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

Sponsor
GlaxoSmithKline (Industry)
Overall Status
Completed
CT.gov ID
NCT02105948
Collaborator
(none)
837
Enrollment
116
Locations
2
Arms
33.1
Actual Duration (Months)
7.2
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a multi-center, randomized, placebo-controlled, double-blind, parallel group trial evaluating mepolizumab 100 mg against placebo given every 4 weeks through subcutaneous (SC) injection.

In severe COPD patients, sputum eosinophils levels are elevated similar as those seen in severe asthmatics. It is hypothesized that the reduction of eosinophils with mepolizumab in COPD patients would translate into a reduction of COPD exacerbations. The study will determine the reduction in exacerbations in subjects who are above and below the baseline blood eosinophil count of at least 150 cells/microlitres. The study will evaluate the efficacy and safety of mepolizumab on the frequency of moderate and severe exacerbations in COPD subjects at high risk of exacerbations, despite the use of optimized standard of care background therapy.

Overall in this study, a total of 800 subjects will be randomised in 1:1 ratio to receive placebo or mepolizumab (100 milligram (mg)) administered SC. The total duration of this study will be approximately 62 weeks, consisting of a 1 to 2 week screening period, 52-week treatment period and 8-week follow-up period.

Condition or Disease Intervention/Treatment Phase
Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
837 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Study MEA117106: Mepolizumab vs. Placebo as add-on Treatment for Frequently Exacerbating COPD Patients
Actual Study Start Date :
Apr 15, 2014
Actual Primary Completion Date :
Jan 17, 2017
Actual Study Completion Date :
Jan 17, 2017

Arms and Interventions

Arm Intervention/Treatment
Experimental: Arm 1

Each subject will receive 100 mg mepolizumab SC injection every 4 weeks (13 administrations during 52 week treatment period) along with optimized standard of care background therapy.

Drug: Mepolizumab
Humanised 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.
Placebo Comparator: Arm 2

Each subject will receive placebo (0.9% sodium chloride) SC injection every 4 weeks (13 administrations during 52 week treatment period) along with optimized standard of care background therapy.

Drug: Placebo
Sterile 0.9% sodium chloride solution

Outcome Measures

Primary Outcome Measures

  1. Rate of Moderate or Severe Exacerbations in Participants in the High Stratum [From randomization to Week 52]

    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.

  2. Rate of Moderate or Severe Exacerbations in the mITT Population [From randomization to Week 52]

    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).

Secondary Outcome Measures

  1. Time to First Moderate/Severe Exacerbation in Participants in the High Stratum [From randomization to Week 52]

    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.

  2. Rate of COPD Exacerbations Requiring an Emergency Department (ED) Visit and/or Hospitalization (Hosp.) in Participants in the High Stratum [From randomization to Week 52]

    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.

  3. Change From Baseline in Mean Total St. George's Respiratory Questionnaire (SGRQ) Score in Participants in the High Stratum [Baseline and Week 52]

    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.

  4. Change From Baseline in Mean COPD Assessment Test (CAT) Score in Participants in the High Stratum [Baseline and Week 52]

    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.

  5. Time to First Moderate/Severe Exacerbation in the mITT Population [From randomization to Week 52]

    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).

  6. Rate of COPD Exacerbations Requiring ED Visit and/or Hosp in the mITT Population [From randomization to Week 52]

    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).

  7. Change From Baseline in Mean Total SGRQ Score in the mITT Population [Baseline and Week 52]

    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. The strata were combined as pre-specified in the protocol and reporting and analysis plan (RAP).

  8. Change From Baseline in Mean CAT Score in the mITT Population [Baseline and Week 52]

    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).

Eligibility Criteria

Criteria

Ages Eligible for Study:
40 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • COPD diagnosis: Subjects with a clinically documented history of COPD for at least 1 year in accordance with the definition by the American Thoracic Society/European Respiratory Society.

  • Severity of COPD: Subjects must present with the following: a measured pre and post-salbutamol Forced expiratory volume in one second/ Forced vital capacity (FEV1/FVC) ratio of <0.70 at Visit 1 to confirm the diagnosis of COPD; a measured post-salbutamol FEV1>20 percent and <=80 percent of predicted normal values calculated using National Health and Nutrition Examination Survey (NHANES) III reference equations at Visit 1.

  • History of exacerbations: A well documented history (like medical record verification) in the 12 months prior to Visit 1 of: at least two moderate COPD exacerbations. Moderate is defined as the use of systemic corticosteroids (IM, intravenous, or oral) and/or treatment with antibiotics, or at least one severe COPD exacerbation. Severe is defined as having required hospitalization. Note: At least one exacerbation must have occurred while the subject was taking Inhaled corticosteroid (ICS) plus long acting beta2-agonist (LABA) plus long acting muscarinic antagonist (LAMA). Note: Prior use of antibiotics alone does not qualify as a moderate exacerbation unless the use was specifically for the treatment of worsening symptoms of COPD.

  • Concomitant COPD therapy: A well documented requirement for optimized standard of care (SoC) background therapy that includes ICS plus 2 additional COPD medications (i.e., triple therapy) for the 12 months prior to Visit 1 and meets the following criteria: Immediately prior to Visit 1, minimum of 3 months of use of an inhaled corticosteroid (at a dose >=500 micrograms (mcg)/day fluticasone propionate dose equivalent plus); or LABA and LAMA.

For subjects who are not continually maintained on ICS plus LABA plus LAMA for the entire 12 months prior to Visit 1 use of following is allowed (but not in the 3 months immediately prior to Visit 1): inhaled corticosteroid at a dose >=500 mcg/day fluticasone propionate dose equivalent plus ; a LABA or a LAMA and use of at least one other class of COPD medication suggested by the 2013 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for patients who are prone to exacerbation (i.e., phosphodiesterase-4-inhibitors, methylxanthines, or a combination of short acting beta-2-agonist and short acting muscarinic antagonist). Note: Subjects must be willing to stay on their SoC COPD medication for the duration of the study.

  • Informed Consent: 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. Subjects must be able to read, comprehend, and write at a level sufficient to complete study related materials.

  • Gender: Male or Eligible Female; To be eligible for entry into the study females of child bearing potential must commit to consistent and correct use of an acceptable method of birth control from the time of consent, for the duration of the trial, and for 4 months after last study drug administration.

  • Age: At least 40 years of age at Visit 1.

  • Smoking status: Subject with confirmed COPD are eligible to participate independent of their smoking status and smoking history, i.e. current smokers, never smokers or ex-smokers can be enrolled into the study; Current smokers are defined as those with a history of cigarette smoking of >=10 pack-years [number of pack years = (number of cigarettes per day / 20) x number of years smoked (e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years)]; Former smokers are defined as those who meet the definition of a current smoker but have stopped smoking for at least 6 months prior to Visit 1; Never smokers are those that do not meet the definition of a current or former smoker.

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

Exclusion Criteria:

  • Subjects having Asthma: Current and Former Smokers: Subjects with a current diagnosis of asthma (those with a prior history are eligible if they meet inclusion criteria for a current diagnosis of COPD); Never-Smokers: Subjects with any history of asthma; Other respiratory disorders: The investigator must judge that COPD is the primary diagnosis accounting for the clinical manifestations of the lung disease. Subjects with alpha-1-antitrypsin deficiency as the underlying cause of COPD are excluded. Also, excluded are subjects with active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, primary pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases. Subjects are also excluded if maintenance use of bi-level positive airway pressure is required for the treatment of respiratory disorder.

