Clinical trial NCT04075331: Mepolizumab for COPD Hospital Eosinophilic Admissions Pragmatic Trial
Official title: A Randomised Controlled Trial of Mepolizumab Initiated Following Admission to Hospital for a Severe Exacerbation of Eosinophilic COPD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: COPD
Eosinophilia
Keywords: COPD
eosinophilia
Chronic Obstructive Pulmonary Disorder
Mepolizumab
Lead sponsor: University of Leicester
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2019-08-30
Enrollment: 238
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Time from randomisation to next hospital readmission or death (all cause)
timeFrame: 48 weeks
Secondary outcomes:
measure: Time from randomisation to first hospital readmission or death due to a respiratory cause
timeFrame: 48 weeks
measure: Total number of hospital readmissions all cause over 48 weeks
timeFrame: 48 weeks
measure: Total number of moderate exacerbations over 48 weeks
timeFrame: 48 weeks
measure: Time from randomisation to treatment failure
timeFrame: 48 weeks
measure: Time from randomisation to death (all cause)
timeFrame: 48 weeks
measure: Time from randomisation to death (respiratory cause)
timeFrame: 48 weeks
measure: Time from randomisation to first hospital readmission (all cause)
timeFrame: 48 weeks
measure: Time from randomisation to first hospital readmission (respiratory cause)
timeFrame: 48 weeks
measure: Length of index hospital admission
timeFrame: 48 weeks
measure: Extended Medical Research Council dyspnoea score (eMRC)
timeFrame: Weeks 0, 4, 8, 12, 24, 36, 48
measure: St George's Respiratory Questionnaire (SGRQ)
timeFrame: Weeks 0, 4, 8, 12, 24, 36, 48
measure: COPD Assessment Tool (CAT)
timeFrame: Weeks 0, 4, 8, 12, 24, 36, 48
measure: Warwick-Edinburgh Mental wellbeing scale (WEMWBS)
timeFrame: Weeks 0, 4, 8, 12, 24, 36, 48
measure: London Chest Activities of Daily Living Questionnaire (LCADL)
timeFrame: Weeks 0, 4, 8, 12, 24, 36, 48
measure: Short physical performance battery (SPPB)
timeFrame: Weeks 0, 4, 8, 12, 24, 36, 48
measure: Physical activity using accelerometry
timeFrame: Weeks 0, 4, 8, 12, 24, 36, 48
measure: Handgrip Strength
timeFrame: Weeks 0, 4, 8, 12, 24, 36, 48
measure: Total Serum eosinophil count (inflammatory markers)
timeFrame: Weeks 0, 4, 8, 12, 24, 36, 48
measure: Percentage sputum eosinophil count (inflammatory markers)
timeFrame: Weeks 0, 4, 8, 12, 24, 36, 48
measure: Adverse Events (AEs)
timeFrame: 48 weeks
measure: Serious Adverse Events (SAEs)
timeFrame: 48 weeks
measure: Heart Rate (beats per minute)
timeFrame: Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
measure: Blood pressure (systolic/diastolic mmHg)
timeFrame: Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
measure: Temperature (degrees)
timeFrame: Weeks 0, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48
Other outcomes:
Locations:
city: Leicester
country: United Kingdom
facility: NIHR Biomedical Research Centre, Respiratory
state: Leicestershire
Study officials:
affiliation: University of Leicester
name: Christopher Brightling
role: STUDY_CHAIR
affiliation: University of Leicester
name: Neil Greening
role: PRINCIPAL_INVESTIGATOR
References: