Phase 3
N=836
Study to Evaluate Efficacy and Safety of Mepolizumab for Frequently Exacerbating Chronic Obstructive Pulmonary Disease (COPD) Patients
Pulmonary Disease, Chronic Obstructive
Bottom Line
View on ClinicalTrials.gov: NCT02105948 ↗Enrolled (actual)
836
Serious AEs
29.4%
Results posted
Apr 2018
Primary outcome: Primary: Rate of Moderate or Severe Exacerbations in Participants in the High Stratum — 1.71; 1.40 Moderate/severe exacerbations per year — p==0.036
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Mepolizumab (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 40+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Jan 2017
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Rate of Moderate or Severe Exacerbations in Participants in the High Stratum |
1.71; 1.40 | =0.036 sig |
| PRIMARY Rate of Moderate or Severe Exacerbations in the mITT Population |
1.52; 1.49 | >0.999 |
| SECONDARY Time to First Moderate/Severe Exacerbation in Participants in the High Stratum |
28.1; 20.2; 45.5; 34.9; 53.4; 45.8 | =0.036 sig |
| SECONDARY Rate of COPD Exacerbations Requiring an Emergency Department (ED) Visit and/or Hospitalization (Hosp.) in Participants in the High Stratum |
0.26; 0.30 | =0.598 |
| SECONDARY Change From Baseline in Mean Total St. George's Respiratory Questionnaire (SGRQ) Score in Participants in the High Stratum |
-3.0; -2.8 | >0.999 |
| SECONDARY Change From Baseline in Mean COPD Assessment Test (CAT) Score in Participants in the High Stratum |
0.0; -0.8 | >0.999 |
| SECONDARY Time to First Moderate/Severe Exacerbation in the mITT Population |
25.1; 23.6; 39.8; 37.4; 49.2; 46.3 | >0.999 |
| SECONDARY Rate of COPD Exacerbations Requiring ED Visit and/or Hosp in the mITT Population |
0.26; 0.29 | >0.999 |
| SECONDARY Change From Baseline in Mean Total SGRQ Score in the mITT Population |
-4.0; -3.2 | >0.999 |
| SECONDARY Change From Baseline in Mean CAT Score in the mITT Population |
-0.4; -1.0 | >0.999 |
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.
Eligibility Criteria
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 20 percent and =500 micrograms (mcg)/day fluticasone propionate dose equivalent plus); or LABA and LAMA.
For subjects who are not continually maintained on ICS plus LABA plus LAMA for the entire 12 months prior to Visit 1 use of following is allowed (but not in the 3 months immediately prior to Visit 1): inhaled corticosteroid at a dose >=500 mcg/day fluticasone propionate dose equivalent plus ; a LABA or a LAMA and use of at least one other class of COPD medication suggested by the 2013 Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for patients who are prone to exacerbation (i.e., phosphodiesterase-4-inhibitors, methylxanthines, or a combination of short acting beta-2-agonist and short acting muscarinic antagonist). Note: Subjects must be willing to stay on their SoC COPD medication for the duration of the study.
- Informed Consent: Able to give written informed consent prior to participation in the study, which will include the ability to comply with the requirements and restrictions listed in the consent form. Subjects must be able to read, comprehend, and write at a level sufficient to complete study related materials.
- Gender: Male or Eligible Female; To be eligible for entry into the study females of child bearing potential must commit to consistent and correct use of an acceptable method of birth control from the time of consent, for the duration of the trial, and for 4 months after last study drug administration.
- Age: At least 40 years of age at Visit 1.
- Smoking status: Subject with confirmed COPD are eligible to participate independent of their smoking status and smoking history, i.e. current smokers, never smokers or ex-smokers can be enrolled into the study; Current smokers are defined as those with a history of cigarette smoking of >=10 pack-years [number of pack years = (number of cigarettes per day / 20) x number of years smoked (e.g., 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years)]; Former smokers are defined as those who meet the definition of a current smoker but have stopped smoking for at least 6 months prior to Visit 1; Never smokers are those that do not meet the definition of a current or former smoker.
- French subjects: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category.
Exclusion Criteria
- Subjects having Asthma: Current and Former Smokers: Subjects with a current diagnosis of asthma (those with a prior history are eligible if they meet inclusion criteria for a current diagnosis of COPD); Never-Smokers: Subjects with any history of asthma; Other respiratory disorders: The investigator must judge that COPD is the primary diagnosis accounting for the clinical manifestations of the lung disease. Subjects with alpha-1-antitrypsin deficiency as the underlying cause of COPD are excluded. Also, excluded are subjects with active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, primary pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases. Subjects are also excluded if maintenance use of bi-level positive airway pressure is required for the treatment of respiratory disorder.
- COPD stability: Subjects with pneumonia, exacerbation, lower respiratory infection within the 4 weeks prior to Visit 1.
- Lung resection: Subjects with lung volume reduction surgery within the 12 months prior to Visit 1.
- Pulmonary rehabilitation program: Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to
Data sourced from ClinicalTrials.gov (NCT02105948). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.