Phase
1B Study Shows Toll-like Receptor 9 Agonist CPG 10101 Decreases HCV RNA in Patients
with Chronic Hepatitis C The
current standard of care for treatment of chronic hepatitis C is pegylated
interferon (Pegasys or PegIntro) plus ribavirin. But this combination does
not produce a sustained virological
response in a significant proportion of patients, especially those with genotype
1 hepatitis C virus (HCV) and African-Americans.
Thus, researchers have
explored various other approaches to treatment. CPG 10101, a synthetic oligodeoxynucleotide,
is a toll-like receptor 9 (TLR-9) agonist with antiviral and immunomodulatory
properties that is being studied as a potential therapy for HCV infection.
As
reported in the October 10, 2007 advance online edition of Hepatology,
researchers conducted a multicenter Phase 1b trial to assess the safety and preliminary
efficacy of CPG 10101.
The study included 60 HCV positive patients (50
with genotype 1) who were randomized to receive either placebo or 1 of 2 CPG 10101
dosing regimens. ›
CPG 10101
at doses of 0.25, 1, 4, 10, or 20 mg injected subcutaneously twice weekly for
4 weeks;
›
CPG
10101 at doses of 0.5 or 0.75 mg/kg injected subcutaneously once weekly for 4
weeks.
Results
›
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
gamma-inducible protein 10 (IP-10) increased by a mean 15,057 pg/ml over baseline
levels (P < 0.01 compared to placebo).
›
Interferon
alpha had a mean 106 pg/ml increase (P < 0.01).
›
2'5'-oligoadenylate
synthetase had a 163 pmol/dl increase (P < 0.01).
›
Decreases
in HCV RNA were dose-dependent, with the greatest group geometric mean maximum
reduction of 1.69 log10 observed in the 0.75 mg/kg dose group (P < 0.05).
›
HCV
RNA decreases of at least 1 log10 were seen in 22 of 40 patients (55%) who received
? 1 mg CPG 10101.
›
3
patients had a greater than 2.5-log10 reduction.
›
CPG
10101 was well tolerated and adverse events were consistent with the drug'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 authors
wrote in conclusion. "The data support further clinical studies of CPG 10101
for treating chronic HCV infection."
11/02/07 Reference
JG
McHutchison, BR Bacon, SC Gordon, and others. Phase 1B, randomized, double-blind,
dose-escalation trial of CPG 10101 in patients with chronic hepatitis C virus.
Hepatology. October 10, 2007 [Epub ahead of print]. | 