  • COPD stability: Subjects with pneumonia, exacerbation, lower respiratory infection within the 4 weeks prior to Visit 1.

  • Lung resection: Subjects with lung volume reduction surgery within the 12 months prior to Visit 1.

  • Pulmonary rehabilitation program: Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Visit 1. Subjects who are in the maintenance phase of a pulmonary rehabilitation program are not excluded.

  • Oxygen: Subjects receiving treatment with oxygen more than 4.0 Litres/minute (L/min). While breathing supplemental oxygen, subjects should demonstrate an oxyhemoglobin saturation greater than or equal to 89 percent.

  • 12-lead Electrocardiography (ECG) finding: An abnormal and significant ECG finding from the 12-lead ECG conducted at Visit 1 if considered to be clinically significant by the Investigator. 12-lead ECGs will be over-read by a centralized independent cardiologist to assist in consistent evaluation of subject eligibility. Results from the 12-lead ECG over-read must be received prior to assessing eligibility at Visit 2.

  • Unstable or life threatening cardiac disease: Subjects with any of the following would be excluded: Myocardial infarction or unstable angina in the last 6 months ; Unstable or life threatening cardiac arrhythmia requiring intervention in the last 3 months; New York Heart Association (NYHA) Class IV Heart failure.

  • Other diseases/abnormalities: Subjects with (historical or) current evidence of clinically significant, neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or haematological abnormalities that are uncontrolled. Significant is defined as any disease that, in the opinion of the investigator, would put the safety of the subject at risk through participation, or which would affect the efficacy or safety analysis if the disease/condition exacerbated during the study.

  • Eosinophilic disease: Subjects with other conditions that could lead to elevated eosinophils such as Hypereosinophilic syndromes including Eosinophilic Granulomatosis with Polyangiitis (EGPA, also known as Churg-Strauss Syndrome), or Eosinophilic Esophagitis.

  • Parasitic infection: Subjects with a pre-existing helminthes infestation within 6 months prior to Visit 1 are also excluded.

  • Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior to Visit 1 (Subjects that had localized carcinoma of the skin or cervix which was resected for cure will not be excluded). Note for South Korea: Korean subjects with a diagnosis of malignancy within 5 years of Visit 1 are excluded.

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

  • Liver disease: 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). Chronic stable hepatitis B and C are acceptable if subject otherwise meets entry criteria (e.g. presence of hepatitis B surface antigen or positive hepatitis C test result within 3 months of screening).

  • Monoclonal antibodies: Subjects who have received any monoclonal antibody within 5 half-lives of Visit 1.

  • Investigational medications: Subjects who have received an investigational drug within 30 days of Visit 1, or within 5 drug half-lives of the investigational drug, whichever is longer (this also includes investigational formulations of a marketed product).

  • Hypersensitivity: Subjects with a known allergy or intolerance to another monoclonal antibody or biologic including history of anaphylaxis to another biologic

  • Inability to read: In the opinion of the investigator, any subject who is unable to read and/or would not be able to complete study related materials.

  • Non-compliance: Subjects at risk of non-compliance, or unable to comply with the study procedures. Any infirmity, disability, or geographic location that would limit compliance for scheduled visits.

  • Questionable validity of consent: Subjects with a history of psychiatric disease, intellectual deficiency, poor motivation or other conditions that will limit the validity of informed consent to participate in the study.

  • Drug or alcohol abuse: A known or suspected history of alcohol or drug abuse within 2 years prior to Visit 1.

  • Previous participation: Subjects who have previously participated in any study of mepolizumab.

  • Affiliation with Investigator Site: Is an investigator, sub-investigator, study coordinator, employee of a participating investigator or study site, or immediate family member of the aforementioned that is involved in this study.

Randomization Criteria

In order to be randomized to study drug the subject must meet the following randomization criteria at Visit 2:

  • Blood eosinophils: While there is no threshold for enrolment, information on eosinophil level should be obtained prior to randomization.

  • Electronic Diary Compliance: Compliance with completion of the eDiary defined as completion of all questions on 5 or more days out of the 7 days immediately preceding Visit 2.

  • 12-lead ECG: No evidence of an abnormal and significant ECG finding from the 12- lead ECG conducted at Visit 1 as indicated on the over-read provided by the centralized independent cardiologist. Subjects with a QT interval corrected with Fridericia's formulas (QTcF)>=450 msec are not eligible. For subjects with a QRS interval >=120 msec, those with QTcF>=480 msec are not eligible. Specific ECG findings that preclude subject eligibility are listed in the protocol.

  • Abnormal chest X-ray (or Computerized Tomography [CT scan]): No chest X-ray (or CT scan) that reveals evidence of clinically significant abnormalities other than those believed to be due to the presence of COPD. If a chest X-ray or CT scan is not available within 6 months prior to Visit 1, then a chest X-ray must be taken at Visit 1 and the results reviewed prior to randomization. For sites in Germany: If a chest X-ray (or CT scan) within 6 months prior to Screening (Visit 1) is not available, the subject will not be eligible for the study.

  • Laboratory abnormality: No evidence of clinically significant abnormality in the haematological, biochemical, or urinalysis screen at Visit 1, as judged by the investigator.

  • Hepatitis B: Subjects who are HBsAg positive or HBcAb positive must not have a HBV DNA level >= 2000 IU/ml.

  • Liver function test: Subjects must meet the following based on results from sample taken at Visit 1: Alanine aminotransferase (ALT) <2x ULN (upper limit of normal); Alkaline Phosphatase (Alk Phos) <=2x ULN; Bilirubin <=1.5x ULN (isolated bilirubin>1.5x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35 percent)

