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

NCT ID: NCT01463644

Last Updated: 2025-09-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2015-09-30

Brief Summary

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?

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.

Conditions

Chronic Obstructive Pulmonary Diseases; Chronic Airways Limitation; Bronchitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

mepolizumab

Group Type: ACTIVE_COMPARATOR

Mepolizumab

Intervention Type: DRUG

This is an anti IL-5 which is given once a month intravenously at the dose of 750 mg.

placebo

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

The placebo will consist of 100 mL normal saline solution (0.9%, 154 mmol/L sodium chloride).

Interventions

Mepolizumab

This is an anti IL-5 which is given once a month intravenously at the dose of 750 mg.

Intervention Type: DRUG

placebo

The placebo will consist of 100 mL normal saline solution (0.9%, 154 mmol/L sodium chloride).

Intervention Type: DRUG

Other Intervention Names

SB-240563; Normal saline

Eligibility Criteria

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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

McMaster University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Parameswaran Nair, MD,PhD,FRCP

Role: PRINCIPAL_INVESTIGATOR

Associate Professor of Medicine,Division of Respirology, McMaster University

Locations

Firestone Institute of Respiratory Health, St Joseph's Hospital

Hamilton, Ontario, Canada

Countries

Canada

References

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.

Reference Type: RESULT

PMID: 28298405 (View on PubMed)

Other Identifiers

RP11-3588

Identifier Type: -

Identifier Source: org_study_id