Placebo-controlled evaluation of a bioengineered, cocaine-metabolizing fusion protein, TV-1380 (AlbuBChE), in the treatment of cocaine dependence

Background: TV-1380 (AlbuChE) is a novel recombinant fusion protein of mutated butyrylcholinesterase (BChE) that has increased catalytic efficiency for cocaine metabolism compared to wild-type BChE. Methods: Intra-muscular injections of TV-1380 (150 mg or 300 mg) or placebo were administered once weekly to participants (n = 66-69 per group) in a randomized, double-blind study to evaluate the ability of TV-1380 to facilitate abstinence in treatment-seeking, cocaine-dependent individuals. The primary endpoint was the proportion of participants achieving abstinence from cocaine during the last three weeks of the 12 week treatment phase, based on daily self-report of no use confirmed by urine testing. Results: Although there were no significant differences between the TV-1380 treatment groups and placebo for the primary endpoint, 6% of participants in the 150 mg and 300 mg TV-1380 groups and no participants in the placebo group achieved abstinence. For the only declared secondary endpoint, there was a dose-dependent increase in the group mean percentage of urine samples testing negative for cocaine metabolites during weeks 5-12 (8.1% and 14.6% for the 150 mg and 300 mg TV-1380 groups, respectively, compared to 4.7% for the placebo group; p = 0.0056 for 300 mg vs. placebo). No meaningful differences in adverse events were seen between treatment groups. Conclusions: While the apparent reduction in cocaine use may be of insufficient magnitude to justify further trials of TV-1380 in cocaine dependence, the results argue for development of improved enzymes with greater catalytic activity. (C) 2016 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license