Study to Evaluate Efficacy and Safety of Mepolizumab for Frequently Exacerbating Chronic Obstructive Pulmonary Disease (COPD) Patients
Study MEA117106: Mepolizumab vs. Placebo as add-on Treatment for Frequently Exacerbating COPD Patients
1 other identifier
interventional
837
15 countries
108
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Apr 2014
Typical duration for phase_3
108 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 3, 2014
CompletedFirst Posted
Study publicly available on registry
April 7, 2014
CompletedStudy Start
First participant enrolled
April 15, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 17, 2017
CompletedStudy Completion
Last participant's last visit for all outcomes
January 17, 2017
CompletedResults Posted
Study results publicly available
April 6, 2018
CompletedAugust 31, 2018
August 1, 2018
2.8 years
April 3, 2014
January 15, 2018
August 2, 2018
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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.
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).
From randomization to Week 52
Secondary Outcomes (8)
Time to First Moderate/Severe Exacerbation in Participants in the High Stratum
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
From randomization to Week 52
Change From Baseline in Mean Total St. George's Respiratory Questionnaire (SGRQ) Score in Participants in the High Stratum
Baseline and Week 52
Change From Baseline in Mean COPD Assessment Test (CAT) Score in Participants in the High Stratum
Baseline and Week 52
Time to First Moderate/Severe Exacerbation in the mITT Population
From randomization to Week 52
- +3 more secondary outcomes
Study Arms (2)
Arm 1
EXPERIMENTALEach 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 COMPARATOREach 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.
Interventions
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.
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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.
- 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
- +15 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- GlaxoSmithKlinelead
Study Sites (116)
GSK Investigational Site
Newport Beach, California, 92663, United States
GSK Investigational Site
Rochester, Minnesota, 55905, United States
GSK Investigational Site
Saint Charles, Missouri, 63301, United States
GSK Investigational Site
New York, New York, 10029, United States
GSK Investigational Site
Charlotte, North Carolina, 28207, United States
GSK Investigational Site
Durham, North Carolina, 27705, United States
GSK Investigational Site
Gastonia, North Carolina, 28054, United States
GSK Investigational Site
Huntersville, North Carolina, 28078, United States
GSK Investigational Site
Wilmington, North Carolina, 28401, United States
GSK Investigational Site
Winston-Salem, North Carolina, 27103, United States
GSK Investigational Site
Dayton, Ohio, 45459, United States
GSK Investigational Site
Medford, Oregon, 97504, United States
GSK Investigational Site
Pittsburgh, Pennsylvania, 15213, United States
GSK Investigational Site
Easley, South Carolina, 29640, United States
GSK Investigational Site
Fort Mill, South Carolina, 29707, United States
GSK Investigational Site
Gaffney, South Carolina, 29340, United States
GSK Investigational Site
Greenville, South Carolina, 29615, United States
GSK Investigational Site
Seneca, South Carolina, 29678, United States
GSK Investigational Site
Spartanburg, South Carolina, 29303, United States
GSK Investigational Site
Abingdon, Virginia, 24210, United States
GSK Investigational Site
Cairns, Queensland, 4870, Australia
GSK Investigational Site
Daw Park, South Australia, 5041, Australia
GSK Investigational Site
Clayton, Victoria, 3168, Australia
GSK Investigational Site
Frankston, Victoria, 3199, Australia
GSK Investigational Site
Murdoch, Western Australia, 6150, Australia
GSK Investigational Site
Nedlands, Western Australia, 6009, Australia
GSK Investigational Site
Liverpool, 2107, Australia
GSK Investigational Site
Brussels, 1000, Belgium
GSK Investigational Site
Brussels, 1200, Belgium
GSK Investigational Site
Erpent, 5101, Belgium
GSK Investigational Site
Leuven, 3000, Belgium
GSK Investigational Site
Liège, 4000, Belgium
GSK Investigational Site
Ostend, 8400, Belgium
GSK Investigational Site
Calgary, Alberta, T2N 4Z6, Canada
GSK Investigational Site
Sherwood Park, Alberta, T8H 0N2, Canada
GSK Investigational Site
Winnipeg, Manitoba, R2K 3S8, Canada
GSK Investigational Site
Toronto, Ontario, M5T 3A9, Canada
GSK Investigational Site
Windsor, Ontario, N8X 5A6, Canada
GSK Investigational Site
Gatineau, Quebec, J8Y 6S8, Canada
GSK Investigational Site
Montreal, Quebec, H2W1T8, Canada
GSK Investigational Site
Montreal, Quebec, H4J 1C5, Canada
GSK Investigational Site
Saint-Charles-Borromée, Quebec, J6E 2B4, Canada
GSK Investigational Site
Sainte-Foy, Quebec, G1V 4G5, Canada
GSK Investigational Site
