Novel Controlled-Release Lemna-Derived IFN- alpha 2b (Locteron): Pharmacokinetics, Pharmacodynamics, and Tolerability in a Phase I Clinical Trial
Locteron, a newly developed controlled-release formulation of Lemna-derived free (unpegylated) recombinant interferon- alpha 2b (IFN- alpha 2b, Biolex Therapeutics, Pittsboro, NC) in poly(ether-ester) microspheres (Poly-Active, OctoPlus N.V., Leiden, the Netherlands), was evaluated in 27 volunteers...
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Published in | Journal of interferon & cytokine research Vol. 28; no. 2; pp. 113 - 122 |
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Main Authors | , , , , , |
Format | Journal Article |
Language | English |
Published |
01.02.2008
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Online Access | Get full text |
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Summary: | Locteron, a newly developed controlled-release formulation of Lemna-derived free (unpegylated) recombinant interferon- alpha 2b (IFN- alpha 2b, Biolex Therapeutics, Pittsboro, NC) in poly(ether-ester) microspheres (Poly-Active, OctoPlus N.V., Leiden, the Netherlands), was evaluated in 27 volunteers injected with either 20, 80, or 320 mu g Locteron (equivalent to 6.25, 25, or 100 X 10 super(6) IU, respectively), 80 mu g pegylated IFN- alpha 2b (PEG-IFN- alpha 2b), microspheres not containing IFN- alpha 2b, or placebo. Serum free or PEG-IFN- alpha 2b and two biomarkers of IFN activity, neopterin and 2',5'-oligoadenylate synthetase (2',5'-OAS), were measured. After injection of 320 mu g Locteron, serum IFN- alpha 2b remained elevated through 14 days. The elimination half-life of Locteron was more than 2-fold that of PEG-IFN- alpha 2b. The effects of 80 mu g Locteron and 80 mu g PEG-IFN- alpha 2b 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 mu g Locteron compared with 7 days after 80 mu g PEG-IFN- alpha 2b. Mild, moderate, or severe influenza-like symptoms developed in all 6 subjects receiving 80 mu g PEG-IFN- alpha 2b. No such symptoms occurred after 20 or 80 mu g Locteron doses. Among the 4 recipients of 320 mu g 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1079-9907 |
DOI: | 10.1089/jir.2007.0073 |