Novel long‐acting ropeginterferon alfa‐2b: Pharmacokinetics, pharmacodynamics and safety in a phase I clinical trial
Aims Ropeginterferon alfa‐2b is a novel, long‐acting pegylated interferon alfa‐2b. We aimed to evaluate its safety, pharmacokinetics (PK) and pharmacodynamics (PD). Methods Thirty‐six subjects received single subcutaneous injection of ropeginterferon alfa‐2b at doses ranging from 24 to 270 μg, and 1...
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Veröffentlicht in: | British journal of clinical pharmacology 2022-05, Vol.88 (5), p.2396-2407 |
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creator | Huang, Yi‐Wen Qin, Albert Fang, Jane Wang, Ting‐Fang Tsai, Chung‐Wei Lin, Ko‐Chung Teng, Ching‐Leou Larouche, Richard |
description | Aims
Ropeginterferon alfa‐2b is a novel, long‐acting pegylated interferon alfa‐2b. We aimed to evaluate its safety, pharmacokinetics (PK) and pharmacodynamics (PD).
Methods
Thirty‐six subjects received single subcutaneous injection of ropeginterferon alfa‐2b at doses ranging from 24 to 270 μg, and 12 subjects received pegylated IFN alfa‐2a subcutaneously at 180 μg. Primary endpoints were safety/PK profiles of ropeginterferon alfa‐2b, while secondary endpoints were to compare PK/PD parameters with pegylated IFN alfa‐2a.
Results
Adverse events in ropeginterferon alfa‐2b and pegylated IFN alfa‐2a groups were similar, and most of them were mild or moderate. Mean Cmax increased from 1.78 to 24.84 ng/mL along with the dose escalations in ropeginterferon alfa‐2b groups and was 12.95 ng/mL for pegylated IFN alfa‐2a. At 180 μg, ropeginterferon alfa‐2b showed statistically significant Cmax geometric mean ratio (1.76; P = .0275). Mean Tmax ranged from 74.52 to 115.69 h for ropeginterferon alfa‐2b groups, and was 84.25 h for pegylated IFN alfa‐2a. Mean AUC0‐t increased from 372.3 to 6258 ng•h/mL with the dose escalations in the ropeginterferon alfa‐2b groups, while for pegylated IFN alfa‐2a it was found to be 2706 ng•h/mL in pegylated IFN alfa‐2a. For neopterin and 2′,5′‐oligoadenylate synthase, mean Emax, Tmax and AUC0‐t of ropeginterferon alfa‐2b were similar to those of pegylated IFNα‐2a at 180 μg.
Conclusion
Ropeginterferon alfa‐2b up to 270 μg was safe and well tolerated. The PK/PD parameters of ropeginterferon alfa‐2b showed increase in dose–response. Ropeginterferon alfa‐2b had higher drug exposures and showed similar safety profile when compared to pegylated IFN alfa‐2a at the same dose level. |
doi_str_mv | 10.1111/bcp.15176 |
format | Article |
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Ropeginterferon alfa‐2b is a novel, long‐acting pegylated interferon alfa‐2b. We aimed to evaluate its safety, pharmacokinetics (PK) and pharmacodynamics (PD).
Methods
Thirty‐six subjects received single subcutaneous injection of ropeginterferon alfa‐2b at doses ranging from 24 to 270 μg, and 12 subjects received pegylated IFN alfa‐2a subcutaneously at 180 μg. Primary endpoints were safety/PK profiles of ropeginterferon alfa‐2b, while secondary endpoints were to compare PK/PD parameters with pegylated IFN alfa‐2a.
