An Open-Label, Single Ascending Dose Phase I Study of F-627, a G-CSF Dimer, In Healthy Male Subjects

Abstract 4722

The management of severe neutropenia in cancer patients after high-dose chemotherapy remains a challenge, although recombinant human G-CSFs including filgrastim, lengogratim and pegfilgrastim have been widely used. We developed F-627, a mammalian expressed recombinant human G-CSF dimer to treat severe neutropenia. In a cyclophosphamide-induced neutropenia monkey model, F-627 significantly reduced the duration and lessened the severity of neutropenia compared to monkeys treated with G-CSF or pegylated G-CSF. We report the phase I results of F-627 in healthy male subjects receiving ascending single dose at 30, 60, 120 and 240 ug/kg by subcutaneous injection. The primary objective of the phase I study was to assess the safety and tolerability of F-627. The secondary objective was to evaluate the pharmacokinetics and pharmacodynamics (PK/PD) responses. F-627 was well tolerated in healthy male volunteers. Dose-dependent PD responses including increased WBC, ANC and CD34 levels in peripheral blood were demonstrated. These results indicate that the mechanism of action of F-627 is similar to the monomer recombinant hG-CSFs, while the mode of action of F-627 is different with unique PK/PD properties in human.