- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04075331
Mepolizumab for COPD Hospital Eosinophilic Admissions Pragmatic Trial (COPD-HELP)
A Randomised Controlled Trial of Mepolizumab Initiated Following Admission to Hospital for a Severe Exacerbation of Eosinophilic COPD
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Patients admitted to hospital with an exacerbation of COPD are at high risk of readmission, of which a proportion are driven by eosinophilic inflammation. Whilst oral corticosteroids are beneficial in exacerbations, a considerable proportion of patients experience treatment failure, with 50% of patients readmitted within 3 months (www.RCPLondon.ac.uk).
Therapy, such as mepolizumab, reduces eosinophil count and has been shown to reduce exacerbation frequency when given in the stable state in both eosinophilic asthma (Papi et al. 2018) and COPD (Yousef, in press).
The investigators hypothesise that starting mepolizumab at the time of a hospitalisation for an exacerbation of COPD in patients with significant eosinophilia will result in a reduction in readmission to hospital in a high risk population.
Therefore, 238 participants will be recruited over an 18-month period and will be randomised into a 48-week treatment period in which they will receive monthly subcutaneous injections of either 100 mg mepolizumab or placebo. Secondary outcomes will be measured at baseline (week 0), 4 weeks, 8 weeks, 12 weeks, 24 weeks, 36 weeks and 48 weeks.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Contact
- Name: Hannah R Gilbert - Senior Trial Manager
- Phone Number: +44 116 373 6976
- Email: mepo@leicester.ac.uk
Study Locations
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Leicestershire
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Leicester, Leicestershire, United Kingdom, LE1 9QP
- NIHR Biomedical Research Centre, Respiratory
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Symptoms typical of COPD when stable (baseline eMRC dyspnoea grade 2 or more).
- A clinician defined exacerbation of COPD requiring admission to hospital.
- Serum eosinophil count of ≥ 300 cells/μL either at time of admission or at any one time in the preceding 12 months.
- Smoking pack years ≥10 years.
- Age ≥ 40 years.
- Established on inhaled corticosteroids (ICS) prior to this admission.
- Willing and able to consent to participate in trial.
- Able to understand written and spoken English.
Exclusion Criteria:
- COPD patients without eosinophilia (defined as persistently < 300 cells/μL within the last 12 months).
- Other conditions that may be the cause of eosinophilia (such as hypereosinophilic syndrome, eosinophilic granulomatosis, eosinophilic oesophagitis or parasitic infection).
- Patients whose treatment is considered palliative (life expectancy < 6 months).
- Other respiratory conditions including active lung cancer, interstitial lung disease, primary pulmonary hypertension or any other conditions that in the view of the investigator will affect the trial.
- Known history of anaphylaxis or hypersensitivity to mepolizumab or any of the excipients (sucrose, sodium phosphate dibasic heptahydrate, polysorbate 80).
- Unstable or life-threatening cardiac disease including myocardial infarction or unstable angina in the last 6 months, unstable or life-threatening cardiac arrhythmia requiring intervention in the last 3 months and New York Heart Association (NYHA) Class IV heart failure.
- Decompensated liver disease or cirrhosis.
- Pregnant, breastfeeding, or lactating women. Women of child-bearing potential must agree to use appropriate methods of birth control and have a negative blood serum pregnancy test performed after randomisation but prior to first dosing with randomised treatment.*
- Participation in an interventional clinical trial within 3 months of visit 1 or receipt of any investigational medicinal product within 3 months or 5 half-lives.
Known blood born infection (e.g. HIV, hepatitis B or C).
- Women of child bearing potential (WOCBP) - A woman is defined as being of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal, unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Placebo Comparator: Placebo
Saline solution
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Saline solution for subcutaneous injection
Other Names:
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Experimental: Mepolizumab
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Mepolizumab 100mg subcutaneous injection
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time from randomisation to next hospital readmission or death (all cause)
Time Frame: 48 weeks
|
To evaluate the efficacy of mepolizumab initiated following hospitalisation on future hospital readmission or death (all cause) compared with placebo and standard medical therapy in severe exacerbations of eosinophilic COPD.
