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Long-Term Safety of PEGylated Coagulation Factor VIII in the Immune-Deficient Rowett Nude Rat
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| Zeitschriftentitel: | Journal of Toxicology |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , |
| In: | Journal of Toxicology, 2017, 2017, S. 1-13 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Hindawi Limited
|
| Schlagwörter: |
| author_facet |
Rasmussen, Caroline E. Nowak, Jette Larsen, Julie M. Moore, Emma Bell, David Liu, Kai Chiu Sorensen, Nanna Skall Kappers, Wendela A. Krogh-Meibom, Thomas Offenberg, Hanne Rasmussen, Caroline E. Nowak, Jette Larsen, Julie M. Moore, Emma Bell, David Liu, Kai Chiu Sorensen, Nanna Skall Kappers, Wendela A. Krogh-Meibom, Thomas Offenberg, Hanne |
|---|---|
| author |
Rasmussen, Caroline E. Nowak, Jette Larsen, Julie M. Moore, Emma Bell, David Liu, Kai Chiu Sorensen, Nanna Skall Kappers, Wendela A. Krogh-Meibom, Thomas Offenberg, Hanne |
| spellingShingle |
Rasmussen, Caroline E. Nowak, Jette Larsen, Julie M. Moore, Emma Bell, David Liu, Kai Chiu Sorensen, Nanna Skall Kappers, Wendela A. Krogh-Meibom, Thomas Offenberg, Hanne Journal of Toxicology Long-Term Safety of PEGylated Coagulation Factor VIII in the Immune-Deficient Rowett Nude Rat Pharmacology Toxicology |
| author_sort |
rasmussen, caroline e. |
| spelling |
Rasmussen, Caroline E. Nowak, Jette Larsen, Julie M. Moore, Emma Bell, David Liu, Kai Chiu Sorensen, Nanna Skall Kappers, Wendela A. Krogh-Meibom, Thomas Offenberg, Hanne 1687-8191 1687-8205 Hindawi Limited Pharmacology Toxicology http://dx.doi.org/10.1155/2017/8496246 <jats:p>Turoctocog alfa pegol (N8-GP) is a glycoPEGylated human recombinant factor VIII for the treatment of hemophilia A. The safety profile of rFVIII, and polyethylene glycols (PEG) technology, is well-established. Conducting long-term toxicity studies in animals using human proteins can be complicated by anti-drug antibody (ADA) development. To evaluate long-term safety of N8-GP, 26- and 52-week toxicity studies were conducted in immune-deficient rats dosed intravenously every fourth day with 0, 50, 150, 500, or 1200 IU/kg N8-GP. Observations included clinical observations, body weight, ophthalmoscopy, hematology, chemistry, coagulation, urinalysis, toxicokinetics, antibody analysis, and macroscopic/microscopic organ examination. Immunohistochemical staining examined the distribution of PEG in the brain. No adverse test item-related findings were seen and PEG was not detected in the brain. Exposure was confirmed for ~75% of the animals dosed with 500 and 1200 IU/kg N8-GP; the high lower limit of quantification of the bioanalysis assay prevented confirmation of exposure in the lower doses. A small number of animals developed ADAs, and the proportion of animals surviving until scheduled termination was >80%. N8-GP was well tolerated, and the immune-deficient rat proved suitable for testing long-term toxicity of human proteins that are immunogenic in animals.</jats:p> Long-Term Safety of PEGylated Coagulation Factor VIII in the Immune-Deficient Rowett Nude Rat Journal of Toxicology |
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| title |
Long-Term Safety of PEGylated Coagulation Factor VIII in the Immune-Deficient Rowett Nude Rat |
| title_unstemmed |
Long-Term Safety of PEGylated Coagulation Factor VIII in the Immune-Deficient Rowett Nude Rat |
| title_full |
Long-Term Safety of PEGylated Coagulation Factor VIII in the Immune-Deficient Rowett Nude Rat |
| title_fullStr |
Long-Term Safety of PEGylated Coagulation Factor VIII in the Immune-Deficient Rowett Nude Rat |
| title_full_unstemmed |
Long-Term Safety of PEGylated Coagulation Factor VIII in the Immune-Deficient Rowett Nude Rat |
| title_short |
Long-Term Safety of PEGylated Coagulation Factor VIII in the Immune-Deficient Rowett Nude Rat |
| title_sort |
long-term safety of pegylated coagulation factor viii in the immune-deficient rowett nude rat |
| topic |
Pharmacology Toxicology |
| url |
http://dx.doi.org/10.1155/2017/8496246 |
| publishDate |
2017 |
| physical |
1-13 |
| description |
<jats:p>Turoctocog alfa pegol (N8-GP) is a glycoPEGylated human recombinant factor VIII for the treatment of hemophilia A. The safety profile of rFVIII, and polyethylene glycols (PEG) technology, is well-established. Conducting long-term toxicity studies in animals using human proteins can be complicated by anti-drug antibody (ADA) development. To evaluate long-term safety of N8-GP, 26- and 52-week toxicity studies were conducted in immune-deficient rats dosed intravenously every fourth day with 0, 50, 150, 500, or 1200 IU/kg N8-GP. Observations included clinical observations, body weight, ophthalmoscopy, hematology, chemistry, coagulation, urinalysis, toxicokinetics, antibody analysis, and macroscopic/microscopic organ examination. Immunohistochemical staining examined the distribution of PEG in the brain. No adverse test item-related findings were seen and PEG was not detected in the brain. Exposure was confirmed for ~75% of the animals dosed with 500 and 1200 IU/kg N8-GP; the high lower limit of quantification of the bioanalysis assay prevented confirmation of exposure in the lower doses. A small number of animals developed ADAs, and the proportion of animals surviving until scheduled termination was >80%. N8-GP was well tolerated, and the immune-deficient rat proved suitable for testing long-term toxicity of human proteins that are immunogenic in animals.</jats:p> |