Results
Adverse events in ropeginterferon alfa‐2b and pegylated IFN alfa‐2a groups were similar, and most of them were mild or moderate. Mean Cmax increased from 1.78 to 24.84 ng/mL along with the dose escalations in ropeginterferon alfa‐2b groups and was 12.95 ng/mL for pegylated IFN alfa‐2a. At 180 μg, ropeginterferon alfa‐2b showed statistically significant Cmax geometric mean ratio (1.76; P = .0275). Mean Tmax ranged from 74.52 to 115.69 h for ropeginterferon alfa‐2b groups, and was 84.25 h for pegylated IFN alfa‐2a. Mean AUC0‐t increased from 372.3 to 6258 ng•h/mL with the dose escalations in the ropeginterferon alfa‐2b groups, while for pegylated IFN alfa‐2a it was found to be 2706 ng•h/mL in pegylated IFN alfa‐2a. For neopterin and 2′,5′‐oligoadenylate synthase, mean Emax, Tmax and AUC0‐t of ropeginterferon alfa‐2b were similar to those of pegylated IFNα‐2a at 180 μg.
Conclusion
Ropeginterferon alfa‐2b up to 270 μg was safe and well tolerated. The PK/PD parameters of ropeginterferon alfa‐2b showed increase in dose–response. Ropeginterferon alfa‐2b had higher drug exposures and showed similar safety profile when compared to pegylated IFN alfa‐2a at the same dose level.</description><identifier>ISSN: 0306-5251</identifier><identifier>EISSN: 1365-2125</identifier><identifier>DOI: 10.1111/bcp.15176</identifier><identifier>PMID: 34907578</identifier><language>eng</language><publisher>England</publisher><subject>Antiviral Agents - adverse effects ; first‐in‐human ; Humans ; interferon ; Interferon alpha-2 - adverse effects ; Interferon-alpha - adverse effects ; pegylated interferon ; phase 1 ; Polyethylene Glycols - adverse effects ; Recombinant Proteins - adverse effects</subject><ispartof>British journal of clinical pharmacology, 2022-05, Vol.88 (5), p.2396-2407</ispartof><rights>2021 British Pharmacological Society</rights><rights>2021 British Pharmacological Society.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3606-ae5bf8c83abb309ab1bb44263552ff110647df21b8c422b914a057b48c1ba2ef3</citedby><cites>FETCH-LOGICAL-c3606-ae5bf8c83abb309ab1bb44263552ff110647df21b8c422b914a057b48c1ba2ef3</cites><orcidid>0000-0002-5196-7030</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fbcp.15176$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fbcp.15176$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34907578$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Huang, Yi‐Wen</creatorcontrib><creatorcontrib>Qin, Albert</creatorcontrib><creatorcontrib>Fang, Jane</creatorcontrib><creatorcontrib>Wang, Ting‐Fang</creatorcontrib><creatorcontrib>Tsai, Chung‐Wei</creatorcontrib><creatorcontrib>Lin, Ko‐Chung</creatorcontrib><creatorcontrib>Teng, Ching‐Leou</creatorcontrib><creatorcontrib>Larouche, Richard</creatorcontrib><title>Novel long‐acting ropeginterferon alfa‐2b: Pharmacokinetics, pharmacodynamics and safety in a phase I clinical trial</title><title>British journal of clinical pharmacology</title><addtitle>Br J Clin Pharmacol</addtitle><description>Aims
Ropeginterferon alfa‐2b is a novel, long‐acting pegylated interferon alfa‐2b. We aimed to evaluate its safety, pharmacokinetics (PK) and pharmacodynamics (PD).
Methods
Thirty‐six subjects received single subcutaneous injection of ropeginterferon alfa‐2b at doses ranging from 24 to 270 μg, and 12 subjects received pegylated IFN alfa‐2a subcutaneously at 180 μg. Primary endpoints were safety/PK profiles of ropeginterferon alfa‐2b, while secondary endpoints were to compare PK/PD parameters with pegylated IFN alfa‐2a.
