Renal Function Improvement Following ANG-3777 Treatment in Patients at High Risk for Delayed Graft Function After Kidney Transplantation

Jonathan S. Bromberg, Matthew R. Weir, A. Osama Gaber, Michael A. Yamin, Itzhak D. Goldberg, Tracy J. Mayne, Weizhong Cal, Matthew Cooper

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Patients (20%-50%) undergoing renal transplantation experience acute kidney injury resulting in delayed graft function. ANG-3777 is an hepatocyte growth factor mimetic that binds to the c-MET receptor. In animal models, ANG-3777 decreases apoptosis, increases proliferation, and promotes organ repair and function. METHODS: This was a randomized, double-blind, placebo-controlled, phase 2 trial of patients undergoing renal transplantation with <50 cc/h urine output for 8 consecutive hours over the first 24 hours posttransplantation, or creatinine reduction ratio <30% from pretransplantation to 24 hours posttransplantation. Subjects were randomized as 2:1 to 3, once-daily IV infusions of ANG-3777, 2 mg/kg (n = 19), or placebo (n = 9). Primary endpoint: time in days to achieve ≥1200 cc urine for 24 hours. RESULTS: Patients treated with ANG-3777 were more likely to achieve the primary endpoint of 1200 cc urine for 24 hours by 28 days posttransplantation (83.3% versus 50% placebo; log-rank test: χ2 = 2.799, P = 0.09). Compared with placebo, patients in the ANG-3777 arm had larger increases in urine output; lower serum creatinine; greater reduction in C-reactive protein and neutrophil gelatinase-associated lipocalin; fewer dialysis sessions and shorter duration of dialysis; fewer hospital days; significantly less graft failure; and higher estimated glomerular filtration rate. Adverse events occurred in a similar percentage of subjects in both arms. Events per subject were twice as high in the placebo arm. CONCLUSIONS: There was an efficacy signal for improved renal function in subjects treated with ANG-3777 relative to placebo, with a good safety profile.

Original languageEnglish (US)
Pages (from-to)443-450
Number of pages8
JournalTransplantation
Volume105
Issue number2
DOIs
StatePublished - Feb 1 2021

ASJC Scopus subject areas

  • Transplantation

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