CPG 10101 (Actilon) is an investigational toll-like receptor 9 (TLR 9) agonist being developed by Coley Pharmaceutical Group. The agent promotes adaptive T-cell immune response against HCV by activating B cells and plasmacytoid dendritic cells and stimulating the innate immune system to produce Th1 cytokines, including those with known antiviral activity (e.g., interferon-alpha).

In a Phase I study, 74 patients with chronic genotype 1 HCV who relapsed within six months following response to treatment of at least 24 weeks with pegylated interferon plus ribavirin were randomly assigned to one of five arms:

• Peginterferon (1.5 μg/kg/week) plus ribavirin (800-1400 mg day)
• CPG 10101 (0.2 mg/kg/week) plus peginterferon plus ribavirin
• CPG 10101 plus peginterferon  
• CPG 10101 plus ribavirin  
• CPG 10101 monotherapy

Results

After 12 weeks, CPG 10101 was generally well tolerated:

• Adverse events were mild to moderate, primarily flu-like symptoms, fever, headache, fatigue, nausea, and insomnia.
• Neutropenia, in most cases mild to moderate, was seen in all treatment arms, including the one that did not receive the study drug.
• No alanine aminotransferase (ALT) flares or hemoglobin decreases were observed.
• Six patients withdrew prematurely or were lost to follow-up; there were no discontinuations due to adverse events in the triple-combination arm.
• One patient in the CPG 10101/peginterferon arm experienced a hypersensitivity reaction.

Reductions in HCV viral load after treatment of at least two weeks for the subset of patients with available data are shown in the table below:

CPG = CPG 10101; PEG = pegylated interferon; RVN = ribavirin

With limited data available, 2 of 7 patients (one in the CPG 10101/peginterferon/ribavirin arm and one in the CPG 10101/peginterferon arm) achieved HCV RNA less than 600 IU/mL at week 8.

Conclusion

More patients in the CPG 10101/pegylated interferon/ribavirin armed achieved undetectable viral load compared with the standard therapy arm. No cases of virological breakthrough were observed. CGP 10101 was not effective as monotherapy.

The researchers concluded, based on the limited data available so far, that addition of CPG 10101 to pegylated interferon with or without ribavirin may improve early antiviral response in relapsed responders to prior therapy. Further trials are underway.

6/06/06

Reference

J. McHutchison, R. Ghalib, E. Lawitz, and others. Early viral response to CPG 10101, a new investigational antiviral TLR9 agonist, in combination with pegylated interferon and/or ribavirin, in prior relapse HCV responders: preliminary report of a randomized Phase 1 study. Abstract S1062. Digestive Disease Week 2006. May 20-25, 2006. Los Angeles, CA.