Phase 2b Study to Investigate the Safety and Efficacy of TIN816 in Sepsis-associated Acute Kidney Injury (SA-AKI)

Eligibility Criteria

• 1. Signed informed consent must be obtained prior to participation in the study.
• 2. ≥ 18 to ≤ 85 years of age
• 3. Admitted to ICU or intermediate care unit/ high dependency care unit (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 AND
• * Acute increase of SOFA score of 2 or more (excluding renal component). The baseline SOFA score should be assumed to be zero unless the participant is known to have pre-existing (acute or chronic) organ dysfunction before the onset of infection
• 5. Diagnosis of AKI Stage 1 or greater per the following criterion at randomization:
• * For participants with hospital-acquired AKI, a stable serum creatinine obtained in the hospital prior to AKI diagnosis should be used as the reference serum creatinine.
• * For participants presenting from community, the reference serum creatinine should be estimated using the following order of preference:
• 1. The most recent value within 3 months of the hospital admission. If not available:
• 2. The most recent value between 3 and 12 months prior to hospital admission. If not available:
• 3. At hospital admission
• 1. Not expected to survive for 24 hours
• 2. Not expected to survive for 30 days due to medical conditions other than SA-AKI
• 3. History of CKD with a documented estimated GFR \<45 mL/min prior to admission to hospital
• 4. eGFR \<45mL/min at admission without any other reference serum eGFR within last 12-months
• 5. Receiving RRT or a decision has been made to initiate RRT within 24 hours after randomization
• 6. Weight is less than 40 kg or more than 125 kg.
• 7. Limitations to the use of mechanical ventilation, RRT or vasopressors/inotropes (N.B. limitations on Cardiopulmonary resuscitation (CPR)e.g., do-not-resuscitate orders are not an exclusion criterion unless associated with likely poor outcome in next 24 hours)
• 8. Sepsis diagnosis according to sepsis inclusion criteria for a period longer than 72 hours prior to ICU admission
• 9. AKI diagnosis according to AKI inclusion criteria over 48 hours after admission to ICU
• 10. Inability to administer study drug within 24 hours of diagnosis of AKI according to AKI inclusion criteria
• 11. Presence of AKI, in the Investigator's opinion, as suggested by clinical manifestation, e.g., prolonged oliguria or severe renal dysfunction on admission without a history of CKD, for a period longer than 24 hours prior to study drug administration
• 12. Evidence of recovery from AKI based on the investigator's clinical judgement prior to randomization
• 13. AKI is most likely attributable to other causes than sepsis, such as nephrotoxic drugs (Non-steroidal anti-inflammatory drugs (NSAIDs), contrast, aminoglycosides, etc.) or renal perfusion-related (acute abdominal aortic aneurysm, dissection, renal artery stenosis), urinary obstruction
• 14. 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)
• 15. Patients who are post-nephrectomy
• 16. Patients with permanent incapacitation
• 17. Patients who are thrombocytopenic at screening (platelet count \<50,000 per microliter) who have active/uncontrolled bleeding or who present current or past conditions indicating high risk for bleeding in the opinion of the investigator (e.g. coagulopathies, previous history of major non-traumatic bleeding etc.)
• 18. Immunosuppressed patients
• * History of immunodeficiency diseases
• * Receiving immunosuppressant treatment or 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 corticosteroids (as per the Surviving Sepsis Guidelines) can be included. See Appendix Section 10.6 Immunosuppresant drugs, (Table 10 5 Immunosuppressant drug exclusions)
• 19. Patients with known or presumed latent or active TB based on clinical history or imaging e.g. patients on TB preventive therapy or close/household contacts of pulmonary TB patients
• 20. Known active hepatitis B or C infection, or 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)
• 21. Acute pancreatitis with no established source of infection
• 22. Active hematological malignancy (previous hematological malignancies that are not actively treated are allowable)
• 23. Burns requiring ICU treatment
• 24. Sepsis attributed to confirmed COVID-19
• 25. 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
• 26. History of hypersensitivity to the study treatment or its excipients or to drugs of similar chemical classes
• 27. Any medical conditions that could significantly increase risk of participants' safety by participating in this study according to investigator's judgement
• 28. Women with a positive pregnancy test, pregnancy or breast feeding
• 29. Women of childbearing potential, unless they are using highly effective methods of contraception for the entire duration of the trial.