Novel long-acting ropeginterferon alfa-2b: Pharmacokinetics, pharmacodynamics and safety in a phase I clinical trial

Aims Ropeginterferon alfa-2b is a novel, long-acting pegylated interferon alfa-2b. We aimed to evaluate its safety, pharmacokinetics (PK) and pharmacodynamics (PD). Methods Thirty-six subjects received single subcutaneous injection of ropeginterferon alfa-2b at doses ranging from 24 to 270 mu g, and 12 subjects received pegylated IFN alfa-2a subcutaneously at 180 mu g. Primary endpoints were safety/PK profiles of ropeginterferon alfa-2b, while secondary endpoints were to compare PK/PD parameters with pegylated IFN alfa-2a. Results Adverse events in ropeginterferon alfa-2b and pegylated IFN alfa-2a groups were similar, and most of them were mild or moderate. Mean C-max increased from 1.78 to 24.84 ng/mL along with the dose escalations in ropeginterferon alfa-2b groups and was 12.95 ng/mL for pegylated IFN alfa-2a. At 180 mu g, ropeginterferon alfa-2b showed statistically significant C-max geometric mean ratio (1.76; P = .0275). Mean T-max ranged from 74.52 to 115.69 h for ropeginterferon alfa-2b groups, and was 84.25 h for pegylated IFN alfa-2a. Mean AUC(0-t) increased from 372.3 to 6258 ng center dot h/mL with the dose escalations in the ropeginterferon alfa-2b groups, while for pegylated IFN alfa-2a it was found to be 2706 ng center dot h/mL in pegylated IFN alfa-2a. For neopterin and 2 ',5 '-oligoadenylate synthase, mean E-max, T-max and AUC(0-t) of ropeginterferon alfa-2b were similar to those of pegylated IFN alpha-2a at 180 mu g. Conclusion Ropeginterferon alfa-2b up to 270 mu g was safe and well tolerated. The PK/PD parameters of ropeginterferon alfa-2b showed increase in dose-response. Ropeginterferon alfa-2b had higher drug exposures and showed similar safety profile when compared to pegylated IFN alfa-2a at the same dose level.