A multicentre, randomised, double-blind, placebo-controlled, parallel group, dose ranging study to determine the effect of mepolizumab on exacerbation rates in subjects with severe uncontrolled refractory asthma.
- Conditions
- severe uncontrolled refractory asthma.MedDRA version: 12.0Level: LLTClassification code 10003553Term: Asthma
- Registration Number
- EUCTR2009-014415-12-DE
- Lead Sponsor
- GlaxoSmithKline Research & Development Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 604
1. Male or female subjects aged =12 years old with a minimum weight of 45Kg.
[For countries where local regulations or the regulatory status of study medication
permit enrolment of adults only, subjects recruited will be =18 years].
2. Subjects with the clinical features of severe refractory asthma similar to those
indicated in the ATS Workshop on Refractory Asthma [ATS workshop, 2000] for
=12 months prior to Visit 1 and mandated through meeting Inclusion Criteria 3, 4
and 5.
3. Subjects with a well-documented requirement for regular treatment with high dose
ICS [i.e. = 880 µg/day fluticasone propionate (FP) or equivalent daily], with or
without maintenance oral corticosteroids (OCS), in the 12 months prior to Visit 1. Please see protocol page 23 for further information.
4. Subjects with a well-documented requirement for controller medication, e.g., longacting
beta-2-agonist (LABA), leukotriene receptor antagonist (LTRA), or
theophylline in the 12 months prior to Visit 1.
5. Subjects with persistent airflow obstruction as indicated by a pre-bronchodilator
FEV1 <80% predicted (NHANES III) recorded at Visit 1 or Visit 2 or peak flow
diurnal variability of >20% on 3 or more days during the run-in period.
6. Subjects with airway inflammation which is likely to be eosinophilic in nature as
indicated by one of the following characteristics demonstrated at Visit 1 or
documented in the previous 12 months:
• An elevated peripheral blood eosinophil level of =300/µL that is related to
asthma or
• Sputum eosinophils =3% or
• Exhaled nitric oxide =50 ppb (can be performed at Visit 1 or Visit 2 pre
randomisation) or
• Prompt deterioration of asthma control (based on documented clinical
history or objective measures) following a =25% reduction in regular
maintenance dose of inhaled or oral corticosteroid dose in the previous 12
months
7. Subjects with a previously confirmed history of two or more asthma exacerbations
requiring treatment with oral or systemic corticosteroids in the 12 months prior to
Visit 1, despite the use of high-dose ICS and additional controller medication. For
subjects receiving maintenance OCS with high-dose ICS plus controller, the OCS
treatment for exacerbations must be a two-fold or greater increase in the dose of
OCS.
8. Evidence of asthma as documented by either:
• Airway reversibility (FEV1=12% and 200 ml) demonstrated1 at Visit 1 or
Visit 2 or documented in the previous 12 months OR
• Airway hyperresponsiveness (PC20 of <8mg/mL or PD20 of <7.8 µ mol
methacholine/histamine) documented in the 12 months prior to Visit 1 OR
• Airflow variability in clinic FEV1 =20% between two consecutive clinic
visits documented in the 12 months prior to Visit 1 ( FEV1 recorded during
an exacerbation will not be valid) OR
• Airflow variability as indicated by >20% diurnal variability in peak flow
observed on 3 or more days during the run-in.
1For reversibility testing at Visit 1 or Visit 2, the Maximum Post-bronchodilator
procedure should be employed in accordance with the methodology used by
Asthma Clinical Research Network (see Study Procedures Manual)
9. ECG assessment (QTcF, machine or manual overread, males or females);
QTcF < 450msec or QTcF < 480 msec for patients with Bundle Branch Block. (please view protocol page 25 for further information
10. Liver Function Tests;
ALT<2 x ULN (upper limit of normal)
AST<2 x ULN
Alk Phos = 1.5 x ULN
Bilirubin = 1.5 x ULN (isolated bilirubin>1.5 ULN is acceptable if
bilirubin is fractionated and di
1. Current smokers or subjects with a smoking history of >=10 pack years (number of pack years = (number of cigarettes per day / 20) x number of years smoked).
2. Presence of a clinically important lung condition other than asthma. This includes current infection, bronchiectasis, pulmonary fibrosis, bronchopulmonary aspergillosis, or diagnoses of emphysema or chronic bronchitis (chronic obstructive pulmonary disease other than asthma) or a history of lung cancer.
3. Subjects with a diagnosis of malignancy or in the process of investigation for a malignancy. Subjects with a past medical history of malignancy can be allowed in the trial provided anyone with a diagnosis of a recurrent malignant tumour or having received treatment for a malignancy within 12 months are excluded. . (Note for South Korea: Korean subjects with a diagnosis or treatment of malignancy within 5 years are excluded).
4. Unstable liver disease (as defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, esophageal or gastric varices or persistent jaundice), cirrhosis, and known biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic gallstones).
5. Subjects with a diagnosis of Churg-Strauss syndrome.
6. Subjects who have taken methotrexate, troleandomycin, oral gold, cyclosporine, azathioprine or any experimental anti-inflammatory therapies within 3 months of screening.
7. Subjects who have received omalizumab [Xolair®] or any other biological for the treatment of inflammatory disease within 130 days of Visit 1.
8. Regular use of oral or systemic corticosteroids for diseases other than asthma within the past 12 months or any intra-articular, short-acting intramuscular corticosteroid with 1 month or intramuscular, long-acting depot corticosteroids within 3 months.
9. Subject with allergy/intolerance to the excipients in the mepolizumab formulation.
10. Subjects who have received treatment with an investigational drug within the past 30 days or five half-lives whichever is longer, prior to the first doses of study medication (this also includes investigational formulations of marketed products).
11. Subjects who are pregnant or breastfeeding. Subjects should not be enrolled if they plan to become pregnant during the time of study participation.
12. Subjects who have clinically significant cardiovascular, endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, haematological or any other system abnormalities that are uncontrolled with standard treatment
13. Subjects with a history (or suspected history) of alcohol misuse or substance abuse within 2 years prior to Visit 1.
14. Subjects with a parasitic infestation within 6 months prior to Week -2 (Visit 1).
15. Subjects with a known immunodeficiency (e.g. human immunodeficiency virus – HIV), other than that explained by the use of corticosteroids taken as therapy for asthma.
16. Subjects who are unable to follow study instructions such as dosing directions, study electronic diary (eDiary) completion, or use of a standard metered dose inhaler.
17. Subjects who have known evidence of lack of adherence to controller medications and/or ability to follow physician’s recommendations.
18. Subjects who have previously participated in a study of mepolizumab and received study medication within 90 days prior to screening.
Re-screening of subjects will be allowed only with approval by the medical monitor
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method