FRI0116 Pharmacokinetic Results from a Phase 1, Single-Centre, Double-Blind, Randomised, Single-Dose, Parallel Group Study Comparing 5 MG/KG IV Infusion of BOW015 and Reference Infliximab in Healthy Male Volunteers

BackgroundBOW015 is an IgG1 monoclonal antibody that binds to TNFα, which is being developed as a biosimilar to reference infliximab (rIFX, Remicade®). Preclinical studies demonstrate statistically significant dose-dependent suppression of synovitis in a murine transgenic arthritis model, with BOW015 and rIFX treatment each producing similar inhibition of joint inflammation. This clinical trial is the first-in-human study of BOW015.ObjectivesTo compare the pharmacokinetics (PK), safety and immunogenicity of BOW015 to rIFX in healthy Caucasian male volunteers.MethodsEighty-four subjects were randomised to receive BOW015 or rIFX. A single 5 mg/kg IV infusion was administered over 2 hours to 43 subjects in the BOW015 group and 41 subjects in the rIFX group in a hospital-based clinical research unit. Subjects were discharged 2 days after the infusion and returned the next day for follow-up and then at 1, 2, 3, 5, 7, 9, and 12 weeks after the infusion. The treatments were compared using analysis of covariance for the PK parameters Cmax, AUC(0-t), and AUC(0-inf). The criterion for PK bioequivalence was that the 90% confidence intervals (CIs) for the geometric mean ratios were contained within the range 0.80 to 1.25.ResultsStudy subjects ranged in age from 18 to 45 years with body weight between 60 to 90 kg and body mass index between 19 and 27 kg/m2. Geometric mean Cmax was 142.47 μg/mL following BOW015 infusion and 126.74 μg/mL following rIFX infusion. Geometric mean AUC(0-t) was 36,211 h.μg/mL and 34,304 h.μg/mL, and geometric mean AUC(0-inf) was 36,775 and 34,801 h.μg/mL following BOW015 and rIFX infusions, respectively. Bioequivalence was demonstrated, with 90% CIs for the treatment mean ratios of 1.07 to 1.18 for Cmax, 0.98 to 1.14 for AUC(0-t), and 0.98 to 1.15 for AUC(0-inf). Apparent terminal phase half-life was similar for BOW015 (307.96 hours) and rIFX (280.22 hours). The range and median of time to peak concentration (tmax) was also similar for BOW015 (range: 2.00–8.00 hours) and rIFX (range: 2.00–12.02 hours). The median tmax for BOW015 (3.97 hours) and for rIFX (2.05 hours) was not clinically significant and may have resulted from the 2-hour interval between samples and relatively slow drug elimination. Twenty six subjects (60.5%) in the BOW015 group reported 50 treatment-emergent adverse events (TEAEs) and 27 subjects (65.9%) in the rIFX group reported 54 TEAEs. No TEAE resulted in withdrawal from the study. At Week 12, 2 subjects in the rIFX group