Primary:To evaluate whether patients with severe eosinophilic asthma who have received longterm treatment with mepolizumab (at least 3 years) need to maintain treatment with mepolizumab to continue to receive benefit.Secondary:To assess the safety…
ID
Source
Brief title
Condition
- Bronchial disorders (excl neoplasms)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Time to first clinically significant exacerbation.
Secondary outcome
Ratio to baseline in blood eosinophil count at weeks 12, 24, 36 and 52. Time to
a decrease in asthma control (ACQ-5 score of >= 0.5 units). Time to first
exacerbation requiring hospitalization or ED visit.
Background summary
Mepolizumab is a fully humanized IgG antibody (IgG1, kappa) which binds to and
inhibits the ability of
IL-5 to bind to the IL-5 receptor. IL-5 receptors are primarily expressed on
eosinophils. IL-5, through
binding to the IL-5 receptor is a major regulator of eosinophils resulting in
accumulation in tissues and
modulation of eosinophil behavior at every stage from maturation to survival.
Mepolizumab reduces
eosinophils in the periphery and in tissues.
Mepolizumab is being developed for the treatment of a.o. severe eosinophilic
asthma.
This new study has been designed to assess the effects of discontinuation of
mepolizumab after at least 3 years of treatment in subjects with severe
eosinophilic asthma.
Study objective
Primary:
To evaluate whether patients with severe eosinophilic asthma who have received
longterm treatment with mepolizumab (at least 3 years) need to maintain
treatment with mepolizumab to continue to receive benefit.
Secondary:
To assess the safety and tolerability.
Study design
52-week, double-blind, parallel-group, multi-center study. Subjects who have
been treated with mepolizumab for at least 3 years. Randomization (1:1) to
• Mepolizumab 100 mg SC every 4 weeks.
• Placebo.
During a variable open-label period (0-132 weeks) subjects may continue with
mepolizumab until the 3 years of treatment have been completed.
Subjects discontinuing double blind treatment due to a clinically significant
asthma exacerbation are eligible to enter optional open-label mepolizumab
treatment for the remainder of the study.
Standard of care asthma therapy throughout the study.
Estimation 300 subjects.
Intervention
Treatment with mepolizumab or placebo.
Study burden and risks
Risk: Adverse events of mepolizumab. Worsening of asthma due to discontinuation
of mepolizumab.
Burden:
Excluding the flexible run-in period:
15 visits in 52 weeks.
13 SC injections with mepolizumab (approx. 1 ml).
Physical examination: 2 times.
Blood draws: 15 times (5-15 ml blood).
Pregnancy test: 15 times.
Pulmonary function tests: 5 times.
ECG: 3 times.
Entire study period: 1. Daily peak flow measurements, 2. Diary symptoms and
escape medication and 3. Diary adverse events, changes in medication, visits to
other MDs.
Questionnaires: ACQ-5 weekly, St George questionnaire 5 times.
Huis ter Heideweg 62
Zeist 3705 LZ
NL
Huis ter Heideweg 62
Zeist 3705 LZ
NL
Listed location countries
Age
Inclusion criteria
• Asthma is being treated with a controller medication for the past 12 weeks.
• Adequate contraception for females of childbearing potential.
Exclusion criteria
• Subjects withdrawn from IP or withdrawn from study participation from either MEA115666 or (MEA)201312 for safety reasons.
• Clinically significant deterioration in health status at the completion of participation or EW from either the MEA115666 or 201312 trials which in the opinion of the investigator would make the subject unsuitable for participation in this study.
• Severe or clinically significant cardiovascular disease uncontrolled with standard treatment or QTcF prolongation on ECG, see protocol page 35 for details.
• A current malignancy or previous history of cancer in remission for less than 12 months, see protocol page 35 for details.
• Any monoclonal antibody (other than Xolair) to treat inflammatory disease within 5 half-lives of Visit 1.
• Known evidence of lack of adherence within studies MEA115666 or 201312 (less than 80%) to controller medications, scheduled study visits and/or ability to follow physician*s recommendations.
• Current smokers.
• Pregnancy or breastfeeding.
• In the opinion of the Investigator, any subject who is unable to read and/or would not be able to complete a questionnaire.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-002361-32-NL |
| CCMO | NL55727.100.15 |
| Other | www.gskclinicalstudyregister.com; registratiebummer 201810 |