A Study to Investigate the Efficacy, Safety, and Tolerability of AZD4144in Participants With Sepsis-associated Acute Kidney Injury.

NCT ID: NCT07215702

Last Updated: 2025-10-15

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 124 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-02
• Study Completion Date: 2027-02-11

Brief Summary

This study will enroll adults aged 18 to 80 years diagnosed with sepsis due to a suspected or confirmed bacterial infection, within 7 days of being admitted to the hospital, and who have also developed acute kidney injury within 72 hours of the onset of sepsis. Eligible participants will be randomly assigned to receive either AZD4144 or a placebo intravenously once daily for the number of days specified in the CSP. During this Treatment Period, participants will undergo daily safety monitoring, as well as blood and urine sample collection and other assessments. After the Treatment Period, participants will continue to be monitored for safety and other assessments during each additional day they remain hospitalized (if applicable) as well as during up to 2 follow up visits after discharge. The main goal is to compare specific kidney function measurements between those participants receiving AZD4144 and those receiving the placebo.

Detailed Description

This is a Phase IIa, randomised, double-blind, placebo-controlled, multicenter study that will be conducted in adult participants (aged 18-80) with sepsis-associated acute kidney injury (SA-AKI). Eligible participants must have sepsis secondary to suspected or confirmed bacterial infection requiring vasopressor or inotrope therapy, and AKI (KDIGO Stage ≥ 1) within a defined time frame of sepsis onset. Participants will be randomised in a 1:1 ratio to receive either intravenous AZD4144 or matching placebo once daily for a fixed treatment period. The study will be comprised of:

• A screening period
• A treatment period, during which participants receive intravenous AZD4144 or placebo daily according to the protocol dosing days.
• A follow-up period that will include daily assessments while still hospitalized and up to two additional outpatient visits at scheduled times after discharge.

Conditions

Sepsis; Acute Kidney Injury

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Arm 1 (AZD4144)

AZD4144 solution for IV infusion

Group Type: EXPERIMENTAL

AZD4144

Intervention Type: DRUG

Intravenous solution of AZD4144 will be administered to randomised participants according to the treatment arm to which they have been assigned.

Arm 2 (Placebo)

Placebo concentrate for solution for infusion

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Intravenous solution of Placebo will be administered to randomised participants according to the treatment arm to which they have been assigned.

Interventions

AZD4144

Intravenous solution of AZD4144 will be administered to randomised participants according to the treatment arm to which they have been assigned.

Intervention Type: DRUG

Placebo

Intravenous solution of Placebo will be administered to randomised participants according to the treatment arm to which they have been assigned.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Age ≥ 18 to ≤ 80 years at the time of signing the informed consent.
• Participants who are admitted to an ICU.
• Diagnosis of sepsis according to criteria defined by The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3) based on:

1. Suspected or confirmed bacterial infection AND

2. 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).

• Vasopressor and/or inotrope therapy for sepsis-induced hypotension
• Diagnosis of AKI with modified KDIGO Stage ≥ 1 persisting after initial volume resuscitation (30 mL/kg or as clinically indicated per investigator discretion) defined as: Increase in serum creatinine to ≥ 1.5 × baseline (pre-AKI reference).
• Outpatient pre-AKI reference eGFR ≥ 30 mL/min/1.73 m2 or admission pre-AKI reference eGFR ≥ 45 mL/min/1.73 m2.
• Body weight ≥ 40 kg or ≤ 125 kg.
• Female or male, assigned at birth, inclusive of all gender identities.
• All FOCBP must have a negative pregnancy test at the Screening visit (Visit 1).
• Contraception:

1. Sexually active fertile male participants with partners of childbearing potential must adhere to the contraception methods detailed in CSP from the time of first administration of study intervention administration until 100 days after the last dose of study intervention.

2. FOCBP must not be lactating and must agree to use an approved method of highly effective contraception, as detailed in the CSP from the time of first administration of study intervention until 100 days after last dose of study intervention.

• Capable of giving signed informed consent (participant or LAR)
• Provision of signed and dated written Optional Genomics Initiative Research Information and Consent Form prior to collection of samples for optional genomics initiative research

Exclusion Criteria

• Any clinical evidence which in the investigator's opinion makes it undesirable for the potential participant to enrol in the study.
• Known history of Stage 4 or 5 CKD with documented sustained eGFR < 30 mL/min/1.73 m2 prior to hospital admission.
• No serum creatinine results available within 12 months of admission and an eGFR < 45 mL/min/1.73 m2 at admission.
• Sepsis diagnosed > 7 days after hospital admission (to include from time of outside admission if patient transferred from another healthcare setting).
• 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.
• Evidence of recovery from AKI prior to randomisation defined as:

1. 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

2. A > 25% reduction in serum creatinine from peak serum creatinine after volume resuscitation prior to randomisation.

• Expected survival from sepsis < 24 hours.
• Expected survival < 90 days due to chronic or pre-existing medical conditions other than SA-AKI
• Known history of renal transplant or bilateral nephrectomy.
• Permanent incapacitation.
• Active cancer or cancer in remission for less than 2 years.
• Known history of immunodeficiency disease or currently receiving immunosuppressant therapy for non-sepsis related disease.
• Severe burns requiring ICU treatment.
• Sepsis attributed to confirmed or presumed fungal or viral infection at time of Screening.
• Has advanced chronic liver disease, confirmed by a Child-Pugh score of 10-15 (Class C).
• Known history of cerebrovascular accident within the last 90 days.
• Known history of heart failure with reduced ejection fraction with documented ejection fraction ≤ 20% before sepsis diagnosis.
• Known hypersensitivity to iohexol or known history of severe adverse reaction to iodinated contrast media.
• Participants with known medical or psychological condition(s), or who, in the judgement of the investigator, should not participate in the study if they are unlikely to comply with study procedures, restrictions, and requirements.
• Current KRT (eg, continuous haemofiltration and haemodialysis/continuous renal replacement therapy, intermittent haemodialysis, and peritoneal dialysis) or planned KRT at randomisation
• Currently receiving active treatment for malignancy.
• Potential participants will be excluded if they have received a certain class of medication during the weeks before enrollment or are anticipated to require a specific class of medication during the trial duration.

