Health Condition 1: J441- Chronic obstructive pulmonary disease with (acute) exacerbation
Conditions
Interventions
Intervention1: Mepolizumab 100 mg SC: 120 mg/mL sucrose, 4.16 mg/mL Sodium phosphate dibasic heptahydrate, 0.95 mg/mL Citric
Acid Monohydrate, 0.2 mg/mL polysorbate 80, 0.019 mg/mL EDTA Disodium Dihyd
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Inclusion criteria
Inclusion criteria: 1. Participant must be at least 40 years of age at Screening Visit 1. 2. Participants with a peripheral blood eosinophil count of more than or equal to 300 cells per microliter (µL) from the hematology sample collected at Screening Visit 0 AND a documented historical blood eosinophil count of more than or equal to 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 more than or equal to 150 cells per µL must meet this threshold at the Screening Visit 1 assessment. 3. 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. 4. Participants must present with a measured pre- and post-salbutamol Forced expiratory volume in one second (FEV1)/Forced vital capacity (FVC) ratio of 5. Participants must have a well-documented history (for example, 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. 6. Participants must have a well-documented requirement for optimized standard of care background therapy that includes inhaled corticosteroids (ICS) plus 2 additional COPD medications (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 1) inhaled corticosteroid at a dose less than or equals to 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 more than or equal to 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). 7. Current or former cigarette smokers with a history of cigarette smoking of more than or equal to 10 pack-years at Screening (Visit 1) calculated as (number of pack years equal to [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]). 8. Contraceptive use for female participant should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 9. A female participant is eligible to participate if she is not pregnant or
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 primary diagnosis accounting for the clinical manifestations of the lung disease. Participants with alpha1-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. 5. Participants receiving treatment with oxygen more than 2 liter (L) per minute at rest over 24 hours. For participants receiving oxygen treatment, participants should demonstrate an oxyhemoglobin saturation greater than or equal to 89percent while breathing supplemental oxygen. 6. Participants with a QT interval, from the electrocardiogram (ECG) conducted at Screening Visit 1, corrected with Fridericias formula (QTcF) more than 450 millisecond (msec) (or QTcF more than 480 msec in participants with bundle branch block). Fridericias 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 participants participation during the study, based on the evaluation of the Investigator. 7. 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. 8. 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 or condition exacerbated during the study. 9. Participants 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. 10. Participants with a known, pre-existing parasitic infestation within 6 months prior to Screening Visit 1. 11. A current malignancy or previous history of cancer in remission for less than 12 months prior to Screening Visit 1 (participants that had localized carcinoma of the skin or cervix which was resected for cure will not be excluded). 12. Participants with a known immunodeficiency (For example, human
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. Timepoint: Annualized rate of moderate/severe exacerbations. Up to Week 104 | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 symptomsTimepoint: Time to first moderate/severe exacerbation. Up to Week 104 Proportion of CAT responders(CAT score from Baseline), at Week 52 Proportion of SGRQ total score responders, at Week 52 Proportion of E-RS- COPD responders, at Week 52 Annualized rate of exacerbations requiring ED visit and or hospitalization, Up to Week 104 | — |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, China, Denmark, France, Germany, Greece, Hungary, India, Ireland, Israel, Italy, Mexico, Netherlands, New Zealand, Poland, Republic of Korea, Spain, Sweden, United Kingdom, United States of America
Contacts
Public ContactRashmi Chitgupi
PPD Pharmaceutical Development India Private Limited
Outcome results
None listed