GSK3772847, an anti-interleukin (IL) 33-receptor monoclonal antibody, is a novel treatment for asthma. The purpose of this study to evaluate the safety and tolerability, PK and PD of single ascending doses of GSK3772847 administered subcutaneously (SC) to healthy participants. This study will also establish the bioavailability of SC formulation and evaluate the safety in particular injection site tolerability of route. Participants will either receive a single dose of 70 milligram (mg) GSK3772847 or placebo in (Cohort 1) and 140 mg GSK3772847 or placebo in Cohorts 2, 3 (Japanese participants) and 4 (Chinese participants). The site of injection will be upper arm; abdomen or thigh for cohorts 1 and 2 with cohorts 3 and 4 will receive injections in the upper arm only. Approximately, the total duration of study will be up to 89 days.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
65
melrilimab (GSK3772837) will be available at a dose strength of 70 milligram per milliliter (mg/mL) in a 3 milliliter (mL) glass vial.
Two doses of melrilimab (GSK3772837) 70 milligram per milliliter (mg/mL) will be administered to achieve a dose strength of 140 milligram per milliliter (mg/mL)
Placebo to match melrilimab (GSK3772847) will be available in the form of solution for injection in a 3 milliliter (mL) glass vial.
GSK Investigational Site
Anaheim, California, United States
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. A SAE is defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, and other situations which involve medical or scientific judgment.
Time frame: Up to Day 85
Area Under the Plasma Concentration Time Curve From 0 to t (AUC[0-t]) of GSK3772847
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3772847. Pharmacokinetic Population consisted of all randomized participants who received at least one dose of study treatment, and for whom at least one pharmacokinetic sample was obtained, analyzed and measurable.
Time frame: Day 1: Pre-dose, 2, 4, 8 hours post-dose; Days 2, 3, 4, 5, 6, 9, 15, 29, 43, 57, 71 and 85
Area Under the Plasma Concentration Time Curve From Time Zero to Infinity (AUC[0-infinity]) of GSK3772847
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3772847.
Time frame: Day 1: Pre-dose, 2, 4, 8 hours post-dose; Days 2, 3, 4, 5, 6, 9, 15, 29, 43, 57, 71 and 85
Maximum Observed Plasma Concentration (Cmax) of GSK3772847
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3772847.
Time frame: Day 1: Pre-dose, 2, 4, 8 hours post-dose; Days 2, 3, 4, 5, 6, 9, 15, 29, 43, 57, 71 and 85
Time to Cmax (Tmax) of GSK3772847
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3772847.
Time frame: Day 1: Pre-dose, 2, 4, 8 hours post-dose; Days 2, 3, 4, 5, 6, 9, 15, 29, 43, 57, 71 and 85
Apparent Terminal Half-life (t1/2) of GSK3772847
Blood samples were collected at indicated time points for pharmacokinetic analysis of GSK3772847.
Time frame: Day 1: Pre-dose, 2, 4, 8 hours post-dose; Days 2, 3, 4, 5, 6, 9, 15, 29, 43, 57, 71 and 85
Maximal Decrease in Ratio to Baseline in Free Soluble Suppressor of Tumorigenicity 2 (ST2) Concentration
Blood samples were collected to measure free soluble ST2 concentration. Maximal decrease from Baseline was the largest decrease calculated across all time points post dose. Ratio to Baseline is defined as post-dose visit value divided by Baseline value. Baseline was the most recent recorded value before dosing on Day 1 (Pre-dose). Pharmacodynamic Population consisted of all randomized participants who received at least one dose of study treatment, and for whom at least one pharmacokinetic sample was obtained, analyzed and measurable.
Time frame: Baseline and up to Day 85/early withdrawal
Maximal Increase in Ratio to Baseline in Total Soluble ST2 Concentration
Blood samples were collected to measure total soluble ST2 concentration. Maximal increase from Baseline was the largest increase calculated across all timepoints post dose. Ratio to Baseline is defined as post-dose visit value divided by Baseline value. Baseline was the most recent recorded value before dosing on Day 1 (Pre-dose).
Time frame: Baseline and up to Day 85/early withdrawal
Number of Participants With Confirmed Positive Anti-GSK3772847 Antibodies
Serum samples were collected at indicated time points and analyzed for the presence of anti-GSK3772847 antibodies using a tiered approach including a screening assay, a confirmation assay and calculation of titer.
Time frame: Days 1, 15, 29, 57 and 85/early withdrawal
Ratio to Baseline in Plasma 4 Beta-hydroxy (4BetaOH) Cholesterol/Cholesterol
Blood samples were collected at indicated time points to measure 4BetaOH cholesterol/cholesterol. Ratio to Baseline is defined as post-dose visit value divided by Baseline value. Baseline value was the latest pre-dose assessment (Day 1 Pre-dose).
Time frame: Baseline, Days 5, 15, 29 and 85/early withdrawal
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