Acute kidney injury MedDRA version: 26.0 Level: PT Classification code 10069339 Term: Acute kidney injury System Organ Class: 10038359 - Renal and urinary disorders
Conditions
Interventions
Product Code: TIN816
Pharmaceutical Form: Powder for solution for injection/infusion
Current Sponsor code: TIN816
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 70
Sponsors
Novartis Pharma AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Signed informed consent must be obtained prior to participation in the study Participants must be able to communicate well with the investigator and to understand and comply with the requirements of the study. Male and female patients =45 years at screening Participants must weigh at least 50 kg and maximum 150 kg to participate in the study and must have a body mass index (BMI) below 40. BMI = Body weight (kg) / [Height (m)]2 At screening, vital signs should be assessed in the sitting or supine position and be within the the following ranges: a. body temperature between 35.0-37.5 °C b. blood pressure (systolic 100-160 mmHg, diastolic =65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: eGFR at screening <15 mL/min/1.73 m2 (calculated using CKD-EPI 2021 equation) Receiving renal replacement therapy currently or at any time within 3 months prior to screening, or scheduled to start RRT shortly after cardiac surgery. Patients with bleeding risk at screening, or identified as such pre surgery if screening was performed earlier than Day -1). The Investigator should make this determination in consideration of the participant's medical history and/or clinical or laboratory evidence of any of the following: History of bleeding with suspected or confirmed bleeding disorder or any other high risk for bleeding in the opinion of the investigator Thrombocytopenia: platelet count <100x109/L History of Platelet dysfunction: e.g. ADP induced platelet aggregation lower than 60 % Pre-existing coagulation factor deficiency: including, but not limited to fibrinogen < 2.5-2.8 g/L or Von Willebrand factor (vWF) = 50 IU/dL. Any emergency surgeries performed less than 30 days before screening, including aortic dissection, and/or major congenital heart defects. Schedules to undergo cardiac surgery off CPB or with hypothermic circulatory arrest Cardiogenic shock or hemodynamic instability within four weeks prior to surgery, requiring inotropes or vasopressors or mechanical devices such as intra-aortic balloon counter-pulsation (IABP). Current or within four weeks prior to surgery, clinically significant arrhythmias associated with syncope, dyspnea or hemodynamic instability. Have received cardiopulmonary resuscitation (CPR) within 30 days prior to cardiac surgery Use of other investigational drugs at the time of enrollment or within 5 half lives of enrollment or until the expected PD effect has returned to baseline, whichever is longer ; or longer if required by local regulations. Patients who are post-nephrectomy Have ongoing sepsis or history of sepsis within the past 8 weeks or untreated diagnosed infection prior to screening visit. Sepsis is defined as presence of a confirmed pathogen, along with fever or hypothermia, and hypoperfusion or hypotension. Recent (within the last three years) and/or recurrent history of autonomic dysfunction (e.g., recurrent episodes of fainting, palpitations, etc.). Pregnant or nursing (lactating women) Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception while taking study treatment and until the end of study. Highly effective contraception methods include: • Total abstinence (when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g. calendar, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. • Female bilateral tubal ligation, female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or total hysterectomy at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment. • Male sterilization (at least 6 months prior to screening). For female participants on the study, the vasectomized male partner should be the sole partner for that participant. • Use of oral (estrogen and progesterone), injected, or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect of TIN816 on serum creatinine level in high-risk patients undergoing major cardio-vascular surgery, versus placebo;Secondary Objective: To evaluate the safety and tolerability of TIN816 To assess the effect of TIN816 on the incidence and severity of AKI in patients at high-risk patients undergoing major cardio-vascular surgery, versus placebo To assess the pharmacokinetics (PK) of TIN816 To assess immunogenicity (IG) of TIN816 To assess the effect of TIN816 on the incidence of AKD in high-risk patients undergoing major cardio-vascular surgery, versus placebo;Primary end point(s): Ratio of the highest serum creatinine value within 5 days post dose versus baseline;Timepoint(s) of evaluation of this end point: Day 1 until Day 6 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Assessment of Safety based on vital signs, physical examination, ECGs, laboratory assessments and collection of AEs assessed from baseline until the end of the study visit AKI stages 1, 2 and 3 as defined by modified AKI Network (AKIN) criteria Serum PK parameters Cmax, Tmax, T1/2, CL, Vz, AUClast and AUCinf of TIN816 Anti-drug antibodies against TIN816 Occurrence of major adverse kidney events at day 90 (MAKE90) Occurence of MAKE30 Occurrence of individual components of the MAKE criteria at Days 30 or 90. ;Timepoint(s) of evaluation of this end point: Safety based on vital signs, physical examination, ECGs, laboratory assessments and collection of AEs : screening, day 2,3,4,30 and 90, EoS AKI stages 1, 2 and 3 as defined by modified AKI Network (AKIN) criteria Day 1 until Day 6 Serum PK parameters Cmax, Tmax, T1/2, CL, Vz, AUClast and AUCinf of TIN816 : from baseline until Day 90 Anti-drug antibodies against TIN816 : from Baseline until Day 90 Occurrence of major adverse kidney events : Day 30 and day 90 Occurrence of individual components of the MAKE criteria : day 30 or day 90 | — |
Countries
Argentina, Belgium, Brazil, Czechia, Czech Republic, Estonia, France, Germany, Hungary, India, Lithuania, Singapore, Spain, Taiwan
Contacts
Public ContactMedizinischer Infoservice (MCC)
Novartis Pharma GmbH
Outcome results
None listed