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Mepolizumab for COPD Hospital Eosinophilic Admissions Pragmatic Trial (COPD-HELP)

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ClinicalTrials.gov Identifier: NCT04075331
Recruitment Status : Recruiting
First Posted : August 30, 2019
Last Update Posted : November 16, 2020
Sponsor:
Collaborators:
Leicester Clinical Trials Unit
GlaxoSmithKline
Information provided by (Responsible Party):
University of Leicester

Brief Summary:
This is a single-centre, double-blinded, randomised, placebo controlled trial comparing mepolizumab 100mg versus placebo in patients with eosinophilic COPD, started following their index admission to hospital.

Condition or disease Intervention/treatment Phase
COPD Eosinophilia Drug: Mepolizumab Drug: Placebo Phase 2 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 238 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Randomised Controlled Trial of Mepolizumab Initiated Following Admission to Hospital for a Severe Exacerbation of Eosinophilic COPD
Actual Study Start Date : September 7, 2020
Estimated Primary Completion Date : January 30, 2023
Estimated Study Completion Date : January 30, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Mepolizumab

Arm Intervention/treatment
Experimental: Mepolizumab
Mepolizumab
Drug: Mepolizumab
Mepolizumab 100mg subcutaneous injection

Placebo Comparator: Placebo
Saline solution
Drug: Placebo
Saline solution for subcutaneous injection
Other Name: Saline solution




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. Time from randomisation to first hospital readmission or death due to a respiratory cause [ Time Frame: 48 weeks ]
  2. Total number of hospital readmissions all cause over 48 weeks [ Time Frame: 48 weeks ]
    (adjusted for time minimum 24 weeks of trial treatment)

  3. Total number of moderate exacerbations over 48 weeks [ Time Frame: 48 weeks ]
    (adjusted for time minimum 24 weeks of trial treatment)

  4. Time from randomisation to treatment failure [ Time Frame: 48 weeks ]
    (defined as readmission, need for further treatment or death)

  5. Time from randomisation to death (all cause) [ Time Frame: 48 weeks ]
  6. Time from randomisation to death (respiratory cause) [ Time Frame: 48 weeks ]
  7. Time from randomisation to first hospital readmission (all cause) [ Time Frame: 48 weeks ]
  8. Time from randomisation to first hospital readmission (respiratory cause) [ Time Frame: 48 weeks ]
  9. Length of index hospital admission [ Time Frame: 48 weeks ]
    Time from admission to discharge of first hospital admission

  10. 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.

  11. St George's Respiratory Questionnaire (SGRQ) [ Time Frame: Weeks 0, 4, 8, 12, 24, 36, 48 ]
    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.

  12. COPD Assessment Tool (CAT) [ Time Frame: Weeks 0, 4, 8, 12, 24, 36, 48 ]
    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.

  13. 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.

  14. 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.

  15. Post-bronchodilator lung function - Forced Expiratory Volume in 1 second (FEV1) [ Time Frame: Weeks 0, 4, 8, 12, 24, 36, 48 ]
  16. Post-bronchodilator lung function - Forced Vital Capacity (FVC) [ Time Frame: Weeks 0, 4, 8, 12, 24, 36, 48 ]
  17. Lung function - Oscillometry [ Time Frame: Weeks 0, 4, 8, 12, 24, 36, 48 ]
  18. Short physical performance battery (SPPB) [ Time Frame: Weeks 0, 4, 8, 12, 24, 36, 48 ]
    This assessment measures lower extremity functioning in older individuals. Lower scores indicate greater impairment.

  19. Physical activity using accelerometry [ Time Frame: Weeks 0, 4, 8, 12, 24, 36, 48 ]
  20. Handgrip Strength [ Time Frame: Weeks 0, 4, 8, 12, 24, 36, 48 ]
  21. Total Serum eosinophil count (inflammatory markers) [ Time Frame: Weeks 0, 4, 8, 12, 24, 36, 48 ]
  22. Percentage sputum eosinophil count (inflammatory markers) [ Time Frame: Weeks 0, 4, 8, 12, 24, 36, 48 ]
  23. Adverse Events (AEs) [ Time Frame: 48 weeks ]
  24. Serious Adverse Events (SAEs) [ Time Frame: 48 weeks ]
  25. Heart Rate (beats per minute) [ Time Frame: Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 ]
  26. Blood pressure (systolic/diastolic mmHg) [ Time Frame: Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 ]
  27. Temperature (degrees) [ Time Frame: Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Symptoms typical of COPD when stable (baseline eMRC dyspnoea grade 2 or more).
  2. A clinician defined exacerbation of COPD requiring admission to hospital.
  3. Serum eosinophil count of ≥ 300 cells/μL either at time of admission or at any one time in the preceding 12 months.
  4. Smoking pack years > 10 years.
  5. Age ≥ 40 years.
  6. Established on inhaled corticosteroids (ICS) prior to this admission.
  7. Willing and able to consent to participate in trial.
  8. Able to understand written and spoken English.

Exclusion Criteria:

  1. COPD patients without eosinophilia (defined as persistently < 300 cells/μL within the last 12 months).
  2. Other conditions that may be the cause of eosinophilia (such as hypereosinophilic syndrome, eosinophilic granulomatosis, eosinophilic oesophagitis or parasitic infection).
  3. Patients whose treatment is considered palliative (life expectancy < 6 months).
  4. 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.
  5. Known history of anaphylaxis or hypersensitivity to mepolizumab or any of the excipients (sucrose, sodium phosphate dibasic heptahydrate, polysorbate 80).
  6. 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.
  7. Decompensated liver disease or cirrhosis.
  8. 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.*
  9. 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.
  10. 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04075331


Contacts
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Contact: Nafisa Boota - Senior Trial Manager +44 (0)116 229 7298 mepo@leicester.ac.uk

Locations
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United Kingdom
NIHR Biomedical Research Centre, Respiratory Recruiting
Leicester, Leicestershire, United Kingdom, LE1 9QP
Contact: Neil Greening    +44 (0)116 258 3474    neil.greening@leicester.ac.uk   
Principal Investigator: Christopher Brightling         
Principal Investigator: Neil Greening         
Sub-Investigator: Wadah Ibrahim         
Sponsors and Collaborators
University of Leicester
Leicester Clinical Trials Unit
GlaxoSmithKline
Investigators
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Study Chair: Christopher Brightling University of Leicester
Principal Investigator: Neil Greening University of Leicester
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Responsible Party: University of Leicester
ClinicalTrials.gov Identifier: NCT04075331    
Other Study ID Numbers: 0690
First Posted: August 30, 2019    Key Record Dates
Last Update Posted: November 16, 2020
Last Verified: November 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by University of Leicester:
COPD
eosinophilia
Chronic Obstructive Pulmonary Disorder
Mepolizumab
Additional relevant MeSH terms:
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Eosinophilia
Leukocyte Disorders
Hematologic Diseases