severe uncontrolled refractory asthma. MedDRA version: 12.0 Level: LLT Classification code 10003553 Term: Asthma
Conditions
Interventions
Product Name: Mepolizumab for Injection
Product Code: SB240563
Pharmaceutical Form: Intravenous infusion
INN or Proposed INN: Mepolizumab
CAS Number: 196078-29-2
Current Sponsor code: SB-240563
Concen
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 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 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 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 1.5 ULN is acceptable if bilirubin is fractionated and di
Exclusion criteria
Exclusion criteria: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the dose response, based on efficacy and safety of three doses of mepolizumab (75 mg, 250 mg and 750 mg) over a 52-week treatment period in adult and adolescent subjects with severe uncontrolled refractory asthma.;Secondary Objective: To assess the pharmacodynamic effect of mepolizumab on the number of eosinophils in blood, serum IL-5 and number of eosinophils in induced sputum.;Primary end point(s): Frequency of clinically significant exacerbations of asthma as defined by: Worsening of asthma requiring use of oral/systemic corticosteroids1and/or hospitalisation and/or Emergency Department (ED) visits.1 For subjects on maintenance oral corticosteroids, an exacerbation requiring oral corticosteroids will be defined as the use of oral/systemic corticosteroids at least double the existing maintenance dose for at least 3 days. Protocol defined exacerbations will be based on objective assessments of asthma. | — |
Countries
France, Germany, United Kingdom
Outcome results
None listed