AVONTEC: Results of a multiple dose clinical proof of concept study with its drug candidate AVT-01 decoy ODN

04-Mar-2008

Avontec GmbH announced the results of a multiple dose, double-blind, randomized, placebo-controlled, multicenter, multinational, unbalanced, parallel-group comparison study with its lead drug candidate AVT-01 decoy oligonucleotide (AVT-01 decoy ODN) in asthmatic patients. In this study, the excellent safety profile of AVT-01 decoy ODN was again confirmed. However, efficacy (statistical significant reduction of airway hyper-responsiveness) as seen before in a single dose randomized, double-blind, placebo-controlled, monocenter cross-over pilot phase IIa study with AVT-01 decoy ODN could not be confirmed.

Avontec's multiple dose phase IIa study was a once daily treatment of AVT-01 on seven consecutive days. The study population comprised 33 male moderate asthmatics treated with AVT-01 decoy ODN and 15 male moderate asthmatics treated with placebo. The study was conducted in two Romanian and one English centers. Primary clinical endpoint was the reduction of bronchial hyperresponsiveness after methacholine challenge measured as the calculated PC20 difference between day 7 and day 0. Secondary efficacy endpoint was the reduction of bronchial hyperresponsiveness after methacholine challenge on treatment day 3.

While there was a trend, yet not a significant difference on day 3 between the AVT-01 decoy ODN and the placebo group, this difference was diminished on day 7 due to an unusually high effect on day 7 in the placebo group. Furthermore, there was an unusual high standard deviation of the primary efficacy criterion, which profoundly reduced the power of this multiple dose phase IIa study. Therefore, the chance to detect a real treatment effect was substantially reduced in this study.

AVT-01 decoy ODN contains a short, double-stranded oligonucleotide "decoy" that effectively inhibits STAT-1, a transcription factor shown to be strongly involved in the regulation of chronic inflammation. AVT-01 decoy ODN reduced inflammation in numerous pharmacological animal models. In pilot clinical studies this drug candidate showed an excellent safety profile and had demonstrable effects on relevant endpoints. Single doses of AVT-01 decoy ODN attenuated bronchial hyperresponsiveness in humans in a pilot clinical trial in asthmatic patients.

https://www.bionity.com/en/news/78888/avontec-results-of-a-multiple-dose-clinical-proof-of-concept-study-with-its-drug-candidate-avt-01-decoy-odn.html