Pulmonary Disease, Chronic ObstructivePhase 3NCT02105948
Study to Evaluate Efficacy and Safety of Mepolizumab for Frequently Exacerbating Chronic Obstructive Pulmonary Disease (COPD) Patients
A Phase 3 study testing Mepolizumab in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 116 sites in 16 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Pulmonary Disease, Chronic Obstructive
- What is being tested?
- Mepolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 837 participants
- Where
- 116 sitesin 16 countries
- Study dates
- 15 Apr 2014to 17 Jan 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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)
Trial locations and contacts
116 sites in 16 countries.
116 sites in 16 countries
United States20 sites
GSK Investigational Site
Abingdon, Virginia, 24210
GSK Investigational Site
Charlotte, North Carolina, 28207
GSK Investigational Site
Dayton, Ohio, 45459
GSK Investigational Site
Durham, North Carolina, 27705
GSK Investigational Site
Easley, South Carolina, 29640
GSK Investigational Site
Fort Mill, South Carolina, 29707
GSK Investigational Site
Gaffney, South Carolina, 29340
GSK Investigational Site
Gastonia, North Carolina, 28054
GSK Investigational Site
Greenville, South Carolina, 29615
GSK Investigational Site
Huntersville, North Carolina, 28078
GSK Investigational Site
Medford, Oregon, 97504
GSK Investigational Site
New York, New York, 10029
GSK Investigational Site
Newport Beach, California, 92663
GSK Investigational Site
Pittsburgh, Pennsylvania, 15213
GSK Investigational Site
Rochester, Minnesota, 55905
GSK Investigational Site
Saint Charles, Missouri, 63301
GSK Investigational Site
Seneca, South Carolina, 29678
GSK Investigational Site
Spartanburg, South Carolina, 29303
GSK Investigational Site
Wilmington, North Carolina, 28401
GSK Investigational Site
Winston-Salem, North Carolina, 27103
Canada11 sites
GSK Investigational Site
Calgary, Alberta, T2N 4Z6
GSK Investigational Site
Gatineau, Quebec, J8Y 6S8
GSK Investigational Site
Montreal, Quebec, H2W1T8
GSK Investigational Site
Montreal, Quebec, H4J 1C5
GSK Investigational Site
Saint-Charles-Borromée, Quebec, J6E 2B4
GSK Investigational Site
Sainte-Foy, Quebec, G1V 4G5
GSK Investigational Site
Sherwood Park, Alberta, T8H 0N2
GSK Investigational Site
Toronto, Ontario, M5T 3A9
GSK Investigational Site
Trois-Rivières, Quebec, G8T 7A1
GSK Investigational Site
Windsor, Ontario, N8X 5A6
GSK Investigational Site
Winnipeg, Manitoba, R2K 3S8
Russia10 sites
GSK Investigational Site
Chelyabinsk, 454106
GSK Investigational Site
Kemerovo, 650000
GSK Investigational Site
Nizhny Novgorod, 603126
GSK Investigational Site
Ryazan, 390039
GSK Investigational Site
Saint Petersburg, 194354
GSK Investigational Site
Saint Petersburg, 194356
GSK Investigational Site
Saint Petersburg, 195271
GSK Investigational Site
Tomsk, 634 050
GSK Investigational Site
Tomsk, 634001
GSK Investigational Site
Yaroslavl, 150003
Mexico9 sites
GSK Investigational Site
Guadalajara, Jalisco, 44100
GSK Investigational Site
Guadalajara, Jalisco, 44500
GSK Investigational Site
Mexico City, 07760
GSK Investigational Site
México DF, 14050
GSK Investigational Site
Monterrey, Nuevo León, 64000
GSK Investigational Site
Monterrey, Nuevo León, 64020
GSK Investigational Site
Monterrey NL, Nuevo León, 64718
GSK Investigational Site
Oaxaca City, 68000
GSK Investigational Site
Zapopan, Jalisco, 45070
Peru8 sites
GSK Investigational Site
Lima, Lima Province, Lima 27
GSK Investigational Site
Lima, Lima 18
GSK Investigational Site
Lima, Lima 1
GSK Investigational Site
Lima, Lima 32
GSK Investigational Site
Pueblo Libre, Lima 21
GSK Investigational Site
San Martín de Porres, Lima region, Lima 31
GSK Investigational Site
San Miguel, Lima region, Lima 32
