Novel Long-Acting Ropeginterferon Alfa-2b: Pharmacokinetics,
Pharmacodynamics, and Safety in a Phase I Clinical Trial
Abstract
AIM Ropeginterferon alfa-2b is a new site-specific conjugated 40 kDa
branched polyethylene-glycol recombinant interferon (IFN). The aim of
the study was to determine its safety, pharmacokinetics (PK) and
pharmacodynamic (PD). METHODS Ropeginterferon alfa-2b was evaluated
first in human in 48 healthy male volunteers after a single dose
subcutaneous injection by either 24, 48, 90, 180, 225, 270mcg of the
product or 180mcg of marketed pegylated (peg)-IFN alfa-2a. Within each
dosing group, 6 subjects received ropeginterferon alfa-2b and 2 subjects
received peg-IFN alfa-2a. RESULTS Dose-related increases in
ropeginterferon alfa-2b PK parameters (Cmax, AUC, and AUC0-t) were
observed over the dose range 24 to 270mcg. The geometric mean values for
these PK parameters of ropeginterferon alfa-2b were higher than that of
peg-IFN alfa-2a at the 180mcg dose level of 176%, 166%, and 182%,
respectively. Mean PD parameters (Emax, Tmax, and AUC0-t) for
ropeginterferon alfa-2b increased with dose for both biomarkers
neopterin and 2’, 5’-OAS. Ropeginterferon alfa-2b has similar PD
profiles as peg-IFN alfa-2a. The treatment related adverse events are
similar between the two study drugs, but the overall incidence was
numerically lower for ropeginterferon alfa-2b (83%) than peg-IFN
alfa-2a (100%) at the 180mcg dose level. CONCLUSIONS Single
subcutaneous dose of Ropeginterferon alfa-2b of up to 270mcg is safe and
well tolerated. It displays dose related increase in PK and PD
parameters, potentially less frequent injection, and better safety
profiles. Ropeginterferon alfa-2b is being developed for diseases in
which previous peg-IFN use has been limited by side effects.