title: C-C motif-ligand 2 inhibition with emapticap pegol (NOX-E36) in type 2 diabetic patients with albuminuria.
abstract: Emapticap pegol (NOX-E36) is a Spiegelmer® that specifically binds and inhibits the pro-inflammatory chemokine C-C motif-ligand 2 (CCL2) (also called monocyte-chemotactic protein 1). The objective of this exploratory study was to evaluate the safety and tolerability as well as the renoprotective and anti-diabetic potential of emapticap in type 2 diabetic patients with albuminuria.
  
  
  
  A randomized, double-blind, placebo-controlled Phase IIa study was initiated in 75 albuminuric type 2 diabetics. Emapticap at 0.5 mg/kg and placebo were administered subcutaneously twice weekly for 12 weeks to 50 and 25 patients, respectively, followed by a treatment-free phase of 12 weeks.
  
  
  
  Twice weekly subcutaneous treatment with emapticap over 3 months was generally safe and well tolerated and reduced the urinary albumin/creatinine ratio (ACR) from baseline to Week 12 by 29% (P < 0.05); versus placebo a non-significant ACR reduction of 15% was observed (P = 0.221). The maximum difference, 26% (P = 0.064) between emapticap and placebo, was seen 8 weeks after discontinuation of treatment. At Week 12, the HbA1c changed by −0.31% in the emapticap versus +0.05% in the placebo group (P = 0.146). The maximum difference for HbA1c was observed 4 weeks after the last dose with −0.35% for emapticap versus +0.12% for placebo (P = 0.026). No relevant change in blood pressure or estimated glomerular filtration rate was seen between the treatment groups throughout the study. A post hoc analysis with exclusion of patients with major protocol violations, dual RAS blockade or haematuria increased the ACR difference between the two treatment arms to 32% at Week 12 (P = 0.014) and 39% at Week 20 (P = 0.010).
  
  
  
  Inhibition of the CCL2/CCL2 receptor axis with emapticap pegol was generally safe and well tolerated. Beneficial effects on ACR and HbA1c were observed in this exploratory study, which were maintained after cessation of treatment. Taken together, emapticap may have disease-modifying effects that warrant further investigation in adequately powered confirmatory studies.
authors.affiliation: Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Menne
authors.affiliation: NOXXON Pharma AG, Berlin, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Eulberg
authors.affiliation: NOXXON Pharma AG, Berlin, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Beyer
authors.affiliation: NOXXON Pharma AG, Berlin, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Baumann
authors.affiliation: Institute for Clinical and Experimental Medicine, Prague, Czech Republic.
authors.forename: Frantisek
authors.initials: F
authors.lastname: Saudek
authors.affiliation: Albert Szent-Györgyi Health Center, University of Szeged, Szeged, Hungary.
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Valkusz
authors.affiliation: Department of Nephrology, Endocrinology and Metabolic Diseases, Medical University of Silesia, Katowice, Poland.
authors.forename: Andrzej
authors.initials: A
authors.lastname: Więcek
authors.affiliation: Department of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Haller
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D052157:Aptamers, Nucleotide / Q000627:therapeutic use*; D018932:Chemokine CCL2 / Q000037:antagonists & inhibitors*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000503:physiopathology; D004311:Double-Blind Method; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D011379:Prognosis
chemical_list: D052157:Aptamers, Nucleotide; C111835:CCL2 protein, human; D018932:Chemokine CCL2; C541611:NOX-E36 aptamer
keywords: albuminuria; diabetes mellitus; diabetic nephropathy; inflammation; macrophage