Safety and prolonged activity of recombinant factor VIII Fc fusion protein in hemophilia A patients
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- Jerry S. Powell
- University of California, Davis, Sacramento, CA;
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- Neil C. Josephson
- Puget Sound Blood Center, Seattle, WA;
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- Doris Quon
- Orthopedic Hospital of Los Angeles, Los Angeles, CA;
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- Margaret V. Ragni
- University of Pittsburgh, Pittsburgh, PA;
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- Gregory Cheng
- Prince of Wales Hospital, Shatin, Hong Kong;
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- Ella Li
- Biogen Idec Inc, Cambridge, MA; and
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- Haiyan Jiang
- Biogen Idec Hemophilia Inc, Weston, MA
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- Lian Li
- Biogen Idec Hemophilia Inc, Weston, MA
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- Jennifer A. Dumont
- Biogen Idec Hemophilia Inc, Weston, MA
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- Jaya Goyal
- Biogen Idec Inc, Cambridge, MA; and
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- Xin Zhang
- Biogen Idec Hemophilia Inc, Weston, MA
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- Jurg Sommer
- Biogen Idec Hemophilia Inc, Weston, MA
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- Justin McCue
- Biogen Idec Inc, Cambridge, MA; and
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- Margaret Barbetti
- Biogen Idec Hemophilia Inc, Weston, MA
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- Alvin Luk
- Biogen Idec Hemophilia Inc, Weston, MA
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- Glenn F. Pierce
- Biogen Idec Hemophilia Inc, Weston, MA
書誌事項
- 公開日
- 2012-03-29
- DOI
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- 10.1182/blood-2011-09-382846
- 公開者
- American Society of Hematology
この論文をさがす
説明
<jats:title>Abstract</jats:title> <jats:p>Current factor VIII (FVIII) products display a half-life (t1/2) of ∼ 8-12 hours, requiring frequent intravenous injections for prophylaxis and treatment of patients with hemophilia A. rFVIIIFc is a recombinant fusion protein composed of a single molecule of FVIII covalently linked to the Fc domain of human IgG1 to extend circulating rFVIII t1/2. This first-in-human study in previously treated subjects with severe hemophilia A investigated safety and pharmacokinetics of rFVIIIFc. Sixteen subjects received a single dose of rFVIII at 25 or 65 IU/kg followed by an equal dose of rFVIIIFc. Most adverse events were unrelated to study drug. None of the study subjects developed anti-rFVIIIFc antibodies or inhibitors. Across dose levels, compared with rFVIII, rFVIIIFc showed 1.54- to 1.70-fold longer elimination t1/2, 1.49- to 1.56-fold lower clearance, and 1.48- to 1.56-fold higher total systemic exposure. rFVIII and rFVIIIFc had comparable dose-dependent peak plasma concentrations and recoveries. Time to 1% FVIII activity above baseline was ∼ 1.53- to 1.68-fold longer than rFVIII across dose levels. Each subject showed prolonged exposure to rFVIIIFc relative to rFVIII. Thus, rFVIIIFc may offer a viable therapeutic approach to achieve prolonged hemostatic protection and less frequent dosing in patients with hemophilia A. This trial was registered at www.clinicaltrials.gov as NCT01027377.</jats:p>
収録刊行物
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- Blood
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Blood 119 (13), 3031-3037, 2012-03-29
American Society of Hematology