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J Hepatol. 2007 Aug;47(2):174-82. Epub 2007 May 4.

Oral resiquimod in chronic HCV infection: safety and efficacy in 2 placebo-controlled, double-blind phase IIa studies.

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1
Division of Gastroenterology/Hepatology, Scripps Clinic, La Jolla, CA, USA. pockros.paul@scrippshealth.org

Abstract

BACKGROUND/AIMS:

To explore safety, pharmacokinetics, and pharmacodynamics of oral administration of resiquimod, a Toll-like receptor 7 and 8 agonist that induces endogenous interferon-alpha, in subjects with chronic hepatitis C virus infection.

METHODS:

Two randomized, double-blind phase IIa studies of resiquimod administered two times per week for 4 weeks. Multicenter study (U.S.): 12 subjects received resiquimod 0.01 mg/kg and 4 received placebo. Single center study (France): 6 subjects received 0.01 mg/kg, 11 received 0.02 mg/kg and 6 received placebo.

RESULTS:

Resiquimod 0.01 mg/kg was tolerated; two 0.2 mg/kg subjects discontinued treatment. More subjects reported severe grade adverse events at 0.02 mg/kg; events were consistent with systemic cytokine induction, including fever, headache, shivering, and lymphopenia. Mean maximum serum resiquimod concentrations were 3.82+/-1.47 and 7.55+/-4.17 ng/mL for 0.01 mg/kg and 0.02 mg/kg, respectively. At 0.02 mg/kg, two, three and one subjects had maximal reductions in viral levels of at least 1-, 2- and 3-logs, respectively; reductions were generally transient. Interferon-alpha levels appeared correlated with decreases in viral titer and lymphocyte counts, as well as increase in neutrophil counts.

CONCLUSIONS:

Oral administration of resiquimod 0.02 mg/kg transiently reduced viral levels but was associated with adverse effects similar to interferon-alpha.

PMID:
17532523
DOI:
10.1016/j.jhep.2007.02.025
[Indexed for MEDLINE]
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