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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02105948




Registration number
NCT02105948
Ethics application status
Date submitted
3/04/2014
Date registered
7/04/2014

Titles & IDs
Public title
Study to Evaluate Efficacy and Safety of Mepolizumab for Frequently Exacerbating Chronic Obstructive Pulmonary Disease (COPD) Patients
Scientific title
Study MEA117106: Mepolizumab vs. Placebo as add-on Treatment for Frequently Exacerbating COPD Patients
Secondary ID [1] 0 0
117106
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pulmonary Disease, Chronic Obstructive 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Mepolizumab
Treatment: Drugs - Placebo

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.

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.


Treatment: Drugs: 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.

Treatment: Drugs: Placebo
Sterile 0.9% sodium chloride solution
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Rate of Moderate or Severe Exacerbations in Participants in the High Stratum
Timepoint [1] 0 0
From randomization to Week 52
Primary outcome [2] 0 0
Rate of Moderate or Severe Exacerbations in the mITT Population
Timepoint [2] 0 0
From randomization to Week 52
Secondary outcome [1] 0 0
Time to First Moderate/Severe Exacerbation in Participants in the High Stratum
Timepoint [1] 0 0
From randomization to Week 52
Secondary outcome [2] 0 0
Rate of COPD Exacerbations Requiring an Emergency Department (ED) Visit and/or Hospitalization (Hosp.) in Participants in the High Stratum
Timepoint [2] 0 0
From randomization to Week 52
Secondary outcome [3] 0 0
Change From Baseline in Mean Total St. George's Respiratory Questionnaire (SGRQ) Score in Participants in the High Stratum
Timepoint [3] 0 0
Baseline and Week 52
Secondary outcome [4] 0 0
Change From Baseline in Mean COPD Assessment Test (CAT) Score in Participants in the High Stratum
Timepoint [4] 0 0
Baseline and Week 52
Secondary outcome [5] 0 0
Time to First Moderate/Severe Exacerbation in the mITT Population
Timepoint [5] 0 0
From randomization to Week 52
Secondary outcome [6] 0 0
Rate of COPD Exacerbations Requiring ED Visit and/or Hosp in the mITT Population
Timepoint [6] 0 0
From randomization to Week 52
Secondary outcome [7] 0 0
Change From Baseline in Mean Total SGRQ Score in the mITT Population
Timepoint [7] 0 0
Baseline and Week 52
Secondary outcome [8] 0 0
Change From Baseline in Mean CAT Score in the mITT Population
Timepoint [8] 0 0
Baseline and Week 52

Eligibility
Key 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.
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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)

