GSK2800528 is being developed as a human anti-tumor necrosis factor (TNF) alpha monoclonal antibody (mAb) for the treatment of immune-inflammatory diseases. The study will be conducted in healthy volunteers and divided into 4 cohorts. Cohorts 1 to 3 will consist of groups of 12 subjects, 9 on active treatment (GSK2800528), and 3 on placebo. Cohort 4 will consist of a group of 9 subjects, all on active treatment (adalimumab).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
45
Drug will be administered at 3 different dose levels by subcutaneous injection.
Subcutaneous injection of. 0.8 mL solution will be administered
Subcutaneous injection of 0.8 mL solution will be administered (40mg)
GSK Investigational Site
London, United Kingdom
Apparent systemic clearance (CL/F) of GSK2800528
Time frame: Up to Day 196
Apparent systemic clearance (CL/F) of adalimumab
Time frame: Up to Day 140
Adverse event (AE) and Serious Adverse event (SAE) reporting
An AE is any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, is associated with liver injury and impaired liver function.
Time frame: Up to Day 196
Laboratory safety assessment for clinical chemistry parameters
Safety data for laboratory clinical chemistry parameters including albumin, creatinine, glucose, sodium, potassium, chloride, calcium, total protein, aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), alkaline phosphatise, total and direct bilirubin, and uric acid will be assessed
Time frame: Up to Day 196
Laboratory safety assessment for hematology parameters
Safety data for laboratory hematology parameters including platelet count, red blood cell (RBC) count, absolute white blood cell (WBC) count, reticulocyte count, hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular haemoglobin concentration (MCHC), mean corpuscular haemoglobin (MCH), neutrophils, lymphocytes, monocytes, eosinophils, and basophils will be assessed.
Time frame: Up to Day 196
Laboratory safety assessment for urinalysis parameters
Safety data for laboratory urinalysis parameters including specific gravity, pH, glucose, protein, blood and ketones by dipstick , and microscopic examination will be assessed
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Time frame: Up to Day 196
Vital signs monitoring (blood pressure, heart rate, body temperature)
Safety data for vital signs including blood pressure, heart rate, and body temperature will be measured
Time frame: Up to Day 196
Electrocardiogram (ECG) monitoring
Supine 12-lead ECG data will be monitored
Time frame: Up to Day 196
Plasma concentrations of GSK2800528 and derived pharmacokinetic parameters other than CL/F
Blood samples for PK analysis of GSK2800528 will be collected to assess plasma concentration and derived PK parameters including maximum observed plasma concentration (Cmax), time to Cmax (tmax), area under the plasma concentration time curve \[AUC(0-t) and AUC(0-infinity)\], and apparent terminal phase half-life (t1/2)
Time frame: Up to Day 196
Plasma concentrations of adalimumab and derived pharmacokinetic parameters other than CL/F
Blood samples for PK analysis of adalimumab will be collected to assess plasma concentration and derived PK parameters including Cmax, tmax, AUC(0-t) and AUC(0-infinity), and t1/2
Time frame: Up to Day 140
Incidence, titers, and specificity of anti-GSK2800528 antibodies.
Time frame: Up to Day 196
Incidence, titers, and specificity of anti-adalimumab antibodies
Time frame: Up to Day 140
Neutralising activity for samples with confirmed anti-drug antibodies
Time frame: Up to Day 196