Potential conflict of interest: Dr. McHutchison advises Coley Pharmaceuticals Group, Inc. He is on the speakers' bureau of, is a consultant for, advises, and received grants from Schering-Plough. He also received grants from Roche. Dr. Afdhal advises Pharmaceuticals Group, Inc. Dr. Jacobson advises Coley Pharmaceuticals Group, Inc.; Gilead; Vertex; GlobeImmune; Human Genome Science; Novartis; Pfizer; GlaxoSmithKline; Idenix; and Bristol-Myers Squibb. He is a consultant for Gilead, Vertex, Merck, GlobeImmune, Human Genome Science, Novartis, Pfizer, GlaxoSmithKline, Idenix, Bristol-Myers Squibb, Intermune, Schering-Plough, and Valeant. He is on the speakers' bureau of Gilead, GlobeImmune, Idenix, Bristol-Myers Squibb, and Schering-Plough. He also received grants from Gilead, Vertex, GlobeImmune, Novartis, Idenix, Schering-Plough, and Valeant. Dr. Davis owns stock in and holds intellectual property rights to Coley Pharmaceuticals Group, Inc. Dr. Bacon is a consultant for, provides research support to, and is on the speakers' bureau of Schering-Plough. He also provides research support to Roche Laboratories, and Bristol-Myers Squibb. He provides research support to and is on the speakers' bureau of Gilead Sciences and Axcan Pharmaceuticals. He provides research support to and advises GlaxoSmithKline and Novartis. He provides research support to and is a consultant for ISIS, Coley Pharmaceuticals Group Inc., and Valeant.
Article first published online: 10 OCT 2007
Copyright © 2007 American Association for the Study of Liver Diseases
Volume 46, Issue 5, pages 1341–1349, November 2007
How to Cite
McHutchison, J. G., Bacon, B. R., Gordon, S. C., Lawitz, E., Shiffman, M., Afdhal, N. H., Jacobson, I. M., Muir, A., Al-Adhami, M., Morris, M. L., Lekstrom-Himes, J. A., Efler, S. M. and Davis, H. L. (2007), Phase 1B, randomized, double-blind, dose-escalation trial of CPG 10101 in patients with chronic hepatitis C virus. Hepatology, 46: 1341–1349. doi: 10.1002/hep.21773
All investigations belong to ALT and the study has been conducted by this group since inception.
- Issue published online: 29 OCT 2007
- Article first published online: 10 OCT 2007
- Manuscript Accepted: 12 APR 2007
- Manuscript Received: 12 FEB 2007
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. (HEPATOLOGY 2007.)