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

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176 Scopus citations


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 (US)
Pages (from-to)1236-1243
Number of pages8
JournalKidney international
Issue number11
StatePublished - Jun 2011


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

ASJC Scopus subject areas

  • Nephrology


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