To determine the safety and efficacy of K0706, a novel c-Abl tyrosine kinase inhibitor (TKI), to slow the progression of Parkinson’s disease.

C-Abl is a tyrosine kinase that has been hypothesized to activate multiple pathways involved in Parkinson’s disease including synuclein aggregation and parkin deactivation. K0706 and other c-Abl TKIs have been shown in multiple animal models to reduce dopaminergic cell death and improve behavioral outcomes. C-Abl TKIs have proven efficacy in treating leukemias related to the Bcr-Abl mutation, but no c-Abl TKIs have completed testing to determine efficacy in Parkinson’s disease.

Sun Pharma Advanced Research Company (SPARC) has conducted a phase 1, multiple ascending dose trial of K0706 in subjects with Parkinson’s disease. Subjects were treated for 2 weeks with K0706 or placebo (3:1 randomization) with blood levels of K0706 measured in all subjects, and CSF levels in a subset. SPARC will next begin a phase 2, multi-center trial of K0706 to determine proof of concept for efficacy to support a phase 3 program. Subjects with early stage PD will be randomized to one of two doses of K0706 or placebo for 9 months; primary outcome will be change in MDS-UPDRS Parts 2+3.

In the phase 1 trial, 46 subjects with Parkinson’s disease have been studied.  K0706 was well tolerated with no serious adverse events, and no consistent adverse events, laboratory or vital sign abnormalities deemed to be drug-related. Plasma concentrations of K0706 increased with dose and reached those found to be efficacious in PD animal models; they along with CSF levels are used to choose the doses for the phase 2 trial.

SPARC’s K0706 is a c-Abl TKI currently being studied for its ability to slow progression in early stage Parkinson’s disease.