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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

6 Mar 2026 → ongoing

Decision date (initial)

2026-01-19

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Astrazeneca

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Therapy, Safety, Pharmacokinetic

To evaluate the effect of AZD4144 on Creatinine Clearance (CrCl)

Secondary objectives 5

1. To evaluate the effect of AZD4144 on additional measures of kidney function
2. To evaluate the effect of AZD4144 on inflammatory biomarkers
3. To assess the PK of AZD4144 in patients with SA-AKI
4. To evaluate the effect of AZD4144 on MAKE30
5. To evaluate the effect of AZD4144 on other clinical observations

Conditions and MedDRA coding

Sepsis-associated acute kidney injury (AKI)

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. Adults aged 18 to 80 years
2. Hospitalized with a diagnosis of sepsis (suspected or confirmed) within 7 days of admission
3. Diagnosis of acute kidney injury (AKI; KDIGO Stage ≥ 1) within 72 hours of sepsis diagnosis.
4. Able to receive the study drug within 36 hours of SA-AKI diagnosis.
5. Provision of informed consent by the participant or legally authorized representative.
6. Diagnosis of sepsis according to criteria defined by The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) based on: (a) Suspected or confirmed bacterial infection AND (b) Acute increase of mSOFA score of 2 or more excluding renal component (change in score measured to account for participants that may meet mSOFA criteria from pre-existing organ dysfunction before the onset of infection).
7. Vasopressor and/or inotrope therapy for sepsis-induced hypotension (norepinephrine [noradrenaline], epinephrine [adrenaline], phenylephrine, dopamine, dobutamine) for ≥ 4 hours after 30 mL/kg or clinically appropriate volume resuscitation prior to randomisation
8. Diagnosis of AKI with modified KDIGO Stage ≥ 1 persisting after initial volume resuscitation (30 mL/kg or as clinically indicated per investigator discretion)
9. Outpatient pre-AKI reference eGFR ≥ 30 mL/min/1.73 m2 or admission pre-AKI reference eGFR ≥ 45 mL/min/1.73 m2.

Exclusion criteria 24

1. Known history of Stage 4 or 5 CKD with documented sustained eGFR < 30 mL/min/1.73 m2 prior to hospital admission.
2. No serum creatinine results available within 12 months of admission and an eGFR < 45 mL/min/1.73 m2 at admission.
3. Sepsis diagnosed > 7 days after hospital admission (to include from time of outside admission if patient transferred from another healthcare setting).
4. AKI attributed to causes other than sepsis, including but not limited to compromised renal perfusion-related causes (surgical complication, acute abdominal aortic aneurysm, dissection, renal artery stenosis, etc), glomerular disease, acute interstitial nephritis, and medication toxicity.
5. Evidence of recovery from AKI prior to randomisation defined as: (a) A reduction of serum creatinine to less than 1.5 times reference serum creatinine in the last available local SoC laboratory result before randomisation or (b) A > 25% reduction in serum creatinine from peak serum creatinine after volume resuscitation prior to randomisation.
6. Expected survival from sepsis < 24 hours.
7. Expected survival < 90 days due to chronic or pre-existing medical conditions other than SA-AKI, including but not limited to cancer, end-stage cardiac disease, cardiac arrest requiring cardiopulmonary resuscitation or with pulseless electrical activity or asystole within the past 30 days, end-stage lung disease, end-stage neurological disease, and end-stage liver disease.
8. Known history of immunodeficiency disease or currently receiving immunosuppressant therapy for non-sepsis related disease, including but not limited to treatment for organ transplant, cancer, or autoimmune disease; current treatment with high-dose steroid therapy (dose equivalent to prednisone/prednisolone 0.5 mg/kg/day) exceeding 2 weeks duration. Steroids administered as management of septic shock are permitted.
9. Sepsis attributed to confirmed or presumed fungal or viral infection at time of Screening. Concomitant bacteraemia with a viral infection is NOT exclusionary (for example presumed bacteraemia in a participant with documented influenza).
10. Known history of cerebrovascular accident within the last 90 days.
11. Known history of heart failure with reduced ejection fraction with documented ejection fraction ≤ 20% before sepsis diagnosis.
12. Known hypersensitivity to iohexol or known history of severe adverse reaction to iodinated contrast media.
13. Current KRT (eg, continuous haemofiltration and haemodialysis/continuous renal replacement therapy, intermittent haemodialysis, and peritoneal dialysis) or planned KRT at randomisation.
14. Active or planned treatment of sepsis with an extracorporeal haemoperfusion device.
15. Participation in any other concurrent ICU which could impact participant clinical outcomes and confound results of this study to, including but not limited to volume resuscitation, vasopressor, or mechanical ventilation studies.
16. Presence of anuria (≥ 12 hours) at randomisation
17. Known history of ST-elevation myocardial infarction or non-ST-elevation myocardial infarction, with or without intervention by percutaneous coronary intervention or coronary artery bypass grafting within the last 90 days.
18. Undergoing extracorporeal membrane oxygenation (ECMO) at randomisation.
19. Neutropenia: ANC < 1.5 × 109/L.
20. Admitting diagnosis of rhabdomyolysis.
21. Admitting diagnosis of trauma with CK > 15000 U/L.
22. Presumed nidus of infection in central nervous system.
23. First dose of IMP unable to be administered within 36 hours of AKI diagnosis.
24. Presence of a do-not-resuscitate order.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Area Under the Curve (AUC) of 24-hour Creatinine Clearance (CrCl)

Secondary endpoints 13

1. Days alive and free of KRT
2. Days alive and free of modified KDIGO AKI Stage 2 or 3
3. AUC: Serum creatinine, Serum cystatin C, mGFR
4. Cmax/Cbaseline: Serum creatinine, Serum cystatin C
5. AUC: Plasma and urine IL-18, Plasma and urine IL-6
6. Plasma concentrations of AZD4144
7. Occurrence of any of the following MAKE30 components: (a) Decrease from pre-AKI reference eGFR of ≥ 25% (b) Initiation of KRT at any time (c) Death from any cause
8. Days alive and free of mechanical ventilation
9. Days alive and outside of the ICU
10. Rehospitalisation
11. Days alive and free of hospitalisation
12. Days alive and free of vasopressor and/or inotrope use
13. AUC mSOFA score

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

9 EU/EEA countries · 38 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 67 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

8 submissions — initial application plus substantial / non-substantial modifications