Mepolizumab in Chronic Obstructive Pulmonary Diseases (COPD) With Eosinophilic Bronchitis

Mepolizumab in COPD With Eosinophilic Bronchitis: A Randomized Clinical Trial

Some patients with chronic obstructive pulmonary diseases (COPD) have large number of specific white blood cells called eosinophils in their airways. These cells are also responsible for causing episodes of worsened respiratory symptoms (exacerbations) and often cause irreversible damage to the airways . This subset of COPD patients often require oral steroids to bring down the number of eosinophils in their airways. Steroids have harmful effects on several of our body systems like bones, blood pressure, blood glucose control and can cause recurrent infections. Mepolizumab is a drug that specifically targets eosinophils reducing the number in the airway. This drug has been shown to be effective in decreasing exacerbation rates and time to exacerbation in asthma patients with eosinophils in their airways. Targeting eosinophils in COPD patients has been shown to reduce severe exacerbations. Hence it is likely that COPD patients with eosinophils in their airways will benefit similarly and have reduced rates and time to exacerbation.

Study Hypothesis:Does mepolizumab decrease sputum eosinophils in patients with fixed airflow obstruction (COPD) and eosinophilic bronchitis?

Study Overview

• Status: Completed
• Conditions: Bronchitis; Chronic Obstructive Pulmonary Diseases; Chronic Airways Limitation
• Intervention / Treatment: Drug: Mepolizumab; Drug: placebo

Detailed Description

It is thus likely that a specific treatment such as anti-IL5 directed against eosinophils would be superior to the current standard treatment in decreasing sputum eosinophil counts and exacerbations and decrease structural changes (remodelling) in patients with COPD who continue to have eosinophils in their airway and whose airway disease has an eosinophil-driven component as evidenced by persistent airway eosinophilia.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • Firestone Institute of Respiratory Health, St Joseph's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis: An established clinical history of COPD in accordance with the definition by the American Thoracic Society/European Respiratory Society as follows: Chronic obstructive pulmonary disease is a preventable and treatable disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases, primarily caused by cigarette smoking. Although COPD affects the lungs, it also produces significant systemic consequences
• Sputum eosinophils > 3% at randomization and on at least one occasion in the past 2 years. If this historic data is not available, documented improvement in Forced expired volume in 1 second (FEV1) of at least 12% with a course of prednisone in the past 2 years will be used as a surrogate for the presence of airway eosinophilia
• FEV1/Vital Capacity (VC) < 70% and FEV1 < 60% of predicted normal values calculated using NHANES III reference equations at Screening Visit
• At least one major exacerbation requiring prednisone in the preceding 12 months. If patients are currently well controlled by optimizing their sputum cell counts (eosinophils < 2%), they should have documented history of exacerbations when their eosinophilia was uncontrolled.
• A signed and dated written informed consent prior to study participation.
• Smoking History: Current or former cigarette smokers with a history of cigarette smoking of greater than 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 have stopped smoking for at least 6 months prior to Screening Visit
• Male or female adults. A female is eligible to enter and participate in the study if she is either of Non-child bearing potential or is of child bearing age and has a negative pregnancy test at screening, and agrees to acceptable contraceptive methods used consistently and correctly

Exclusion Criteria:

• Current asthma (12% reversibility to a bronchodilator)
• Sputum eosinophils < 3% on fluticasone (or equivalent) of 250µg bid.
• Inability to use salmeterol or tiotropium
• Significant co-morbidity that prevents from participating in the study
• Known bronchiectasis or immune deficiency disorders that would predispose the patients to recurrent infections.
• Pregnancy or intent to become pregnant and lactating females
• Drug or Alcohol Abuse: A known or suspected history of alcohol or drug abuse within 2 years prior to Screening Visit

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: placebo	Drug: placebo; The placebo will consist of 100 mL normal saline solution (0.9%, 154 mmol/L sodium chloride).; Other Names: Normal saline
Active Comparator: mepolizumab	Drug: Mepolizumab; This is an anti IL-5 which is given once a month intravenously at the dose of 750 mg.; Other Names: SB-240563

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage Decrease of Sputum Eosinophils From Baseline to End of Therapy (6 Months)	The results will be expressed as absolute changes in percent sputum eosinophil counts from baseline to end of therapy (at 6 months). Change is difference in sputum eosinophils between baseline/time zero to end of therapy/6 months. A larger number represents a greater degree in the reduction of sputum eosinophils.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Patients With a Major Exacerbation.	Exacerbation: a sustained worsening of the patient's respiratory condition, from the stable state and beyond normal day-to-day variations, necessitating a change in regular medication in a patient with underlying COPD Major exacerbation will be defined as a symptomatic deterioration requiring treatment with antibiotics, oral or intravenous corticosteroids, hospitalization, or a combination of these.	Baseline to 6 months

Collaborators and Investigators

• Sponsor: McMaster University
• Investigators: Principal Investigator: Parameswaran Nair, MD,PhD,FRCP, Associate Professor of Medicine,Division of Respirology, McMaster University

Publications and helpful links

General Publications

• Dasgupta A, Kjarsgaard M, Capaldi D, Radford K, Aleman F, Boylan C, Altman LC, Wight TN, Parraga G, O'Byrne PM, Nair P. A pilot randomised clinical trial of mepolizumab in COPD with eosinophilic bronchitis. Eur Respir J. 2017 Mar 15;49(3):1602486. doi: 10.1183/13993003.02486-2016. Print 2017 Mar. No abstract available.

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): August 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: October 28, 2011
• First Submitted That Met QC Criteria: November 1, 2011
• First Posted (Estimated): November 2, 2011

Study Record Updates

• Last Update Posted (Estimated): September 24, 2025
• Last Update Submitted That Met QC Criteria: September 22, 2025
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Keywords: COPD; exacerbation; Mepolizumab; eosinophilic bronchitis; anti-interleukin 5 (IL5)
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Pathological Conditions, Signs and Symptoms; Pulmonary Disease, Chronic Obstructive; Bronchitis; Pharmaceutical Preparations; Crystalloid Solutions; Isotonic Solutions; Solutions; Saline Solution; mepolizumab
• Other Study ID Numbers: RP11-3588

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED