title: Novel controlled-release Lemna-derived IFN-alpha2b (Locteron): pharmacokinetics, pharmacodynamics, and tolerability in a phase I clinical trial.
abstract: Locteron, a newly developed controlled-release formulation of Lemna-derived free (unpegylated) recombinant interferon-alpha2b (IFN-alpha2b, Biolex Therapeutics, Pittsboro, NC) in poly(ether-ester) microspheres (PolyActive, OctoPlus N.V., Leiden, the Netherlands), was evaluated in 27 volunteers injected with either 20, 80, or 320 microg Locteron (equivalent to 6.25, 25, or 100 x 10(6) IU, respectively), 80 microg pegylated IFN-alpha2b (PEG-IFN-alpha2b), microspheres not containing IFN-alpha2b, or placebo. Serum free or PEG-IFN-alpha2b and two biomarkers of IFN activity, neopterin and 2',5'-oligoadenylate synthetase (2',5'-OAS), were measured. After injection of 320 microg Locteron, serum IFN-alpha2b remained elevated through 14 days. The elimination half-life of Locteron was more than 2-fold that of PEG-IFN-alpha2b. The effects of 80 microg Locteron and 80 microg PEG-IFN-alpha2b on both neopterin and 2',5'-OAS were in a comparable range. Serum persistence of both these biomarkers was similar at 14 days after 320 microg Locteron compared with 7 days after 80 microg PEG-IFN-alpha2b. Mild, moderate, or severe influenza-like symptoms developed in all 6 subjects receiving 80 microg PEG-IFN-alpha2b. No such symptoms occurred after 20 or 80 microg Locteron doses. Among the 4 recipients of 320 microg Locteron, 1 experienced mild and 2 experienced moderate influenza-like symptoms. Locteron merits further clinical investigation as a hepatitis C therapy suitable for dosing once per 2 weeks.
authors.affiliation: OctoPlus N.V., Leiden, the Netherlands.
authors.forename: Leo G J
authors.initials: LG
authors.lastname: De Leede
authors.forename: John E
authors.initials: JE
authors.lastname: Humphries
authors.forename: Anne C
authors.initials: AC
authors.lastname: Bechet
authors.forename: Ewoud J
authors.initials: EJ
authors.lastname: Van Hoogdalem
authors.forename: Ruud
authors.initials: R
authors.lastname: Verrijk
authors.forename: David G
authors.initials: DG
authors.lastname: Spencer
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000097:blood; D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D015415:Biomarkers / Q000097:blood; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D006526:Hepatitis C / Q000188:drug therapy; D006801:Humans; D007267:Injections; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000493:pharmacokinetics; D007372:Interferons / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D008863:Microspheres; D008875:Middle Aged; D019798:Neopterin / Q000097:blood; D011092:Polyethylene Glycols; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D003692:Delayed-Action Preparations; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; C527994:locteron; D011092:Polyethylene Glycols; D019798:Neopterin; D007372:Interferons; D015088:2',5'-Oligoadenylate Synthetase; C417083:peginterferon alfa-2b