophil counts \>=150 cells/µL at Screening or \>=300 cells/ µL in the 12 months prior were assigned to the high stratum group. These participants were randomized to and received mepolizumab 100 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.
Time to First Moderate/Severe Exacerbation in the mITT Population Week 8	25.1 Percentage of participants Interval 21.3 to 29.6	23.6 Percentage of participants Interval 19.8 to 28.0
Time to First Moderate/Severe Exacerbation in the mITT Population Week 16	39.8 Percentage of participants Interval 35.2 to 44.6	37.4 Percentage of participants Interval 32.9 to 42.3
Time to First Moderate/Severe Exacerbation in the mITT Population Week 24	49.2 Percentage of participants Interval 44.5 to 54.1	46.3 Percentage of participants Interval 41.6 to 51.3
Time to First Moderate/Severe Exacerbation in the mITT Population Week 32	57.3 Percentage of participants Interval 52.6 to 62.2	54.1 Percentage of participants Interval 49.3 to 59.0
Time to First Moderate/Severe Exacerbation in the mITT Population Week 40	63.8 Percentage of participants Interval 59.1 to 68.5	59.7 Percentage of participants Interval 54.9 to 64.5
Time to First Moderate/Severe Exacerbation in the mITT Population Week 48	67.3 Percentage of participants Interval 62.7 to 71.9	62.5 Percentage of participants Interval 57.8 to 67.2
Time to First Moderate/Severe Exacerbation in the mITT Population Week 52	71.2 Percentage of participants Interval 66.6 to 75.6	65.5 Percentage of participants Interval 60.7 to 70.1

SECONDARY outcome

Timeframe: From randomization to Week 52

Population: mITT Population

COPD exacerbations requiring ED visit and/or hosp occurring from the start of IP up to the Week 52 visit, including exacerbations reported after early discontinuation from IP by participants who remained in the study, were included in the analysis. The analysis was performed on mITT Population. The strata were combined as pre-specified in the protocol and reporting and analysis plan (RAP).

Outcome measures

Outcome measures
Measure	Placebo - High Stratum n=419 Participants Participants with blood eosinophil counts \>=150 cells/µL at Screening or \>=300 cells/µL in the 12 months prior were assigned to the high stratum group. These participants were randomized to and received placebo by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.	Mepolizumab 100 mg - High Stratum n=417 Participants Participants with blood eosinophil counts \>=150 cells/µL at Screening or \>=300 cells/ µL in the 12 months prior were assigned to the high stratum group. These participants were randomized to and received mepolizumab 100 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.
Rate of COPD Exacerbations Requiring ED Visit and/or Hosp in the mITT Population	0.26 Exacerbations requiring ED/hosp per year Interval 0.21 to 0.33	0.29 Exacerbations requiring ED/hosp per year Interval 0.23 to 0.36

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: mITT Population. Participants analyzed represents those with a Baseline and at least one post-Baseline assessment, and with no missing covariates.

Outcome measures

Outcome measures
Measure	Placebo - High Stratum n=396 Participants Participants with blood eosinophil counts \>=150 cells/µL at Screening or \>=300 cells/µL in the 12 months prior were assigned to the high stratum group. These participants were randomized to and received placebo by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.	Mepolizumab 100 mg - High Stratum n=397 Participants Participants with blood eosinophil counts \>=150 cells/µL at Screening or \>=300 cells/ µL in the 12 months prior were assigned to the high stratum group. These participants were randomized to and received mepolizumab 100 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.
Change From Baseline in Mean Total SGRQ Score in the mITT Population	-4.0 Score on SGRQ scale Standard Error 0.81	-3.2 Score on SGRQ scale Standard Error 0.80

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: mITT Population. Participants analyzed represents those with a Baseline and at least one post-Baseline assessment, and with no missing covariates.

The CAT is an 8-item questionnaire developed for use in routine clinical practice to measure the health status of participants with COPD. Each question is assessed on a 6-point scale ranging from 0 (no impairment) to 5 (maximum impairment) with the CAT score ranging from 0-40. Higher scores indicate greater disease impact with reductions indicating improvement. The Baseline value will be the last measurement collected prior to the first dose of investigational product. Change from Baseline is calculated as the post-dose visit value minus the Baseline value. Participants with a Baseline and at least one post-Baseline assessment were included in the analysis. Mean change from Baseline in CAT score at Week 52 has been presented. The strata were combined as pre-specified in the protocol and reporting and analysis plan (RAP).

Outcome measures

Outcome measures
Measure	Placebo - High Stratum n=392 Participants Participants with blood eosinophil counts \>=150 cells/µL at Screening or \>=300 cells/µL in the 12 months prior were assigned to the high stratum group. These participants were randomized to and received placebo by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.	Mepolizumab 100 mg - High Stratum n=401 Participants Participants with blood eosinophil counts \>=150 cells/µL at Screening or \>=300 cells/ µL in the 12 months prior were assigned to the high stratum group. These participants were randomized to and received mepolizumab 100 mg by SC injection every 4 weeks for up to 52 weeks in addition to their SoC therapy. Salbutamol MDI was issued for use as rescue medication throughout the study.
Change From Baseline in Mean CAT Score in the mITT Population	-0.4 Score on CAT scale Standard Error 0.35	-1.0 Score on CAT scale Standard Error 0.34

Adverse Events

Placebo - High Stratum

Serious events: 80 serious events

Other events: 146 other events

Deaths: 8 deaths

Mepolizumab 100 mg - High Stratum

Serious events: 65 serious events

Other events: 136 other events

Deaths: 6 deaths

Placebo - Low Stratum

Serious events: 51 serious events

Other events: 116 other events

Deaths: 9 deaths

Mepolizumab 100 mg - Low Stratum

Serious events: 50 serious events

Other events: 108 other events

Deaths: 10 deaths

Serious adverse events

Other adverse events

Additional Information

GSK Response Center

GlaxoSmithKline

Phone: 866-435-7343

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER