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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT01691521
Registration number
NCT01691521
Ethics application status
Date submitted
20/09/2012
Date registered
24/09/2012
Date last updated
6/08/2018
Titles & IDs
Public title
Efficacy and Safety Study of Mepolizumab Adjunctive Therapy in Subjects With Severe Uncontrolled Refractory Asthma
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Scientific title
MEA115588 A Randomised, Double-blind, Double-dummy, Placebo-controlled, Parallel-group, Multi-centre Study of the Efficacy and Safety of Mepolizumab Adjunctive Therapy in Subjects With Severe Uncontrolled Refractory Asthma
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Secondary ID [1]
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115588
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Asthma
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Condition category
Condition code
Respiratory
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Asthma
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Mepolizumab IV
Treatment: Drugs - Mepolizumab SC
Treatment: Drugs - IV Placebo
Treatment: Drugs - SC Placebo
Experimental: Mepolizumab IV - Mepolizumab 75 mg will be administered intravenously approximately every 4 weeks with the last dose at week 32. Subjects in the Mepolizumab IV arm will receive mepolizumab 75 mg intravenously and placebo SC once every 4 weeks with the last dose at Week 28 (total of 8 doses)
Experimental: Mepolizumab SC - Subjects in the Mepolizumab SC arm will receive mepolizumab 100 mg SC and placebo IV once every 4 weeks with the last dose at Week 28 (total of 8 doses)
Placebo Comparator: Placebo - Subjects in the Placebo arm will receive matching placebo SC and placebo IV once every 4 weeks with the last dose at Week 28 (total of 8 doses)
Treatment: Drugs: Mepolizumab IV
Mepolizumab 75 mg IV will be administered every 4 weeks with the last dose at Week 28
Treatment: Drugs: Mepolizumab SC
Mepolizumab 100 mg SC will be administered every 4 weeks with the last dose at Week 28
Treatment: Drugs: IV Placebo
Normal saline (placebo) will be administered IV every 4 weeks with the last dose at Week 28
Treatment: Drugs: SC Placebo
Normal saline (placebo) will be administered SC every 4 weeks with the last dose at Week 28
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Number of Clinically Significant Exacerbations of Asthma Per Year
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Assessment method [1]
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Clinically significant exacerbations of asthma are defined as worsening of asthma which required use of systemic corticosteroids (IV or oral steroid like prednisone, for at least 3 days or a single intramuscular (IM) corticosteroid (CS) dose is required. For maintenance of systemic corticosteroids, at least double the existing maintenance dose for at least 3 days was required) and/or hospitalization and/or emergency department (ED) visits. The frequency of clinically significant exacerbations of asthma over the 32-week treatment period is expressed as the number of exacerbations per year. Analysis of the number of exacerbations performed using a negative binomial model with covariates of treatment group, baseline maintenance OCS therapy (OCS vs. no OCS), region, exacerbations in the year prior to the study (as an ordinal variable) and baseline % predicted FEV1, and with logarithm of time on treatment as an offset variable.
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Timepoint [1]
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From randomization (Week 0) to Week 32 or if Early Withdrawal (EW) 4 weeks post last dose
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Secondary outcome [1]
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Number of Clinically Significant Exacerbations Requiring Hospitalization (Including Intubation and Admittance to an Intensive Care Unit [ICU]) or ED Visits Per Year
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Assessment method [1]
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Clinically significant exacerbations of asthma are defined as worsening of asthma which required use of systemic corticosteroids (IV or oral steroid like prednisone, for at least 3 days or a single intramuscular (IM) corticosteroid (CS) dose is required. For maintenance of systemic corticosteroids, at least double the existing maintenance dose for at least 3 days was required) and/or hospitalization and/or emergency department (ED) visits. The frequency of clinically significant exacerbations of asthma over the 32-week treatment period is expressed as the number of exacerbations per year. Analysis of the number of exacerbations performed using a negative binomial model with covariates of treatment group, baseline maintenance OCS therapy (OCS vs. no OCS), region, exacerbations in the year prior to the study (as an ordinal variable) and baseline % predicted FEV1, and with logarithm of time on treatment as an offset variable.
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Timepoint [1]
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From randomization (Week 0) to Week 32 or if Early Withdrawal (EW) 4 weeks post last dose
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Secondary outcome [2]
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Number of Clinically Significant Exacerbations Requiring Hospitalization (Including Intubation and Admittance to an ICU) Per Year
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Assessment method [2]
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Clinically significant exacerbations of asthma is defined as worsening of asthma which required use of systemic corticosteroids (IV or oral steroid like prednisone, for at least 3 days or a single intramuscular (IM) corticosteroid (CS) dose is required. For maintenance of systemic corticosteroids, at least double the existing maintenance dose for at least 3 days was required) and/or hospitalization. The frequency of clinically significant exacerbations of asthma over the 32-week treatment period is expressed as the number of exacerbations per year. Analysis of the number of exacerbations performed using a negative binomial model with covariates of treatment group, baseline maintenance OCS therapy (OCS vs. no OCS), region, exacerbations in the year prior to the study (as an ordinal variable) and baseline % predicted FEV1, and with logarithm of time on treatment as an offset variable.
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Timepoint [2]
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From randomization (Week 0) to Week 32 or if Early Withdrawal (EW) 4 weeks post last dose
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Secondary outcome [3]
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Mean Change From Baseline in Clinic Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) at Week 32
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Assessment method [3]
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FEV1 is defined as the volume of air expelled from the lungs in 1 second. Pre-bronchodilator FEV1 measurements were taken by spirometry. The change from Baseline is defined as the difference between the value of the endpoint at the time point of interest and the baseline value. Analysis performed using mixed model repeated measures with covariates of baseline, region, baseline maintenance OCS therapy (OCS vs. no OCS), exacerbations in the year prior to the study (as an ordinal variable), treatment and visit, plus interaction terms for visit by baseline and visit by treatment group.
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Timepoint [3]
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Baseline, Week 32
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Secondary outcome [4]
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Mean Change From Baseline in the St. George's Respiratory Questionnaire Total Score at Week 32
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Assessment method [4]
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The St. George's Respiratory Questionnaire is an established instrument, comprising 50 questions, evaluating symptoms, activity, and impacts; to measure Quality of Life in participants with diseases of airway obstruction and to elicit the participant's opinion of his/her health. The lowest possible value is zero and the highest possible value is 100. The higher values correspond to greater impairment in quality of life. The questionnaire was administered at Baseline (Visit 2) and at the Exit Visit (approximately 4 weeks after the last dose of study treatment). The change from baseline is defined as the difference between the value of the endpoint at the time point of interest and the baseline value. Analysis performed using analysis of covariance with covariates of baseline, region, baseline maintenance OCS therapy (OCS vs. no OCS), exacerbations in the year prior to the study (as an ordinal variable), baseline % predicted FEV1, and treatment.
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Timepoint [4]
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Baseline, Week 32
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Eligibility
Key inclusion criteria
- Able to give written informed consent prior to participation in the study
- At least 12 years of age at visit 1 and a minimum weight of 45 kilogram (kg)
- A well-documented requirement for regular treatment with high dose inhaled
corticosteroid (ICS) in the 12 months prior to Visit 1 with or without maintenance
oral corticosteroids (OCS)
- Current treatment with an additional controller medication, besides ICS, for at least
3 months or a documented failure in the past 12 months of an additional controller
medication for at least 3 successive months
- Prior documentation of eosinophilic asthma or high likelihood of eosinophilic asthma
- At Visit 1, a pre-bronchodilator FEV1 <80% (for subjects >= 18 years of age), a
pre-bronchodilator FEV1 <90% or FEV1:FVC ratio <0.8 (for subjects 12-17 years of age).
