GSK2330811 is a humanised monoclonal antibody, that blocks Oncostatin M (OSM), which is being developed for the treatment of inflammatory and fibrotic diseases. This first time in human study will evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD) and immunogenicity profile of single ascending subcutaneous (s.c.) doses of GSK2330811, in healthy subjects. This study will be a randomised, double-blind (sponsor open), placebo-controlled, single centre, single dose escalation study of s.c. administrations of GSK2330811 in healthy subjects. Approximately 40 subjects will be enrolled in the study, across 5 cohorts. Each cohort is planned to consist of 8 subjects, randomised such that 6 subjects will receive GSK2330811 and 2 subjects will receive placebo. The starting dose for the study will be 0.1 milligram (mg)/kilogram (kg) s.c. single dose and the highest dose will be 6 mg/kg s.c. single dose. Subjects will be admitted to the clinical unit on the day prior to dosing (Day -1). On Day 1, each subject will receive a s.c. dose of GSK2330811 or placebo. Subjects will then remain as an in-patient until discharged on Day 8, after assessments have been performed. The duration of the study, including screening, is approximately 19 weeks for Cohorts 1 to 4 and 23 weeks for Cohort 5.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
41
GSK2330811 will be supplied as clear or opalescent, colourless, yellow to brown liquid administered as single dose s.c.
Placebo will be supplied as Normal Saline (0.9% weight by volume \[w/v\] Sodium Chloride) administered as single dose s.c.
GSK Investigational Site
Cambridge, United Kingdom
Safety and tolerability as assessed by number of subjects with adverse event (AEs) and serious adverse events (SAEs)
Time frame: From Day 1 up to Day 105 (For Cohort 5 up to Day 133)
Safety and tolerability as assessed by composite of clinical laboratory tests: clinical chemistry, hematology and urinalysis
Clinical laboratory tests will include clinical chemistry, hematology and urinalysis.
Time frame: From Day 1 up to Day 105(For Cohort 5 up to Day 133)
Safety and tolerability as assessed by composite of vital signs assessment: blood pressure, heart rate and temperature
Vital signs assessment including systolic and diastolic blood pressure, heart rate and body temperature.
Time frame: From Day 1 up to Day 105 (For Cohort 5 up to Day 133)
Safety as assessed by electrocardiogram (ECG) measurements
ECGs will be measured in the semi-supine position. Triplicate 12-lead ECGs will be recorded at screening, Day 1 pre-dose and Day 5 and single 12-lead ECGs at all other time points.
Time frame: From Day 1 up to Day 105
Composite PK parameters including Cmax, AUC, t1/2 and Vss/F after single s.c. doses of GSK2330811 in healthy subjects
PK parameters will include maximum observed concentration (Cmax), area under concentration-time curve (AUC), terminal phase half-life (t1/2), and Steady State Volume of Distribution / Bioavailability (Vss/F)
Time frame: Samples will be collected at pre-dose and at 8 hours post dose on Day 1 and single sample on Day 2, Day 3, Day 5, Day 7, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 84, Day 105 and Day 133
Plasma concentrations of GSK2330811
Plasma concentration of GSK2330811 will be determined from blood samples collected at various time points indicated in timeframe.
Time frame: Samples will be collected at pre-dose, and at 8 hours post dose on Day 1 and single sample on Day 2, Day 3, Day 5, Day 7, Day 10, Day 14, Day 21, Day 28, Day 42, Day 56, Day 84, Day 105 and Day 133
Incidence, specificity and titers of anti-GSK2330811 antibodies
Serum samples from 4 millilitre (mL) of whole blood will be collected to evaluate incidence, specificity and titers of anti-GSK2330811 antibodies
Time frame: Samples will be collected at pre-dose, Day 14, Day 28 and Day 105.
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