Anti-TGF-b1 antibody therapy in patients with diabetic nephropathy

TGF-b has been implicated as a major pathogenic factor in diabetic nephropathy. This randomized, doubleblind, phase 2 study assessed whether modulating TGF-b1 activity with a TGF-b1-specific, humanized, neutralizingmonoclonal antibody (TGF-b1mAb) is safe and more effective than placebo in slowing renal function loss in patients with diabetic nephropathy on chronic stable renin-Angiotensin systeminhibitor treatment.We randomized 416 patients aged$25 years with type 1 or type 2 diabetes, a serum creatinine (SCr) level of 1.3- 3.3 mg/dl for women and 1.5-3.5 mg/dl for men (or EGFR of 20-60 ml/min per 1.73 m2), and a 24-hour urine protein-To-creatinine ratio$800mg/g to TGF-b1mAb (2-, 10-, or 50-mgmonthly subcutaneous dosing for 12 months) or placebo.We assessed a change in SCr frombaseline to 12months as the primary efficacy variable. Although theDataMonitoringCommittee didnot identify safety issues,we terminatedthe trial 4months early for futility on the basis of their recommendation. The placebo group had a mean6SD change in SCr from baseline to end of treatment of 0.3360.67mg/dl. Least squaresmean percentagechangeinSCr frombaseline to end of treatment did not differ between placebo (14%; 95% confidence interval [95% CI], 9.7% to 18.2%) and TGF-b1mAb treatments (20%[95%CI, 15.3%to 24.3%], 19%[95%CI, 14.2%to 23.0%], and 19%[95%CI, 14.0% to 23.3%] for 2-, 10-, and 50-mg doses, respectively). Thus, TGF-b1 mAb added to renin-Angiotensin system inhibitors did not slow progression of diabetic nephropathy.