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

Inclusion Criteria

• •1. Signed informed consent must be obtained prior to participation in the study.
• •2. ≥ 18 and ≤ 85 years of age.
• •3. Admitted to ICU or intermediate/HDU.
• •4. 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)
• •5. 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.
• •8. Presence of AKI for a period longer than 48 hours prior to study drug administration as suggested by clinical manifestations, e.g., prolonged oliguria or severe renal dysfunction (eg, serum creatinine \> 4 mg/dL) on admission without a history of CKD.
• •9. Evidence of recovery from AKI based on the investigator's clinical judgement prior to randomization.
• •10. 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.
• •11. 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).
• •12. Patients who are post-nephrectomy.
• •13. Patients who are on dual antiplatelet therapy.
• •14. Patients who are thrombocytopenic at screening (Platelet count \<100,000 microliter) or other high risk for bleeding in the opinion of the investigator.
• •15. Immunosuppressed patients:
• •History of immunodeficiency diseases or known HIV test positive. Is receiving immunosuppressant treatment or is on chronic high doses (high-dose therapy exceeding 2 weeks of treatment) of steroids equivalent to prednisone/prednisolone 0.5 mg/kg/day, including solid organ transplant patients. Patients with septic shock treated with hydrocortisone (e.g., 3 × 100 mg) can be included.
• •16. Active hepatitis (defined as (a) abnormal liver enzymes (Alanine aminotransferase (ALT), Gamma-glutamyl transferase (GGT), ALP \> 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).
• •17. Acute pancreatitis with no established source of infection.
• •18. Active hematological malignancy (previous hematological malignancies that are not actively treated are allowable).
• •19. Burns requiring ICU treatment.
• •20. Sepsis attributed to confirmed COVID-19.
• •21. 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.
• •22. History of hypersensitivity to the study treatment or its excipients or to drugs of similar chemical classes.
• •23. Any medical conditions that could significantly increase risk of participants' safety by participating in this study according to investigator's judgement.
• •24. Women with a positive pregnancy test, pregnancy or breast feeding.
• •25. Women of child-bearing potential