AZD4144 / AstraZeneca - LARVOL DELTA

Safety, Tolerability, Pharmacokinetics, and Target Engagement of Oral AZD4144, a Small Molecule NLRP3 Inhibitor (AHA 2026) - "Abstract is embargoed at this time."

Clinical • PK/PD data • Cardiovascular • Heart Failure • NLRP3

Investigating the Effect of Itraconazole on the Pharmacokinetics of AZD4144 in Healthy Participants (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open

A Phase I Study to Investigate the Effect of Hepatic Impairment on the Pharmacokinetics, Safety, and Tolerability of AZD4144 (clinicaltrials.gov) - P1 | N=30 | Not yet recruiting | Sponsor: AstraZeneca

New P1 trial • Hepatology

The NLRP3 inflammasome in chronic kidney disease progression: systematic review of preclinical models reveals a critical gap in pyroptosis research and therapeutic translation. (PubMed, Mol Biol Rep) - "Furthermore, despite multiple preclinical studies, only AZD4144, an AstraZeneca NLRP3 inhibitor, is currently in clinical trials for CKD. Overall, NLRP3 is a validated driver of CKD progression across diverse models. The lack of evaluation of NLRP3-mediated pyroptosis in CKD, along with limited clinical trials evaluating NLRP3 inflammasome inhibitors, highlights key research and translational gaps in CKD treatment."

Journal • Preclinical • Review • Chronic Kidney Disease • Fibrosis • Immunology • Inflammation • Metabolic Disorders • Nephrology • Renal Disease • IL18 • IL1B • NLRP3

Investigating the Effect of Itraconazole on the Pharmacokinetics of AZD4144 in Healthy Participants (clinicaltrials.gov) - P1 | N=32 | Not yet recruiting | Sponsor: AstraZeneca

New P1 trial

A Study of Absorption, Distribution, Metabolism and Excretion (ADME) of [14C]AZD4144 (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion

A Phase IIa Study to Assess the Efficacy, Safety, and Tolerability of AZD4144 in Participants with Sepsis-associated Acute Kidney Injury (SERENIA) (ERA 2026) - "Conclusion AZD4144 was safe and well-tolerated in healthy and renally impaired individuals and has demonstrated effective target engagement ex vivo. SERENI A aims to further assess the efficacy and safety of AZD4144 in adults with SA-AKI ."

Clinical • P2a data • Acute Kidney Injury • Cardiovascular • Congestive Heart Failure • Heart Failure • Hypotension • Infectious Disease • Nephrology • Renal Disease • Septic Shock • IL18 • IL1B • IL6 • NLRP3

SERENIA: A Study to Investigate the Efficacy, Safety, and Tolerability of AZD4144in Participants With Sepsis-associated Acute Kidney Injury. (clinicaltrials.gov) - P2 | N=124 | Recruiting | Sponsor: AstraZeneca

Trial initiation date • Acute Kidney Injury • Infectious Disease • Nephrology • Renal Disease • Septic Shock • CST3

A Study of Absorption, Distribution, Metabolism and Excretion (ADME) of [14C]AZD4144 (clinicaltrials.gov) - P1 | N=8 | Active, not recruiting | Sponsor: AstraZeneca

New P1 trial

D9440C00004: A trial to learn how well AZD4144 works, how safe it is, and how it moves throughout the body over time in adults with acute kidney injury caused by sepsis (clinicaltrialsregister.eu) - P1/2 | N=66 | Not yet recruiting | Sponsor: AstraZeneca AB

New P1/2 trial • Acute Kidney Injury • Infectious Disease • Nephrology • Renal Disease • Septic Shock

SERENIA: A Study to Investigate the Efficacy, Safety, and Tolerability of AZD4144in Participants With Sepsis-associated Acute Kidney Injury. (clinicaltrials.gov) - P2 | N=124 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Kidney Injury • Infectious Disease • Nephrology • Renal Disease • Septic Shock • CST3

A Phase 1b Study to Assess the Safety, Tolerability, and Pharmacodynamics of AZD4144 in Participants With Established Atherosclerotic Cardiovascular and Chronic Kidney Disease. (clinicaltrials.gov) - P1 | N=29 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • Nephrology • Renal Disease

Inhibition of NLRP3 Signalling Improves Kidney Function in Preclinical Models of AKI (KIDNEY WEEK 2025) - "NLRP3 inhibition significantly reduces kidney injury in preclinical models of AKI. These findings support the therapeutic potential of AZD4144 for AKI."

