A Multi-center, Randomized, Double-blind, Parallel-group, Placebo-controlled Study of Mepolizumab 100 mg SC as add-on Treatment in Participants With COPD Experiencing Frequent Exacerbations and Characterized by Eosinophil Levels (Study 208657)

GlaxoSmithKline1 site in 1 country806 target enrollmentOctober 30, 2019

ConditionsPulmonary Disease, Chronic Obstructive

InterventionsMepolizumab Placebo

DrugsMepolizumab Placebo

Overview

Phase: Phase 3
Intervention: Mepolizumab
Conditions: Pulmonary Disease, Chronic Obstructive
Sponsor: GlaxoSmithKline
Enrollment: 806
Locations: 1
Primary Endpoint: Annualized Rate of Moderate or Severe Exacerbations
Status: Completed
Last Updated: 8 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials Related News

Overview

Brief 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.

Registry

clinicaltrials.gov

Start Date

October 30, 2019

End Date

August 8, 2024

Last Updated

8 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

GlaxoSmithKline

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Participant must be at least 40 years of age at Screening Visit
•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 \<0.70 at Screening Visit 1 to confirm the diagnosis of COPD and with a measured post-salbutamol FEV1\>20% and \<=80% of predicted normal values calculated using NHANES III reference equations at Screening Visit
•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.
•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 \>=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 \<1%, during the intervention period and for at least 16 weeks after the last dose of study intervention. The principal investigator (PI) should evaluate the effectiveness of the contraceptive method in relation to the first dose of study intervention.
•A WOCBP must have a negative highly sensitive pregnancy urine test within 24 hours before the first dose of study intervention. If a urine test cannot be confirmed as negative (For example, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.

Exclusion Criteria

•Participants with a past history or concurrent diagnosis of asthma are excluded regardless of whether they have active or inactive disease.
•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.
•Participants with pneumonia, COPD exacerbation, or lower respiratory tract infection within the 4 weeks prior to Screening Visit
•Participants with lung volume reduction surgery within the 12 months prior to Screening Visit
•Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Screening Visit
•Participants who are in the maintenance phase of a pulmonary rehabilitation program are not excluded.
•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 89% while breathing supplemental oxygen.
•Participants with a QT interval, from the electrocardiogram (ECG) conducted at Screening Visit 1, corrected with Fridericia's formula (QTcF) \>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.

Arms & Interventions

Mepolizumab 100 mg

Participants with Chronic Obstructive Pulmonary Disease (COPD) received a 100 milligrams (mg) dose of mepolizumab as a subcutaneous injection every 4 weeks. Participants remained in the study for an assessment period of minimum of 52 weeks and a maximum of 104 weeks.

Intervention: Mepolizumab

Placebo

Participants with COPD received matching placebo as a subcutaneous injection every 4 weeks. Participants remained in the study for an assessment period of minimum of 52 weeks and a maximum of 104 weeks.

Intervention: Placebo

Outcomes

Primary Outcomes

Annualized Rate of Moderate or Severe Exacerbations

Time Frame: Up to Week 104

Annualized rate of moderate or severe exacerbations were assessed. Moderate exacerbations are defined as clinically significant exacerbations that require treatment with oral or systemic corticosteroids and/or antibiotics. Severe exacerbations are defined per protocol as clinically significant exacerbations that require in-patient hospitalization (that is greater than or equal to \[\>=\] 24 hours) or result in death.

Secondary Outcomes

Time to First Moderate or Severe Exacerbation(At week 8,16, 24, 32, 40, 48, 52, 56, 64, 72, 80, 88, 96, 104)
Percentage of COPD Assessment Test (CAT) Responders With >=2 Point Reduction From Baseline at Week 52(Baseline and Week 52)
Percentage of St. George's Respiratory Questionnaire for COPD (SGRQ) Total Score Responders With >=4 Point Reduction From Baseline at Week 52(Baseline and Week 52)
Percentage of Evaluating Respiratory Symptoms in COPD (E-RS: COPD) Responders With >=2 Point Reduction From Baseline(Baseline and 4-weeks prior to Week 52)
Annualized Rate of Exacerbations Requiring Emergency Department (ED) Visit and/or Hospitalization(Up to Week 104)