GSK Investigational Site
Santiago de Surco, Lima region, Lima 33
Spain8 sites
GSK Investigational Site
Alicante, 03004
GSK Investigational Site
Barcelona, 08025
GSK Investigational Site
Barcelona, 08036
GSK Investigational Site
L'Hospitalet de Llobregat, 08907
GSK Investigational Site
Lugo, 27003
GSK Investigational Site
Málaga, 29010
GSK Investigational Site
Palma de Mallorca, 07120
GSK Investigational Site
Pozuelo de Alarcón/Madrid, 28223
Australia7 sites
GSK Investigational Site
Cairns, Queensland, 4870
GSK Investigational Site
Clayton, Victoria, 3168
GSK Investigational Site
Daw Park, South Australia, 5041
GSK Investigational Site
Frankston, Victoria, 3199
GSK Investigational Site
Liverpool, 2107
GSK Investigational Site
Murdoch, Western Australia, 6150
GSK Investigational Site
Nedlands, Western Australia, 6009
France7 sites
GSK Investigational Site
Bayonne, 64109
GSK Investigational Site
Grenoble, 38043
GSK Investigational Site
Lyon, 69317
GSK Investigational Site
Marseille, 13915
GSK Investigational Site
Montpellier, 34295
GSK Investigational Site
Perpignan, 66000
GSK Investigational Site
Suresnes, 92150
Belgium6 sites
GSK Investigational Site
Brussels, 1000
GSK Investigational Site
Brussels, 1200
GSK Investigational Site
Erpent, 5101
GSK Investigational Site
Leuven, 3000
GSK Investigational Site
Liège, 4000
GSK Investigational Site
Ostend, 8400
Greece6 sites
GSK Investigational Site
Athens, 106 76
GSK Investigational Site
Athens, 11527
GSK Investigational Site
Haidari / Athens, 124 62
GSK Investigational Site
Rethymnon, Crete, 74100
GSK Investigational Site
Thessaloniki, 56429
GSK Investigational Site
Thessaloniki, 57010
Italy6 sites
GSK Investigational Site
Milan, Lombardy, 20123
GSK Investigational Site
Naples, Campania, 80131
GSK Investigational Site
Parma, Emilia-Romagna, 43125
GSK Investigational Site
Perugia, Umbria, 06156
GSK Investigational Site
Pietra Ligure (SV), Liguria, 17027
GSK Investigational Site
Pisa, Tuscany, 56124
Poland5 sites
GSK Investigational Site
Bialystok, 15-044
GSK Investigational Site
Elblag, 82-300
GSK Investigational Site
Krakow, 31-024
GSK Investigational Site
Ostrów Wielkopolski, 63-400
GSK Investigational Site
Skierniewice, 96-100
Czechia4 sites
GSK Investigational Site
Karlovy Vary, 360 17
GSK Investigational Site
Prague, 140 46
GSK Investigational Site
Tábor, 39003
GSK Investigational Site
Teplice, 415 10
Estonia4 sites
GSK Investigational Site
Tallinn, 10138
GSK Investigational Site
Tallinn, 13419
GSK Investigational Site
Tallinn, 13619
GSK Investigational Site
Tartu, 51014
Norway3 sites
GSK Investigational Site
Bodø, 8005
GSK Investigational Site
Kløfta, 2040
GSK Investigational Site
Trondheim, 7027
Sweden2 sites
GSK Investigational Site
Lund, SE-221 85
GSK Investigational Site
Stockholm, SE-141 86
About this study
Official title: Study MEA117106: Mepolizumab vs. Placebo as add-on Treatment for Frequently Exacerbating COPD Patients
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.
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Being tested
- Mepolizumab, Placebo
- Keywords
- eosinophils, SB240563, exacerbations, Chronic Obstructive Pulmonary Disease, mepolizumab
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MepolizumabDrug
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.
PlaceboDrug
Sterile 0.9% sodium chloride solution
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | 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. Receives: Drug: Mepolizumab |
| Arm 2 | Placebo comparator | 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. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Moderate or Severe Exacerbations in Participants in the High Stratum
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.
