A pilot study evaluating GSK1070806 inhibition of interleukin-18 in renal transplant delayed graft function

Introduction Delayed graft function (DGF) following renal transplantation is a manifestation of acute kidney injury (AKI) leading to poor long-term outcome. Current treatments have limited effectiveness in preventing DGF. Interleukin-18 (IL18), biomarker AKI, induces interferon-? expression and immune activation. GSK1070806, an anti-IL18 monoclonal antibody, neutralizes activated (mature) IL18 released from damaged cells inflammasome This phase IIa, single-arm trial assessed the effect single dose GSK1070806 on DGF occurrence post donation after circulatory death (DCD) transplantation. Methods The 3 mg/kg intravenous was selected based prior studies physiologically pharmacokinetic (PBPK) modeling, indicating high likelihood rapid level target engagement when administered allograft reperfusion. Utilization Bayesian sequential design with background standard-of-care rate 50% literature, confirmed via extensive registry data analyses, enabled statistical efficacy assessment minimal sample size. primary endpoint frequency, defined as dialysis requirement ?7 days (except for hyperkalemia). Secondary endpoints included safety, pharmacokinetics pharmacodynamic biomarkers. Results administration associated IL18-GSK1070806 complex detection increased total serum levels due half-life prolongation induced by binding. Interferon-??induced chemokine declined or remained unchanged most patients. Although study concluded Bayesian-defined stopping point, 4/7 enrolled patients (57%) had DGF, exceeding rate, additional two patients, although not reaching protocol-defined definition, demonstrated function. Six seven experienced serious adverse events (SAEs), including treatment-related SAEs. Conclusion Overall, using PBPK modeling only small size, it deemed unlikely that would be efficacious DCD transplant population. Trial registration NCT02723786 .