A Phase IIa, Randomised, Double-blind, Placebo-controlled, Multicentre Study to Assess the Efficacy, Safety, and Tolerability of AZD4144 in Participants With Sepsis-associated Acute Kidney Injury (SERENIA)
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.
• 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:
‣ Suspected or confirmed bacterial infection AND
⁃ 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:
‣ 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.
⁃ 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