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. 2020 Nov 13;6(2):296-303.
doi: 10.1016/j.ekir.2020.11.001. eCollection 2021 Feb.

Phase 3 trial Design of the Hepatocyte Growth Factor Mimetic ANG-3777 in Renal Transplant Recipients With Delayed Graft Function

Flavio Vincenti  1 , Jim Kim  2 , Deborah Gouveia  3 , Gabrielle Pelle  3 , Tracy J Mayne  3 , John F Neylan  3
Affiliations

Phase 3 trial Design of the Hepatocyte Growth Factor Mimetic ANG-3777 in Renal Transplant Recipients With Delayed Graft Function

Flavio Vincenti et al. Kidney Int Rep. .

Abstract

Introduction: One-third of kidney transplantation patients experience acute kidney injury (AKI) resulting in delayed graft function (DGF), associated with increased risk of graft failure and mortality. Preclinical and phase 2 data indicate that treatment with ANG-3777 (formerly BB3), a hepatocyte growth factor (HGF) mimetic, may improve long-term kidney function and reduce health care resource use and cost, but these data require validation in a phase 3 randomized controlled trial.

Methods: The Graft Improvement Following Transplant (GIFT) trial is a multicenter, double-blind randomized controlled trial, designed to determine the efficacy and safety of ANG-3777 in renal transplantation patients showing signs of DGF. Subjects are randomized 1:1 to ANG-3777 (2 mg/kg) administered intravenously once daily for 3 consecutive days starting within 30 hours after transplantation, or to placebo.

Results: The primary endpoint is estimated glomerular filtration rate (eGFR) at 12 months. Secondary endpoints include proportion of subjects with eGFR >30 at days 30, 90, 180, and 360; proportion of subjects whose graft function is slow, delayed, or primary nonfunction; length of hospitalization; and duration of dialysis through day 30. Adverse events are assessed throughout the study.

Conclusion: GIFT will generate data that are important to advancing treatment of DGF in this medically complex population.

Keywords: ANG-3777; acute kidney injury; delayed graft function; eGFR; hepatocyte growth factor; kidney transplantation.

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Figures

None
Graphical abstract
Figure 1
Figure 1
Structure and biologic function of HGF: HGF/c-MET signaling pathways are associated with angiogenesis as well as cell survival, proliferation, mobility, and cytoskeletal changes. Reprinted with permission, Nakamura T, Mizuno S. The discovery of hepatocyte growth factor (HGF) and its significance for cell biology, life sciences and clinical medicine. Proc Jpn Acad Ser B Phys Biol Sci. 2010;86:588-610. ©2010 The Japan Academy.
Figure 2
Figure 2
Estimated Glomerular Filtration Rate Over Time by Study Arm: Results from phase 2 randomized controlled trial indicating improvements in eGFR beginning 14 days post-transplant. Reprinted with permission, Bromberg JS, Weir MR, Gaber AO, Yamin MA, Goldberg ID, Mayne TJ, Cai W, Cooper M. Renal function improvement following ANG-3777 treatment in patients at high risk for delayed graft function after kidney transplantation. Transplantation. 2021;105:443–450. Copyright 2020 The Authors. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY).
Figure 3
Figure 3
Study schematic depicting randomization, intervention, and schedule of assessments. ∗Review of medical records between study visit days for eGFR, CNI dose and trough, adverse events, and select concomitant medications. ACE, angiotensin-converting enzyme; ARBs, angiotensin receptor blockers; CNI, calcineurin inhibitor; CRP, C-reactive protein; eGFR, estimated glomerular filtration rate; KIM-1, kidney injury molecule–1; LOS, length of stay; NGAL, neutrophil gelatinase–associated lipocalin.
See this image and copyright information in PMC

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