Renal function improvement following ANG-3777 treatment in patients at high risk for delayed graft function after kidney transplantation.

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Bromberg JS, Weir MR, Gaber AO, Browne BJ, Yamin MA, Goldberg ID, Mayne TJ, Cooper M

Renal function improvement following ANG-3777 treatment in patients at high risk for delayed graft function after kidney transplantation.

Transplantation. 2020 Apr 6. doi: 10.1097/TP.0000000000003255.

PubMed ID
32265417 [ View in PubMed
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Abstract

BACKGROUND: Twenty to 50% of renal transplantation patients experience acute kidney injury resulting in delayed graft function (DGF). ANG-3777 is an HGF mimetic which 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 renal transplantation patients with <50 cc/h urine output for eight consecutive hours over the first 24 hours post-transplantation; and/or creatinine reduction ratio <30% from pretransplantation to 24 hours post-transplantation. Subjects were randomized 2:1 to three, once-daily IV infusions of ANG-3777, 2 mg/kg (n=19) or placebo (n=9). Primary endpoint: time in days to achieving >/= 1200 cc urine over 24 hours. RESULTS: Patients treated with ANG-3777 were more likely to achieve the primary endpoint of 1200 cc urine over 24 hours by 28 days post-transplantation (78.9% vs 44.4% placebo; log-rank test: chi = 2.799, p = 0.09). Compared to placebo, patients in the ANG-3777 arm had larger increases in urine output; lower SCr; greater reduction in C-reactive protein (CRP) and neutrophil gelatinase-associated lipocalin (NGAL); fewer dialysis sessions and shorter duration of dialysis; fewer hospital days; significantly less graft failure; and higher eGFR. 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.

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