Trial Outcomes & Findings for Mepolizumab as Add-on Treatment IN Participants With COPD Characterized by Frequent Exacerbations and Eosinophil Level (NCT NCT04133909)

Last Updated: 2025-08-15

Results Overview

Annualized rate of moderate or severe exacerbations were assessed. Moderate exacerbations are defined as clinically significant exacerbations that require treatment with oral or systemic corticosteroids and/or antibiotics. Severe exacerbations are defined per protocol as clinically significant exacerbations that require in-patient hospitalization (that is greater than or equal to \[\>=\] 24 hours) or result in death.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

806 participants

Primary outcome timeframe

Up to Week 104

Results posted on

2025-08-15

Participant Flow

The study enrolled 806 participants from multiple locations and regions worldwide.

Among the 806 participants, two were randomized in error and subsequently withdrawn from the study (one from the Mepolizumab 100 milligrams (mg) group and one from the Placebo group) without receiving any study intervention. The modified intention-to- treat (mITT) population consisted of 804 participants who were randomized and received at least one dose of the trial medication.

Participant milestones

Participant milestones
Measure	Mepolizumab 100 mg Participants with Chronic Obstructive Pulmonary Disease (COPD) received a 100 milligrams (mg) dose of mepolizumab as a subcutaneous injection every 4 weeks. Participants remained in the study for an assessment period of minimum of 52 weeks and a maximum of 104 weeks.	Placebo Participants with COPD received matching placebo as a subcutaneous injection every 4 weeks. Participants remained in the study for an assessment period of minimum of 52 weeks and a maximum of 104 weeks.
Overall Study STARTED	404	402
Overall Study mITT Population	403	401
Overall Study COMPLETED	339	331
Overall Study NOT COMPLETED	65	71

Reasons for withdrawal

Reasons for withdrawal
Measure	Mepolizumab 100 mg Participants with Chronic Obstructive Pulmonary Disease (COPD) received a 100 milligrams (mg) dose of mepolizumab as a subcutaneous injection every 4 weeks. Participants remained in the study for an assessment period of minimum of 52 weeks and a maximum of 104 weeks.	Placebo Participants with COPD received matching placebo as a subcutaneous injection every 4 weeks. Participants remained in the study for an assessment period of minimum of 52 weeks and a maximum of 104 weeks.
Overall Study Death	11	11
Overall Study Adverse Event	4	5
Overall Study Lost to Follow-up	3	5
Overall Study Physician Decision	4	7
Overall Study Withdrawal by Subject	40	35
Overall Study Lack of Efficacy	2	7
Overall Study Randomized in error	1	1

Baseline Characteristics

Mepolizumab as Add-on Treatment IN Participants With COPD Characterized by Frequent Exacerbations and Eosinophil Level

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Mepolizumab 100 mg n=403 Participants Participants with Chronic Obstructive Pulmonary Disease (COPD) received a 100 milligrams (mg) dose of mepolizumab as a subcutaneous injection every 4 weeks. Participants remained in the study for an assessment period of minimum of 52 weeks and a maximum of 104 weeks.	Placebo n=401 Participants Participants with COPD received matching placebo as a subcutaneous injection every 4 weeks. Participants remained in the study for an assessment period of minimum of 52 weeks and a maximum of 104 weeks.	Total n=804 Participants Total of all reporting groups
Age, Continuous	66.4 YEARS STANDARD_DEVIATION 8.10 • n=5 Participants	66.0 YEARS STANDARD_DEVIATION 7.91 • n=7 Participants	66.2 YEARS STANDARD_DEVIATION 8.00 • n=5 Participants
Sex: Female, Male Female	127 Participants n=5 Participants	126 Participants n=7 Participants	253 Participants n=5 Participants
Sex: Female, Male Male	276 Participants n=5 Participants	275 Participants n=7 Participants	551 Participants n=5 Participants
Race/Ethnicity, Customized White	338 Participants n=5 Participants	335 Participants n=7 Participants	673 Participants n=5 Participants
Race/Ethnicity, Customized All Other Races	65 Participants n=5 Participants	66 Participants n=7 Participants	131 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to Week 104

Population: The analysis was performed on Modified Intent-to-Treat (mITT) population which included all randomized participants who received at least one dose of trial medication. Participants were analyzed by randomized treatment.

