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A phase I trial of an antisense inhibitor of hepatitis C virus (ISIS 14803), administered to chronic hepatitis C patients.

Publication ,  Journal Article
McHutchison, JG; Patel, K; Pockros, P; Nyberg, L; Pianko, S; Yu, RZ; Dorr, FA; Kwoh, TJ
Published in: J Hepatol
January 2006

BACKGROUND/AIMS: ISIS 14803 is a 20-unit antisense phosphorothioate oligodeoxynucleotide that binds to hepatitis C virus (HCV) RNA at the translation initiation region of the internal ribosome entry site (IRES) and inhibits protein expression in cell culture and mouse models. This Phase I, open-label, dose-escalation trial of ISIS 14803 was performed in chronic HCV patients. METHODS: At least 7 days after receiving an initial single dose, twenty-eight patients received 0.5-3 mg/kg ISIS 14803 thrice weekly for 4 weeks by intravenous infusion or subcutaneous injection. RESULTS: In most patients, the 4-week treatment did not reduce plasma HCV RNA. However, 3 patients receiving > or =2 mg/kg had transient HCV reductions of 1.2-1.7 log(10) that persisted < or =32 days. These reductions were accompanied by asymptomatic, self-resolving elevations in serum alanine transaminase (ALT) levels to >10x the upper limit of normal. Two other patients had ALT flares without plasma HCV reduction. No clinical signs, symptoms of hepatic dysfunction, or laboratory changes in albumin or prothrombin time accompanied ALT elevations. CONCLUSIONS: ISIS 14803 treatment was associated with HCV reductions in only 3/28 patients. ALT flares in 5 patients also occurred. Further studies to evaluate ISIS 14803 treatment and the mechanisms of the ALT flares are now required.

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Published In

J Hepatol

DOI

ISSN

0168-8278

Publication Date

January 2006

Volume

44

Issue

1

Start / End Page

88 / 96

Location

Netherlands

Related Subject Headings

  • Viremia
  • Treatment Outcome
  • Thionucleotides
  • RNA, Viral
  • Oligonucleotides, Antisense
  • Middle Aged
  • Male
  • Humans
  • Hepatitis C, Chronic
  • Hepacivirus
 

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McHutchison, J. G., Patel, K., Pockros, P., Nyberg, L., Pianko, S., Yu, R. Z., … Kwoh, T. J. (2006). A phase I trial of an antisense inhibitor of hepatitis C virus (ISIS 14803), administered to chronic hepatitis C patients. J Hepatol, 44(1), 88–96. https://doi.org/10.1016/j.jhep.2005.09.009
McHutchison, John G., Keyur Patel, Paul Pockros, Lisa Nyberg, Stephen Pianko, Rosie Z. Yu, F Andrew Dorr, and T Jesse Kwoh. “A phase I trial of an antisense inhibitor of hepatitis C virus (ISIS 14803), administered to chronic hepatitis C patients.J Hepatol 44, no. 1 (January 2006): 88–96. https://doi.org/10.1016/j.jhep.2005.09.009.
McHutchison JG, Patel K, Pockros P, Nyberg L, Pianko S, Yu RZ, et al. A phase I trial of an antisense inhibitor of hepatitis C virus (ISIS 14803), administered to chronic hepatitis C patients. J Hepatol. 2006 Jan;44(1):88–96.
McHutchison, John G., et al. “A phase I trial of an antisense inhibitor of hepatitis C virus (ISIS 14803), administered to chronic hepatitis C patients.J Hepatol, vol. 44, no. 1, Jan. 2006, pp. 88–96. Pubmed, doi:10.1016/j.jhep.2005.09.009.
McHutchison JG, Patel K, Pockros P, Nyberg L, Pianko S, Yu RZ, Dorr FA, Kwoh TJ. A phase I trial of an antisense inhibitor of hepatitis C virus (ISIS 14803), administered to chronic hepatitis C patients. J Hepatol. 2006 Jan;44(1):88–96.
Journal cover image

Published In

J Hepatol

DOI

ISSN

0168-8278

Publication Date

January 2006

Volume

44

Issue

1

Start / End Page

88 / 96

Location

Netherlands

Related Subject Headings

  • Viremia
  • Treatment Outcome
  • Thionucleotides
  • RNA, Viral
  • Oligonucleotides, Antisense
  • Middle Aged
  • Male
  • Humans
  • Hepatitis C, Chronic
  • Hepacivirus