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

Transplantation. 2021 Feb 1;105(2):443-450. doi: 10.1097/TP.0000000000003255.


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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Acute Kidney Injury / drug therapy*
  • Acute Kidney Injury / etiology
  • Acute Kidney Injury / physiopathology
  • Adult
  • Aged
  • Creatinine / blood
  • Delayed Graft Function / drug therapy*
  • Delayed Graft Function / etiology
  • Delayed Graft Function / physiopathology
  • Double-Blind Method
  • Female
  • Glomerular Filtration Rate / drug effects
  • Humans
  • Kidney / drug effects*
  • Kidney / physiopathology
  • Kidney / surgery*
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Pyrazoles / adverse effects
  • Pyrazoles / therapeutic use*
  • Recovery of Function
  • Thiophenes / adverse effects
  • Thiophenes / therapeutic use*
  • Time Factors
  • Treatment Outcome
  • United States
  • Urodynamics / drug effects


  • Pyrazoles
  • Thiophenes
  • Creatinine
  • terevalefim