Participants with a known hypersensitivity to AZD4144 or any of the excipients of the product.

• Receipt of another IMP within 30 days, 5 half-lives, or the time frame of expected PD effect from most recent dose, whichever is longest.
• Previous receipt of AZD4144.
• Active or planned treatment of sepsis with an extracorporeal haemoperfusion device.
• Participation in any other concurrent ICU study 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.
• Presence of anuria (≥ 12 hours) at randomisation.
• Any clinically important abnormalities in rhythm, conduction, or morphology of the resting 12-lead ECG, at Screening, as judged by the investigator.
• Prolonged QTcF > 470 ms.
• Known history of QT prolongation associated with other medications that required discontinuation of that medication.
• Congenital long QT syndrome.
• 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.
• Ventricular arrhythmia requiring treatment.
• Known or presumed latent or active tuberculosis.
• Acute pancreatitis with no established source of infection.
• Undergoing extracorporeal membrane oxygenation (ECMO) at randomisation.
• Neutropenia: ANC < 1.5 × 109/L.
• Admitting diagnosis of rhabdomyolysis.
• Admitting diagnosis of trauma with CK > 15000 U/L.
• Presumed nidus of infection in central nervous system.
• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
• Previous randomisation in the present study.
• For females only - currently pregnant (confirmed with positive pregnancy test) or breast-feeding.
• First dose of IMP unable to be administered within 36 hours of AKI diagnosis.
• Presence of a do-not-resuscitate order.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Research Site

Tucson, Arizona, United States

Research Site

Newport Beach, California, United States

Research Site

Baltimore, Maryland, United States

Research Site

Boston, Massachusetts, United States

Research Site

Detroit, Michigan, United States

Research Site

The Bronx, New York, United States

Research Site

Winston-Salem, North Carolina, United States

Research Site

Corvallis, Oregon, United States

Research Site

Philadelphia, Pennsylvania, United States

Research Site

Charleston, South Carolina, United States

Research Site

Salt Lake City, Utah, United States

Research Site

CABA, , Argentina

Research Site

Ciudad de Buenos Aires, , Argentina

Research Site

La Plata, , Argentina

Research Site

Rosario, , Argentina

Research Site

Brussels, , Belgium

Research Site

Brussels, , Belgium

Research Site

Genk, , Belgium

Research Site

Ottignies, , Belgium

Research Site

Montreal, Quebec, Canada

Research Site

Montreal, Quebec, Canada

Research Site

Québec, Quebec, Canada

Research Site

Prague, , Czechia

Research Site

Prague, , Czechia

Research Site

Aalborg, , Denmark

Research Site

Aarhus N, , Denmark

Research Site

Hvidovre, , Denmark

Research Site

Angers, , France

Research Site

La Roche-sur-Yon, , France

Research Site

Limoges, , France

Research Site

Strasbourg, , France

Research Site

Tours, , France

Research Site

Aachen, , Germany

Research Site

Frankfurt, , Germany

Research Site

Greifswald, , Germany

Research Site

Heidelberg, , Germany

Research Site

Kiel, , Germany

Research Site

Leipzig, , Germany

Research Site

Athens, , Greece

Research Site

Thessaloniki, , Greece

Research Site

Budapest, , Hungary

Research Site

Debrecen, , Hungary

Research Site

Kaposvár, , Hungary

Research Site

Pécs, , Hungary

Research Site

Szeged, , Hungary

Research Site

Tatabánya, , Hungary

Research Site

Milan, , Italy

Research Site

Padua, , Italy

Research Site

Roma, , Italy

Research Site

Rozzano, , Italy

Research Site

Barcelona, , Spain

Research Site

Jerez de la Frontera, , Spain

Research Site

Valencia, , Spain

Research Site

Adapazarı, , Turkey (Türkiye)

Research Site

Ankara, , Turkey (Türkiye)

Research Site

Kahramanmaraş, , Turkey (Türkiye)

Research Site

Kocaeli, , Turkey (Türkiye)

Research Site

Brighton, , United Kingdom

Research Site

Guildford, , United Kingdom

Research Site

Liverpool, , United Kingdom

Research Site

London, , United Kingdom

Countries

United States; Argentina; Belgium; Canada; Czechia; Denmark; France; Germany; Greece; Hungary; Italy; Spain; Turkey (Türkiye); United Kingdom

Central Contacts

AstraZeneca Clinical Study Information Center

Role: CONTACT

information.center@astrazeneca.com

1-877-240-9479

Other Identifiers

2025-522232-13-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

54675

Identifier Type: OTHER

Identifier Source: secondary_id

D9440C00004

Identifier Type: -

Identifier Source: org_study_id