Outcome measures

Outcome measures
Measure	Mepolizumab 100 mg n=403 Participants Participants with Chronic Obstructive Pulmonary Disease (COPD) received a 100 milligrams (mg) dose of mepolizumab as a subcutaneous injection every 4 weeks. Participants remained in the study for an assessment period of minimum of 52 weeks and a maximum of 104 weeks.	Placebo n=401 Participants Participants with COPD received matching placebo as a subcutaneous injection every 4 weeks. Participants remained in the study for an assessment period of minimum of 52 weeks and a maximum of 104 weeks.
Annualized Rate of Moderate or Severe Exacerbations	0.80 Exacerbations per year Interval 0.7 to 0.91	1.01 Exacerbations per year Interval 0.89 to 1.15

SECONDARY outcome

Timeframe: At week 8,16, 24, 32, 40, 48, 52, 56, 64, 72, 80, 88, 96, 104

The time to first moderate or severe exacerbation was determined as the number of days from the date of first dose to the date of the first moderate or severe exacerbation. Kaplan-Meier estimate of the cumulative percentage of participants with a moderate or severe exacerbation within each treatment arm over time were produced.

Outcome measures

Outcome measures
Measure	Mepolizumab 100 mg n=403 Participants Participants with Chronic Obstructive Pulmonary Disease (COPD) received a 100 milligrams (mg) dose of mepolizumab as a subcutaneous injection every 4 weeks. Participants remained in the study for an assessment period of minimum of 52 weeks and a maximum of 104 weeks.	Placebo n=401 Participants Participants with COPD received matching placebo as a subcutaneous injection every 4 weeks. Participants remained in the study for an assessment period of minimum of 52 weeks and a maximum of 104 weeks.
Time to First Moderate or Severe Exacerbation At week 72	55.9 Percentage of Participants Interval 49.8 to 62.2	60.5 Percentage of Participants Interval 54.7 to 66.4
Time to First Moderate or Severe Exacerbation At week 8	11.3 Percentage of Participants Interval 8.5 to 14.8	15.1 Percentage of Participants Interval 11.9 to 19.0
Time to First Moderate or Severe Exacerbation At week 16	21.6 Percentage of Participants Interval 17.9 to 26.0	25.6 Percentage of Participants Interval 21.6 to 30.2
Time to First Moderate or Severe Exacerbation At week 24	28.3 Percentage of Participants Interval 24.2 to 33.1	35.4 Percentage of Participants Interval 30.9 to 40.3
Time to First Moderate or Severe Exacerbation At week 32	33.6 Percentage of Participants Interval 29.1 to 38.5	41.6 Percentage of Participants Interval 36.9 to 46.7
Time to First Moderate or Severe Exacerbation At week 40	39.8 Percentage of Participants Interval 35.1 to 44.8	47.1 Percentage of Participants Interval 42.3 to 52.2
Time to First Moderate or Severe Exacerbation At week 48	44.9 Percentage of Participants Interval 40.1 to 50.1	51.4 Percentage of Participants Interval 46.6 to 56.5
Time to First Moderate or Severe Exacerbation At week 52	46.1 Percentage of Participants Interval 41.2 to 51.2	53.4 Percentage of Participants Interval 48.5 to 58.5
Time to First Moderate or Severe Exacerbation At week 56	46.7 Percentage of Participants Interval 41.7 to 51.9	54.0 Percentage of Participants Interval 49.0 to 59.2
Time to First Moderate or Severe Exacerbation At week 64	51.4 Percentage of Participants Interval 45.8 to 57.2	58.9 Percentage of Participants Interval 53.3 to 64.6
Time to First Moderate or Severe Exacerbation At week 80	59.0 Percentage of Participants Interval 52.6 to 65.5	62.3 Percentage of Participants Interval 56.2 to 68.4
Time to First Moderate or Severe Exacerbation At week 88	60.6 Percentage of Participants Interval 54.1 to 67.2	64.2 Percentage of Participants Interval 57.9 to 70.5
Time to First Moderate or Severe Exacerbation At week 96	62.3 Percentage of Participants Interval 55.6 to 69.0	67.2 Percentage of Participants Interval 60.5 to 73.8
Time to First Moderate or Severe Exacerbation At week 104	64.5 Percentage of Participants Interval 57.5 to 71.4	68.3 Percentage of Participants Interval 61.4 to 74.9

SECONDARY outcome

Timeframe: Baseline and Week 52

Population: The analysis was performed on mITT population which included all randomized participants who received at least one dose of trial medication. Participants were analyzed by randomized treatment. Only those participants with data available at the baseline were analyzed. Percentages were rounded-off to the nearest whole number.

The CAT is an 8-item questionnaire used to measure the health status of participants with COPD. Participants rated their experience on a 6-point scale, ranging from 0 (no impairment) to 5 (maximum impairment), with a scoring range of 0 (no impact)-40 (maximum impact). Higher scores indicate greater disease impact, and lower score indicates lesser disease impact. Participants were considered responders if they had a 2-point or more improvement (reduction) in CAT Score from baseline. Participants who withdrew from the study prior to Week 52 were included in the analysis as non-responders. The baseline value was the last measurement collected prior to the first dose of investigational product.

Outcome measures

Outcome measures
Measure	Mepolizumab 100 mg n=391 Participants Participants with Chronic Obstructive Pulmonary Disease (COPD) received a 100 milligrams (mg) dose of mepolizumab as a subcutaneous injection every 4 weeks. Participants remained in the study for an assessment period of minimum of 52 weeks and a maximum of 104 weeks.	Placebo n=394 Participants Participants with COPD received matching placebo as a subcutaneous injection every 4 weeks. Participants remained in the study for an assessment period of minimum of 52 weeks and a maximum of 104 weeks.
Percentage of COPD Assessment Test (CAT) Responders With >=2 Point Reduction From Baseline at Week 52	41 Percentage of participants	46 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and Week 52

The St George's Respiratory Questionnaire for COPD (SGRQ-C) is a 40-item questionnaire. The total SGRQ score is calculated by summing up the weights of all positively answered items across the entire questionnaire, dividing by the total possible weight for all questionnaire items. The total score was expressed as a percentage of overall impairment, with 0 (best possible health status) and 100 (the worst possible health status). Higher scores indicated greater impairment of health, and lower scores indicate a lesser impairment on health. A participant was considered a responder if they had a 4-point or more improvement (reduction) in the SGRQ-C total score from baseline. Participants who withdrew from the study prior to Week 52 were included in the analysis as non- responders.

Outcome measures

Outcome measures
Measure	Mepolizumab 100 mg n=390 Participants Participants with Chronic Obstructive Pulmonary Disease (COPD) received a 100 milligrams (mg) dose of mepolizumab as a subcutaneous injection every 4 weeks. Participants remained in the study for an assessment period of minimum of 52 weeks and a maximum of 104 weeks.	Placebo n=393 Participants Participants with COPD received matching placebo as a subcutaneous injection every 4 weeks. Participants remained in the study for an assessment period of minimum of 52 weeks and a maximum of 104 weeks.
Percentage of St. George's Respiratory Questionnaire for COPD (SGRQ) Total Score Responders With >=4 Point Reduction From Baseline at Week 52	50 Percentage of participants	46 Percentage of participants

SECONDARY outcome

Timeframe: Baseline and 4-weeks prior to Week 52

The E-RS: COPD consists of 11 items from the 14 item Exacerbations of Chronic Pulmonary Disease Tool (EXACT) instrument (completed each evening using an eDiary). E-RS: COPD is intended to capture information related to the respiratory symptoms of COPD, that is, breathlessness, cough, sputum production, chest congestion, and chest tightness. The E-RS: COPD has a scoring range of 0 (no symptoms)-40 (most severe symptoms), higher scores indicate more severe symptoms. A participant is considered a responder if they have a 2-unit or more improvement (reduction) in their average E-RS: COPD total score during a 4-week period prior to Week 52 (Weeks 49-52) compared to baseline. The average of daily scores in 4-weekly intervals were calculated and data is presented for Weeks 49-52. Participants who withdrew from study prior to the start of the Weeks 49-52 time-period were included in the analysis as a non-responder.

Outcome measures

Outcome measures
Measure	Mepolizumab 100 mg n=403 Participants Participants with Chronic Obstructive Pulmonary Disease (COPD) received a 100 milligrams (mg) dose of mepolizumab as a subcutaneous injection every 4 weeks. Participants remained in the study for an assessment period of minimum of 52 weeks and a maximum of 104 weeks.	Placebo n=399 Participants Participants with COPD received matching placebo as a subcutaneous injection every 4 weeks. Participants remained in the study for an assessment period of minimum of 52 weeks and a maximum of 104 weeks.
Percentage of Evaluating Respiratory Symptoms in COPD (E-RS: COPD) Responders With >=2 Point Reduction From Baseline	31 Percentage of participants	34 Percentage of participants

SECONDARY outcome

Timeframe: Up to Week 104

Annualized rate of exacerbations requiring ED visit or hospitalization were evaluated. This included moderate exacerbations which led to a visit to the ED and severe exacerbations, were defined as clinically significant exacerbations that require in-patient hospitalization (\>= 24 hours) or result in death.

