Asthma MedDRA version: 14.0 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Interventions
Product Name: Mepolizumab for Injection
Product Code: SB240563
Pharmaceutical Form: Injection
INN or Proposed INN: Mepolizumab
CAS Number: 196078-29-2
Current Sponsor code: SB-240563
Concentration uni
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males or eligible females between 18 and 65 years of age inclusive, at the time of signing the informed consent; Non-childbearing potential is defined as pre menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal defined as 12 months of spontaneous amenorrhea [in questionable cases a blood sample with simultaneous follicle stimulating hormone (FSH) > 40 MlU/ml and estradiol 0.2 cells 10^9/L) within 12 months of screening and evidence of elevated blood eosinophilia levels (>0.2 cells 10^9/L) at screening. 7. Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form. Are the trial subjects under 18? no 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 58 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. QTcF =450 msec; or QTcF = 480 msec in subjects with Bundle Branch Block. 2. AST, ALT, alkaline phosphatase and bilirubin = 1.5xULN (isolated bilirubin 10 pack years calculated as follows:view protocol for further information. 5. Presence of a clinically important lung condition other than asthma including current infection, bronchiectasis, pulmonary fibrosis, bronchopulmonary aspergillosis, Churg-Strauss syndrome, or diagnoses of emphysema or chronic bronchitis (chronic obstructive pulmonary disease other than asthma) or a history of lung cancer. 6. An asthma exacerbation or respiratory tract infection within six weeks prior to screening (an exacerbation is defined as worsening asthma requiring the use of systemic corticosteroids and/or emergency department visit, hospitalisation). 7. Subjects with a parasitic infestation within six months of screening. 8. A current malignancy or previous history of cancer in remission for less than five years prior screening (except for localized carcinoma of the skin that has been resected for cure). 9. 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. 10. 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). 11. Subjects with a known immunodeficiency (e.g. human immunodeficiency virus – HIV). 12. A positive pre-study Hepatitis B surface antigen or positive Hepatitis C antibody result within three months of screening. 13. Subjects who have received omalizumab [Xolair] within 130 days of administration of the first dose of study medication. 14. Subjects with recent history (within two years prior to screening) of alcohol misuse or substance abuse prior screening. 15. A positive pre-study drug/alcohol test at screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To demonstrate that the PK/PD relationship between the exposure of SC administered mepolizumab and a marker of response, plasma eosinophil, is comparable to that observed following IV administration;Secondary Objective: • To assess the relative bioavailability of mepolizumab administered subcutaneously, as compared to mepolizumab administered intravenously, in asthmatic adult subjects with elevated blood eosinophil levels. • To assess the immunogenicity of repeat doses of mepolizumab. • To assess the safety and tolerability of repeat doses of mepolizumab when administered subcutaneously and intravenously to asthmatic adult subjects with elevated blood eosinophil levels ;Primary end point(s): • Change from baseline in blood eosinophil levels as assessed by the exposure-response relationship • Area under the blood eosinophil time curve (AUC), maximum change from baseline in blood eosinophils (Emax), time to maximum change in blood eosinohil levels (Tmaxeos), time to 50% eosinophil repletion (Trep) • Area under the plasma-concentration time curve (AUC), maximum plasma concentration (Cmax), time to Cmax (Tmax) and terminal half-life (t½) of mepolizumab;Timepoint(s) of evaluation of this end point: Day1, Day 3, Day 7, Day 28, Day 56, Day 70, Day 84, Day 112 and Day 140. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • AUC and Cmax of mepolizumab (Day1, Day 3, Day 7, Day 28, Day 56, Day 70, Day 84, Day 112 and Day 140) • Levels of anti-mepolizumab antibodies (Day 1, Day 112 and Day 140) • Spontaneous and elicited adverse events (AEs), (Day1, Day 3, Day 7, Day 28, Day 56, Day 70, Day 84, Day 112 and Day 140) vital signs,(Day-14, Day 1, Day 28, Day 56, Day 84, day 112 and Day 140) electrocardiograms (ECGs) (Day -14, Day 3)and clinical laboratory values (Day -14, Day1, Day 3, Day 7, Day 28, Day 56, Day 70, Day 84, Day 112 and Day 140) ;Timepoint(s) of evaluation of this end point: Day1, Day 3, Day 7, Day 28, Day 56, Day 70, Day 84, Day 112 and Day 140. | — |
Countries
Estonia, Germany, United States
Contacts
Public ContactClinical Trials Helpdesk
GlaxoSmithKline
Outcome results
None listed