Phase 1B, randomized, double-blind, dose-escalation trial of CPG 10101 in patients with chronic hepatitis C virus

John G. McHutchison, Bruce R. Bacon, Stuart C. Gordon, Eric Lawitz, Mitchell Shiffman, Nezam H. Afdhal, Ira M. Jacobson, Andrew Muir, Mohammed Al-Adhami, Mary L. Morris, Julie A. Lekstrom-Himes, Susan M. Efler, Heather L. Davis

Research output: Contribution to journalArticlepeer-review

100 Scopus citations


CPG 10101, a synthetic oligodeoxynucleotide (ODN), is a toll-like receptor 9 (TLR9) agonist with antiviral and immunomodulatory properties that could potentially influence chronic infection with HCV. In this multicenter Phase 1b trial, 60 HCV-positive patients (50 genotype 1 HCV) were randomized and received either placebo or CPG 10101 at 0.25, 1, 4, 10, or 20 mg subcutaneously (SC) twice weekly for 4 weeks or at 0.5 or 0.75 mg/kg SC once weekly for 4 weeks. Dose-dependent cytokine induction was observed after administration of CPG 10101. At 24 hours after administering the highest dose of 0.75 mg/kg CPG 10101, interferon (IFN)-γ-inducible protein 10 (IP-10) had a mean increase over baseline levels (±SD) of 15,057 (±9769) pg/ml (P < 0.01, compared to placebo); IFN-α had a 106 (±63.3) pg/ml increase (P < 0.01); and 2′5′-oligoadenylate synthetase (OAS) had a 163 (±120.6) pmol/dl increase (P < 0.01). Decreases in HCV RNA also were dose-dependent, with the greatest group geometric mean maximum reduction of 1.69 ± 0.618 log10 (P < 0.05) observed in the 0.75 mg/kg dose group. Decreases ≥1 log10 were seen in 22 of 40 patients who received ≥1 mg CPG 10101, with 3 patients exceeding a 2.5-log10 reduction. CPG 10101 was well tolerated, and adverse events were consistent with CPG 10101's mechanism of action. Conclusion: In this Phase 1 study, CPG 10101 was associated with dose-dependent increases in markers of immune activation and decreases in HCV RNA levels. The data support further clinical studies of CPG 10101 for treating chronic HCV infection.

Original languageEnglish (US)
Pages (from-to)1341-1349
Number of pages9
Issue number5
StatePublished - Nov 2007

ASJC Scopus subject areas

  • Hepatology


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