Outcome measures

Outcome measures
Measure	Mepolizumab 100 mg n=403 Participants Participants with Chronic Obstructive Pulmonary Disease (COPD) received a 100 milligrams (mg) dose of mepolizumab as a subcutaneous injection every 4 weeks. Participants remained in the study for an assessment period of minimum of 52 weeks and a maximum of 104 weeks.	Placebo n=401 Participants Participants with COPD received matching placebo as a subcutaneous injection every 4 weeks. Participants remained in the study for an assessment period of minimum of 52 weeks and a maximum of 104 weeks.
Annualized Rate of Exacerbations Requiring Emergency Department (ED) Visit and/or Hospitalization	0.13 Exacerbations per year Interval 0.1 to 0.18	0.20 Exacerbations per year Interval 0.15 to 0.27

Adverse Events

Mepolizumab 100 mg

Serious events: 101 serious events

Other events: 195 other events

Deaths: 11 deaths

Placebo

Serious events: 115 serious events

Other events: 182 other events

Deaths: 11 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Mepolizumab 100 mg n=403 participants at risk Participants with Chronic Obstructive Pulmonary Disease (COPD) received a 100 milligrams (mg) dose of mepolizumab as a subcutaneous injection every 4 weeks. Participants remained in the study for an assessment period of minimum of 52 weeks and a maximum of 104 weeks.	Placebo n=401 participants at risk Participants with COPD received matching placebo as a subcutaneous injection every 4 weeks. Participants remained in the study for an assessment period of minimum of 52 weeks and a maximum of 104 weeks.
Gastrointestinal disorders Diarrhoea	5.5% 22/403 • Number of events 23 • Up to Week 104 Data for All-Cause Mortality, Serious and Other (Non-Serious) Adverse Events were collected for the mITT population (all randomized participants, excluding those who were randomized in error). Safety population included all randomized participants who received at least one dose of trial medication.	3.0% 12/401 • Number of events 19 • Up to Week 104 Data for All-Cause Mortality, Serious and Other (Non-Serious) Adverse Events were collected for the mITT population (all randomized participants, excluding those who were randomized in error). Safety population included all randomized participants who received at least one dose of trial medication.
Infections and infestations COVID-19	11.9% 48/403 • Number of events 52 • Up to Week 104 Data for All-Cause Mortality, Serious and Other (Non-Serious) Adverse Events were collected for the mITT population (all randomized participants, excluding those who were randomized in error). Safety population included all randomized participants who received at least one dose of trial medication.	11.7% 47/401 • Number of events 48 • Up to Week 104 Data for All-Cause Mortality, Serious and Other (Non-Serious) Adverse Events were collected for the mITT population (all randomized participants, excluding those who were randomized in error). Safety population included all randomized participants who received at least one dose of trial medication.
Infections and infestations Influenza	4.7% 19/403 • Number of events 24 • Up to Week 104 Data for All-Cause Mortality, Serious and Other (Non-Serious) Adverse Events were collected for the mITT population (all randomized participants, excluding those who were randomized in error). Safety population included all randomized participants who received at least one dose of trial medication.	4.5% 18/401 • Number of events 20 • Up to Week 104 Data for All-Cause Mortality, Serious and Other (Non-Serious) Adverse Events were collected for the mITT population (all randomized participants, excluding those who were randomized in error). Safety population included all randomized participants who received at least one dose of trial medication.
Infections and infestations Nasopharyngitis	10.2% 41/403 • Number of events 57 • Up to Week 104 Data for All-Cause Mortality, Serious and Other (Non-Serious) Adverse Events were collected for the mITT population (all randomized participants, excluding those who were randomized in error). Safety population included all randomized participants who received at least one dose of trial medication.	8.7% 35/401 • Number of events 46 • Up to Week 104 Data for All-Cause Mortality, Serious and Other (Non-Serious) Adverse Events were collected for the mITT population (all randomized participants, excluding those who were randomized in error). Safety population included all randomized participants who received at least one dose of trial medication.
Infections and infestations Pneumonia	4.5% 18/403 • Number of events 24 • Up to Week 104 Data for All-Cause Mortality, Serious and Other (Non-Serious) Adverse Events were collected for the mITT population (all randomized participants, excluding those who were randomized in error). Safety population included all randomized participants who received at least one dose of trial medication.	4.2% 17/401 • Number of events 20 • Up to Week 104 Data for All-Cause Mortality, Serious and Other (Non-Serious) Adverse Events were collected for the mITT population (all randomized participants, excluding those who were randomized in error). Safety population included all randomized participants who received at least one dose of trial medication.
Infections and infestations Upper respiratory tract infection	6.0% 24/403 • Number of events 40 • Up to Week 104 Data for All-Cause Mortality, Serious and Other (Non-Serious) Adverse Events were collected for the mITT population (all randomized participants, excluding those who were randomized in error). Safety population included all randomized participants who received at least one dose of trial medication.	5.0% 20/401 • Number of events 30 • Up to Week 104 Data for All-Cause Mortality, Serious and Other (Non-Serious) Adverse Events were collected for the mITT population (all randomized participants, excluding those who were randomized in error). Safety population included all randomized participants who received at least one dose of trial medication.