- Previously confirmed history of two or more exacerbations requiring treatment with
systemic CS
- Male or Eligible Female (females of childbearing potential must commit to consistent
and correct use of an acceptable method of birth control)
- French subjects will be included only if either affiliated to or a beneficiary of a
social security category.
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Minimum age
12
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
- Current smokers or former smokers with a smoking history of >=10 pack years
- Presence of a known pre-existing, clinically important lung condition other than
asthma
- A current malignancy or previous history of malignancy in less than 12 months
- Known, pre-existing, unstable liver disease cirrhosis and known biliary abnormalities
- Known, pre-existing severe or clinically significant cardiovascular disease
- known, pre-existing other concurrent clinically significant medical conditions that
are uncontrolled with standard treatment
- Subjects with any eosinophilic diseases
- QTc(F) =450msec or QTc(F) =480 msec
- A history of alcohol/substance abuse
- Subject with known immunodeficiency
- Subjects who have received omalizumab within 130 days of Visit 1 or any monoclonal
antibody (other than Xolair) to treat inflammatory disease within 5 half-lives of
Visit 1
- Subjects who have received treatment with an investigational drug within the past 30
days or five terminal phase half-lives of the drug whichever is longer
- Subjects with allergy/intolerance to a monoclonal antibody or biologic.
- Subjects who are pregnant or breastfeeding
- Subjects who have known evidence of lack of adherence to controller medications and/or
ability to follow physician's recommendations
- Previously participated in any study with mepolizumab and received investigational
product (including placebo)
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
8/10/2012
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
18/01/2014
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Sample size
Target
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Accrual to date
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Final
580
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Recruitment in Australia
Recruitment state(s)
NSW,SA,VIC,WA
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Recruitment hospital [1]
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GSK Investigational Site - New Lambton
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GSK Investigational Site - Bedford Park
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GSK Investigational Site - Clayton
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GSK Investigational Site - Nedlands
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GSK Investigational Site - Parkville
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2305 - New Lambton
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Recruitment postcode(s) [2]
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5042 - Bedford Park
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3168 - Clayton
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6009 - Nedlands
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Recruitment postcode(s) [5]
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3052 - Parkville
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Recruitment outside Australia
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Bradford
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Plymouth
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Southampton
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
GlaxoSmithKline
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Address
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Ethics approval
Ethics application status
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Summary
Brief summary
This study will evaluate two dose regimens of mepolizumab [75mg intravenous (i.v.) or 100mg
subcutaneous (SC) every 4 weeks] compared with placebo over a 32 week treatment period in
subjects with severe refractory asthma with elevated blood eosinophils. Efficacy will be
measured by a reduction in the frequency of asthma exacerbations. Additional efficacy
assessments will include measurements of lung function, symptom scores, and quality of life.
Safety will be assessed by clinical laboratory samples, ECGs, immunogenicity and adverse
events.
This study is intended to replicate the Phase IIb/III study MEA112997. Subjects in MEA115588,
who meet all eligibility criteria at screening visit, will enter the run-in period. Those
subjects that are not able/eligible to be randomised at the end of the 6 week run-in period
will be deemed run-in failures. Subjects will remain on their current maintenance therapy
throughout the run-in, double-blind treatment administration and follow-up periods. Subjects
who meet the randomisation eligibility criteria will be randomised in a 1:1:1 ratio to
receive one of the following treatments every 4 weeks for a total of 8 doses: Mepolizumab 75
miligram (mg) i.v. and placebo SC, or Mepolizumab 100 mg SC and placebo i.v. or Placebo i.v.
and placebo SC.
Subjects that receive all 8 doses of double-blind treatment, and meet the eligibility
criteria for the Open-Label Extension (OLE) Study, will be offered the opportunity to
participate in the OLE trial.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT01691521
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Public notes
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GSK Clinical Trials
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GlaxoSmithKline
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Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT01691521
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