A phase 1, single-dose study of fresolimumab, an anti-TGF-Β antibody, in treatment-resistant primary focal segmental glomerulosclerosis

Howard Trachtman, Fernando C. Fervenza, Debbie S. Gipson, Peter Heering, David R W Jayne, Harm Peters, Stefano Rota, Giuseppe Remuzzi, L. Christian Rump, Lorenz K. Sellin, Jeremy P W Heaton, James B. Streisand, Marjie L. Hard, Steven R. Ledbetter, Flavio Vincenti

Research output: Contribution to journalArticlepeer-review


Primary focal segmental glomerulosclerosis (FSGS) is a disease with poor prognosis and high unmet therapeutic need. Here, we evaluated the safety and pharmacokinetics of single-dose infusions of fresolimumab, a human monoclonal antibody that inactivates all forms of transforming growth factor-Β (TGF-Β), in a phase I open-label, dose-ranging study. Patients with biopsy-confirmed, treatment-resistant, primary FSGS with a minimum estimated glomerular filtration rate (eGFR) of 25 ml/min per 1.73 m 2, and a urine protein to creatinine ratio over 1.8 mg/mg were eligible. All 16 patients completed the study in which each received one of four single-dose levels of fresolimumab (up to 4 mg/kg) and was followed for 112 days. Fresolimumab was well tolerated with pustular rash the only adverse event in two patients. One patient was diagnosed with a histologically confirmed primitive neuroectodermal tumor 2 years after fresolimumab treatment. Consistent with treatment-resistant FSGS, there was a slight decline in eGFR (median decline baseline to final of 5.85 ml/min per 1.73 m 2). Proteinuria fluctuated during the study with the median decline from baseline to final in urine protein to creatinine ratio of 1.2 mg/mg with all three Black patients having a mean decline of 3.6 mg/mg. The half-life of fresolimumab was 14 days, and the mean dose-normalized Cmax and area under the curve were independent of dose. Thus, single-dose fresolimumab was well tolerated in patients with primary resistant FSGS. Additional evaluation in a larger dose-ranging study is necessary.

Original languageEnglish
Pages (from-to)1236-1243
Number of pages8
JournalKidney International
Issue number11
Publication statusPublished - Jun 2011


  • clinical study
  • fresolimumab
  • FSGS
  • TGF-β antagonism

ASJC Scopus subject areas

  • Nephrology


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