Switzerland-based Genkyotex has started a multinational Phase II clinical study of GKT137831, a first in class inhibitor targeting NOX1 and NOX4 enzymes, for treatment of patients with diabetic nephropathy.
Both the NOX enzymes play a major role in the development of diabetic complications and chronic kidney disease in particular.
Initiation of the placebo controlled, double-blind, randomised Phase II trial is based on the results of Phase I studies in more than 100 subjects, which showed GKT137831 to be safe and well-tolerated when administered orally once and twice daily.
University of California professor of medicine and dCenter for Renal Translational Medicine director Kumar Sharma said there is a significant need for more effective therapies for diabetic nephropathy, particularly as the prevalence of this disease continues to increase.
"The central role of NOX enzymes in diabetic kidney disease suggests that GKT137831 may confer broad therapeutic benefits to patients," Sharma said.
"Studies to date in preclinical models of the disease have shown very promising results and we look forward to seeing data from diabetic patients."
The Phase II study has been designed to assess the safety and efficacy of GKT137831 in 120 patients with Type 2 diabetes and residual albuminuria despite maximal inhibition of the renin angiotensin aldosterone system.
The trial's primary endpoint is the change in the urine albumin-to-creatinine ratio (UACR) versus baseline, while the secondary endpoints include changes in markers of glucose metabolism, adipose tissue dysfunction and inflammation, and in predictive markers of progression to end-stage renal disease.
According to the company, GKT137831 is the first targeted NOX inhibitor to be trialled in patients. The trial will provide extensive data about the role of NOX and NOX inhibition in this group of patients with nephropathy.
The study will be carried out at the newly opened investigational sites in North America and will also be rolled out to centres in Europe and Australia.
The company expects to release the results of the Phase II trial in the first half of 2015.
According to Genkyotex, the competitive therapeutic profile of GKT137831 has been validated in several animal models of diabetes and diabetic nephropathy.
GKT137831, which is administered orally, is currently under development for the treatment of diabetic nephropathy, other diabetic complications, idiopathic pulmonary fibrosis, atherosclerosis and liver fibrosis.
Image: Histopathological image of diabetic glomerulosclerosis with nephrotic syndrome. Photo: courtesy of KGH.