Primary: To provide extended treatment with mepolizumab to subjects with severe asthma and a history of improved disease control while receiving mepolizumab as defined by this protocol.Secondary: To collect data on long term clinical data.
ID
Source
Brief title
Condition
- Bronchial disorders (excl neoplasms)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
NA.
Secondary outcome
Adverse events, antibodies, exacerbations, asthma control questionnaire, FEV1.
Background summary
Mepolizumab is currently under clinical development for severe asthma.
Mepolizumab is a humanized antiinterleukin 5 (anti-IL5) antibody (IgG Kappa)
that binds to and inactivates IL-5. IL-5 is the principle eosinophilic
regulatory cytokine. It is critical for the development and release of
eosinophils from the bone marrow, enhances adhesion to endothelial cells, and
promotes the persistence and activation of eosinophils. Eosinophils are thought
to play a major role in maintaining airway inflammation. Mepolizumab binds with
high affinity to human interleukin-5 and blocks its binding to and the
activation of the IL-5 receptor (CD125). It is hypothesized that blocking IL-5
with mepolizumab will have a positive effect in reducing eosinophilic
inflammation in patients with severe refractory asthma who are dependent on
maintenance steroid to treat their asthma. This concept has been previously
investigated in a small study (N= 20) of asthmatics with persistent sputum
eosinophils. The results of this study demonstrated that mepolizumab was well
tolerated and effective in reducing the dose of prednisone while preventing
exacerbations, decreasing blood and sputum eosinophil numbers, and improving
lung function and quality of life.
Recently a study of IV mepolizumab of over 600 subjects with severe refractory
uncontrolled asthma has been completed. All 3 doses investigated (75mg, 250 mg
and 750mg) resulted in a clinically significant reduction in the frequency of
severe exacerbations when compared to placebo and produced a marked and
sustained suppression of blood eosinophils. The safety profile was similar
across all treatment arms and was similar to placebo.
A PK/PD model has been developed for mepolizumab with data obtained from prior
studies. Two of these 5 studies administered mepolizumab via the subcutaneous
(SC) route. The model well describes the relationship between plasma
mepolizumab concentration and eosinophil counts (irrespective of the route of
administration. Based on prior PK studies, the bioavailability of mepolizumab
administered SC is approximately 75% and therefore a dose of 100mg SC is
anticipated to provide similar exposure to the 75mg IV effective dose. A SC
route of administration has been chosen for the current study as it is
generally preferred by patients and is easy to administer.
The current study is an extension of the study MEA115661 (that was itself an
extension study of MEA115575). Patients who have completed this previous study
may use mepolizumab in this extension study. The purpose is primarily to
guarantee further availability of mepolizumab to the trial subjects until the
drug is available on prescription in our country.
Study objective
Primary: To provide extended treatment with mepolizumab to subjects with severe
asthma and a history of improved disease control while receiving mepolizumab as
defined by this protocol.
Secondary: To collect data on long term clinical data.
Study design
Open-label non-comparative phase III study. Treatment with Mepolizumab 100 mg
s.c. every 4 weeks
Continuation of standard treatment for asthma.
Salbutamol rescue medication.
Study duration max. 3 year and 4 months.
Follow-up phase 4 weeks.
Approx. 375 patients.
Intervention
Treatment with mepolizumab.
Study burden and risks
Risk: adverse events of study treatment.
Burden: approx. 45 visits in max. 3 year and 4 months. Duration 1-2h.
S.c. injections (1 ml) with mepolizumab every 4 weeks during max. 3 year and 4
months.
Blood draws every 6 months (approx. 10 ml/occasion).
Pregnancy test every visit.
Physical examination 2x.
Pulmonary function test every 6 months.
ECG every 6 months during the first 2 years.
Asthma Control Questionnaire every 3 months.
Huis ter Heideweg 62
Zeist 3705 LZ
NL
Huis ter Heideweg 62
Zeist 3705 LZ
NL
Listed location countries
Age
Inclusion criteria
* Visit 14 of MEA115661 completed.
* Asthma has been treated with an ICS for the last 8 months with fluticasone propionate *500 mcg/day (or equivalent).
* Life-threatening /serious debilitating asthma (see protocol page 23 for details).
* Documented clinical benefit (see protocol page 24 for details).
* Adequate contraception during the study and the following 4 months for females of childbearing potential.
* If either criteria on disease severity or clinical benifit are not met: subjects who are considered to be at risk of experiencing a life-threatening event, or whose functional health status will become significantly worse if returned to standard of care, as judged by the investigator and agreed by GSK.
Exclusion criteria
* Received placebo in MEA115575 and able to discontinue oral corticosteroid therapy by the end of the study.
* Pregnancy or breastfeeding
* Current smokers.
* Baseline ECG which has a clinically significant abnormality.
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 |
|---|---|
| Other | clinicaltrials.gov; registratienummer n.n.b. |
| EudraCT | EUCTR2014-000314-54-NL |
| CCMO | NL48592.060.14 |