Contacts and Locations

Locations

Site City State Country Postal Code
1 GSK Investigational Site Newport Beach California United States 92663
2 GSK Investigational Site Rochester Minnesota United States 55905
3 GSK Investigational Site Saint Charles Missouri United States 63301
4 GSK Investigational Site New York New York United States 10029
5 GSK Investigational Site Charlotte North Carolina United States 28207
6 GSK Investigational Site Durham North Carolina United States 27705
7 GSK Investigational Site Gastonia North Carolina United States 28054
8 GSK Investigational Site Huntersville North Carolina United States 28078
9 GSK Investigational Site Wilmington North Carolina United States 28401
10 GSK Investigational Site Winston-Salem North Carolina United States 27103
11 GSK Investigational Site Dayton Ohio United States 45459
12 GSK Investigational Site Medford Oregon United States 97504
13 GSK Investigational Site Pittsburgh Pennsylvania United States 15213
14 GSK Investigational Site Easley South Carolina United States 29640
15 GSK Investigational Site Fort Mill South Carolina United States 29707
16 GSK Investigational Site Gaffney South Carolina United States 29340
17 GSK Investigational Site Greenville South Carolina United States 29615
18 GSK Investigational Site Seneca South Carolina United States 29678
19 GSK Investigational Site Spartanburg South Carolina United States 29303
20 GSK Investigational Site Abingdon Virginia United States 24210
21 GSK Investigational Site Cairns Queensland Australia 4870
22 GSK Investigational Site Daw Park South Australia Australia 5041
23 GSK Investigational Site Clayton Victoria Australia 3168
24 GSK Investigational Site Frankston Victoria Australia 3199
25 GSK Investigational Site Murdoch Western Australia Australia 6150
26 GSK Investigational Site Nedlands Western Australia Australia 6009
27 GSK Investigational Site Liverpool Australia 2107
28 GSK Investigational Site Brussels Belgium 1000
29 GSK Investigational Site Brussels Belgium 1200
30 GSK Investigational Site Erpent Belgium 5101
31 GSK Investigational Site Leuven Belgium 3000
32 GSK Investigational Site Liège Belgium 4000
33 GSK Investigational Site Oostende Belgium 8400
34 GSK Investigational Site Calgary Alberta Canada T2N 4Z6
35 GSK Investigational Site Sherwood Park Alberta Canada T8H 0N2
36 GSK Investigational Site Winnipeg Manitoba Canada R2K 3S8
37 GSK Investigational Site Toronto Ontario Canada M5T 3A9
38 GSK Investigational Site Windsor Ontario Canada N8X 5A6
39 GSK Investigational Site Gatineau Quebec Canada J8Y 6S8
40 GSK Investigational Site Montreal Quebec Canada H2W1T8
41 GSK Investigational Site Montreal Quebec Canada H4J 1C5
42 GSK Investigational Site Sainte-Foy Quebec Canada G1V 4G5
43 GSK Investigational Site St-Charles-Borromée Quebec Canada J6E 2B4
44 GSK Investigational Site Trois Rivières Quebec Canada G8T 7A1
45 GSK Investigational Site Karlovy Vary Czechia 360 17
46 GSK Investigational Site Praha 4 Czechia 140 46
47 GSK Investigational Site Tabor Czechia 39003
48 GSK Investigational Site Teplice Czechia 415 10
49 GSK Investigational Site Tallinn Estonia 10138
50 GSK Investigational Site Tallinn Estonia 13419
51 GSK Investigational Site Tallinn Estonia 13619
52 GSK Investigational Site Tartu Estonia 51014
53 GSK Investigational Site Bayonne cedex France 64109
54 GSK Investigational Site Grenoble cedex 9 France 38043
55 GSK Investigational Site Lyon cedex 04 France 69317
56 GSK Investigational Site Marseille cedex 20 France 13915
57 GSK Investigational Site Montpellier cedex 5 France 34295
58 GSK Investigational Site Perpignan France 66000
59 GSK Investigational Site Suresnes France 92150
60 GSK Investigational Site Athens Greece 106 76
61 GSK Investigational Site Athens Greece 11527
62 GSK Investigational Site Haidari / Athens Greece 124 62
63 GSK Investigational Site Rethymnon, Crete Greece 74100
64 GSK Investigational Site Thessaloniki Greece 56429
65 GSK Investigational Site Thessaloniki Greece 57010
66 GSK Investigational Site Napoli Campania Italy 80131
67 GSK Investigational Site Parma Emilia-Romagna Italy 43125
68 GSK Investigational Site Pietra Ligure (SV) Liguria Italy 17027
69 GSK Investigational Site Milano Lombardia Italy 20123
70 GSK Investigational Site Pisa Toscana Italy 56124
71 GSK Investigational Site Perugia Umbria Italy 06156
72 GSK Investigational Site Guadalajara Jalisco Mexico 44100
73 GSK Investigational Site Guadalajara Jalisco Mexico 44500
74 GSK Investigational Site Zapopan Jalisco Mexico 45070
75 GSK Investigational Site Monterrey NL Nuevo León Mexico 64718
76 GSK Investigational Site Monterrey Nuevo León Mexico 64000
77 GSK Investigational Site Monterrey Nuevo León Mexico 64020
78 GSK Investigational Site Mexico City Mexico 07760
79 GSK Investigational Site México DF Mexico 14050
80 GSK Investigational Site Oaxaca Mexico 68000
81 GSK Investigational Site Bodø Norway 8005
82 GSK Investigational Site Kløfta Norway 2040
83 GSK Investigational Site Trondheim Norway 7027
84 GSK Investigational Site Lima 27 Lima Peru Lima 27
85 GSK Investigational Site San Martin de Porres Lima Peru Lima 31
86 GSK Investigational Site San Miguel Lima Peru Lima 32
87 GSK Investigational Site Santiago de Surco Lima Peru Lima 33
88 GSK Investigational Site Lima Peru Lima 18
89 GSK Investigational Site Lima Peru Lima 1
90 GSK Investigational Site Lima Peru Lima 32
91 GSK Investigational Site Pueblo Libre Peru Lima 21
92 GSK Investigational Site Bialystok Poland 15-044
93 GSK Investigational Site Elblag Poland 82-300
94 GSK Investigational Site Krakow Poland 31-024
95 GSK Investigational Site Ostrow Wielkopolski Poland 63-400
96 GSK Investigational Site Skierniewice Poland 96-100
97 GSK Investigational Site Chelyabinsk Russian Federation 454106
98 GSK Investigational Site Kemerovo Russian Federation 650000
99 GSK Investigational Site Nizhniy Novgorod Russian Federation 603126
100 GSK Investigational Site Ryazan Russian Federation 390039
101 GSK Investigational Site Saint-Petersburg Russian Federation 194354
102 GSK Investigational Site Saint-Petersburg Russian Federation 195271
103 GSK Investigational Site St. Petersburg Russian Federation 194356
104 GSK Investigational Site Tomsk Russian Federation 634 050
105 GSK Investigational Site Tomsk Russian Federation 634001
106 GSK Investigational Site Yaroslavl Russian Federation 150003
107 GSK Investigational Site Alicante Spain 03004
108 GSK Investigational Site Barcelona Spain 08025
109 GSK Investigational Site Barcelona Spain 08036
110 GSK Investigational Site L'Hospitalet de Llobregat Spain 08907
111 GSK Investigational Site Lugo Spain 27003
112 GSK Investigational Site Malaga Spain 29010
113 GSK Investigational Site Palma de Mallorca Spain 07120
114 GSK Investigational Site Pozuelo De Alarcón/Madrid Spain 28223
115 GSK Investigational Site Lund Sweden SE-221 85
116 GSK Investigational Site Stockholm Sweden SE-141 86

Sponsors and Collaborators

  • GlaxoSmithKline

Investigators

  • Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Publications

None provided.
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT02105948
Other Study ID Numbers:
  • 117106
First Posted:
Apr 7, 2014
Last Update Posted:
Aug 31, 2018
Last Verified:
Aug 1, 2018
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Keywords provided by GlaxoSmithKline
eosinophils
SB240563
exacerbations
Chronic Obstructive Pulmonary Disease
mepolizumab
Additional relevant MeSH terms:
Lung Diseases
Pulmonary Disease, Chronic Obstructive

Study Results

Participant Flow

Recruitment Details 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.
Pre-assignment Detail 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.
Arm/Group Title Placebo - High Stratum Mepolizumab 100 mg - High Stratum Placebo - Low Stratum Mepolizumab 100 mg - Low Stratum
Arm/Group Description 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. 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. 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. 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.
Period Title: Overall Study
STARTED 229 233 190 184
Completed Investigational Product (IP) 185 203 148 149
Not Completed IP 44 30 42 35
Withdrew IP Due to: Adverse Event 20 16 15 13
Withdrew IP Due to: Lack of Efficacy 5 2 8 2
Withdrew IP Due to: Protocol Deviation 1 3 3 0
Withdrew IP Due to: Lost to Follow-up 0 0 1 2
Withdrew IP Due to: Withdrawal by Subj. 16 8 11 15
Withdrew IP Due to: Physician Decision 2 1 4 2
Withdrew IP Due to: Stopping Criteria 0 0 0 1
COMPLETED 202 213 162 157
NOT COMPLETED 27 20 28 27

