Pharmacokinetics and Safety of TIN816 in Patients With Sepsis-associated Acute Kidney Injury

Inclusion Criteria

• Signed informed consent must be obtained prior to participation in the study.
• ≥ 18 and ≤ 85 years of age.
• Admitted to ICU or intermediate/HDU.
• 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 infection SOFA score of 2 or more (excluding renal component)

• Diagnosis of AKI Stage 1 or greater per the following criterion at randomization :

An absolute increase in serum or plasma creatinine (CR) by ≥0.3 mg/dL (≥26.5 µmol/L) within 48 hours or presumed to have occurred in the previous 48 hours as compared to the reference creatinine baseline.

For hospital-acquired AKI, a stable serum creatinine obtained in the hospital prior to AKI should be used as reference baseline, otherwise, baseline serum creatinine in the following order of preference:

Median value within 3 months of the hospital admission. If not available:

Median value between 3 and 6 months prior to hospital admission. If not available:

At hospital admission.

Exclusion criteria

• Not expected to survive for 24 hours.
• Not expected to survive for 30 days due to medical conditions other than SA-AKI.
• History of CKD with a documented estimated GFR 4 mg/dL) on admission without a history of CKD.
• Evidence of recovery from AKI based on the investigator's clinical judgement prior to randomization.
• AKI is most likely attributable to causes other than sepsis such as nephrotoxic drugs (Non-steroidal anti-inflammatory drugs (NSAIDs), contrast, aminoglycosides), other medical conditions (e.g. heart failure, liver failure, acute abdominal aortic aneurysm, dissection, renal artery stenosis) or urinary obstruction.
• Documented (biopsy proven) or suspected history of acute or sub-acute kidney diseases such as rapidly progressive glomerular nephritis (RPGN) and acute interstitial nephritis (AIN).
• Patients who are post-nephrectomy.
• Patients who are on dual antiplatelet therapy.
• Patients who are thrombocytopenic at screening (Platelet count 3x Upper Limit of Normal (ULN) or (b)) for active hepatitis B or C infection, a positive Hepatitis B Virus (HBV) or Hepatitis C Virus (HCV) serology or patients with advanced chronic liver disease, confirmed by a Child-Pugh score of 10-15 (Class C).
• Acute pancreatitis with no established source of infection.
• Active hematological malignancy (previous hematological malignancies that are not actively treated are allowable).
• Burns requiring ICU treatment.
• Sepsis attributed to confirmed COVID-19.
• Use of other investigational drugs within 5 half-lives of enrollment within 30 days (e.g., small molecules) / or until the expected pharmacodynamic effect has returned to baseline (e.g., biologics), whichever is longer; or longer if required by local regulations.
• History of hypersensitivity to the study treatment or its excipients or to drugs of similar chemical classes.
• Any medical conditions that could significantly increase risk of participants' safety by participating in this study according to investigator's judgement.
• Women with a positive pregnancy test, pregnancy or breast feeding.
• Women of child-bearing potential