Kidney Week

Abstract: SA-OR013

SERENIA: A Phase 2a Study to Assess the Safety, Efficacy, and Tolerability of AZD4144 in Sepsis-Associated AKI

Session Information

• AKI Trials, Therapeutics, and Risk Stratification
  October 24, 2026 | Location: Room 603, Convention Center
  Abstract Time: 05:00 PM - 05:10 PM

Category: Acute Kidney Injury

• 102 AKI: Clinical, Outcomes, and Trials

Authors

• Schaffner, Hannah, Translational Science and Clinical Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, United States

Hannah Schaffner, PharmD

• MacPhee, Iain, Late Clinical Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals, AstraZeneca, Cambridge, United Kingdom

Iain MacPhee, MBChB, PhD

• Olson, Stephen, Late Clinical Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, United States

Stephen Olson, MD

• Caballero-Corbalán, José, Translational Science and Clinical Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden

José Caballero-Corbalán, MD, PhD

• Bhattacharya, Chandrali S., Clinical Pharmacology & Pharmacometrics, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, United States

Chandrali S. Bhattacharya, PhD

• Varma, Vijayalakshmi, Translational Science and Clinical Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, Maryland, United States

Vijayalakshmi Varma, PhD

• Knutsson, Mikael, Biometrics, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden

Mikael Knutsson

• Boag, Katie, Clinical Operations, BioPharmaceuticals R&D, AstraZeneca, Mississauga, Ontario, Canada

Katie Boag

• Middlemiss, Jessica, Clinical Operations, BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom

Jessica Middlemiss

• Kolodziejek-Straczynska, Izabella Aneta, Clinical Operations, BioPharmaceuticals R&D, AstraZeneca, Warsaw, Poland

Izabella Aneta Kolodziejek-Straczynska, PhD

• Rehnstrom, Erika, Clinical Operations, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden

Erika Rehnstrom, PhD

• Pearce, Andy, Projects, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Cambridge, United Kingdom

Andy Pearce, MSc, PhD

• Hofherr, Alexis, Translational Science and Clinical Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden

Alexis Hofherr

Background

NLRP3 pathway biomarkers strongly correlate with AKI severity. NLRP3 inflammasome-driven cytokine release, pyroptosis, and NETosis are thought to perpetuate maladaptive repair in AKI. AZD4144 is a small-molecule NLRP3 inhibitor in clinical development for AKI.

Methods

Two phase 1 studies assessed the safety, tolerability, pharmacokinetics, and target engagement of AZD4144 in healthy and renally impaired individuals.
SERENIA is a phase 2a, randomized, double-blind, placebo-controlled study of IV AZD4144 in adults with SA-AKI. Sepsis is defined as suspected or confirmed bacterial infection and ≥2-point increase in renal-independent SOFA score. AKI is defined as a 1.5-fold increase in serum creatinine from baseline following appropriate volume resuscitation, diagnosed ≤72 hours following sepsis diagnosis. Key inclusion criteria: Vasopressor/inotrope use ≥4 hours; Pre-morbid baseline eGFR ≥30 or ≥45 mL/min/1.73 m2 at admission. Key exclusion criteria: Admission >7 days prior to sepsis diagnosis; AKI ≤36 hours prior to first dose of AZD4144; Current or planned KRT; AKI recovery prior to randomization.
Approximately 124 participants will be evenly randomized to IV AZD4144 or placebo administered once daily for seven days, with follow-up to Day 30. Primary endpoint: 24-hour CrCl AUC Days 1–7. Key secondary endpoints: Days alive and free of KRT; Days alive and free of modified KDIGO AKI Stage 2 or 3; AUC day 1-7 of sCr, sCysC, mGFR, IL-18, and IL-6; MAKE30.

Results

In 79 healthy participants, IV AZD4144 was safe and well-tolerated with predictable PK and >90% ex vivo inhibition of IL-18 and IL-1β. In 41 participants with normal or impaired renal function, AZD4144 was safe and well-tolerated. Plasma exposure was elevated relative to controls in participants with mild, moderate, and severe renal impairment [AUCinf (h*umol/L): 25.7 (normal), 27.7 (mild), 31.2 (moderate), 50.7 (severe)] and was minimally affected by IHD in participants with ESKD.
The efficacy, safety, and tolerability of IV AZD4144 in individuals with SA-AKI is currently under evaluation in SERENIA. Here, we present baseline characteristics of the randomized study population.

Conclusion

AZD4144 was safe and well-tolerated in healthy and renally impaired individuals and has demonstrated effective target engagement ex vivo. SERENIA aims to further assess the efficacy and safety of AZD4144 in adults with SA-AKI.

Acknowledgment

The following individuals contributed to research design and/or conduct: Daniel Hovdal, Ian Wallace, Joanna Parkinson, Jasia King, Annika Yeiter, Pramod Math, Ann-Kerstin Ekelund, Susanna Eketjäll, Cecilia Falkenberg, Jeffy John, Kerstin Lösel, Isabelle Leefa, Berit Purschel, Yula Niron, Elena Martinez, Adriana Gomez, Yordanka Stoycheva, Vineetha Vishwanathan, Babitha George, Guillaume Narbonne, Anders Bjurström, Jennifer Schmoll, Erlend Johannessen Egeland, Yao-Yao Zhu, Yuejia Xu

Funding

• Commercial Support – AstraZeneca