Baseline Characteristics

Arm/Group Title Placebo - High Stratum Mepolizumab 100 mg - High Stratum Placebo - Low Stratum Mepolizumab 100 mg - Low Stratum Total
Arm/Group Description 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. 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. 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. 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 of all reporting groups
Overall Participants 229 233 190 184 836
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
65.3
(8.53)
65.2
(8.36)
65.2
(8.62)
66.1
(9.14)
65.4
(8.64)
Sex: Female, Male (Count of Participants)
Female
79
34.5%
84
36.1%
77
40.5%
76
41.3%
316
37.8%
Male
150
65.5%
149
63.9%
113
59.5%
108
58.7%
520
62.2%
Race/Ethnicity, Customized (Count of Participants)
American Indian/ Alaska native Heritage
14
6.1%
19
8.2%
22
11.6%
14
7.6%
69
8.3%
Asian- East Asian Heritage
0
0%
2
0.9%
0
0%
0
0%
2
0.2%
Asian- Japanese Heritage
3
1.3%
0
0%
1
0.5%
1
0.5%
5
0.6%
Black/ African American Heritage
4
1.7%
2
0.9%
3
1.6%
2
1.1%
11
1.3%
White- Arabic/ North African Heritage
2
0.9%
1
0.4%
0
0%
1
0.5%
4
0.5%
White- White/ Caucasian/ European Heritage
190
83%
198
85%
145
76.3%
143
77.7%
676
80.9%
Multiple - American Indian/Alaska Native and White
16
7%
11
4.7%
19
10%
23
12.5%
69
8.3%

Outcome Measures

1. Primary Outcome
Title Rate of Moderate or Severe Exacerbations in Participants in the High Stratum
Description 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.
Time Frame From randomization to Week 52

Outcome Measure Data

Analysis Population Description
mITT-H Population
Arm/Group Title Placebo - High Stratum Mepolizumab 100 mg - High Stratum
Arm/Group Description 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. 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.
Measure Participants 229 233
Least Squares Mean (95% Confidence Interval) [Moderate/severe exacerbations per year]
1.71
1.40
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - High Stratum, Mepolizumab 100 mg - High Stratum
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value =0.036
Comments Adjusted p-value to account for two treatment comparisons
Method Negative binomial model
Comments
Method of Estimation Estimation Parameter Rate ratio (mepolizumab/placebo)
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.68 to 0.98
Parameter Dispersion Type:
Value:
Estimation Comments Analysis using a negative binomial model with covariates of treatment, geographic region, no.of moderate/severe exacerbations in previous year, Baseline percent predicted for FEV1,smoking status and offset of log (time in on-and off-treatment period)
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - High Stratum, Mepolizumab 100 mg - High Stratum
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value =0.029
Comments Unadjusted p-value.
Method Negative binomial mode
Comments
Method of Estimation Estimation Parameter Rate ratio (mepolizumab/placebo)
Estimated Value 0.82
Confidence Interval (2-Sided) 95%
0.68 to 0.98
Parameter Dispersion Type:
Value:
Estimation Comments Analysis using a negative binomial model with covariates of treatment, geographic region, no.of moderate/severe exacerbations in previous year, Baseline percent predicted FEV1, smoking status and offset of log (time in on- and off-treatment period)
2. Primary Outcome
Title Rate of Moderate or Severe Exacerbations in the mITT Population
Description 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).
Time Frame From randomization to Week 52

Outcome Measure Data

Analysis Population Description
mITT Population
Arm/Group Title Placebo Mepolizumab 100 mg
Arm/Group Description 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. 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.
Measure Participants 419 417
Least Squares Mean (95% Confidence Interval) [Moderate/severe exacerbations per year]
1.52
1.49
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - High Stratum, Mepolizumab 100 mg - High Stratum
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value >0.999
Comments Adjusted p-value to account for two treatment comparisons
Method Negative Binomial Model
Comments
Method of Estimation Estimation Parameter Rate ratio (mepolizumab/placebo)
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.85 to 1.12
Parameter Dispersion Type:
Value:
Estimation Comments Analysis using a negative binomial model with covariates of treatment, geographic region, no.of moderate/severe exacerbations in previous year, Baseline percent predicted FEV1, smoking status and offset of log (time in on- and off-treatment period)
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - High Stratum, Mepolizumab 100 mg - High Stratum
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value =0.731
Comments Unadjusted p-value.
Method Negative binomial mode
Comments
Method of Estimation Estimation Parameter Rate ratio (mepolizumab/placebo)
Estimated Value 0.98
Confidence Interval (2-Sided) 95%
0.85 to 1.12
Parameter Dispersion Type:
Value:
Estimation Comments Analysis using a negative binomial model with covariates of treatment, geographic region, no.of moderate/severe exacerbations in previous year, Baseline percent predicted FEV1, smoking status and offset of log (time in on- and off-treatment period)
3. Secondary Outcome
Title Time to First Moderate/Severe Exacerbation in Participants in the High Stratum
Description 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.
Time Frame From randomization to Week 52

Outcome Measure Data

Analysis Population Description
mITT-H Population
Arm/Group Title Placebo - High Stratum Mepolizumab 100 mg - High Stratum
Arm/Group Description 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. 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.
Measure Participants 229 233
Week 8
28.1
12.3%
20.2
8.7%
Week 16
45.5
19.9%
34.9
15%
Week 24
53.4
23.3%
45.8
19.7%
Week 32
60.9
26.6%
55.3
23.7%
Week 40
68.5
29.9%
59.3
25.5%
Week 48
71.8
31.4%
62.0
26.6%
Week 52
75.2
32.8%
64.6
27.7%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - High Stratum, Mepolizumab 100 mg - High Stratum
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value =0.036
Comments Adjusted p-value
Method Cox Proportional Hazards Model
Comments
Method of Estimation Estimation Parameter Hazard ratio (Mepolizumab/placebo)
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.60 to 0.94
Parameter Dispersion Type:
Value:
Estimation Comments Analysis performed using a Cox Proportional Hazards Model with covariates of treatment, geographic region, no. moderate/severe exacerbations in previous year, Baseline percent predicted FEV1 and smoking status
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - High Stratum, Mepolizumab 100 mg - High Stratum
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value =0.012
Comments Unadjusted p-value
Method Cox Proportional Hazards Model
Comments
Method of Estimation Estimation Parameter Hazard ratio (Mepolizumab/placebo)
Estimated Value 0.75
Confidence Interval (2-Sided) 95%
0.60 to 0.94
Parameter Dispersion Type:
Value:
Estimation Comments Analysis performed using a Cox Proportional Hazards Model with covariates of treatment, geographic region, no. moderate/severe exacerbations in previous year, Baseline percent predicted FEV1 and smoking status
4. Secondary Outcome
Title Rate of COPD Exacerbations Requiring an Emergency Department (ED) Visit and/or Hospitalization (Hosp.) in Participants in the High Stratum
Description 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.
Time Frame From randomization to Week 52