Results
Adverse events in ropeginterferon alfa‐2b and pegylated IFN alfa‐2a groups were similar, and most of them were mild or moderate. Mean Cmax increased from 1.78 to 24.84 ng/mL along with the dose escalations in ropeginterferon alfa‐2b groups and was 12.95 ng/mL for pegylated IFN alfa‐2a. At 180 μg, ropeginterferon alfa‐2b showed statistically significant Cmax geometric mean ratio (1.76; P = .0275). Mean Tmax ranged from 74.52 to 115.69 h for ropeginterferon alfa‐2b groups, and was 84.25 h for pegylated IFN alfa‐2a. Mean AUC0‐t increased from 372.3 to 6258 ng•h/mL with the dose escalations in the ropeginterferon alfa‐2b groups, while for pegylated IFN alfa‐2a it was found to be 2706 ng•h/mL in pegylated IFN alfa‐2a. For neopterin and 2′,5′‐oligoadenylate synthase, mean Emax, Tmax and AUC0‐t of ropeginterferon alfa‐2b were similar to those of pegylated IFNα‐2a at 180 μg.
Conclusion
Ropeginterferon alfa‐2b up to 270 μg was safe and well tolerated. The PK/PD parameters of ropeginterferon alfa‐2b showed increase in dose–response. Ropeginterferon alfa‐2b had higher drug exposures and showed similar safety profile when compared to pegylated IFN alfa‐2a at the same dose level.</description><subject>Antiviral Agents - adverse effects</subject><subject>first‐in‐human</subject><subject>Humans</subject><subject>interferon</subject><subject>Interferon alpha-2 - adverse effects</subject><subject>Interferon-alpha - adverse effects</subject><subject>pegylated interferon</subject><subject>phase 1</subject><subject>Polyethylene Glycols - adverse effects</subject><subject>Recombinant Proteins - adverse effects</subject><issn>0306-5251</issn><issn>1365-2125</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kEtuFDEQhi1ERCaPBRdAXoKUSVx-dPewg1FeUgRZJOtW2WMPBre7sXtIZpcj5IycJE5mwo7alFT11a_SR8h7YMdQ6kSb4RgU1NUbMgFRqSkHrt6SCROsmiquYJfs5fyTMRBQqXdkV8gZq1XdTMj9t_6PDTT0cfn34RHN6OOSpn6wSx9Hm5xNfaQYHJYt15_p9Q9MHZr-l4929CYf0WE7WawjdmVCMS5oRmfHNfXl9hnIll5SE3z0BgMdk8dwQHYchmwPt32f3J6d3swvplffzy_nX66mRlTle7RKu8Y0ArUWbIYatJaSV0Ip7hwAq2S9cBx0YyTnegYSmaq1bAxo5NaJffJxkzuk_vfK5rHtfDY2BIy2X-WWV8AkcFmLgn7aoCb1OSfr2iH5DtO6BdY-i26L6PZFdGE_bGNXurOLf-Sr2QKcbIA7H-z6_0nt1_n1JvIJzqiKfw</recordid><startdate>202205</startdate><enddate>202205</enddate><creator>Huang, Yi‐Wen</creator><creator>Qin, Albert</creator><creator>Fang, Jane</creator><creator>Wang, Ting‐Fang</creator><creator>Tsai, Chung‐Wei</creator><creator>Lin, Ko‐Chung</creator><creator>Teng, Ching‐Leou</creator><creator>Larouche, Richard</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-5196-7030</orcidid></search><sort><creationdate>202205</creationdate><title>Novel long‐acting ropeginterferon alfa‐2b: Pharmacokinetics, pharmacodynamics and safety in a phase I clinical trial</title><author>Huang, Yi‐Wen ; Qin, Albert ; Fang, Jane ; Wang, Ting‐Fang ; Tsai, Chung‐Wei ; Lin, Ko‐Chung ; Teng, Ching‐Leou ; Larouche, Richard</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3606-ae5bf8c83abb309ab1bb44263552ff110647df21b8c422b914a057b48c1ba2ef3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Antiviral Agents - adverse effects</topic><topic>first‐in‐human</topic><topic>Humans</topic><topic>interferon</topic><topic>Interferon alpha-2 - adverse effects</topic><topic>Interferon-alpha - adverse effects</topic><topic>pegylated interferon</topic><topic>phase 1</topic><topic>Polyethylene Glycols - adverse effects</topic><topic>Recombinant Proteins - adverse effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Huang, Yi‐Wen</creatorcontrib><creatorcontrib>Qin, Albert</creatorcontrib><creatorcontrib>Fang, Jane</creatorcontrib><creatorcontrib>Wang, Ting‐Fang</creatorcontrib><creatorcontrib>Tsai, Chung‐Wei</creatorcontrib><creatorcontrib>Lin, Ko‐Chung</creatorcontrib><creatorcontrib>Teng, Ching‐Leou</creatorcontrib><creatorcontrib>Larouche, Richard</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>British journal of clinical pharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Huang, Yi‐Wen</au><au>Qin, Albert</au><au>Fang, Jane</au><au>Wang, Ting‐Fang</au><au>Tsai, Chung‐Wei</au><au>Lin, Ko‐Chung</au><au>Teng, Ching‐Leou</au><au>Larouche, Richard</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Novel long‐acting ropeginterferon alfa‐2b: Pharmacokinetics, pharmacodynamics and safety in a phase I clinical trial</atitle><jtitle>British journal of clinical pharmacology</jtitle><addtitle>Br J Clin Pharmacol</addtitle><date>2022-05</date><risdate>2022</risdate><volume>88</volume><issue>5</issue><spage>2396</spage><epage>2407</epage><pages>2396-2407</pages><issn>0306-5251</issn><eissn>1365-2125</eissn><abstract>Aims
Ropeginterferon alfa‐2b is a novel, long‐acting pegylated interferon alfa‐2b. We aimed to evaluate its safety, pharmacokinetics (PK) and pharmacodynamics (PD).
Methods
Thirty‐six subjects received single subcutaneous injection of ropeginterferon alfa‐2b at doses ranging from 24 to 270 μg, and 12 subjects received pegylated IFN alfa‐2a subcutaneously at 180 μg. Primary endpoints were safety/PK profiles of ropeginterferon alfa‐2b, while secondary endpoints were to compare PK/PD parameters with pegylated IFN alfa‐2a.
Results
Adverse events in ropeginterferon alfa‐2b and pegylated IFN alfa‐2a groups were similar, and most of them were mild or moderate. Mean Cmax increased from 1.78 to 24.84 ng/mL along with the dose escalations in ropeginterferon alfa‐2b groups and was 12.95 ng/mL for pegylated IFN alfa‐2a. At 180 μg, ropeginterferon alfa‐2b showed statistically significant Cmax geometric mean ratio (1.76; P = .0275). Mean Tmax ranged from 74.52 to 115.69 h for ropeginterferon alfa‐2b groups, and was 84.25 h for pegylated IFN alfa‐2a. Mean AUC0‐t increased from 372.3 to 6258 ng•h/mL with the dose escalations in the ropeginterferon alfa‐2b groups, while for pegylated IFN alfa‐2a it was found to be 2706 ng•h/mL in pegylated IFN alfa‐2a. For neopterin and 2′,5′‐oligoadenylate synthase, mean Emax, Tmax and AUC0‐t of ropeginterferon alfa‐2b were similar to those of pegylated IFNα‐2a at 180 μg.
Conclusion
Ropeginterferon alfa‐2b up to 270 μg was safe and well tolerated. The PK/PD parameters of ropeginterferon alfa‐2b showed increase in dose–response. Ropeginterferon alfa‐2b had higher drug exposures and showed similar safety profile when compared to pegylated IFN alfa‐2a at the same dose level.</abstract><cop>England</cop><pmid>34907578</pmid><doi>10.1111/bcp.15176</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-5196-7030</orcidid><oa>free_for_read</oa></addata></record> |
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source | MEDLINE; Access via Wiley Online Library; EZB-FREE-00999 freely available EZB journals; Wiley Online Library (Open Access Collection) |
subjects | Antiviral Agents - adverse effects first‐in‐human Humans interferon Interferon alpha-2 - adverse effects Interferon-alpha - adverse effects pegylated interferon phase 1 Polyethylene Glycols - adverse effects Recombinant Proteins - adverse effects |
title | Novel long‐acting ropeginterferon alfa‐2b: Pharmacokinetics, pharmacodynamics and safety in a phase I clinical trial |
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