Date: 2015-09-09
Type of information: Results
phase: 2
Announcement: results
Company: Genkyotex (Switzerland)
Product: GKT137831
Action
mechanism: enzyme inhibitor/NOX inhibitor. NOX enzymes exist in seven isoforms and produce reactive oxygen species (ROS). ROS can cause tissue damage and modify biological pathways that are important in a number of pathologies, including metabolic, cardiovascular, pulmonary and neurological diseases. In the kidney, NOX4 is the most abundantly expressed isoform and even further upregulated in diabetic nephropathy. The causal role of NOX enzymes in diabetic complications is well recognised. NOX4 plays a key role in glomerular damage and kidney fibrosis, which lead to albuminuria and end-stage renal disease, respectively. NOX1 is also involved in angiogenesis, atherosclerosis and other diabetic co-morbidities, making the inhibition of both the NOX1 and NOX4 enzymes by GKT137831. This competitive therapeutic profile of GKT137831 has been validated in several animal models of diabetes and diabetic nephropathy.
Disease: diabetic nephropathy
Therapeutic area: Metabolic diseases - Renal diseases - Kidney diseases
Country: Australia, Canada, Czech Republic, Germany, Poland, USA
Trial
details: Genkyotex’s multicenter, placebo-controlled, double-blind, randomized, Phase 2 trial enrolled 155 patients with diabetic kidney disease at sites in the US, Canada, Europe, and Australia. The primary endpoint of the study was the change from baseline in the urine albumin-to-creatinine ratio (UACR, a validated measure of efficacy in diabetic nephropathy). Secondary endpoints include changes in markers of insulin resistance, pancreatic beta cell and adipose tissue dysfunction, and vascular inflammation, as well as predictive markers of progression to end-stage renal disease. (NCT02010242)
Latest
news: * On September 9, 2015, Genkyotex, a leading developer of selective NOX inhibitors, announced top-line data from its Phase 2 clinical program with GKT137831, its lead NOX1&4 inhibitor. In patients with diabetic kidney disease, GKT137831 demonstrated an excellent safety profile and statistically significant reduction in both liver enzyme and inflammatory marker levels. Treatment with GKT137831 for 12 weeks resulted in fewer adverse events than placebo, confirming its excellent safety profile. However, a reduction in albuminuria, the primary efficacy endpoint of the study, was not achieved within this timeframe. To date, 173 individuals have been safely exposed to GKT137831. “Our NOX1&4 development plan involves multiple fibrotic indications for GKT137831, and we are encouraged by its excellent safety profile and pharmacodynamic activity. We will continue to explore the potential of GKT137831 in fibrotic indications,” explained Dr. Ursula Ney, CEO of Genkyotex. ”The data from the Phase 2 study shows a statistically significant effect on markers of liver injury and inflammation, confirming pre-clinical data obtained in multiple models of fibrotic disorders and providing the clinical foundation for the potential development of GKT137831 in the treatment of nonalcoholic steatohepatitis, systemic sclerosis and idiopathic pulmonary fibrosis. We are currently finalizing Phase 2 study designs, which we plan to begin in 2016.” * On November 5, 2013, Genkyotex has announced the initiation of a multinational Phase II clinical study of GKT137831 in patients with diabetic nephropathy. GKT137831 is a first in class inhibitor targeting NOX1 and NOX4 enzymes, both of which play a key role in the development of diabetic complications and chronic kidney disease in particular. In phase I studies in more than 100 subjects, GKT137831 was found to be safe and well tolerated when administered orally once and twice daily. Investigational sites are being opened in North America and the study will be rolled out to centres in Europe and Australia as well. Genkyotex looks forward to reporting on data in the first half of 2015.
* On November 13, 2014, Genkyotex announced the completion of patient enrollment into its Phase 2 trial of GKT137831 in diabetic nephropathy. In addition, the trial’s independent Safety Monitoring Board has conducted its first scheduled safety review and recommended that the trial should continue as planned. “We are on track to report key data from our Phase II trial of GKT137831 in mid- 2015,” said Dr. Philippe Wiesel, Chief Medical Officer of Genkyotex. * On September 9, 2013, Genkyotex has announced that the FDA has approved the company’s Investigational New Drug (IND) application to begin a Phase II clinical study of GKT137831 in patients with diabetic nephropathy. GKT137831 is a first in class inhibitor targeting NOX1 and NOX4 enzymes. Enrollment of patients into the multinational Phase II study is expected to begin during Q4, 2013.
“This IND approval is a major milestone for Genkyotex. As the first company developing an inhibitor of the NOX enzyme pathway, GKT137831, we are delighted to receive validation by the FDA of our extensive preclinical and Phase I data package as well as approval for our Phase II clinical trial design,” said Ursula Ney, Genkyotex\'s Chief Executive Officer. “Our focus is now on completing preparations for enrollment of the first patients with diabetic nephropathy into the global Phase II clinical proof of concept study, which will include investigational centres in North America, Europe and Australia.”
