Experimental Drug for Diabetic Kidney Disease to Begin Clinical Testing

Novel treatment may prevent patients with type 1 diabetes from developing end-stage renal disease.

Genkyotex recently announced the initiation of a phase 2 clinical trial of an investigational drug, GTX831, in patients with type 1 diabetes (T1D) with kidney disease.

The trial will be led by Mark Cooper, head of the Department of Diabetes at Monash University and Jonathan Shaw, MD, deputy director of Clinical and Population Health at the Baker Heart and Diabetes Institute, according to a press release. The clinical trial will be conducted at Baker Institute, but will have 15 sites throughout Australia.

“We are very excited to be commencing this study which arises in part from original research performed in our laboratories and which was initially supported by JDRF [Australia],” Cooper said. “This work is a classic example of bench to bedside clinical translation. We appreciate JDRF greatly assisting us in providing us with an opportunity to bring this new treatment forward for what is a major burden of T1D kidney disease.”

Diabetic kidney disease is a condition where progressive glomerulosclerosis and fibrosis leads to end-stage renal disease among patients with diabetes.

GKT831 works by inhibiting NOX1 and 4 and has demonstrated anti-fibrotic activity in preclinical models, including those with diabetic kidney disease, according to the release.

In a previous phase 2 trial, GKT831 was observed to have a favorable safety profile and achieved reductions in efficacy measures in patients with type 2 diabetes; however, the investigators did not observe improvements in albuminuria, which was the trial’s primary endpoint.

The new clinical trial will analyze the effect of GKT831 on the urine albumin-to-creatinine ratio among 142 patients with T1D who have albuminuria, despite standard therapy. Patients will receive 200-mg of oral GKT831 or placebo twice per day for 48 weeks.

The primary endpoint of the trial will be the difference in urine albumin-to-creatinine ratio at baseline and 48 weeks. A secondary endpoint of the trial will be the effect of experimental drug on renal function, as measured by glomerular filtration rate, according to the release.

“We are delighted to be working with professor Cooper and his team to pursue the clinical evaluation of GKT831 in this severe diabetic complication,” said Philippe Wiesel, MD, chief medical officer of Genkyotex. “The design of this phase 2 trial was informed by previous phase 2 results in patients with type 2 diabetes and kidney disease performed by Genkyotex, in particular the extended 48-week treatment duration, a more homogenous and earlier stage patient population, and a higher dose throughout the dosing period. We also wish to thank JDRF for supporting this study, as well as previous preclinical studies, which has enabled a number of investigators to evaluate GKT831’s impact on ophthalmic, vascular, and renal complications caused by type 1 diabetes.”