AVI BioPharma, Inc. reported results from the second phase of its multicenter study in patients with chronic active hepatitis C virus (HCV) infection. The second phase of this exploratory trial was designed to assess the safety, tolerability, pharmacokinetics (PK), and viral and clinical response to treatment with AVI's proprietary NeuGene antisense compound, AVI-4065, in HCV patients.
Preliminary results from this study were presented in May at the International Conference on Antiviral Research (ICAR).
AVI-4065 exhibited favourable safety and tolerability profiles in the 12 patients completing the clinical treatment phase of the protocol, with no serious drug-related adverse events or tolerability issues observed during treatment or follow-up. Consistent with the preliminary results, the therapeutic threshold required for efficacy of the drug was not achieved at the treatment dose used in this protocol.
Significant differences were observed in the plasma PK in patients compared with what was noted in healthy volunteers: notably, a longer plasma half-life (approximately 26 hours compared with 13 hours), a lower peak plasma concentration (initially 1.2 compared with 1.6 ug/ml), and a slower plasma clearance (approximately 15 compared with 40 ml/min). These observations demonstrate a direct pharmacodynamic response to HCV infection.
The peak plasma concentration (Cmax) was expected to reach the predicted therapeutic threshold of approximately 3.5 ug/ml during the treatment protocol, but rose to only 2.0 ug/ml after 14 days of therapy. With an initial Cmax of 1.2 ug/ml and final Cmax of 2.0 ug/ml, the therapeutic threshold predicted from preclinical models to be required for efficacy was not achieved.
"Although it is always disappointing not to achieve clear clinical success on an initial trial targeting a new disease, it is encouraging that we observed a significant pharmacodynamic effect that we believe can be fine-tuned to provide a clinical benefit," said Denis R. Burger, Ph.D., AVI chief executive officer. "We are fortunate that NeuGene antisense technology provides flexibility for clinical protocol modification."