Measured: From randomization to Week 52
Rate of Moderate or Severe Exacerbations in the mITT Population
Moderate and severe exacerbations occurring from the start of IP up to the Week 52 visit, including exacerbations reported after early discontinuation from IP by participants who remained in the study, were included in the analysis. The analysis was performed on the mITT Population which comprised of all randomized participants who received at least one dose of trial medication. The strata were combined as pre-specified in the protocol and reporting and analysis plan (RAP).
Measured: From randomization to Week 52
Secondary outcomes (8)
Time to First Moderate/Severe Exacerbation in Participants in the High Stratum
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.
Measured: From randomization to Week 52
Rate of COPD Exacerbations Requiring an Emergency Department (ED) Visit and/or Hospitalization (Hosp.) in Participants in the High Stratum
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.
Measured: From randomization to Week 52
Change From Baseline in Mean Total St. George's Respiratory Questionnaire (SGRQ) Score in Participants in the High Stratum
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.
Measured: Baseline and Week 52
Change From Baseline in Mean COPD Assessment Test (CAT) Score in Participants in the High Stratum
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.
Measured: Baseline and Week 52
Time to First Moderate/Severe Exacerbation in the mITT Population
Kaplan Meier estimates of the probability of a moderate/severe exacerbation are expressed as the percentage of participants with an exacerbation over time (by Week 8, 16, 24, 32, 40, 48, 52). The analysis was performed on the mITT population and included exacerbations reported on-treatment and those reported after early discontinuation from IP by participants who remained in the study. The strata were combined as pre-specified in the protocol and reporting and analysis plan (RAP).
Measured: From randomization to Week 52
Rate of COPD Exacerbations Requiring ED Visit and/or Hosp in the mITT Population
COPD exacerbations requiring ED visit and/or hosp occurring from the start of IP up to the Week 52 visit, including exacerbations reported after early discontinuation from IP by participants who remained in the study, were included in the analysis. The analysis was performed on mITT Population. The strata were combined as pre-specified in the protocol and reporting and analysis plan (RAP).
Measured: From randomization to Week 52
Change From Baseline in Mean Total SGRQ Score in the mITT Population
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).
Measured: Baseline and Week 52
Change From Baseline in Mean CAT Score in the mITT Population
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).
Measured: Baseline and Week 52
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Apr 2014 (estimated)
- Study start15 Apr 2014
- Primary completion17 Jan 2017
- Study completion17 Jan 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Disease, Chronic ObstructiveStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 837 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02105948
- Sponsor's protocol ID
- 117106
- Status last verified
- Aug 2018
- First submitted
- 3 Apr 2014
- Last updated
- 31 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: IPD for this study will be made available via the Clinical Study Data Request site.
Publications
Pavord ID, Chapman KR, Bafadhel M, Sciurba FC, Bradford ES, Schweiker Harris S, Mayer B, Rubin DB, Yancey SW, Paggiaro P. Mepolizumab for Eosinophil-Associated COPD: Analysis of METREX and METREO. Int J Chron Obstruct Pulmon Dis. 2021 Jun 16;16:1755-1770. doi: 10.2147/COPD.S294333. eCollection 2021.
PubMed 34163157Condreay LD, Gao C, Bradford E, Yancey SW, Ghosh S. No genetic associations with mepolizumab efficacy in COPD with peripheral blood eosinophilia. Respir Med. 2019 Aug;155:26-28. doi: 10.1016/j.rmed.2019.07.004. Epub 2019 Jul 5.
PubMed 31295674Pavord ID, Chanez P, Criner GJ, Kerstjens HAM, Korn S, Lugogo N, Martinot JB, Sagara H, Albers FC, Bradford ES, Harris SS, Mayer B, Rubin DB, Yancey SW, Sciurba FC. Mepolizumab for Eosinophilic Chronic Obstructive Pulmonary Disease. N Engl J Med. 2017 Oct 26;377(17):1613-1629. doi: 10.1056/NEJMoa1708208. Epub 2017 Sep 11.