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| author | Rasmussen, Caroline E., Nowak, Jette, Larsen, Julie M., Moore, Emma, Bell, David, Liu, Kai Chiu, Sorensen, Nanna Skall, Kappers, Wendela A., Krogh-Meibom, Thomas, Offenberg, Hanne |
| author_facet | Rasmussen, Caroline E., Nowak, Jette, Larsen, Julie M., Moore, Emma, Bell, David, Liu, Kai Chiu, Sorensen, Nanna Skall, Kappers, Wendela A., Krogh-Meibom, Thomas, Offenberg, Hanne, Rasmussen, Caroline E., Nowak, Jette, Larsen, Julie M., Moore, Emma, Bell, David, Liu, Kai Chiu, Sorensen, Nanna Skall, Kappers, Wendela A., Krogh-Meibom, Thomas, Offenberg, Hanne |
| author_sort | rasmussen, caroline e. |
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| description | <jats:p>Turoctocog alfa pegol (N8-GP) is a glycoPEGylated human recombinant factor VIII for the treatment of hemophilia A. The safety profile of rFVIII, and polyethylene glycols (PEG) technology, is well-established. Conducting long-term toxicity studies in animals using human proteins can be complicated by anti-drug antibody (ADA) development. To evaluate long-term safety of N8-GP, 26- and 52-week toxicity studies were conducted in immune-deficient rats dosed intravenously every fourth day with 0, 50, 150, 500, or 1200 IU/kg N8-GP. Observations included clinical observations, body weight, ophthalmoscopy, hematology, chemistry, coagulation, urinalysis, toxicokinetics, antibody analysis, and macroscopic/microscopic organ examination. Immunohistochemical staining examined the distribution of PEG in the brain. No adverse test item-related findings were seen and PEG was not detected in the brain. Exposure was confirmed for ~75% of the animals dosed with 500 and 1200 IU/kg N8-GP; the high lower limit of quantification of the bioanalysis assay prevented confirmation of exposure in the lower doses. A small number of animals developed ADAs, and the proportion of animals surviving until scheduled termination was >80%. N8-GP was well tolerated, and the immune-deficient rat proved suitable for testing long-term toxicity of human proteins that are immunogenic in animals.</jats:p> |
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| spelling | Rasmussen, Caroline E. Nowak, Jette Larsen, Julie M. Moore, Emma Bell, David Liu, Kai Chiu Sorensen, Nanna Skall Kappers, Wendela A. Krogh-Meibom, Thomas Offenberg, Hanne 1687-8191 1687-8205 Hindawi Limited Pharmacology Toxicology http://dx.doi.org/10.1155/2017/8496246 <jats:p>Turoctocog alfa pegol (N8-GP) is a glycoPEGylated human recombinant factor VIII for the treatment of hemophilia A. The safety profile of rFVIII, and polyethylene glycols (PEG) technology, is well-established. Conducting long-term toxicity studies in animals using human proteins can be complicated by anti-drug antibody (ADA) development. To evaluate long-term safety of N8-GP, 26- and 52-week toxicity studies were conducted in immune-deficient rats dosed intravenously every fourth day with 0, 50, 150, 500, or 1200 IU/kg N8-GP. Observations included clinical observations, body weight, ophthalmoscopy, hematology, chemistry, coagulation, urinalysis, toxicokinetics, antibody analysis, and macroscopic/microscopic organ examination. Immunohistochemical staining examined the distribution of PEG in the brain. No adverse test item-related findings were seen and PEG was not detected in the brain. Exposure was confirmed for ~75% of the animals dosed with 500 and 1200 IU/kg N8-GP; the high lower limit of quantification of the bioanalysis assay prevented confirmation of exposure in the lower doses. A small number of animals developed ADAs, and the proportion of animals surviving until scheduled termination was >80%. N8-GP was well tolerated, and the immune-deficient rat proved suitable for testing long-term toxicity of human proteins that are immunogenic in animals.</jats:p> Long-Term Safety of PEGylated Coagulation Factor VIII in the Immune-Deficient Rowett Nude Rat Journal of Toxicology |
| spellingShingle | Rasmussen, Caroline E., Nowak, Jette, Larsen, Julie M., Moore, Emma, Bell, David, Liu, Kai Chiu, Sorensen, Nanna Skall, Kappers, Wendela A., Krogh-Meibom, Thomas, Offenberg, Hanne, Journal of Toxicology, Long-Term Safety of PEGylated Coagulation Factor VIII in the Immune-Deficient Rowett Nude Rat, Pharmacology, Toxicology |
| title | Long-Term Safety of PEGylated Coagulation Factor VIII in the Immune-Deficient Rowett Nude Rat |
| title_full | Long-Term Safety of PEGylated Coagulation Factor VIII in the Immune-Deficient Rowett Nude Rat |
| title_fullStr | Long-Term Safety of PEGylated Coagulation Factor VIII in the Immune-Deficient Rowett Nude Rat |
| title_full_unstemmed | Long-Term Safety of PEGylated Coagulation Factor VIII in the Immune-Deficient Rowett Nude Rat |
| title_short | Long-Term Safety of PEGylated Coagulation Factor VIII in the Immune-Deficient Rowett Nude Rat |
| title_sort | long-term safety of pegylated coagulation factor viii in the immune-deficient rowett nude rat |
| title_unstemmed | Long-Term Safety of PEGylated Coagulation Factor VIII in the Immune-Deficient Rowett Nude Rat |
| topic | Pharmacology, Toxicology |
| url | http://dx.doi.org/10.1155/2017/8496246 |