Chronic inflammation in the airways and the lungs COPD
Conditions
Interventions
Subjects will receive a subcuteanous injection with mepolizumab or placebo once 
every 4 weeks for a total period of max 104 weeks.
Sponsors
GlaxoSmithKline
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1.Participant must be at least 40 years of age at Screening Visit 1. 2. A peripheral blood eosinophil count of >=300 cells/µL from the hematology sample collected at Screening Visit 0. AND A documented historical blood eosinophil count of >=150/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 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/µL must meet this threshold at the Screening Visit 1 assessment in order to return for Randomization Visit 2. 3.Participants 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. 4.Participants must present with the following: • A measured pre- and post-salbutamol FEV1/FVC ratio of <0.70 at Screening Visit 1 to confirm the diagnosis of COPD. • A measured post-salbutamol FEV1>20% and <=80% of predicted normal values calculated using NHANES III reference equations at Screening Visit 1. 5. Participants must have a well-documented history (e.g., medical record verification) in the 12 months prior to Screening Visit 1 of: • Two or more moderate COPD exacerbations that were treated with systemic corticosteroids (intramuscular (IM), intravenous, or oral) with or without antibiotics. OR • At least one severe COPD exacerbation requiring hospitalization Note: At least one exacerbation must have occurred while the participant was taking inhaled triple therapy, ICS plus LABA plus LAMA unless documented intolerance or safety risk with either of the two long-acting bronchodilators. If intolerance is documented, ICS plus LABA or ICS plus LAMA would be allowable after discussion with the Medical Monitor. Note: COPD exacerbations related to COVID-19 infection must not be counted as COPD exacerbations for inclusion in the study. 6. Participants must have a well-documented requirement for optimized standard of care background therapy that includes ICS plus 2 additional COPD medications (i.e., ICS-based triple therapy) for the 12 months prior to Screening Visit 1 and meets the following criteria: • Immediately prior to Screening Visit 1, minimum of 3 months of use of an a) inhaled corticosteroid at a dose >=500 mcg/day fluticasone propionate dose equivalent plus b) LABA and c) 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): a.inhaled corticosteroid at a dose >=500 mcg/day fluticasone propionate dose equivalent plus b.inhaled LABA or inhaled LAMA and c.Phosphodiesterase-4-inhibitors, methylxanthines, or scheduled daily use of short acting beta2-agonist (SABA) and/or short acting muscarinic antagonist (SAMA). Note: Where intolerance or safety risk is documented for either LAMA or LABA, ICS-based inhaled dual
Exclusion criteria
Exclusion criteria: 1. Participants with a past history or concurrent diagnosis of asthma are excluded regardless of whether they have active or inactive disease. 2. The Investigator must judge that COPD is the primarydiagnosis accounting for the clinical manifestations of the lung disease. Participantswith a1- antitrypsin deficiency as the underlying cause of COPD are excluded. Also,excluded are participants with active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, primary pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases. 3. Participants with pneumonia, COPD exacerbation, or lower respiratory tract infection within the 4 weeks prior to Screening Visit 1. 4. Participants with lung volume reduction surgery within the 12 months prior to Screening Visit 1. 5. Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Screening Visit 1. Participants who are in the maintenance phase of a pulmonary rehabilitation program are not excluded. 6. Participants receiving treatment with oxygen more than 2 L/min at rest over 24 hrs. For participants receiving oxygen treatment, participants should demonstrate an oxyhemoglobin saturation greater than or equal to 89% while breathing supplemental oxygen. 7. Participants with a QT interval, from the ECG conducted at Screening Visit 1, corrected with Fridericia's formula (QTcF) >450 msec (or QTcF >480 msec in participants with bundle branch block). QTcF is the QT interval corrected for heart rate according to Fridericia*s formula that is selected for this study. It is either machine-read or manually over-read. when not automatically machine read. This specific 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. Note: Where a single ECG demonstrates a prolonged QTcF interval, obtain two more ECGs readings at a minimum of 2 min apart over a brief recording period (e.g., 5-10 min), The average of the triplicate QTcF measurements should be used to determine eligibility. 8. 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 9. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary objective: To evaluate the efficacy of mepolizumab 100 mg subcutaneous (SC) compared to placebo, given every 4 weeks in liquid formulation by safety syringe (SS) to COPD participants at high risk of exacerbations despite the use of optimized COPD maintenance therapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary objective: To evaluate mepolizumab 100 mg SC compared to placebo given every 4 weeks in liquid formulation by SS on additional efficacy assessments, health related quality of life (HRQoL), health care utilization, and symptoms | — |
Countries
Netherlands
Outcome results
None listed