Outcome Measure Data

Analysis Population Description
mITT-H Population
Arm/Group Title Placebo - High Stratum Mepolizumab 100 mg - High Stratum
Arm/Group Description 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. 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.
Measure Participants 229 233
Least Squares Mean (95% Confidence Interval) [Exacerbations requiring ED/hosp per year]
0.26
0.30
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - High Stratum, Mepolizumab 100 mg - High Stratum
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value =0.598
Comments Adjusted p-value
Method Negative binomial model
Comments
Method of Estimation Estimation Parameter Rate ratio (mepolizumab/placebo)
Estimated Value 1.16
Confidence Interval (2-Sided) 95%
0.77 to 1.75
Parameter Dispersion Type:
Value:
Estimation Comments Analysis using a negative binomial model with covariates of treatment, geographic region, no. moderate/severe exacerbations in previous year, Baseline percent predicted FEV1, smoking status and offset of log (time in on- and off-treatment period).
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - High Stratum, Mepolizumab 100 mg - High Stratum
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value =0.479
Comments Unadjusted p-value
Method Negative binomial model
Comments
Method of Estimation Estimation Parameter Rate ratio (mepolizumab/placebo)
Estimated Value 1.16
Confidence Interval (2-Sided) 95%
0.77 to 1.75
Parameter Dispersion Type:
Value:
Estimation Comments Analysis using a negative binomial model with covariates of treatment, geographic region, no. moderate/severe exacerbations in previous year, Baseline percent predicted FEV1, smoking status and offset of log (time in on- and off-treatment period).
5. Secondary Outcome
Title Change From Baseline in Mean Total St. George's Respiratory Questionnaire (SGRQ) Score in Participants in the High Stratum
Description 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.
Time Frame Baseline and Week 52

Outcome Measure Data

Analysis Population Description
mITT-H Population. Participants analyzed represents those with a Baseline and at least one post-Baseline assessment, and with no missing covariates.
Arm/Group Title Placebo - High Stratum Mepolizumab 100 mg - High Stratum
Arm/Group Description 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. 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.
Measure Participants 214 226
Least Squares Mean (Standard Error) [Score on SGRQ scale]
-3.0
(1.11)
-2.8
(1.06)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - High Stratum, Mepolizumab 100 mg - High Stratum
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value >0.999
Comments Adjusted p-value
Method Mixed Model Repeated Measure Analysis
Comments
Method of Estimation Estimation Parameter Mean Difference (Mepolizumab - Placebo)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-2.8 to 3.2
Parameter Dispersion Type:
Value:
Estimation Comments Analysis performed using mixed model repeated measures with covariates of baseline SGRQ Total Score, geographic region, smoking status, treatment and visit, plus interaction terms for visit by Baseline and visit by treatment group.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - High Stratum, Mepolizumab 100 mg - High Stratum
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value =0.901
Comments Unadjusted p-value
Method Mixed Model Repeated Measure Analysis
Comments
Method of Estimation Estimation Parameter Mean Difference (Mepolizumab - Placebo)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
-2.8 to 3.2
Parameter Dispersion Type:
Value:
Estimation Comments Analysis performed using mixed model repeated measures with covariates of baseline SGRQ Total Score, geographic region, smoking status, treatment and visit, plus interaction terms for visit by Baseline and visit by treatment group.
6. Secondary Outcome
Title Change From Baseline in Mean COPD Assessment Test (CAT) Score in Participants in the High Stratum
Description 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.
Time Frame Baseline and Week 52

Outcome Measure Data

Analysis Population Description
mITT-H Population. Participants analyzed represents those with a Baseline and at least one post-Baseline assessment, and with no missing covariates.
Arm/Group Title Placebo - High Stratum Mepolizumab 100 mg - High Stratum
Arm/Group Description 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. 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.
Measure Participants 212 224
Least Squares Mean (Standard Error) [Score on CAT scale]
0.0
(0.47)
-0.8
(0.45)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - High Stratum, Mepolizumab 100 mg - High Stratum
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value >0.999
Comments Adjusted p-value
Method Mixed Model Repeated Measures Analysis
Comments
Method of Estimation Estimation Parameter Mean Difference (Mepolizumab - Placebo)
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-2.0 to 0.5
Parameter Dispersion Type:
Value:
Estimation Comments Analysis performed using mixed model repeated measures with covariates of baseline CAT score, geographic region, smoking status, treatment and visit, plus interaction terms for visit by Baseline and visit by treatment group.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - High Stratum, Mepolizumab 100 mg - High Stratum
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value =0.244
Comments Unadjusted p-value
Method Mixed Model Repeated Measures Analysis
Comments
Method of Estimation Estimation Parameter Mean Difference (Mepolizumab - Placebo)
Estimated Value -0.8
Confidence Interval (2-Sided) 95%
-2.0 to 0.5
Parameter Dispersion Type:
Value:
Estimation Comments Analysis performed using mixed model repeated measures with covariates of baseline CAT score, geographic region, smoking status, treatment and visit, plus interaction terms for visit by Baseline and visit by treatment group.
7. Secondary Outcome
Title Time to First Moderate/Severe Exacerbation in the mITT Population
Description 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).
Time Frame From randomization to Week 52

Outcome Measure Data

Analysis Population Description
mITT Population
Arm/Group Title Placebo Mepolizumab 100 mg
Arm/Group Description 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. 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.
Measure Participants 419 417
Week 8
25.1
11%
23.6
10.1%
Week 16
39.8
17.4%
37.4
16.1%
Week 24
49.2
21.5%
46.3
19.9%
Week 32
57.3
25%
54.1
23.2%
Week 40
63.8
27.9%
59.7
25.6%
Week 48
67.3
29.4%
62.5
26.8%
Week 52
71.2
31.1%
65.5
28.1%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - High Stratum, Mepolizumab 100 mg - High Stratum
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value >0.999
Comments Adjusted p-value
Method Cox Proportional Hazards Model
Comments
Method of Estimation Estimation Parameter Hazard ratio (Mepolizumab/Placebo)
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
0.75 to 1.05
Parameter Dispersion Type:
Value:
Estimation Comments Analysis performed using a Cox Proportional Hazards Model with covariates of treatment, geographic region, no. moderate/severe exacerbations in previous year, Baseline percent predicted FEV1 and smoking status
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - High Stratum, Mepolizumab 100 mg - High Stratum
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value =0.160
Comments Unadjusted p-value
Method Cox Proportional Hazards Model
Comments
Method of Estimation Estimation Parameter Hazard ratio (Mepolizumab/Placebo)
Estimated Value 0.89
Confidence Interval (2-Sided) 95%
0.75 to 1.05
Parameter Dispersion Type:
Value:
Estimation Comments Analysis performed using a Cox Proportional Hazards Model with covariates of treatment, geographic region, no. moderate/severe exacerbations in previous year, Baseline percent predicted FEV1 and smoking status
8. Secondary Outcome
Title Rate of COPD Exacerbations Requiring ED Visit and/or Hosp in the mITT Population
Description 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).
Time Frame From randomization to Week 52

