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

NCT01463644 | Completed Phase 3 Results

• 1 other identifier: RP11-3588
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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?

Conditions

Chronic Obstructive Pulmonary Diseases; Chronic Airways Limitation; Bronchitis

Keywords

Mepolizumab; COPD; eosinophilic bronchitis; exacerbation; anti-interleukin 5 (IL5)

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Proportion of Patients With a Major Exacerbation.

  Baseline to 6 months

Study Arms (2)

mepolizumab

ACTIVE COMPARATOR

Drug: Mepolizumab

placebo

PLACEBO COMPARATOR

Drug: placebo

Interventions

Mepolizumab DRUG

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

Also known as: SB-240563

mepolizumab

placebo DRUG

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

Also known as: Normal saline

placebo

Eligibility Criteria

• Age: 40 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• McMaster University: lead

Study Sites (1)

Firestone Institute of Respiratory Health, St Joseph's Hospital

Hamilton, Ontario, L8N 4A6, Canada

Location

Related Publications (1)

• 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.

  PMID: 28298405 RESULT

Related Links

• Link to final manuscript

MeSH Terms

Conditions

Pulmonary Disease, Chronic Obstructive; Bronchitis

Interventions

mepolizumab; Saline Solution

Condition Hierarchy (Ancestors)

Lung Diseases, Obstructive; Lung Diseases; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Respiratory Tract Infections; Infections; Bronchial Diseases

Intervention Hierarchy (Ancestors)

Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Limitations and Caveats

There were recruitment challenges forcing us to restrict our sample size, which reduced the study power to approximately 60%.

Results Point of Contact

• Title: Dr. Parameswaran Nair
• Organization: McMaster University

parames@mcmaster.ca

905-522-1155

Study Officials

• Parameswaran Nair, MD,PhD,FRCP

  Associate Professor of Medicine,Division of Respirology, McMaster University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2011
• First Posted: November 2, 2011
• Study Start: January 1, 2012
• Primary Completion: August 1, 2015
• Study Completion: September 1, 2015
• Last Updated: September 24, 2025
• Results First Posted: September 24, 2025

Record last verified: 2024-11

Locations

CA (1)