Trois-Rivières, Quebec, G8T 7A1, Canada
GSK Investigational Site
Karlovy Vary, 360 17, Czechia
GSK Investigational Site
Prague, 140 46, Czechia
GSK Investigational Site
Tábor, 39003, Czechia
GSK Investigational Site
Teplice, 415 10, Czechia
GSK Investigational Site
Tallinn, 10138, Estonia
GSK Investigational Site
Tallinn, 13419, Estonia
GSK Investigational Site
Tallinn, 13619, Estonia
GSK Investigational Site
Tartu, 51014, Estonia
GSK Investigational Site
Bayonne, 64109, France
GSK Investigational Site
Grenoble, 38043, France
GSK Investigational Site
Lyon, 69317, France
GSK Investigational Site
Marseille, 13915, France
GSK Investigational Site
Montpellier, 34295, France
GSK Investigational Site
Perpignan, 66000, France
GSK Investigational Site
Suresnes, 92150, France
GSK Investigational Site
Athens, 106 76, Greece
GSK Investigational Site
Athens, 11527, Greece
GSK Investigational Site
Haidari / Athens, 124 62, Greece
GSK Investigational Site
Rethymnon, Crete, 74100, Greece
GSK Investigational Site
Thessaloniki, 56429, Greece
GSK Investigational Site
Thessaloniki, 57010, Greece
GSK Investigational Site
Napoli, Campania, 80131, Italy
GSK Investigational Site
Parma, Emilia-Romagna, 43125, Italy
GSK Investigational Site
Pietra Ligure (SV), Liguria, 17027, Italy
GSK Investigational Site
Milan, Lombardy, 20123, Italy
GSK Investigational Site
Pisa, Tuscany, 56124, Italy
GSK Investigational Site
Perugia, Umbria, 06156, Italy
GSK Investigational Site
Guadalajara, Jalisco, 44100, Mexico
GSK Investigational Site
Guadalajara, Jalisco, 44500, Mexico
GSK Investigational Site
Zapopan, Jalisco, 45070, Mexico
GSK Investigational Site
Monterrey, Nuevo León, 64000, Mexico
GSK Investigational Site
Monterrey, Nuevo León, 64020, Mexico
GSK Investigational Site
Monterrey NL, Nuevo León, 64718, Mexico
GSK Investigational Site
Mexico City, 07760, Mexico
GSK Investigational Site
México DF, 14050, Mexico
GSK Investigational Site
Oaxaca City, 68000, Mexico
GSK Investigational Site
Bodø, 8005, Norway
GSK Investigational Site
Kløfta, 2040, Norway
GSK Investigational Site
Trondheim, 7027, Norway
GSK Investigational Site
Lima, Lima Province, Lima 27, Peru
GSK Investigational Site
San Martín de Porres, Lima region, Lima 31, Peru
GSK Investigational Site
San Miguel, Lima region, Lima 32, Peru
GSK Investigational Site
Santiago de Surco, Lima region, Lima 33, Peru
GSK Investigational Site
Lima, Lima 18, Peru
GSK Investigational Site
Lima, Lima 1, Peru
GSK Investigational Site
Lima, Lima 32, Peru
GSK Investigational Site
Pueblo Libre, Lima 21, Peru
GSK Investigational Site
Bialystok, 15-044, Poland
GSK Investigational Site
Elblag, 82-300, Poland
GSK Investigational Site
Krakow, 31-024, Poland
GSK Investigational Site
Ostrów Wielkopolski, 63-400, Poland
GSK Investigational Site
Skierniewice, 96-100, Poland
GSK Investigational Site
Chelyabinsk, 454106, Russia
GSK Investigational Site
Kemerovo, 650000, Russia
GSK Investigational Site
Nizhny Novgorod, 603126, Russia
GSK Investigational Site
Ryazan, 390039, Russia
GSK Investigational Site
Saint Petersburg, 194354, Russia
GSK Investigational Site
Saint Petersburg, 194356, Russia
GSK Investigational Site
Saint Petersburg, 195271, Russia
GSK Investigational Site
Tomsk, 634 050, Russia
GSK Investigational Site
Tomsk, 634001, Russia
GSK Investigational Site
Yaroslavl, 150003, Russia
GSK Investigational Site
Alicante, 03004, Spain
GSK Investigational Site
Barcelona, 08025, Spain
GSK Investigational Site
Barcelona, 08036, Spain
GSK Investigational Site
L'Hospitalet de Llobregat, 08907, Spain
GSK Investigational Site
Lugo, 27003, Spain
GSK Investigational Site
Málaga, 29010, Spain
GSK Investigational Site
Palma de Mallorca, 07120, Spain
GSK Investigational Site
Pozuelo de Alarcón/Madrid, 28223, Spain
GSK Investigational Site
Lund, SE-221 85, Sweden
GSK Investigational Site
Stockholm, SE-141 86, Sweden
Related Publications (3)
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.
PMID: 34163157DERIVEDCondreay 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.
PMID: 31295674DERIVEDPavord 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.
PMID: 28893134DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Results Point of Contact
- Title
- GSK Response Center
- Organization
- GlaxoSmithKline
Study Officials
- STUDY DIRECTOR
GSK Clinical Trials
GlaxoSmithKline
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 3, 2014
First Posted
April 7, 2014
Study Start
April 15, 2014
Primary Completion
January 17, 2017
Study Completion
January 17, 2017
Last Updated
August 31, 2018
Results First Posted
April 6, 2018
Record last verified: 2018-08
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Time Frame
- IPD is available via the Clinical Study Data Request site (click on the link provided below)
- Access Criteria
- Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
IPD for this study will be made available via the Clinical Study Data Request site.