Primary:To describe in a pragmatic setting whether there is an improvement in asthma control from the beginning to the end of the study,when directly switched to mepolizumab, in subjects with a severe eosinophilic asthma phenotype not optimally…
ID
Source
Brief title
Condition
- Bronchial disorders (excl neoplasms)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Mean change from baseline in ACQ-5 score at Week 32.
Secondary outcome
Mean change from baseline in SGRQ score at week 32, frequency of clinically
significant asthma exacerbations, ratio to baseline in blood eosinophils at
week 32, percentage of subjects achieving a 0.5-point or greater reduction from
baseline in ACQ-5 score at week 32, percentage of subjects achieving a 4-point
or greater reduction from baseline in SGRQ score at week 32, Mean change from
baseline in pre and post bronchodilator FEV1 at week 32, frequency of
exacerbations requiring ED visit/hospitalization, subject/clinician rated
response to therapy, Mean change from baseline in treatment satisfaction
questionnaire, adverse events.
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 efficacy and safety of
mepolizumab in subjects with severe asthma, who have been switched from a
treatment with omalizumab to treatment with mepolizumab.
Study objective
Primary:
To describe in a pragmatic setting whether there is an improvement in asthma
control from the beginning to the end of the study,when directly switched to
mepolizumab, in subjects with a severe eosinophilic asthma phenotype not
optimally controlled on omalizumab.
Secondary:
Improvement in Health related Quality of Life, frequency of asthma
exacerbations, pharmacodynamic effects, response to asthma clinical parameters,
safety, immunogenicity and tolerability.
Study design
Multi-centre, open-label single arm trial. Screening/run-in period 1-6 weeks.
Treatment period (mepolizumab 100 mg, 8 SC injections in total, 1 injection
every 4 weeks) 32 weeks.
Switch from omalizumab to mepolizumab for all subjects.
155 subjects screened, 120 treated, 100 completed treatment period.
Intervention
Treatment with mepolizumab.
Study burden and risks
Risk: Adverse events of mepolizumab.
Burden:
10-11 visits in 33-38 weeks.
8 SC injections with mepolizumab (approx. 1 ml).
Physical examination: 2 times.
Blood draws: 10 times (2-35 ml blood, 170 ml in total).
Pregnancy test: 10 times.
Alcohol/drugs screen (urine): at screening.
Pulmonary function tests: at screening 1 single test, thereafter 4 visits with
test pre and post bronchodilator.
ECG: 3 times.
Questionnaires (1-3): 10 times.
Diary during entire study period: adverse events, changes in medication, visits
to other MDs.
Optional: pharmacogenetic testing (6 ml blood), exit interview (incl. audio
taping).
Huis ter Heideweg 62
Zeist 3705 LZ
NL
Huis ter Heideweg 62
Zeist 3705 LZ
NL
Listed location countries
Age
Inclusion criteria
* At least 12 years (NL: 18 years) of age.
* Asthma for *2 years that meets the National Heart and Lung Institute or GINA guidelines.
* Persistent airflow obstruction (*18 years: FEV1 <80% predicted, 12-17 years: <90% predicted) or FEV1/FVC ratio <0.8).
* Eosinophilic asthma, see protocol page 25 for details.
* Well-documented requirement for regular treatment with high-dose inhaled corticosteroid in the 12 months prior to Visit 1 with or without maintenance oral corticosteroids, see protocol page 25 for details.
* Additional controller medication, besides ICS: current treatment for at least 3 months or failure in the past 12 months for at least 3 successive months.
* ACQ-5 score *1.5.
* Omalizumab based on weight and IgE levels for at least the 4 months.
* History of two or more exacerbations in the past 12 months. For subjects receiving omalizumab for *8 months: at least one exacerbation must have occurred while on omalizumab treatment, see protocol page 26 for details.
* Adequate contraception for females of childbearing potential.
Exclusion criteria
* Presence of a known pre-existing, clinically important lung condition other than asthma.
* Diagnosis of chronic hepatitis B, as evidenced by positive Hepatitis B surface antigen.
* Clinically significant cardiovascular disease uncontrolled with standard treatment, see protocol page 28 for details.
* Other conditions that could lead to elevated eosinophils, see protocol page 28 for details.
* Known immunodeficiency, other than that explained by the use of corticosteroids for asthma.
* Current smokers or former smokers with a smoking history of *10 pack years see protocol page 29 for details.
* Pregnancy or breastfeeding
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 | EUCTR2015-003697-32-NL |
| CCMO | NL55615.100.15 |
| Other | www.gskclinicalstudyregister.com; regsitratienummer 204471 |