PubMed 28893134
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study MEA117106: Mepolizumab vs. Placebo as add-on Treatment for Frequently Exacerbating COPD Patients
- ClinicalTrials.gov ID
- NCT02105948
- Acronym / sponsor ID
- 117106
- Conditions
- Pulmonary Disease, Chronic Obstructive
- Keywords
- eosinophils, SB240563, exacerbations, Chronic Obstructive Pulmonary Disease, mepolizumab
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 837 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 15 Apr 2014 (actual)
- Primary completion
- 17 Jan 2017 (actual)
- Study completion
- 17 Jan 2017 (actual)
- First posted
- 7 Apr 2014 (estimated)
- Results
- Posted 6 Apr 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: MepolizumabEach 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. |
| Arm 2 | Placebo comparator | Drug: PlaceboEach 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. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (31 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MepolizumabHumanised IgG antibody (IgG1, kappa) with human heavy and light chain frameworks, provided as a lyophilised cake in sterile vial. Vial to be reconstituted with Sterile Water for Injection, just prior to use. | Drug | Arm 1 |
| PlaceboSterile 0.9% sodium chloride solution | Drug | Arm 2 |
Primary outcome
Rate of Moderate or Severe Exacerbations in Participants in the High Stratum
Time frame: 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.
Rate of Moderate or Severe Exacerbations in the mITT Population
Time frame: 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).
8 secondary outcomes
Time to First Moderate/Severe Exacerbation in Participants in the High Stratum
Time frame: From randomization to Week 52
Rate of COPD Exacerbations Requiring an Emergency Department (ED) Visit and/or Hospitalization (Hosp.) in Participants in the High Stratum
Time frame: From randomization to Week 52
Change From Baseline in Mean Total St. George's Respiratory Questionnaire (SGRQ) Score in Participants in the High Stratum
Time frame: Baseline and Week 52
Change From Baseline in Mean COPD Assessment Test (CAT) Score in Participants in the High Stratum
Time frame: Baseline and Week 52
Time to First Moderate/Severe Exacerbation in the mITT Population
Time frame: From randomization to Week 52
Rate of COPD Exacerbations Requiring ED Visit and/or Hosp in the mITT Population
Time frame: From randomization to Week 52
Change From Baseline in Mean Total SGRQ Score in the mITT Population
Time frame: Baseline and Week 52
Change From Baseline in Mean CAT Score in the mITT Population
Time frame: Baseline and Week 52
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34163157Pavord ID, Chapman KR, Bafadhel M, Sciurba FC, Bradford ES, Schweiker Harris S, Mayer B, Rubin DB, Yancey SW, Paggiaro P. Mepolizumab for Eosinophil-Associated COPD: Analysis of METREX and METREO. Int J Chron Obstruct Pulmon Dis. 2021 Jun 16;16:1755-1770. doi: 10.2147/COPD.S294333. eCollection 2021.
- Derived from this study: PubMed 31295674Condreay LD, Gao C, Bradford E, Yancey SW, Ghosh S. No genetic associations with mepolizumab efficacy in COPD with peripheral blood eosinophilia. Respir Med. 2019 Aug;155:26-28. doi: 10.1016/j.rmed.2019.07.004. Epub 2019 Jul 5.
- Derived from this study: PubMed 28893134Pavord ID, Chanez P, Criner GJ, Kerstjens HAM, Korn S, Lugogo N, Martinot JB, Sagara H, Albers FC, Bradford ES, Harris SS, Mayer B, Rubin DB, Yancey SW, Sciurba FC. Mepolizumab for Eosinophilic Chronic Obstructive Pulmonary Disease. N Engl J Med. 2017 Oct 26;377(17):1613-1629. doi: 10.1056/NEJMoa1708208. Epub 2017 Sep 11.
- IPD for this study will be made available via the Clinical Study Data Request site.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
116 sites in 16 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Mepolizumab in people with Pulmonary Disease, Chronic Obstructive, run by GlaxoSmithKline at 116 sites in 16 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 116 sites in United States, Canada, Russia, Mexico, Peru and 11 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Apr 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of Moderate or Severe Exacerbations in Participants in the High Stratum (time frame: From randomization to Week 52). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02105948, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2018.