Date: 2014-04-04
Type of information: Results
phase: 2a
Announcement: results
Company: Noxxon Pharma (Germany)
Product: emapticap pegol (anti-CCL2/MCP-1 Spiegelmer® NOX-E36 (Spiegelmers are the chemically synthesized, nonimmunogenic alternative to antibodies.)
Action
mechanism: Emapticap pegol (NOX-E36)’s mode of action is to specifically bind and neutralize the pro-inflammatory chemokine CCL2/MCP-1. This protein recruits immune cells to sites of inflammation and it plays an important role in complications of type 2 diabetes through recruitment of immune cells to adipose tissue, pancreatic islets and the kidney. CCL2 also triggers down-regulation of the protein nephrin, a key component of the renal filtration apparatus expressed by the kidney’s podocyte cells. Inhibition of CCL2 is thus anticipated to be of benefit for type 2 diabetes patients with nephropathy. Preclinical studies have demonstrated that treatment with a SpiegelmerR CCL2 inhibitor can significantly delay the decline in kidney function as well as disease progression in animal models of diabetes.
Disease: diabetic nephropathy
Therapeutic area: Renal diseases - Metabolic diseases - Kidney diseases
Country:
Trial
details: Noxxon Pharma’s multi-center, double-blind study will be conducted on 75 patients with Type II diabetes mellitus and albuminuria with a treatment duration of 12 weeks. 50 patients will be administered subcutaneous doses of 0.5 mg/kg of NOX-E36 twice weekly and the remaining 25 patients will receive placebo. The dose choice of 0.5 mg/kg of NOX-E36 is based on data from an earlier Phase Ib study which evaluated the pharmacodynamic effects of three different doses of NOX-E36 in diabetics during four weeks of treatment. All patients in the Phase IIa study will also be on the current standard of care to control hypertension, hyperglycemia and dyslipidemia.
The study will evaluate efficacy, pharmacokinetics, safety and tolerability of treatment with NOX-E36. The primary efficacy analysis will be based on a change from baseline in the albumin to creatinine ratio (ACR); renal, glycemic and inflammatory efficacy markers will also be followed during the trial. Interim evaluation of primary and secondary efficacy parameters is planned following completion of treatment of 25, 50 and 75 patients.
Latest
news: * On April 4, 2014, NOXXON Pharma has announced that Phase IIa proof-of-concept data from the emapticap pegol (NOX-E36) trial in diabetic nephropathy were presented at the ISN Nexus Symposium in Bergamo, Italy.The objective of this randomized, double-blind placebo-controlled multi-center international study was to evaluate the efficacy, pharmacokinetics, safety and tolerability of treatment with emapticap pegol. Seventy-five type 2 diabetic patients with albuminuria on current standard of care to control hypertension, hyperglycemia and dyslipidemia were treated for 12 weeks with twice-weekly subcutaneous emapticap pegol or placebo. This treatment period was followed by a 12 week observational period to study the long-term effect of emapticap pegol treatment on albuminuria. Importantly, the underlying standard of care mandatorily included stable renin-angiotensin system (RAS) blockade, which has been demonstrated to reduce albuminuria and to slow progression of diabetic nephropathy. Emapticap pegol was found to be safe and well tolerated with no treatment-related serious adverse events. For the primary efficacy analysis, patients with major protocol violations, on dual RAS blockade, or with concomitant hematuria and leukocyturia were excluded. Results showed relevant, statistically significant reductions in urinary albumin excretion and improved glycemic control. Importantly, these effects were independent of hemodynamic changes and maintained after cessation of treatment, suggesting that emapticap pegol interferes with the underlying pathophysiology of diabetic nephropathy. Long-lasting effects on urinary albumin after cessation of treatment are not seen with agents currently approved to treat diabetic nephropathy (ACE inhibitors and ARBs) or with other agents that act primarily via a hemodynamic mechanism of action such as endothelin A receptor antagonists. * On July 24, 2013, Noxxon Pharma has announced the successful completion of patient recruitment of its NOX-E36 Phase IIa clinical trial the treatment of diabetic nephropathy. The planned interim efficacy analysis of the first third of patients completing therapy in this Phase IIa study has now been completed with promising results. The primary efficacy analysis is based on the change in albuminuria from baseline at the end of the treatment period, expressed as albumin to creatinine ratio (ACR). Recently increased patient recruitment will allow efficacy analysis of all 75 patients later this year and full analysis of the study in early 2014. * On June 19, 2012, Noxxon Pharma has announced the treatment of the first patient in a Phase IIa clinical trial of its anti-CCL2/MCP-1 (C-C Chemokine Ligand 2 or Monocyte Chemoattractant Protein-1) Spiegelmer® NOX-E36 in patients with diabetic nephropathy. About 1 in 3 patients with diabetes mellitus develops diabetic nephropathy, a progressive kidney disease that is one of the main causes of end-stage renal disease and the need for dialysis. The recruitment of immune cells by the chemokine CCL2 into the kidney along with direct effects of CCL2 on cells of the kidney are believed to be important in the progression of this disease. This phase IIa study is the fourth clinical study of NOX-E36 that Noxxon Pharma has initiated and the Company is building up a positive bank of data supporting this product’s potential in treating subjects with renal impairment. Noxxon plans to provide interim results from this trial later this year.
