Phase 3
N=806
Mepolizumab as Add-on Treatment IN Participants With COPD Characterized by Frequent Exacerbations and Eosinophil Level
Pulmonary Disease, Chronic Obstructive
Bottom Line
View on ClinicalTrials.gov: NCT04133909 ↗Enrolled (actual)
806
Serious AEs
26.9%
Results posted
Aug 2025
Primary outcome: Primary: Annualized Rate of Moderate or Severe Exacerbations — 0.80; 1.01 Exacerbations per year — p=0.011
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Mepolizumab (Biological); Placebo (Drug)
- Age
- Adult, Older Adult · 40+ yrs
- Sex
- All
- Sponsor
- GlaxoSmithKline
- Primary completion
- Aug 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Annualized Rate of Moderate or Severe Exacerbations |
0.80; 1.01 | 0.011 sig |
| SECONDARY Time to First Moderate or Severe Exacerbation |
11.3; 15.1; 21.6; 25.6; 28.3; 35.4 | 0.009 sig |
| SECONDARY Percentage of COPD Assessment Test (CAT) Responders With >=2 Point Reduction From Baseline at Week 52 |
41; 46 | 0.161 |
| SECONDARY Percentage of St. George's Respiratory Questionnaire for COPD (SGRQ) Total Score Responders With >=4 Point Reduction From Baseline at Week 52 |
50; 46 | 0.291 |
| SECONDARY Percentage of Evaluating Respiratory Symptoms in COPD (E-RS: COPD) Responders With >=2 Point Reduction From Baseline |
31; 34 | 0.209 |
| SECONDARY Annualized Rate of Exacerbations Requiring Emergency Department (ED) Visit and/or Hospitalization |
0.13; 0.20 | 0.032 sig |
Summary
This is a multi-center, randomized, placebo-controlled, double-blind, parallel group study designed to confirm the benefits of mepolizumab treatment on moderate or severe exacerbations in chronic obstructive pulmonary disease (COPD) participants given as an add on to their optimized maintenance COPD therapy. The maximum duration of participant participation is approximately 109 weeks, consisting of 2 screening visits (up to 3 weeks), a run-in period (up to 2 weeks), and an intervention period of at least 52 weeks and up to 104 weeks. 800 participants will be randomized in a 1:1 ratio to receive mepolizumab 100 milligrams (mg) or placebo every 4 weeks for at least 13 doses (52 weeks treatment period) up to a maximum of 26 doses (104 weeks treatment period). The number of randomized participants may increase up to approximately 1400.
Eligibility Criteria
Inclusion Criteria
- Participant must be at least 40 years of age at Screening Visit 1.
- Participants with a peripheral blood eosinophil count of >=300 cells per microliter (μL) from the hematology sample collected at Screening Visit 0 AND a documented historical blood eosinophil count of >=150 cells per μL in the 12 months prior to Screening Visit 0 that meets the following: It must have been measured between 12 months and 1 month prior to Screening Visit 0, and it must not have been measured within 14 days of a COPD exacerbation. Participants with no documented historical blood eosinophil count of >=150 cells per µL must meet this threshold at the Screening Visit 1 assessment.
- Participants with a clinically documented history of COPD for at least 1 year in accordance with the definition by the American Thoracic Society or European Respiratory Society.
- Participants must present with a measured pre- and post-salbutamol Forced expiratory volume in one second (FEV1)/Forced vital capacity (FVC) ratio of 20% and =500 microgram (mcg) per day fluticasone propionate dose equivalent plus 2) Long acting beta2-agonist (LABA) and 3) Long acting muscarinic antagonist (LAMA) unless documentation of safety or intolerance issues related to LABA or LAMA. For participants who are not continually maintained on ICS plus LABA plus LAMA for the entire 12 months prior to Visit 1 use of the following is allowed (but not in the 3 months immediately prior to Visit 1); inhaled corticosteroid at a dose >=500 mcg per day fluticasone propionate dose equivalent plus inhaled LABA or inhaled LAMA and Phosphodiesterase-4-inhibitors, methylxanthines, or scheduled daily use of short acting beta2-agonist (SABA) and/or short acting muscarinic antagonist (SAMA).
- Current or former cigarette smokers with a history of cigarette smoking of >=10 pack-years at Screening (Visit 1) calculated as (number of pack years = [number of cigarettes per day/20] multiplied by number of years smoked [For example, 20 cigarettes per day for 10 years or 10 cigarettes per day for 20 years]).
- Contraceptive use for female participant should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: She is not a woman of childbearing potential (WOCBP) or she is a WOCBP and using a contraceptive method that is highly effective, with a failure rate of 450 millisecond (msec) (or QTcF >480 msec in participants with bundle branch block). Fridericia's formula must be used to determine eligibility and discontinuation for an individual participant. Participants are excluded if an abnormal ECG finding from the 12-lead ECG conducted at Screening Visit 1 is considered to be clinically significant and would impact the participant's participation during the study, based on the evaluation of the Investigator.
- Participants with any of the following would be excluded: myocardial infarction or unstable angina in the 6 months prior to Screening Visit 1; unstable or life threatening cardiac arrhythmia requiring intervention in the 3 months prior to Screening Visit 1; New York Heart Association (NYHA) Class IV Heart failure.
- Participants with (historical or) current evidence of clinically significant, neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or hematological abnormalities that are uncontrolled. Significant is defined as any disease that, in the opinion of the Investigator, would put the safety of the participant at risk through participation, or which could affect the efficacy or safety analysis if the disease/condition exacerbated during the study.
- Participants with other conditions that could lead to elevated eosinophils such as Hypereosinophilic syndromes including Eosinophilic Granulomatosis with Polyangiit
Data sourced from ClinicalTrials.gov (NCT04133909). 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.