Severe Eosinophilic Asthma MedDRA version: 18.1 Level: LLT Classification code 10068462 Term: Eosinophilic asthma System Organ Class: 100000004855
Conditions
Interventions
Product Name: Mepolizumab
Product Code: PRD907320
Pharmaceutical Form: Lyophilisate for solution for injection
INN or Proposed INN: Mepolizumab
CAS Number: 196078-29-2
Current Sponsor code: SB-240563
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria for Part A 1. Between 6 and 11 years of age inclusive, at the time of screening. 2. Diagnosis of severe asthma, defined by the regional asthma guidelines (i.e., NIH, GINA, etc.), for at least 12 months prior to Visit 1. If the subject is naïve to the study site, the subject/guardian must self-report a physician diagnosis of asthma and the investigator must confirm by review of medical history with the subject/guardian. 3. Eosinophilic airway inflammation that is related to asthma characterized as eosinophilic in nature as indicated by: - elevated peripheral blood eosinophil count of =300 cells/µL demonstrated in the past 12 months OR - elevated peripheral blood eosinophil count of =150 cells/µL at visit 1. 4. A well-documented requirement for regular treatment with inhaled corticosteroid (=400 µg/day fluticasone propionate (DPI) or equivalent daily) in the 12 months prior to Visit 1 with or without maintenance oral corticosteroids (OCS). 5. Current treatment with an additional controller medication 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), or theophylline.] 6. FEV1: Persistent airflow obstruction at either visit 1 or Visit 2 (FEV1 performed prior to first dose of study medication) as indicated by: - A pre-bronchodilator FEV1 =65 years) no F.1.
Exclusion criteria
Exclusion criteria: Exclusion Criteria for Part A 1. Subjects with any history of life threatening asthma (e.g. requiring intubation), immunosuppressive medications intake or immunodeficiency disorder 2. Subjects with any medical condition or circumstance making the volunteer unsuitable for participation in the study. 3. Significant abnormality of rate, interval, conduction or rhythm in the 12-lead ECG, determined by the investigator in conjunction with the age and gender of the child at Visit 1. 4. ALT, and bilirubin > 2xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%) at Visit 1. 5. Parent/guardian has a history of psychiatric disease, intellectual deficiency, substance abuse, or other condition (e.g. inability to read, comprehend and write) which will limit the validity of consent to participate in this study. 6. Unwillingness or inability of the subject or parent/guardian to follow the procedures outlined in the protocol. 7. Subject who is mentally or legally incapacitated. 8. Children who are wards of the state or government. 9. A subject will not be eligible for this study if he/she is an immediate family member of the participating investigator, sub-investigator, study coordinator, or employee of the participating investigator. 10. Xolair: 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. History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or Medical Monitor, contraindicates their participation. 13. Hypersensitivity: Subjects with allergy/intolerance to a monoclonal antibody or biologic. 14. The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Pharmacokinetic/Pharmacodynamic Phase (Part A) - To characterize the pharmacokinetics of mepolizumab administered subcutaneously to subjects aged 6 to 11 years old with severe eosinophilic asthma ? - To characterize the pharmacodynamics of mepolizumab administered subcutaneously to subjects aged 6 to 11 years old with severe eosinophilic asthma Long-Term Safety / Long-Term Pharmacodynamic Phase (Part B) - To assess the long-term (52 weeks) safety and tolerability of mepolizumab when administered subcutaneously to subjects aged 6 to 11* years old with severe eosinophilic asthma ;Secondary Objective: Pharmacokinetic/Pharmacodynamic Phase (Part A) - To compare the bodyweight-adjusted clearance between adults and subjects aged 6 to 11 years old with severe eosinophilic asthma when mepolizumab is administered subcutaneously - To characterize asthma control following subcutaneous administration of mepolizumab to subjects aged 6 to 11 years old with severe eosinophilic asthma - To assess the safety and tolerability of mepolizumab when administered subcutaneously to subjects aged 6 to 11 years old with severe eosinophilic asthma Long-Term Safety / Long-Term Pharmacodynamic Phase (Part B) -To characterize the long-term (52 weeks) durability of pharmacodynamics of mepolizumab administered subcutaneously to subjects aged 6 to 11* years old with severe eosinophilic asthma;Primary end point(s): Pharmacokinetic/Pharmacodynamic Phase (Part A) 1. Population-PK model derived estimates of clearance, area under the plasma-concentration time curve (AUC(0-inf), maximum plasma concentration (Cmax), and terminal phase elimination half-life (t1/2) of mepolizumab 2. Change from baseline in blood eosinophil count at week 12 Long-Term Safety / Long-Term Pharmacodynamic Phase (Part B) - Incidence of Adverse Events - Frequency of positive antimepolizumab binding antibodies and neutralizing antibodies - Incidence of clinically significant changes in vital sign meas | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Pharmacokinetic/Pharmacodynamic Phase (Part A) 1. Bodyweight-adjusted clearance estimates obtained by population PK methods. 2. Change from Baseline in ACQ-7 measured at week 12 3. Change from Baseline in ACQ-7 measured at week 4,8,16 and 20 4. Incidence of Adverse Events 5. Incidence of clinically significant changes in clinical laboratory parameters 6. Frequency of positive antimepolizumab binding antibodies and neutralizing antibodies 7. Incidence of clinically significant changes in vital sign measurements Long-Term Safety / Long-Term Pharmacodynamic Phase (Part B) -Change from Week 20 (Visit 9) in absolute blood eosinophil count at weeks 32, 44, 56, 68, 72 and 80.;Timepoint(s) of evaluation of this end point: 1. At week 4, 8, 9, 12, 16, 20 and if applicable at the Early Withdrawal visit 2. At week 12 3. At week 4,8,16 and 20 4. Throughout the study 5. - Clinical chemistry will be at weeks 4, 8, 12 and 20 - Haematology will be at weeks 0, 4, 8, 9, 12, 16 and 20 6. Prior to dosing at week 0, and at weeks 16, 20 and EW 7. Weeks 1, 4, 8, 9, 12, 16, 20 and early withdrawal (if applicable) | — |
Countries
Japan, United Kingdom, United States
Contacts
Public ContactClinical Trials Helpdesk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed