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. 2017 Apr 7;2(5):800-810.
doi: 10.1016/j.ekir.2017.03.011. eCollection 2017 Sep.

A Phase 2, Double-Blind, Placebo-Controlled, Randomized Study of Fresolimumab in Patients With Steroid-Resistant Primary Focal Segmental Glomerulosclerosis

Flavio Vincenti  1 , Fernando C Fervenza  2 , Kirk N Campbell  3 , Montserrat Diaz  4 , Loreto Gesualdo  5 , Peter Nelson  6 , Manuel Praga  7 , Jai Radhakrishnan  8 , Lorenz Sellin  9 , Ajay Singh  10 , Denyse Thornley-Brown  11 , Francisco Veríssimo Veronese  12 , Beverly Accomando  13 , Sara Engstrand  14 , Steven Ledbetter  14 , Julie Lin  14 , John Neylan  14 , James Tumlin  15 ; Focal Segmental Glomerulosclerosis Study Group
Affiliations

A Phase 2, Double-Blind, Placebo-Controlled, Randomized Study of Fresolimumab in Patients With Steroid-Resistant Primary Focal Segmental Glomerulosclerosis

Flavio Vincenti et al. Kidney Int Rep. .

Abstract

Introduction: Steroid-resistant focal segmental glomerulosclerosis (SR-FSGS) is a common glomerulopathy associated with nephrotic range proteinuria. Treatment goals are reduction in proteinuria, which can delay end-stage renal disease.

Methods: Patients with SR-FSGS were enrolled in a randomized, double-blind placebo-controlled trial of fresolimumab, a monoclonal anti-transforming growth factor-β antibody, at 1 mg/kg or 4 mg/kg for 112 days, followed double-blind for 252 days (NCT01665391). The primary efficacy endpoint was the percentage of patients achieving partial (50% reduction) or complete (< 300 mg/g Cr) remission of proteinuria.

Results: Of 36 enrolled patients, 10, 14, and 12 patients received placebo, fresolimumab 1 mg/kg, and fresolimumab 4 mg/kg, respectively. The baseline estimated glomerular filtration rate (eGFR) and urinary protein/creatinine ratio were 63 ml/min/1.73 m2 and 6190 mg/g, respectively. The study was closed before reaching its target of 88 randomized patients. None of the prespecified efficacy endpoints for proteinuria reduction were achieved; however, at day 112, the mean percent change in urinary protein/creatinine ratio (a secondary efficacy endpoint) was -18.5% (P = 0.008), +10.5% (P = 0.52), and +9.0% (P = 0.91) in patients treated with fresolimumab 1 mg/kg, fresolimumab 4 mg/kg, and placebo, respectively. There was a nonsignificant trend toward greater estimated glomerular filtration rate decline in the placebo group compared to either of the fresolimumab-treated arms up to day 252.

Discussion: The study was underpowered and did not meet the primary or secondary endpoints. However, fresolimumab was well tolerated and is appropriate for continued evaluation in larger studies with adequate power.

Keywords: fresolimumab; monoclonal antibody; proteinuria; steroid-resistant primary focal segmental glomerulosclerosis.

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Figures

Figure 1
Figure 1
Consolidated Standards of Reporting Trials (CONSORT) diagram.
Figure 2
Figure 2
(a) Estimated mean percent change in urinary protein/creatinine ratio (Up/c) from baseline to day 112/visit 6 by treatment assignment. (b) Mean (± SE) percent change from baseline in estimated glomerular filtration rate (eGFR) over time by treatment assignment.
Figure S1
Figure S1
Focal segmental glomerulosclerosis (FSGS) patients assigned to 1 mg/kg (n = 14).
Figure S2
Figure S2
Focal segmental glomerulosclerosis (FSGS) patients assigned to placebo (n = 10).
Figure S3
Figure S3
Focal segmental glomerulosclerosis (FSGS) patients assigned to 1 mg/kg with > 1 partial remission event (n = 6).
Figure S4
Figure S4
Focal segmental glomerulosclerosis (FSGS) patients assigned to 4 mg/kg (n = 12; 3 treated with other immunosuppressant medications).
Figure S5
Figure S5
Postinfusion fresolimumab serum concentrations (mean ± SE).
See this image and copyright information in PMC

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