Mepolizumab in COPD With Eosinophilic Bronchitis: A Randomized Clinical Trial
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- McMaster University
- Enrollment
- 18
- Locations
- 1
- Primary Endpoint
- Percentage Decrease of Sputum Eosinophils From Baseline to End of Therapy (6 Months)
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 40 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
mepolizumab
Intervention: Mepolizumab (Drug)
placebo
Intervention: placebo (Drug)
Outcomes
Primary Outcomes
Percentage Decrease of Sputum Eosinophils From Baseline to End of Therapy (6 Months)
Time Frame: 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.
Secondary Outcomes
- Proportion of Patients With a Major Exacerbation.(Baseline to 6 months)