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
15/04/2014
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
17/01/2017
Sample size
Target
Accrual to date
Final
837
Recruitment in Australia
Recruitment state(s)
QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
GSK Investigational Site - Cairns
Recruitment hospital [2] 0 0
GSK Investigational Site - Daw Park
Recruitment hospital [3] 0 0
GSK Investigational Site - Clayton
Recruitment hospital [4] 0 0
GSK Investigational Site - Frankston
Recruitment hospital [5] 0 0
GSK Investigational Site - Murdoch
Recruitment hospital [6] 0 0
GSK Investigational Site - Nedlands
Recruitment hospital [7] 0 0
GSK Investigational Site - Liverpool
Recruitment postcode(s) [1] 0 0
4870 - Cairns
Recruitment postcode(s) [2] 0 0
5041 - Daw Park
Recruitment postcode(s) [3] 0 0
3168 - Clayton
Recruitment postcode(s) [4] 0 0
3199 - Frankston
Recruitment postcode(s) [5] 0 0
6150 - Murdoch
Recruitment postcode(s) [6] 0 0
6009 - Nedlands
Recruitment postcode(s) [7] 0 0
2107 - Liverpool
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Minnesota
Country [3] 0 0
United States of America
State/province [3] 0 0
Missouri
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
North Carolina
Country [6] 0 0
United States of America
State/province [6] 0 0
Ohio
Country [7] 0 0
United States of America
State/province [7] 0 0
Oregon
Country [8] 0 0
United States of America
State/province [8] 0 0
Pennsylvania
Country [9] 0 0
United States of America
State/province [9] 0 0
South Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Virginia
Country [11] 0 0
Belgium
State/province [11] 0 0
Brussels
Country [12] 0 0
Belgium
State/province [12] 0 0
Erpent
Country [13] 0 0
Belgium
State/province [13] 0 0
Leuven
Country [14] 0 0
Belgium
State/province [14] 0 0
Liège
Country [15] 0 0
Belgium
State/province [15] 0 0
Oostende
Country [16] 0 0
Canada
State/province [16] 0 0
Alberta
Country [17] 0 0
Canada
State/province [17] 0 0
Manitoba
Country [18] 0 0
Canada
State/province [18] 0 0
Ontario
Country [19] 0 0
Canada
State/province [19] 0 0
Quebec
Country [20] 0 0
Czechia
State/province [20] 0 0
Karlovy Vary
Country [21] 0 0
Czechia
State/province [21] 0 0
Praha 4
Country [22] 0 0
Czechia
State/province [22] 0 0
Tabor
Country [23] 0 0
Czechia
State/province [23] 0 0
Teplice
Country [24] 0 0
Estonia
State/province [24] 0 0
Tallinn
Country [25] 0 0
Estonia
State/province [25] 0 0
Tartu
Country [26] 0 0
France
State/province [26] 0 0
Bayonne cedex
Country [27] 0 0
France
State/province [27] 0 0
Grenoble cedex 9
Country [28] 0 0
France
State/province [28] 0 0
Lyon cedex 04
Country [29] 0 0
France
State/province [29] 0 0
Marseille cedex 20
Country [30] 0 0
France
State/province [30] 0 0
Montpellier cedex 5
Country [31] 0 0
France
State/province [31] 0 0
Perpignan
Country [32] 0 0
France
State/province [32] 0 0
Suresnes
Country [33] 0 0
Greece
State/province [33] 0 0
Athens
Country [34] 0 0
Greece
State/province [34] 0 0
Haidari / Athens
Country [35] 0 0
Greece
State/province [35] 0 0
Rethymnon, Crete
Country [36] 0 0
Greece
State/province [36] 0 0
Thessaloniki
Country [37] 0 0
Italy
State/province [37] 0 0
Campania
Country [38] 0 0
Italy
State/province [38] 0 0
Emilia-Romagna
Country [39] 0 0
Italy
State/province [39] 0 0
Liguria
Country [40] 0 0
Italy
State/province [40] 0 0
Lombardia
Country [41] 0 0
Italy
State/province [41] 0 0
Toscana
Country [42] 0 0
Italy
State/province [42] 0 0
Umbria
Country [43] 0 0
Mexico
State/province [43] 0 0
Jalisco
Country [44] 0 0
Mexico
State/province [44] 0 0
Nuevo León
Country [45] 0 0
Mexico
State/province [45] 0 0
Mexico City
Country [46] 0 0
Mexico
State/province [46] 0 0
México DF
Country [47] 0 0
Mexico
State/province [47] 0 0
Oaxaca
Country [48] 0 0
Norway
State/province [48] 0 0
Bodø
Country [49] 0 0
Norway
State/province [49] 0 0
Kløfta
Country [50] 0 0
Norway
State/province [50] 0 0
Trondheim
Country [51] 0 0
Peru
State/province [51] 0 0
Lima
Country [52] 0 0
Peru
State/province [52] 0 0
Pueblo Libre
Country [53] 0 0
Poland
State/province [53] 0 0
Bialystok
Country [54] 0 0
Poland
State/province [54] 0 0
Elblag
Country [55] 0 0
Poland
State/province [55] 0 0
Krakow
Country [56] 0 0
Poland
State/province [56] 0 0
Ostrow Wielkopolski
Country [57] 0 0
Poland
State/province [57] 0 0
Skierniewice
Country [58] 0 0
Russian Federation
State/province [58] 0 0
Chelyabinsk
Country [59] 0 0
Russian Federation
State/province [59] 0 0
Kemerovo
Country [60] 0 0
Russian Federation
State/province [60] 0 0
Nizhniy Novgorod
Country [61] 0 0
Russian Federation
State/province [61] 0 0
Ryazan
Country [62] 0 0
Russian Federation
State/province [62] 0 0
Saint-Petersburg
Country [63] 0 0
Russian Federation
State/province [63] 0 0
St. Petersburg
Country [64] 0 0
Russian Federation
State/province [64] 0 0
Tomsk
Country [65] 0 0
Russian Federation
State/province [65] 0 0
Yaroslavl
Country [66] 0 0
Spain
State/province [66] 0 0
Alicante
Country [67] 0 0
Spain
State/province [67] 0 0
Barcelona
Country [68] 0 0
Spain
State/province [68] 0 0
L'Hospitalet de Llobregat
Country [69] 0 0
Spain
State/province [69] 0 0
Lugo
Country [70] 0 0
Spain
State/province [70] 0 0
Malaga
Country [71] 0 0
Spain
State/province [71] 0 0
Palma de Mallorca
Country [72] 0 0
Spain
State/province [72] 0 0
Pozuelo De Alarcón/Madrid
Country [73] 0 0
Sweden
State/province [73] 0 0
Lund
Country [74] 0 0
Sweden
State/province [74] 0 0
Stockholm

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
GlaxoSmithKline
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
GSK Clinical Trials
Address 0 0
GlaxoSmithKline
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
IPD for this study will be made available via the Clinical Study Data Request site.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
IPD is available via the Clinical Study Data Request site (click on the link provided below)
Available to whom?
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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://clinicalstudydatarequest.com


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT02105948