Outcome Measure Data

Analysis Population Description
mITT Population
Arm/Group Title Placebo Mepolizumab 100 mg
Arm/Group Description 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. 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.
Measure Participants 419 417
Least Squares Mean (95% Confidence Interval) [Exacerbations requiring ED/hosp per year]
0.26
0.29
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - High Stratum, Mepolizumab 100 mg - High Stratum
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value >0.999
Comments Adjusted p-value
Method Negative binomial model
Comments
Method of Estimation Estimation Parameter Rate ratio (mepolizumab/placebo)
Estimated Value 1.10
Confidence Interval (2-Sided) 95%
0.81 to 1.49
Parameter Dispersion Type:
Value:
Estimation Comments Analysis using a negative binomial model with covariates of treatment, geographic region, no. moderate/severe exacerbations in previous year, Baseline percent predicted FEV1, smoking status and offset of log (time in on- and off-treatment period).
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - High Stratum, Mepolizumab 100 mg - High Stratum
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value =0.556
Comments Unadjusted p-value
Method Negative binomial model
Comments
Method of Estimation Estimation Parameter Rate ratio (mepolizumab/placebo)
Estimated Value 1.10
Confidence Interval (2-Sided) 95%
0.81 to 1.49
Parameter Dispersion Type:
Value:
Estimation Comments Analysis using a negative binomial model with covariates of treatment, geographic region, no. moderate/severe exacerbations in previous year, Baseline percent predicted FEV1, smoking status and offset of log (time in on- and off-treatment period).
9. Secondary Outcome
Title Change From Baseline in Mean Total SGRQ Score in the mITT Population
Description 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. The strata were combined as pre-specified in the protocol and reporting and analysis plan (RAP).
Time Frame Baseline and Week 52

Outcome Measure Data

Analysis Population Description
mITT Population. Participants analyzed represents those with a Baseline and at least one post-Baseline assessment, and with no missing covariates.
Arm/Group Title Placebo Mepolizumab 100 mg
Arm/Group Description 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. 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.
Measure Participants 396 397
Least Squares Mean (Standard Error) [Score on SGRQ scale]
-4.0
(0.81)
-3.2
(0.80)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - High Stratum, Mepolizumab 100 mg - High Stratum
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value >0.999
Comments Adjusted p-value
Method Mixed Model Repeated Measures Analysis
Comments
Method of Estimation Estimation Parameter Mean difference (Mepolizumab - Placebo)
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
-1.5 to 2.9
Parameter Dispersion Type:
Value:
Estimation Comments Analysis performed using mixed model repeated measures with covariates of baseline SGRQ Total Score, geographic region, smoking status, treatment and visit, plus interaction terms for visit by Baseline and visit by treatment group.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - High Stratum, Mepolizumab 100 mg - High Stratum
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value =0.532
Comments Unadjusted p-value
Method Mixed Model Repeated Measures Analysis
Comments
Method of Estimation Estimation Parameter Mean difference (Mepolizumab - Placebo)
Estimated Value 0.7
Confidence Interval (2-Sided) 95%
-1.5 to 2.9
Parameter Dispersion Type:
Value:
Estimation Comments Analysis performed using mixed model repeated measures with covariates of baseline SGRQ Total Score, geographic region, smoking status, treatment and visit, plus interaction terms for visit by Baseline and visit by treatment group.
10. Secondary Outcome
Title Change From Baseline in Mean CAT Score in the mITT Population
Description 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).
Time Frame Baseline and Week 52

Outcome Measure Data

Analysis Population Description
mITT Population. Participants analyzed represents those with a Baseline and at least one post-Baseline assessment, and with no missing covariates.
Arm/Group Title Placebo Mepolizumab 100 mg
Arm/Group Description 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. 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.
Measure Participants 392 401
Least Squares Mean (Standard Error) [Score on CAT scale]
-0.4
(0.35)
-1.0
(0.34)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo - High Stratum, Mepolizumab 100 mg - High Stratum
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value >0.999
Comments Adjusted p-value
Method Mixed Model Repeated Measures Analysis
Comments
Method of Estimation Estimation Parameter Mean difference (Mepolizumab - Placebo)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-1.5 to 0.4
Parameter Dispersion Type:
Value:
Estimation Comments Analysis performed using mixed model repeated measures with covariates of baseline CAT score, geographic region, smoking status, treatment and visit, plus interaction terms for visit by Baseline and visit by treatment group.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Placebo - High Stratum, Mepolizumab 100 mg - High Stratum
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value =0.252
Comments Unadjusted p-value
Method Mixed Model Repeated Measures Analysis
Comments
Method of Estimation Estimation Parameter Mean difference (Mepolizumab - Placebo)
Estimated Value -0.6
Confidence Interval (2-Sided) 95%
-1.5 to 0.4
Parameter Dispersion Type:
Value:
Estimation Comments Analysis performed using mixed model repeated measures with covariates of baseline CAT score, geographic region, smoking status, treatment and visit, plus interaction terms for visit by Baseline and visit by treatment group.