|
48 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time from randomisation to first hospital readmission or death due to a respiratory cause
Time Frame: 48 weeks
|
48 weeks
|
|
Total number of hospital readmissions all cause over 48 weeks
Time Frame: 48 weeks
|
(adjusted for time minimum 24 weeks of trial treatment)
|
48 weeks
|
Total number of moderate exacerbations over 48 weeks
Time Frame: 48 weeks
|
(adjusted for time minimum 24 weeks of trial treatment)
|
48 weeks
|
Time from randomisation to treatment failure
Time Frame: 48 weeks
|
(defined as readmission, need for further treatment or death)
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48 weeks
|
Time from randomisation to death (all cause)
Time Frame: 48 weeks
|
48 weeks
|
|
Time from randomisation to death (respiratory cause)
Time Frame: 48 weeks
|
48 weeks
|
|
Time from randomisation to first hospital readmission (all cause)
Time Frame: 48 weeks
|
48 weeks
|
|
Time from randomisation to first hospital readmission (respiratory cause)
Time Frame: 48 weeks
|
48 weeks
|
|
Length of index hospital admission
Time Frame: 48 weeks
|
Time from admission to discharge of first hospital admission
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48 weeks
|
Extended Medical Research Council dyspnoea score (eMRC)
Time Frame: Weeks 0, 4, 8, 12, 24, 36, 48
|
This scale measures perceived respiratory disability.
Participants rate their grades of breathlessness on a scale of 1 (least) to 5 (worst).
The extension divides the grade 5 rating into 'a' (independent) and 'b' (dependent) to establish dependence on others for washing and dressing.
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Weeks 0, 4, 8, 12, 24, 36, 48
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St George's Respiratory Questionnaire (SGRQ)
Time Frame: Weeks 0, 4, 8, 12, 24, 36, 48
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This 50-item questionnaire measures health status (quality of life) in patients with diseases of airway obstruction.
Scores are broken down into 'symptoms' (normal participant range 9-15), 'activity' (normal participant range 7-12), 'impacts' (normal participant range 1-3), and a total score (normal participant range 5-7).
Higher scores indicate poorer health status.
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Weeks 0, 4, 8, 12, 24, 36, 48
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COPD Assessment Tool (CAT)
Time Frame: Weeks 0, 4, 8, 12, 24, 36, 48
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The COPD Assessment Test (CAT) is a questionnaire for people with Chronic Obstructive Pulmonary Disease (COPD).
It is designed to measure the impact of COPD on a person's life, and how this changes over time.
Scores range from 0-40, with higher scores indicating greater impact of COPD on a patient's life.
|
Weeks 0, 4, 8, 12, 24, 36, 48
|
Warwick-Edinburgh Mental wellbeing scale (WEMWBS)
Time Frame: Weeks 0, 4, 8, 12, 24, 36, 48
|
This scale measures mental wellbeing using a 14-item scale.
The scoring range for each item is from 1 - 5 and the total score is from 14-70, with higher scores indicating better mental wellbeing.
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Weeks 0, 4, 8, 12, 24, 36, 48
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London Chest Activities of Daily Living Questionnaire (LCADL)
Time Frame: Weeks 0, 4, 8, 12, 24, 36, 48
|
This 15-item questionnaire measures dyspnoea during routine daily activities in patients with COPD.
It consists of four components: 'Self-care', 'Domestic', 'Physical' and 'Leisure'.
Patients score from 0: 'I wouldn't do anyway', to 5: 'Someone else does this for me (or helps)', with higher scores representing maximal disability.
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Weeks 0, 4, 8, 12, 24, 36, 48
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Short physical performance battery (SPPB)
Time Frame: Weeks 0, 4, 8, 12, 24, 36, 48
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This assessment measures lower extremity functioning in older individuals.
Lower scores indicate greater impairment.
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Weeks 0, 4, 8, 12, 24, 36, 48
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Physical activity using accelerometry
Time Frame: Weeks 0, 4, 8, 12, 24, 36, 48
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Weeks 0, 4, 8, 12, 24, 36, 48
|
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Handgrip Strength
Time Frame: Weeks 0, 4, 8, 12, 24, 36, 48
|
Weeks 0, 4, 8, 12, 24, 36, 48
|
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Total Serum eosinophil count (inflammatory markers)
Time Frame: Weeks 0, 4, 8, 12, 24, 36, 48
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Weeks 0, 4, 8, 12, 24, 36, 48
|
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Percentage sputum eosinophil count (inflammatory markers)
Time Frame: Weeks 0, 4, 8, 12, 24, 36, 48
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Weeks 0, 4, 8, 12, 24, 36, 48
|
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Adverse Events (AEs)
Time Frame: 48 weeks
|
48 weeks
|
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Serious Adverse Events (SAEs)
Time Frame: 48 weeks
|
48 weeks
|
|
Heart Rate (beats per minute)
Time Frame: Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
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Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
|
|
Blood pressure (systolic/diastolic mmHg)
Time Frame: Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
|
Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
|
|
Temperature (degrees)
Time Frame: Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
|
Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Christopher Brightling, University of Leicester
- Principal Investigator: Neil Greening, University of Leicester
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 0690
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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