Kidney Week

Abstract: INFO05-FR

A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Dose-Finding Phase 2b Trial to Assess the Safety and Efficacy of TIN816 in the Treatment of Adult Patients with Sepsis-Associated AKI

Session Information

• Informational Posters - 2
  October 25, 2024 | Location: Exhibit Hall, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• No subcategory defined

Authors

• Murray, Patrick T., School of Medicine, University College Dublin, Dublin, Ireland

Patrick T. Murray, MD, FASN

• Demiselle, Julien, French National Institute of Health and Medical Research (INSERM), UMR 1260, Regenerative Nanomedicine (RNM), Center for Research in Biomedicine of Strasbourg (CRBS), Federation of Translational Medicine of Strasbourg (FMTS), University of Strasbourg, Strasbourg, France

Julien Demiselle, MD

• De Schryver, Nicolas, Intensive Care Unit, Clinique Saint-Pierre, Ottignies, Belgium

Nicolas De Schryver, MD

• Faguer, Stanislas, Department of Nephrology and Organ Transplantation and Reference Center for Rare Renal Diseases, Rangueil University Hospital, Toulouse, France

Stanislas Faguer, MD, PhD

• Fivez, Tom, Intensive Care Unit, ZOL Genk General Hospital, Genk, Belgium

Tom Fivez, MD, PhD

• Bagshaw, Sean M., Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta and Alberta Health Services, 2-124E Clinical Sciences Building, 8440-112 St NW, T6G 2B7, Edmonton, Alberta, Canada

Sean M. Bagshaw, MD

• Joannidis, Michael, Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University of Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria

Michael Joannidis, MD

• Koyner, Jay L., Section of Nephrology, Department of Medicine, University of Chicago, 5841 South Maryland Ave, Suite S-506, MC 5100, 60637, Chicago, Illinois, United States

Jay L. Koyner, MD, FASN

• Shaw, Andrew, Department of Intensive Care and Resuscitation, Cleveland Clinic, 9500 Euclid Avenue, 44195, Cleveland, Ohio, United States

Andrew Shaw, MD

• Rowland, Matthew J., Novartis Pharmaceuticals UK Ltd, London, United Kingdom

Matthew J. Rowland, MBBS, PhD

• Ibram, Ghionul, Novartis Pharmaceutical Corporation, East Hanover, New Jersey, United States

Ghionul Ibram

• Calonder, Claudio, Novartis Pharma AG, Basel, Basel-Stadt, Switzerland

Claudio Calonder, MSc, PhD

• Chen, Chien-Wei, Novartis Pharmaceutical Corporation, East Hanover, New Jersey, United States

Chien-Wei Chen, PhD

• Zhou, Yinong, Novartis Pharmaceutical Corporation, East Hanover, New Jersey, United States

Yinong Zhou, MD

• Renfurm, Ronny W., Novartis Pharma AG, Basel, Basel-Stadt, Switzerland

Ronny W. Renfurm, MD, MBA

Description

Sepsis-associated acute kidney injury (SA-AKI) is the most common form of severe acute kidney injury (AKI) and there is no approved pharmacological intervention. TIN816 is a human recombinant CD39 enzyme with potent anti-inflammatory, anti-thrombotic and tissue repair and protective effects. TIN816 may have potential to improve outcomes in patients with SA-AKI. This Phase 2b trial aims to characterize the dose–response relationship and evaluate the safety and efficacy of three different doses of TIN816 compared to placebo in patients with SA-AKI.

This is a multicenter, randomized, double-blind, placebo-controlled trial of 320 critically ill patients with SA-AKI. Inclusion criteria for patients include: age ≥18 to ≤85 years, admitted to intensive, intermediate or high dependency care unit, diagnosis of sepsis and Kidney Disease: Improving Global Outcomes (KDIGO) stage I AKI or greater. Exclusion criteria include: known chronic kidney disease (CKD) (eGFR <45 mL/min), receiving renal replacement therapy (RRT), documented or suspected history of acute or sub-acute kidney disease and thrombocytopenia or any other increased risk for bleeding. Patients will be randomly allocated to one of four treatment arms: single dose of TIN816 (4 mg/kg, 2 mg/kg or 1 mg/kg) or single dose of placebo – all given as IV infusion over 2 hours within 24 hours of AKI diagnosis. The primary objective of the study is to characterize the dose–response relationship of TIN816 on renal function measured by creatinine clearance (CrCl) in patients with SA-AKI. Secondary and exploratory objectives include the evaluation of safety and tolerability, all-cause mortality of TIN816 vs placebo, the effect of TIN816 vs placebo in reducing major adverse kidney events (MAKE), as well as the pharmacodynamic and pharmacokinetic characterization of TIN816.

This dose-finding, Phase 2b study will provide evidence towards the safety and efficacy of TIN816 in the treatment of patients with SA-AKI (ClinicalTrials.gov: NCT05996835).

Funding

• The study is sponsored by Novartis Pharma AG, Basel, Switzerland. Editorial and medical writing support for this abstract was provided by Rangariroyashe Chipika and Carol Crawford (Novartis Ireland Limited, Dublin, Ireland) and funded by Novartis Pharma AG, Basel, Switzerland in accordance with the Good Publication Practice (GPP 2022) guidelines (http://www.ismpp.org/gpp-2022).