DMX-200 combines a drug called irbesartan, an off-patent compound used to treat hypertension and nephropathy in type II diabetic patients and propagermanium, which is used for the treatment for hepatitis B in Japan and available as a dietary supplement in the USA.
The company has previously published preclinical data showing that combining the drugs blocks an inflammatory response, which prevents the kidneys from functioning properly and releasing protein into the urine, called proteinuria.
The primary goal of the study will be to quickly demonstrate the safety of DMX-200 in patients with chronic kidney disease. Secondary endpoints include reduction of levels of protein in the urine in patients with the disease.
Sun Biomedical Limited Executive Chairman, Dr James Williams, said: “We believe DMX-200 has a number of potential advantages compared with current therapeutic approaches. To expedite our path to market we intend pursuing registration initially for an orphan indication. Analysis of the interim data of up to the first 15 patients in the study will be used to inform and support regulatory paths required to achieve this outcome.”
“The phase II study initiated today underscores our commitment to rapidly developing effective new therapies for the unmet needs of patients with chronic kidney disease,” Dr Williams said.
About the Phase II Trial
The trial is a single arm, open label trial in adult patients with chronic kidney disease (with proteinuria). The primary end points are the incidence and severity of adverse events and the clinically significant changes in the safety profile of participants. The secondary end points are obtained from statistical analysis of biomarker data at each time point including change from baseline, and the proportion of responders defined as those participants achieving normalisation of proteinuria (proteinuria within normal limits) or those participants achieving a 50% reduction in proteinuria.
The trial has two parts, Part A is a dose escalation trial recruiting up to 30 patients. All patients recruited to the trial will be on stable irbesartan therapy, and will be treated with propagermanium dosed orally three times per day. Each patient will commence on 30mg PPG/day and the dose increased each 28 days to a maximum of 240 mg/day, or until proteinuria is absent or reduced to a level the clinician considers acceptable.
The company expects to carry out an interim analysis of the Part A data to confirm the safety of the therapy and observe any biomarker changes on up to 15 patients. It is expected interim data will be available by mid-2016.
Part B is an expansion study, in which up to 30 patients are recruited on the best dose identified from Part A. The company expects to review the design of Part B in consultation with the FDA and in light of all data available to the company, prior to commencement of Part B. These discussions will be in line with the company’s strategy of pursuing registration for an orphan indication in which the sufferers exhibit chronic kidney disease. Orphan indications of chronic kidney disease include Focal Segmental Glomerulosclerosis (FSGS), Membranous Nephropathy (MN) and Minimal Change Disease (MCD). The trial has commenced at three sites in Melbourne, Australia, and may be expanded into other jurisdictions to meet recruitment targets and regulatory goals.