Efficacy, Safety, Tolerability and Pharmacokinetic (PK) Study of GSK1070806 for the Prevention of Delayed Graft Function (DGF) in Adult Subjects After Renal Transplantation

Summary

This is a phase 2 study to evaluate the efficacy, safety, tolerability and pharmacokinetics of GSK1070806 in subjects undergoing renal transplantation. GSK1070806 is an anti-interleukin 18 (IL18) monoclonal antibody, which binds to IL-18 and inhibits signaling through the IL-18 receptor. Recipients of donor kidneys, retrieved after circulatory death of the donor, will be administered a single intravenous infusion of GSK1070806 to test whether inhibition of IL-18 can reduce the rate of Delayed Graft Function (DGF) and graft rejection. Subjects will be followed for 12 months post dose/transplant. Up to 40 adult subjects will be enrolled in this study.

Timeline

Start

2016-08-27

Primary completion

2017-03-31

Completion

2018-03-06

Outcome

Missed primary endpoint

Stopped: “Lack of efficacy”

paper 4/7 enrolled patients (57%) had DGF, exceeding the 50% standard-of-care rate PMID 33684160 ↗

paper it was deemed unlikely that GSK1070806 would be efficacious in preventing DGF PMID 33684160 ↗

Publications

• Wlodek E, Kirkpatrick RB, Andrews S, Noble R, Schroyer R, Scott J, Watson CJE, Clatworthy M, Harrison EM, Wigmore SJ, Stevenson K, Kingsmore D, Sheerin NS, Bestard O, Stirnadel-Farrant HA, Abberley L, Busz M, DeWall S, Birchler M, Krull D, Thorneloe KS, Weber A, Devey L. A pilot study evaluating GSK1070806 inhibition of interleukin-18 in renal transplant delayed graft function. PLoS One. 2021 Mar 8;16(3):e0247972. doi: 10.1371/journal.pone.0247972. eCollection 2021.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	GSK1070806	Monoclonal antibody	3 mg/kg	Intravenous
Background	Azathioprine	Small molecule	—	—
Background	Basiliximab	Monoclonal antibody	—	—
Background	Mycophenolate Mofetil	Small molecule	—	—
Background	Tacrolimus	Small molecule	—	—

Indications