Severe asthma MedDRA version: 14.1 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Sponsors
GlaxoSmithKline Research and Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects eligible for enrolment in the study must meet all of the following criteria: 1. Informed Consent and Study Compliance: Subjects must be able to give written informed consent prior to participation in the study, which will include the ability to comply with the equirements and restrictions listed in the consent form. Subjects must be able to read, comprehend, and write at a level sufficient to complete study related materials. 2. Age: At least 12 years of age at Visit 1 and a minimum weight of 45kg [For those countries where local regulations permit enrolment of adults only, subject recruitment will be restricted to those who are >18 years of age] 3. Systemic Corticosteroids: Subjects with severe asthma and a well-documented requirement for regular treatment with maintenance systemic corticosteroids in the 6 months prior to Visit 1 and using a stable oral corticosteroid dose for 4 weeks prior to Visit 1. Subjects must be taking 5.0 – 35 mg/day of prednisone or equivalent at Visit 1 and must agree to switch to study required prednisone/prednisolone as their oral corticosteroid and use it per protocol for the duration of the study. 4. Inhaled Corticosteroids: A documented requirement for regular treatment with high dose inhaled corticosteroid in the 6 months prior to Visit 1. • For 18 years of age and older: • ICS dose must be =880 mcg/day fluticasone propionate (FP) (ex-actuator) or equivalent daily. • For ICS/LABA combination preparations, the highest approved maintenance dose in the local country will meet this ICS criterion. • For ages 12-17 • ICS dose must be =440 µg/day fluticasone propionate (FP) (ex-actuator) or equivalent daily. • For ICS/LABA combination preparations, the mid-strength approved maintenance dose in the local country will meet this ICS criterion. 5. Controller Medication: Current treatment with an additional controller medication for at least 3 months OR documentation of having used and failed an additional controller medication for at least 3 successive months during the prior 12 months [e.g., long-acting beta2-agonist (LABA), leukotriene receptor antagonist (LTRA), or theophylline]. 6. Eosinophilic asthma: Prior documentation of eosinophilic asthma or high likelihood of eosinophilic asthma as per Randomisation Criteria 1 and 2. 7. Gender: Male or Eligible Female To be eligible for entry into the study, females of childbearing potential (FCBP) must commit to consistent and correct use of an acceptable method of birth control beginning with consent for the duration of the trial and for 4 months after the last study drug administration. Subjects in France: In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category. Are the trial subjects under 18? yes Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 84 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 24
Exclusion criteria
Exclusion criteria: Subjects meeting any of the following criteria must not be enrolled in the study: 1. Smoking history: Current smokers or former smokers with a smoking history of =10 pack years. A former smoker is defined as a subject who quit smoking at least 6 months prior to Visit 1. 2. Concurrent Respiratory Disease: Presence of a clinically important lung condition other than asthma. This includes but is not limited to 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. Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior screening (Subjects that had localized carcinoma (ie, basal or squamous cell) of the skin which was resected for cure will not be excluded). 4. Liver Disease: 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. Cardiovascular: Subjects who have severe or clinically significant cardiovascular disease uncontrolled with standard treatment. 6. Other Concurrent Medical Conditions: Subjects who have known, pre-existing, clinically significant endocrine, autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, haematological or any other system abnormalities that are uncontrolled with standard treatment. 7. Eosinophilic Diseases: Subjects with other conditions that could lead to elevated eosinophils such as Hypereosiniophilic Syndromes, including Churg-Strauss Syndrome, or Eosinophilic Esophaghitis. Subjects with a known, pre-existing parasitic infestation within 6 months prior to Visit 1 are also to be excluded. 8. ECG: ECG assessment QTcF = 450msec or QTcF = 480 msec for subjects with Bundle Branch Block. 9. Immunodeficiency: A known immunodeficiency (e.g. human immunodeficiency virus – HIV), other than that explained by the use of corticosteroids taken as therapy for asthma. 10. Omalizumab Use: Subjects who have received omalizumab [Xolair] within 130 days of Visit 1. 11. Other Biologics: Subjects who have received any biological (other than Xolair) to treat inflammatory disease within 5 half-lives of Visit 1 12. Investigational Medications: Subjects who have received treatment with an investigational drug within the past 30 days or five terminal phase half-lives of the drug whichever is longer, prior to Visit 1 (this also includes investigational formulations of marketed products). 13. Hypersensitivity: Subjects with a known allergy or intolerance to a monoclonal antibody or biologic. 14. Pregnancy: Subjects who are pregnant or breastfeeding. Patients should not be enrolled if they plan to become pregnant during the time of study participation. 15. Alcohol/Substance Abuse: A history (or suspected history) of alcohol misuse or substance abuse within 2 years prior to Visit 1. 16. Adherence: Subjects who have known evidence of lack of adherence to controller medications and/or ability to follow physician’s recommendations. 17. Previous participation: Subjects who have previously any study of mepolizumab and received Investigational Product. Re-screening of subjects will be allowed only upon approval by the medical monitor.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the effects of mepolizumab adjunctive therapy with placebo on reducing the use of maintenance oral corticosteroids (OCS) in systemic corticosteroid dependent subjects with severe refractory asthma with elevated eosinophils.;Secondary Objective: To compare the efficacy, safety, and tolerability of mepolizumab compared with placebo, in subjects with severe refractory asthma with elevated eosinophils including an evaluation of the effects of mepolizumab on markers of asthma impairment and risk including, asthma symptoms, pulmonary function, exacerbation rate and quality of life as assessed by the St. George’s Respiratory Questionnaire.;Primary end point(s): The primary efficacy endpoint is the percent reduction of oral corticosteroid (OCS) dose at week 24 compared to the baseline dose.;Timepoint(s) of evaluation of this end point: One timepoint, Week 24 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • The proportion of subjects who achieve a reduction of 50% or greater in their daily OCS dose, compared to baseline dose, during weeks 20-24 while maintaining asthma control. • The proportion of subjects who achieve a reduction of OCS dose to less than or equal to 5.0mg, while maintaining asthma control during weeks 20 – 24 • The proportion of subjects who achieve a total reduction of OCS dose while maintaining asthma control during weeks 20 - 24 • Median percentage reduction from baseline in daily OCS dose at week 24 • Proportion of eligible subject who achieve complete reduction of OCS • Annualised rate of clinically significant exacerbations • Annualised rate of exacerbations requiring hospitalization • Annualised rate of exacerbations requiring hospitalization or ED visits • Mean change from baseline in St. George’s Respiratory Questionnaire at week 24 • Mean change from baseline in clinic pre-bronchodilator FEV1 at week 24 ;Timepoint(s) of evaluation of this end point: 24 | — |
Countries
Australia, Canada, Germany, Mexico, Netherlands, United Kingdom, United States
Contacts
Public ContactClinical Trials Helpdesk
GlaxoSmithKline
Outcome results
None listed