Adverse Events

Time Frame Serious adverse events (SAEs) collected from the start of study participation until the end of follow up (up to Week 60). On-treatment non-serious adverse events were reported from start of study treatment until 4 weeks after last dose, up to Week 52.
Adverse Event Reporting Description AEs and SAEs were collected in Safety Population which comprised of all randomized participants who received at least one dose of study treatment.
Arm/Group Title Placebo - High Stratum Mepolizumab 100 mg - High Stratum Placebo - Low Stratum Mepolizumab 100 mg - Low Stratum
Arm/Group Description 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. 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. 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. 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.
All Cause Mortality
Placebo - High Stratum Mepolizumab 100 mg - High Stratum Placebo - Low Stratum Mepolizumab 100 mg - Low Stratum
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 8/229 (3.5%) 6/233 (2.6%) 9/190 (4.7%) 10/184 (5.4%)
Serious Adverse Events
Placebo - High Stratum Mepolizumab 100 mg - High Stratum Placebo - Low Stratum Mepolizumab 100 mg - Low Stratum
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 80/229 (34.9%) 65/233 (27.9%) 51/190 (26.8%) 50/184 (27.2%)
Blood and lymphatic system disorders
Anaemia 2/229 (0.9%) 2 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Cardiac disorders
Atrial fibrillation 2/229 (0.9%) 2 4/233 (1.7%) 5 1/190 (0.5%) 1 0/184 (0%) 0
Cardiac failure congestive 3/229 (1.3%) 3 1/233 (0.4%) 1 0/190 (0%) 0 3/184 (1.6%) 6
Acute myocardial infarction 1/229 (0.4%) 1 1/233 (0.4%) 1 2/190 (1.1%) 2 1/184 (0.5%) 1
Cardiac failure 1/229 (0.4%) 2 1/233 (0.4%) 1 0/190 (0%) 0 1/184 (0.5%) 1
Cardiac arrest 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 1/184 (0.5%) 1
Cardiac failure chronic 1/229 (0.4%) 1 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Myocardial infarction 1/229 (0.4%) 1 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Myocardial ischaemia 1/229 (0.4%) 1 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Ventricular tachycardia 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 1 1/184 (0.5%) 1
Acute coronary syndrome 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Angina pectoris 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Atrial flutter 0/229 (0%) 0 0/233 (0%) 0 0/190 (0%) 0 1/184 (0.5%) 1
Atrioventricular block second degree 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Bundle branch block left 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Cardiac failure acute 0/229 (0%) 0 0/233 (0%) 0 0/190 (0%) 0 1/184 (0.5%) 1
Cardiomyopathy 0/229 (0%) 0 0/233 (0%) 0 0/190 (0%) 0 1/184 (0.5%) 1
Cardiopulmonary failure 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Congestive cardiomyopathy 0/229 (0%) 0 0/233 (0%) 0 0/190 (0%) 0 1/184 (0.5%) 1
Cor pulmonale 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Palpitations 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Pericarditis 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Sinus tachycardia 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Ventricular extrasystoles 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Gastrointestinal disorders
Gastrointestinal haemorrhage 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 1/184 (0.5%) 1
Abdominal hernia 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Abdominal pain 0/229 (0%) 0 0/233 (0%) 0 0/190 (0%) 0 1/184 (0.5%) 1
Colitis 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Constipation 0/229 (0%) 0 0/233 (0%) 0 0/190 (0%) 0 1/184 (0.5%) 1
Diverticulum 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Haemorrhoidal haemorrhage 0/229 (0%) 0 0/233 (0%) 0 0/190 (0%) 0 1/184 (0.5%) 1
Haemorrhoids 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Intestinal fistula 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Intestinal haemorrhage 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Intestinal obstruction 0/229 (0%) 0 0/233 (0%) 0 0/190 (0%) 0 1/184 (0.5%) 1
Mallory-Weiss syndrome 0/229 (0%) 0 0/233 (0%) 0 0/190 (0%) 0 1/184 (0.5%) 1
Pancreatitis 0/229 (0%) 0 0/233 (0%) 0 0/190 (0%) 0 1/184 (0.5%) 1
Pancreatitis acute 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Pneumoperitoneum 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Rectal polyp 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Small intestinal obstruction 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
General disorders
Death 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Generalised oedema 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Multiple organ dysfunction syndrome 0/229 (0%) 0 0/233 (0%) 0 0/190 (0%) 0 1/184 (0.5%) 1
Non-cardiac chest pain 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Infections and infestations
Pneumonia 16/229 (7%) 19 12/233 (5.2%) 15 13/190 (6.8%) 15 11/184 (6%) 13
Infective exacerbation of chronic obstructive airways disease 1/229 (0.4%) 1 2/233 (0.9%) 2 0/190 (0%) 0 1/184 (0.5%) 1
Sepsis 0/229 (0%) 0 1/233 (0.4%) 1 1/190 (0.5%) 1 1/184 (0.5%) 1
Urinary tract infection 2/229 (0.9%) 2 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Bronchitis 2/229 (0.9%) 2 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Cellulitis 1/229 (0.4%) 2 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Diverticulitis 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 1/184 (0.5%) 1
Gastroenteritis 1/229 (0.4%) 1 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Lower respiratory tract infection 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 1/184 (0.5%) 1
Abscess limb 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Appendicitis 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Bronchiolitis 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Clostridium difficile infection 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Cystitis 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Escherichia urinary tract infection 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Influenza 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Klebsiella infection 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Lung infection 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Peritonitis 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Pneumococcal infection 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Pneumonia klebsiella 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Pyelonephritis 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Respiratory tract infection 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Respiratory syncytial virus infection 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Rhinovirus infection 0/229 (0%) 0 0/233 (0%) 0 0/190 (0%) 0 1/184 (0.5%) 1
Salmonellosis 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Staphylococcal sepsis 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Injury, poisoning and procedural complications
Femur fracture 1/229 (0.4%) 1 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Foot fracture 0/229 (0%) 0 1/233 (0.4%) 1 1/190 (0.5%) 1 0/184 (0%) 0
Contusion 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Facial bones fracture 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 2 0/184 (0%) 0
Fibula fracture 0/229 (0%) 0 0/233 (0%) 0 0/190 (0%) 0 1/184 (0.5%) 1
Head injury 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Hip fracture 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Injection related reaction 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Jaw fracture 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Laceration 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Meniscus injury 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Periorbital haematoma 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Procedural haemorrhage 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Respiratory fume inhalation disorder 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Spinal fracture 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Thermal burn 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Tibia fracture 0/229 (0%) 0 0/233 (0%) 0 0/190 (0%) 0 1/184 (0.5%) 1
Wound haemorrhage 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Investigations
Influenza B virus test positive 0/229 (0%) 0 0/233 (0%) 0 0/190 (0%) 0 1/184 (0.5%) 1
Transaminases increased 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Metabolism and nutrition disorders
Dehydration 1/229 (0.4%) 1 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Fluid overload 0/229 (0%) 0 0/233 (0%) 0 2/190 (1.1%) 2 0/184 (0%) 0
Hyponatraemia 1/229 (0.4%) 1 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Malnutrition 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 1/184 (0.5%) 1
