Anti-TGF- β 1 Antibody Therapy in Patients with Diabetic Nephropathy

• Published in: Journal of the American Society of Nephrology 2017-03, Vol.28 (3), p.953
• Main Authors: Voelker, James, Berg, Paul H, Sheetz, Matthew, Duffin, Kevin, Shen, Tong, Moser, Brian, Greene, Tom, Blumenthal, Samuel S, Rychlik, Ivan, Yagil, Yoram, Zaoui, Philippe, Lewis, Julia B
• Format: Article
• Language: English
• Subjects: Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - therapeutic use; Diabetic Nephropathies - drug therapy; Diabetic Nephropathies - immunology; Double-Blind Method; Female; Humans; Male; Middle Aged; Transforming Growth Factor beta1 - immunology
• ISSN: 1533-3450
• DOI: 10.1681/ASN.2015111230

TGF- has been implicated as a major pathogenic factor in diabetic nephropathy. This randomized, double-blind, phase 2 study assessed whether modulating TGF- 1 activity with a TGF- 1-specific, humanized, neutralizing monoclonal antibody (TGF- 1 mAb) is safe and more effective than placebo in slowing renal function loss in patients with diabetic nephropathy on chronic stable renin-angiotensin system inhibitor 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 m ), and a 24-hour urine protein-to-creatinine ratio ≥800 mg/g to TGF- 1 mAb (2-, 10-, or 50-mg monthly subcutaneous dosing for 12 months) or placebo. We assessed a change in SCr from baseline to 12 months as the primary efficacy variable. Although the Data Monitoring Committee did not identify safety issues, we terminated the trial 4 months early for futility on the basis of their recommendation. The placebo group had a mean±SD change in SCr from baseline to end of treatment of 0.33±0.67 mg/dl. Least squares mean percentage change in SCr from baseline to end of treatment did not differ between placebo (14%; 95% confidence interval [95% CI], 9.7% to 18.2%) and TGF- 1 mAb 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- 1 mAb added to renin-angiotensin system inhibitors did not slow progression of diabetic nephropathy.