Subjects with severe asthma MedDRA version: 19.0 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Trade Name: Nucala
Product Name: Mepolizumab
Product Code: SB-240563
Pharmaceutical Form: Lyophilisate and solvent for solution for injection
INN or Proposed INN: Mepolizumab
CAS Number: 196078-29-2
C
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A subject will be eligible for inclusion in this study only if all of the following criteria apply: AGE 1. At least 12 years of age at the time of signing the informed consent. [For those countries where local regulations permit enrolment of adults only, subject recruitment will be restricted to those who are 18 years of age] TYPE OF SUBJECT AND DIAGNOSIS INCLUDING DISEASE SEVERITY 2. Asthma: A physician diagnosis of asthma for =2 years that meets the National Heart and Lung Institute guidelines 3. FEV1: Persistent airflow obstruction as indicated by: For subjects =18 years of age at Visit 1, a pre-bronchodilator FEV1 <80% predicted recorded at Visit 1 For subjects 12-17 years of age at Visit 1, a pre-bronchodilator FEV1 <90% predicted recorded at Visit 1 OR FEV1/FVC ratio <0.8 recorded at Visit 1 4. Eosinophilic asthma: Airway inflammation characterized as eosinophilic in nature as indicated by one of the following: a. A peripheral blood eosinophil count of =300 cells/µL that is related to asthma demonstrated in the past 12 months prior to Visit 1 OR b. A peripheral blood eosinophil count of =150 cells/µL at Visit 1 that is related to asthma. 5. Inhaled Corticosteroid: A well-documented requirement for regular treatment with high-dose inhaled corticosteroid (ICS) in the 12 months prior to Visit 1 with or without maintenance oral corticosteroids (OCS). 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 subjects 12-17 years of age at Visit 1: ICS dose must be =440 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. 6. Controller medication: Current treatment with an additional controller medication, besides ICS, for at least 3 months or a documented failure in the past 12 months of an additional controller medication for at least 3 successive months. [e.g., long-acting beta- 2-agonist (LABA), leukotriene receptor antagonist (LTRA), long-acting anticholinergic (tiotropium bromide), or theophylline.] 7. Asthma symptoms not optimally controlled: An ACQ-5 score of =1.5 recorded at Visit 1. 8. Omalizumab Treatment: Receiving omalizumab, based on weight and IgE levels, for at least the 4 months prior to Visit 1. 9. Exacerbation history: Previously confirmed history of two or more exacerbations requiring treatment with systemic corticosteroids (intramuscular, intravenous, or oral) in the 12 months prior to Visit 1 despite the use of high-dose ICS. For subjects receiving omalizumab for =8 months, at least one exacerbation must have occurred while on omalizumab treatment. For subjects receiving maintenance oral corticosteroids, the corticosteroid treatment for the exacerbations must have been a two-fold dose increase or greater. SEX 10. Male or eligible Female Females: a. Non-reproductive potential defined as: •Pre-menopausal females with one of the following: •Documented tubal ligation •Documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion •Hysterectomy •Documented Bilateral Oophorectomy •Postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous folli
Exclusion criteria
Exclusion criteria: CONCURRENT CONDITIONS/MEDICAL HISTORY (INCLUDES LIVER FUNCTION AND QTc INTERVAL) 1. Concurrent Respiratory Disease: Presence of a known pre-existing, 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. 2. Malignancy: A current malignancy or previous history of cancer in remission for less than 12 months prior to screening (subjects that had localized carcinoma of the skin which was resected for cure will not be excluded). 3. Liver disease: Subjects must not be enrolled in the study if: At screening (Visit 1) ALT >2xULN; and bilirubin >1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin 450 msec or QTc > 480 msec in subjects with Bundle Branch Block at screening Visit 1 7. 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. 8. Eosinophilic Diseases: Subjects with other conditions that could lead to elevated eosinophils such as Hypereosinophilic Syndromes, including Churg-Strauss Syndrome (Eosinophilic Granulomatosis with Polyangiitis; EGPA), or Eosinophilic Esophagitis. Subjects with a known, pre-existing parasitic infestation within 6 months prior to Visit 1 are also to be excluded. 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. CONCOMITANT MEDICATIONS 10. Other Monoclonal Antibodies: Subjects who have received any monoclonal antibody (other than omalizumab) to treat inflammatory disease within 5 half-lives of Visit 1. RELEVANT HABITS 11. Smoking history: Current smokers or former smokers with a smoking history of =10 pack years (number of pack years = (number of cigarettes per day / 20) x number of years smoked). A former smoker is defined as a subject who quit smoking at least 6 months prior to Screening Visit 1. 12. Alcohol/Substance Abuse: A history (or suspected history) of alcohol misuse or substance abuse within 2 years prior to Visit 1. 13. Adherence: Subjects who have know
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 Objective: • To determine whether there is an improvement in Health related Quality of Life (HR-QoL) when directly switched to mepolizumab, in subjects with a severe eosinophilic asthma phenotype not optimally controlled on omalizumab • To determine the frequency of asthma exacerbations, when directly switched to mepolizumab, in subjects with a severe eosinophilic asthma phenotype not optimally controlled on omalizumab. • To evaluate the pharmacodynamic effects when directly switched to mepolizumab, in subjects with a severe eosinophilic asthma phenotype not optimally controlled on omalizumab. ;Primary end point(s): Mean change from baseline in ACQ- 5 score at Week 32;Timepoint(s) of evaluation of this end point: Week 32 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): •Mean change from baseline in SGRQ score at Week 32 •Frequency of clinically significant asthma exacerbations over 32 week treatment •Ratio to baseline in blood eosinophils at Week 32;Timepoint(s) of evaluation of this end point: Week 32 | — |
Countries
Argentina, Belgium, Canada, France, Germany, Netherlands, Spain, Sweden, United States
Contacts
Public ContactGSK Clinical Support Help Desk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed