This is a 12-week, randomized, double-blind, single-dose pharmacokinetic (PK) study. Approximately 114 healthy male participants (screening occurred within 28 days prior to dosing) will be randomized 1:1:1 to either TRS003, China-approved bevacizumab, and US-licensed Avastin® groups. Study drug will be dispensed as a single 3 mg/kg dose for intravenous infusion within 90 minutes. PK and immunogenicity samples will be collected and safety will be assessed. The primary objective of this study was to demonstrate pharmacokinetic similarity between TRS003, China-approved bevacizumab and US-licensed Avastin®, as measured by AUC0-inf in healthy male participants after a single 3 mg/kg dose.
The primary assessment of PK similarity will be based upon a 90 percentage confidence interval (CI) for the ratio of the geometric means (TRS003, China-approved bevacizumab and US-licensed Avastin®) for AUC0-inf on PK analysis set. If the 90 percentage CI of the ratio of the geometric means for AUC0-inf is within the range of 80-125 percentage, then PK similarity will be concluded. Secondary PK parameters such as but not limited to Cmax, AUClast will be analyzed using the same statistical approach. A nonparametric approach, for example, Wilcoxon signed-rank test, will be taken to evaluate parameters such as t1/2. Exploratory analyses may be performed for other PK parameters as deemed appropriate. All adverse events (AEs) will be listed and summarized using descriptive methodology. The incidence of AEs for each treatment will be presented by severity and association with the study drugs. Clinical laboratory parameters, vital signs, and electrocardiogram (ECG) parameters will be listed and summarized using descriptive statistics. The number and percentage of participants testing positive for anti-drug antibodies (ADAs) will be summarized by treatment and time point.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
DOUBLE
Enrollment
114
25mg/mL (4 mL/vial) Injection,Single dose of 3mg/kg Intravenous infusion for 90 minutes
25mg/mL (4 mL/vial) Injection,Single dose of 3mg/kg Intravenous infusion for 90 minutes
25mg/mL (4 mL/vial) Injection,Single dose of 3mg/kg Intravenous infusion for 90 minutes
WCCT Global, Inc.
Cypress, California, United States
AUC0-inf,Area Under the Serum Concentration Versus Time Curve,Time 0 to Infinity
The primary assessment of PK similarity will be based upon a 90 percentage CI for the ratio of the geometric means (TRS003, China-approved bevacizumab and US-licensed Avastin®) for AUC0-inf on PK analysis set. If the 90 percentage CI of the ratio of the geometric means for AUC0-inf is within the range of 80-125 percentage, then PK similarity will be concluded.
Time frame: Pre-dose, 0 hour (End of infusion, EOI), 0.5 hour, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours, 336 hours, 672 hours, 1008 hours, 1344 hours, 1680 hours, and 2016 hours post EOI
Cmax, Maximum Drug Concentration
To assess other PK parameters such as Cmax, following a single dose of TRS003, China-approved bevacizumab and US-licensed Avastin® in healthy male participants. If the 90 percentage CI of the ratio of the geometric means for Cmax is within the range of 80-125 percentage, then PK similarity will be concluded.
Time frame: Pre-dose, 0 hour (End of infusion, EOI), 0.5 hour, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours, 336 hours, 672 hours, 1008 hours, 1344 hours, 1680 hours, and 2016 hours post EOI
AUC0-last, Area Under the Serum Concentration-time Curve,Time 0 to Last
To assess other PK parameters such as AUClast, following a single dose of TRS003, China-approved bevacizumab and US-licensed Avastin® in healthy male participants. If the 90 percentage CI of the ratio of the geometric means for AUC0-last is within the range of 80-125 percentage, then PK similarity will be concluded.
Time frame: Pre-dose, 0 hour (End of infusion, EOI), 0.5 hour, 4 hours, 8 hours, 24 hours, 48 hours, 96 hours, 168 hours, 336 hours, 672 hours, 1008 hours, 1344 hours, 1680 hours, and 2016 hours post EOI
Number of Participants Who Develop Detectable Anti-drug Antibody (ADA)
To determine the number of participants with immunogenicity against TRS003, China-approved bevacizumab, and US-licensed Avastin® in healthy male participants, blood samples will be collected for ADA analyses.
Time frame: Pre-dose, 336 hours, 672 hours, 1344 hours and 2016 hours after EOI (End of infusion)
Number of Participants With Adverse Events (AEs)
Adverse events will be classified using the MedDRA classification system. The severity of the toxicities will be graded according to the NCI CTCAE version 4.03.
Time frame: Within 85 days following the drug administration
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.