Acute kidney injury Due to sepsis MedDRA version: 21.1 Level: PT Classification code 10069339 Term: Acute kidney injury System Organ Class: 10038359 - Renal and urinary disorders MedDRA version: 20.0 Level: PT Classification code 10040047 Term: Sepsis System Organ Class: 10021881 - Infections and infestations
Conditions
Sponsors
Novartis Farmacéutica, S.A.
Eligibility
Sex/Gender
All
Inclusion criteria
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/high dependency care unit. 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: - 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: 1. Median value within 3 months of the hospital admission. If not available: 2. Median value between 3 and 6 months prior to hospital admission. If not available: 3. At hospital admission. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 19 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1
Exclusion criteria
Exclusion criteria: 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 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 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 at Screening. 25. Women of child-bearing potential
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To characterize the pharmacokinetic profile of TIN816;Secondary Objective: To assess safety and tolerability of TIN816 vs placebo;Primary end point(s): To characterize the pharmacokinetic (PK) profile of TIN816 IV infusion Cmax : The maximum (peak) observed serum drug concentration AUClast : The AUC from time zero to the last measurable concentration sampling time (tlast) (mass × time × volume-1) AUCinf : The AUC from time zero to infinity Tmax : The time to reach observed maximum drug concentration following TIN816 administration T1/2 : Terminal half life Cl : Total clearance of drug from serum after intravascular administration Vz : Volume of distribution from a systemic dose;Timepoint(s) of evaluation of this end point: Cmax : Baseline day 1, Day 2, day 3, day 5, day 8, day 14, day 30, day 60 and day 90 AUClast : Baseline day 1, Day 2, day 3, day 5, day 8, day 14, day 30, day 60 and day 90 AUCinf : Baseline day 1, Day 2, day 3, day 5, day 8, day 14, day 30, day 60 and day 90 Tmax : Baseline day 1, Day 2, day 3, day 5, day 8, day 14, day 30, day 60 and day 90 T1/2 : Baseline day 1, Day 2, day 3, day 5, day 8, day 14, day 30, day 60 and day 90 Cl : Baseline day 1, Day 2, day 3, day 5, day 8, day 14, day 30, day 60 and day 90 Vz : Baseline day 1, Day 2, day 3, day 5, day 8, day 14, day 30, day 60 and day 90 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Number of participants with treatment emergent adverse events (AEs) and Serious Adverse Events (SAEs);Timepoint(s) of evaluation of this end point: Baseline up to 90 days | — |
Countries
Belgium, France, Germany, Hungary, Spain
Contacts
Public ContactTrial Monitoring Organization (TMo)
Novartis Farmacéutica, S.A.
Outcome results
None listed