Hypercalcaemia 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Hypoglycaemia 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Cholelithiasis 0/229 (0%) 0 2/233 (0.9%) 2 1/190 (0.5%) 1 0/184 (0%) 0
Cholecystitis acute 0/229 (0%) 0 1/233 (0.4%) 1 1/190 (0.5%) 1 0/184 (0%) 0
Acute hepatic failure 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Musculoskeletal and connective tissue disorders
Bursitis 1/229 (0.4%) 1 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Arthralgia 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Arthritis 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Lumbar spinal stenosis 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Musculoskeletal chest pain 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Osteonecrosis 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Spinal osteoarthritis 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bladder cancer 2/229 (0.9%) 2 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Lung adenocarcinoma 1/229 (0.4%) 1 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Breast cancer 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Colon cancer 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Laryngeal cancer recurrent 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Lung neoplasm malignant 0/229 (0%) 0 0/233 (0%) 0 0/190 (0%) 0 1/184 (0.5%) 1
Lung adenocarcinoma stage IV 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Non-small cell lung cancer 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Renal neoplasm 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Retinal melanoma 0/229 (0%) 0 0/233 (0%) 0 0/190 (0%) 0 1/184 (0.5%) 1
Small cell lung cancer 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Squamous cell carcinoma of lung 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Squamous cell carcinoma of skin 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
T-cell lymphoma 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Nervous system disorders
Syncope 1/229 (0.4%) 1 1/233 (0.4%) 1 1/190 (0.5%) 1 1/184 (0.5%) 1
Transient ischaemic attack 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 1/184 (0.5%) 1
Brain injury 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Cerebral haematoma 0/229 (0%) 0 0/233 (0%) 0 0/190 (0%) 0 1/184 (0.5%) 1
Cerebral infarction 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Dizziness 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Generalised tonic-clonic seizure 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Sensory loss 0/229 (0%) 0 0/233 (0%) 0 0/190 (0%) 0 1/184 (0.5%) 1
Product Issues
Device dislocation 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Psychiatric disorders
Abnormal behaviour 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Alcohol abuse 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Confusional state 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Personality change due to a general medical condition 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Renal and urinary disorders
Acute kidney injury 0/229 (0%) 0 2/233 (0.9%) 2 0/190 (0%) 0 0/184 (0%) 0
Renal colic 0/229 (0%) 0 1/233 (0.4%) 1 1/190 (0.5%) 1 0/184 (0%) 0
Urinary retention 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 1/184 (0.5%) 1
Acute prerenal failure 0/229 (0%) 0/233 (0%) 0 0/190 (0%) 0 1/184 (0.5%) 1
Anuria 0/229 (0%) 0 0/233 (0%) 0 0/190 (0%) 0 1/184 (0.5%) 1
Bladder dilatation 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Calculus urinary 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Nephrolithiasis 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Renal failure 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Reproductive system and breast disorders
Benign prostatic hyperplasia 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease 43/229 (18.8%) 61 33/233 (14.2%) 59 31/190 (16.3%) 44 31/184 (16.8%) 42
Respiratory failure 5/229 (2.2%) 5 5/233 (2.1%) 5 0/190 (0%) 0 1/184 (0.5%) 1
Acute respiratory failure 3/229 (1.3%) 4 2/233 (0.9%) 4 3/190 (1.6%) 3 0/184 (0%) 0
Pneumothorax 1/229 (0.4%) 1 1/233 (0.4%) 1 1/190 (0.5%) 1 0/184 (0%) 0
Pulmonary embolism 0/229 (0%) 0 2/233 (0.9%) 2 0/190 (0%) 0 0/184 (0%) 0
Alveolitis allergic 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Bronchopneumopathy 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Bronchospasm 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Cough 0/229 (0%) 0 0/233 (0%) 0 0/190 (0%) 0 1/184 (0.5%) 1
Dyspnoea 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Interstitial lung disease 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Organising pneumonia 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Respiratory arrest 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Vascular disorders
Deep vein thrombosis 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Haematoma 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Hypertension 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Hypotension 0/229 (0%) 0 0/233 (0%) 0 1/190 (0.5%) 1 0/184 (0%) 0
Orthostatic hypotension 1/229 (0.4%) 1 0/233 (0%) 0 0/190 (0%) 0 0/184 (0%) 0
Peripheral ischaemia 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Subclavian vein thrombosis 0/229 (0%) 0 1/233 (0.4%) 1 0/190 (0%) 0 0/184 (0%) 0
Other (Not Including Serious) Adverse Events
Placebo - High Stratum Mepolizumab 100 mg - High Stratum Placebo - Low Stratum Mepolizumab 100 mg - Low Stratum
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 146/229 (63.8%) 136/233 (58.4%) 116/190 (61.1%) 108/184 (58.7%)
Gastrointestinal disorders
Diarrhoea 6/229 (2.6%) 8 10/233 (4.3%) 11 9/190 (4.7%) 17 8/184 (4.3%) 11
Nausea 8/229 (3.5%) 18 6/233 (2.6%) 7 4/190 (2.1%) 6 4/184 (2.2%) 5
Abdominal pain 3/229 (1.3%) 4 4/233 (1.7%) 4 9/190 (4.7%) 9 4/184 (2.2%) 4
Constipation 5/229 (2.2%) 6 5/233 (2.1%) 6 1/190 (0.5%) 1 6/184 (3.3%) 7
General disorders
Injection site reaction 7/229 (3.1%) 12 7/233 (3%) 9 5/190 (2.6%) 6 5/184 (2.7%) 13
Oedema peripheral 5/229 (2.2%) 5 8/233 (3.4%) 9 8/190 (4.2%) 8 1/184 (0.5%) 1
Pyrexia 9/229 (3.9%) 12 7/233 (3%) 9 4/190 (2.1%) 6 1/184 (0.5%) 2
Asthenia 8/229 (3.5%) 8 4/233 (1.7%) 4 0/190 (0%) 0 3/184 (1.6%) 3
Non-cardiac chest pain 2/229 (0.9%) 2 5/233 (2.1%) 6 6/190 (3.2%) 6 2/184 (1.1%) 2
Influenza like illness 7/229 (3.1%) 8 2/233 (0.9%) 2 2/190 (1.1%) 3 0/184 (0%) 0
Infections and infestations
Nasopharyngitis 32/229 (14%) 49 38/233 (16.3%) 50 31/190 (16.3%) 39 26/184 (14.1%) 34
Upper respiratory tract infection 10/229 (4.4%) 10 10/233 (4.3%) 12 11/190 (5.8%) 16 11/184 (6%) 13
Influenza 10/229 (4.4%) 13 8/233 (3.4%) 9 13/190 (6.8%) 16 8/184 (4.3%) 12
Sinusitis 7/229 (3.1%) 8 14/233 (6%) 16 6/190 (3.2%) 6 5/184 (2.7%) 5
Pharyngitis 12/229 (5.2%) 13 7/233 (3%) 9 6/190 (3.2%) 6 5/184 (2.7%) 5
Urinary tract infection 9/229 (3.9%) 12 8/233 (3.4%) 9 4/190 (2.1%) 4 7/184 (3.8%) 8
Oral candidiasis 7/229 (3.1%) 9 8/233 (3.4%) 8 5/190 (2.6%) 6 6/184 (3.3%) 8
Pneumonia 10/229 (4.4%) 11 4/233 (1.7%) 4 2/190 (1.1%) 2 5/184 (2.7%) 5
Bronchitis 7/229 (3.1%) 10 5/233 (2.1%) 6 3/190 (1.6%) 6 4/184 (2.2%) 4
Gastroenteritis 1/229 (0.4%) 1 4/233 (1.7%) 4 5/190 (2.6%) 5 7/184 (3.8%) 7
Conjunctivitis 0/229 (0%) 0 3/233 (1.3%) 3 1/190 (0.5%) 1 6/184 (3.3%) 6
Injury, poisoning and procedural complications
Contusion 3/229 (1.3%) 6 7/233 (3%) 7 5/190 (2.6%) 6 5/184 (2.7%) 5
Musculoskeletal and connective tissue disorders
Back pain 16/229 (7%) 17 17/233 (7.3%) 20 15/190 (7.9%) 17 16/184 (8.7%) 19
Pain in extremity 6/229 (2.6%) 15 7/233 (3%) 7 10/190 (5.3%) 12 12/184 (6.5%) 12
Arthralgia 8/229 (3.5%) 16 9/233 (3.9%) 11 11/190 (5.8%) 11 4/184 (2.2%) 5
Myalgia 4/229 (1.7%) 8 4/233 (1.7%) 4 7/190 (3.7%) 8 4/184 (2.2%) 5
Musculoskeletal pain 9/229 (3.9%) 10 3/233 (1.3%) 5 3/190 (1.6%) 4 2/184 (1.1%) 2
Muscle spasms 3/229 (1.3%) 3 4/233 (1.7%) 4 7/190 (3.7%) 7 1/184 (0.5%) 1
Cough 9/229 (3.9%) 10 12/233 (5.2%) 17 6/190 (3.2%) 7 9/184 (4.9%) 11
Nervous system disorders
Headache 31/229 (13.5%) 71 24/233 (10.3%) 36 25/190 (13.2%) 47 18/184 (9.8%) 36
Dizziness 6/229 (2.6%) 6 3/233 (1.3%) 4 11/190 (5.8%) 12 7/184 (3.8%) 9
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain 6/229 (2.6%) 7 15/233 (6.4%) 15 12/190 (6.3%) 13 9/184 (4.9%) 12
Chronic obstructive pulmonary disease 7/229 (3.1%) 13 10/233 (4.3%) 15 8/190 (4.2%) 13 10/184 (5.4%) 22
Dyspnoea 8/229 (3.5%) 10 11/233 (4.7%) 15 4/190 (2.1%) 4 6/184 (3.3%) 9
Skin and subcutaneous tissue disorders
Rash 3/229 (1.3%) 3 7/233 (3%) 7 1/190 (0.5%) 1 2/184 (1.1%) 2
Pruritus 1/229 (0.4%) 1 3/233 (1.3%) 3 7/190 (3.7%) 7 0/184 (0%) 0
Vascular disorders
Hypertension 5/229 (2.2%) 5 8/233 (3.4%) 8 3/190 (1.6%) 3 4/184 (2.2%) 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.

Results Point of Contact

Name/Title GSK Response Center
Organization GlaxoSmithKline
Phone 866-435-7343
Email
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT02105948
Other Study ID Numbers:
  • 117106
First Posted:
Apr 7, 2014
Last Update Posted:
Aug 31, 2018
Last Verified:
Aug 1, 2018