Preclinical • Acute Kidney Injury • Cardiovascular • Infectious Disease • Nephrology • Renal Disease • Reperfusion Injury • Septic Shock • IL18 • IL1B • NLRP3

Safety, Tolerability, Pharmacokinetics, and Target Engagement of Single and Multiple Ascending Doses of Intravenous AZD4144, a Small Molecule NLRP3 Inhibitor for Treatment of AKI (KIDNEY WEEK 2025) - "AZD4144 demonstrated robust, dose-dependent, durable inhibition (>90%) of IL-1β and Il-18 production by PBMCs stimulated ex vivo. Conclusion AZD4144 was safe and well tolerated in healthy participants, had pharmacokinetics supporting once daily IV infusion, and displayed robust, dose-dependent inhibition of ex vivo stimulated IL-18 and IL-1b secretion."

Clinical • PK/PD data • Acute Kidney Injury • Chronic Kidney Disease • Infectious Disease • Inflammation • Nephrology • Renal Disease • IL18 • IL1B • NLRP3

A Study to Investigate the Safety, Tolerability and Pharmacodynamics of AZD4144 in Participants With Obesity (clinicaltrials.gov) - P1 | N=28 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion • Genetic Disorders • Obesity

A Phase 1b Study to Assess the Safety, Tolerability, and Pharmacodynamics of AZD4144 in Participants With Established Atherosclerotic Cardiovascular and Chronic Kidney Disease. (clinicaltrials.gov) - P1 | N=29 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Atherosclerosis • Cardiovascular • Chronic Kidney Disease • Nephrology • Renal Disease

SERENIA: A Study to Investigate the Efficacy, Safety, and Tolerability of AZD4144in Participants With Sepsis-associated Acute Kidney Injury. (clinicaltrials.gov) - P2 | N=124 | Not yet recruiting | Sponsor: AstraZeneca

New P2 trial • Acute Kidney Injury • Infectious Disease • Nephrology • Renal Disease • Septic Shock • CST3

A Study to Investigate the Safety, Tolerability and Pharmacodynamics of AZD4144 in Participants With Obesity (clinicaltrials.gov) - P1 | N=28 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Genetic Disorders • Obesity

A Study to Investigate the Relative Bioavailability of 2 Different Formulations of AZD4144, the Effect of Food and Omeprazole on the Pharmacokinetics of AZD4144 in Healthy Participants (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: AstraZeneca | Recruiting ➔ Completed

Trial completion

Discovery of AZD4144, a Selective and Potent NLRP3 Inhibitor for the Treatment of Inflammatory Diseases. (PubMed, J Med Chem) - "The compound inhibits NLRP3 selectively with high potency, has beneficial pharmacokinetic properties, and shows a favorable off-target pharmacology profile. We also show that AZD4144 binds directly to NLRP3 and competes with MCC950 for binding to the protein, indicating that the likely mode of inhibition of AZD4144 is to stabilize the inactive form of NLRP3."

Journal • Cardiovascular • Infectious Disease • Inflammation • NLRP3

A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AZD4144 as Well as the Impact of AZD4144 on the Pharmacokinetics of Rosuvastatin and Furosemide in Healthy Participants (clinicaltrials.gov) - P1 | N=91 | Completed | Sponsor: AstraZeneca | Recruiting ➔ Completed

Trial completion

A Study to Investigate How AZD4144 Affects the Pharmacokinetics of Rosuvastatin in Healthy Participants (clinicaltrials.gov) - P1 | N=12 | Completed | Sponsor: AstraZeneca | Active, not recruiting ➔ Completed

Trial completion

A Study to Investigate How AZD4144 Affects the Pharmacokinetics of Rosuvastatin in Healthy Participants (clinicaltrials.gov) - P1 | N=12 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed

A Study to Investigate the Relative Bioavailability of 2 Different Formulations of AZD4144, the Effect of Food and Omeprazole on the Pharmacokinetics of AZD4144 in Healthy Participants (clinicaltrials.gov) - P1 | N=32 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open

A Study to Investigate the Pharmacokinetics, Safety, and Tolerability of AZD4144 in Participants With Severe Renal Impairment, End-stage Kidney Disease, and in Healthy Participants (clinicaltrials.gov) - P1 | N=41 | Completed | Sponsor: AstraZeneca | Recruiting ➔ Completed | N=24 ➔ 41

Enrollment change • Trial completion • Chronic Kidney Disease • Nephrology • Renal Disease