A randomized controlled dose-escalation study of SSS07, a humanized rabbit anti-human TNF alpha antibody, in healthy Chinese adults.

AIMS:SSS07 is a rabbit derived humanized anti-human TNF-α antibody. This study aimed to explore the pharmacokinetics, safety, and immunogenicity of SSS07 when administrated subcutaneously in healthy adults. METHODS:This was a double-blind, dose-escalation study of SSS07 in 71 adults. Dose cohorts were set to 5 mg, 15 mg, 30 mg, 50 mg, 75 mg, and 100 mg. In each dosage group, other than 100 mg, twelve healthy participants were randomly assigned to receive a single dose of SSS07 (n = 10) or placebo (n = 2). Blood samples were taken for pharmacokinetics and immunogenicity analysis. RESULTS:No deaths, serious adverse events or drug-related withdrawals occurred in this trial. No drug limited toxicity appeared. After subcutaneous injection, SSS07 was absorbed slowly with Tmax ranging from 60 to 264 h but eliminated quickly with a short half-life ranging from 21.69 to 78.4 h (1-3 days). From 5 mg to 100 mg, dose-exposure proportionality analysis found a 90% confidence interval (CI) of β of Cmax (1.015-1.193), AUC0-t (1.096-1.263) and AUC0-∞ (0.999-1.174) partially within the range 0.926-1.074. The plasma concentration of TNF-α decreased significantly post-dose, but a few days later, levels of TNF-α elevated rapidly and exceeded its baseline value. All participants receiving SSS07 were found to be anti-drug antibody positive during the study. CONCLUSIONS:A single-dose injection of SSS07 was safe and well-tolerated in healthy adults. Doses of SSS07 from 5 mg to 100 mg could not be regarded as nonlinear, based on dose-exposure proportionality analysis. A high incidence of anti-drug antibodies indicated strong immunogenicity, which may influence the pharmacokinetics profile and interfere with the TNF-α inhibition capability of SSS07.