Infections and infestations Urinary tract infection	4.5% 18/403 • Number of events 20 • Up to Week 104 Data for All-Cause Mortality, Serious and Other (Non-Serious) Adverse Events were collected for the mITT population (all randomized participants, excluding those who were randomized in error). Safety population included all randomized participants who received at least one dose of trial medication.	1.7% 7/401 • Number of events 7 • Up to Week 104 Data for All-Cause Mortality, Serious and Other (Non-Serious) Adverse Events were collected for the mITT population (all randomized participants, excluding those who were randomized in error). Safety population included all randomized participants who received at least one dose of trial medication.
Musculoskeletal and connective tissue disorders Arthralgia	5.7% 23/403 • Number of events 29 • Up to Week 104 Data for All-Cause Mortality, Serious and Other (Non-Serious) Adverse Events were collected for the mITT population (all randomized participants, excluding those who were randomized in error). Safety population included all randomized participants who received at least one dose of trial medication.	4.2% 17/401 • Number of events 20 • Up to Week 104 Data for All-Cause Mortality, Serious and Other (Non-Serious) Adverse Events were collected for the mITT population (all randomized participants, excluding those who were randomized in error). Safety population included all randomized participants who received at least one dose of trial medication.
Musculoskeletal and connective tissue disorders Back pain	6.5% 26/403 • Number of events 46 • Up to Week 104 Data for All-Cause Mortality, Serious and Other (Non-Serious) Adverse Events were collected for the mITT population (all randomized participants, excluding those who were randomized in error). Safety population included all randomized participants who received at least one dose of trial medication.	5.7% 23/401 • Number of events 38 • Up to Week 104 Data for All-Cause Mortality, Serious and Other (Non-Serious) Adverse Events were collected for the mITT population (all randomized participants, excluding those who were randomized in error). Safety population included all randomized participants who received at least one dose of trial medication.
Nervous system disorders Headache	7.9% 32/403 • Number of events 62 • Up to Week 104 Data for All-Cause Mortality, Serious and Other (Non-Serious) Adverse Events were collected for the mITT population (all randomized participants, excluding those who were randomized in error). Safety population included all randomized participants who received at least one dose of trial medication.	7.0% 28/401 • Number of events 41 • Up to Week 104 Data for All-Cause Mortality, Serious and Other (Non-Serious) Adverse Events were collected for the mITT population (all randomized participants, excluding those who were randomized in error). Safety population included all randomized participants who received at least one dose of trial medication.
Respiratory, thoracic and mediastinal disorders Cough	3.2% 13/403 • Number of events 15 • Up to Week 104 Data for All-Cause Mortality, Serious and Other (Non-Serious) Adverse Events were collected for the mITT population (all randomized participants, excluding those who were randomized in error). Safety population included all randomized participants who received at least one dose of trial medication.	3.7% 15/401 • Number of events 17 • Up to Week 104 Data for All-Cause Mortality, Serious and Other (Non-Serious) Adverse Events were collected for the mITT population (all randomized participants, excluding those who were randomized in error). Safety population included all randomized participants who received at least one dose of trial medication.
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.7% 19/403 • Number of events 30 • Up to Week 104 Data for All-Cause Mortality, Serious and Other (Non-Serious) Adverse Events were collected for the mITT population (all randomized participants, excluding those who were randomized in error). Safety population included all randomized participants who received at least one dose of trial medication.	5.2% 21/401 • Number of events 38 • Up to Week 104 Data for All-Cause Mortality, Serious and Other (Non-Serious) Adverse Events were collected for the mITT population (all randomized participants, excluding those who were randomized in error). Safety population included all randomized participants who received at least one dose of trial medication.
Vascular disorders Hypertension	4.0% 16/403 • Number of events 16 • Up to Week 104 Data for All-Cause Mortality, Serious and Other (Non-Serious) Adverse Events were collected for the mITT population (all randomized participants, excluding those who were randomized in error). Safety population included all randomized participants who received at least one dose of trial medication.	6.5% 26/401 • Number of events 29 • Up to Week 104 Data for All-Cause Mortality, Serious and Other (Non-Serious) Adverse Events were collected for the mITT population (all randomized participants, excluding those who were randomized in error). Safety population included all randomized participants who received at least one dose of trial medication.

Additional Information

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Email: [email protected]

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.
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