Pharmacokinetics and Safety of TIN816 in Patients With Sepsis-associated Acute Kidney Injury
A Participant and Investigator-blinded, Randomized, Placebo-controlled Phase 2a Study to Investigate the Pharmacokinetics, Pharmacodynamics, Safety and Tolerability of TIN816 in Patients With Sepsis-associated Acute Kidney Injury
ClinicalTrials.gov Identifier: NCT05507437
Novartis Reference Number: CTIN816B12201
Last Update: Jan 26, 2023
All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation.
The purpose of this study is to characterize the pharmacokinetic (PK) and pharmacodynamic (PD) profile and to evaluate the safety and tolerability of TIN816 in hospitalized adult participants in an intensive care setting with a diagnosis of sepsis-associated acute kidney injury (SA-AKI).
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.
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 <45 ml/min prior to development of AKI.
Receiving RRT or a decision has been made to initiate RRT within 24 hours of admission.
Weight is less than 40 kg or more than 125 kg .
Has life support limitations (eg, do not resuscitate, do not dialyze, do not intubate).
AKI diagnosis according to the AKI inclusion criteria for a period longer than 48 hours prior to study drug administration.
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.
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 <100,000 microliter) or other high risk for bleeding in the opinion of the investigator.
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.
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).
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