A Randomized, Multi-centric, Placebo-controlled, Participant and Investigator-blinded Study to Evaluate the Safety, Tolerability and Efficacy of TIN816 in Adult Patients at Risk for Acute Kidney Injury Following Cardiac Surgery.

Novartis Pharmaceuticals3 sites in 2 countries98 target enrollmentMarch 3, 2023

InterventionsTIN816 Placebo

Overview

Phase: Phase 2
Intervention: TIN816
Conditions: Not specified
Sponsor: Novartis Pharmaceuticals
Enrollment: 98
Locations: 3
Primary Endpoint: Ratio of the highest serum creatinine value up to and including Study Day 6 versus baseline
Status: Terminated
Last Updated: 4 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

Detailed Description

This is a randomized, multi-centric, placebo-controlled, participant and investigator-blinded study to evaluate the safety, tolerability and efficacy of TIN816 in adult patients at risk for acute kidney injury following cardiac surgery. The screening period will last up to 30 days and the whole study will last up to 120 days. Approximately 120 subjects will be randomized to TIN816 or placebo. Efficacy will be evaluated 5 days after treatment.

Registry

clinicaltrials.gov

Start Date

March 3, 2023

End Date

June 23, 2025

Last Updated

4 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Novartis Pharmaceuticals

Responsible Party

Sponsor

Eligibility 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
•BMI = Body weight (kg) / \[Height (m)\]
•At screening, vital signs should be assessed in the sitting or supine position and be within the following ranges:
•body temperature between 35.0-37.5 °C
•blood pressure (systolic 100-160 mmHg, diastolic \< 100 mmHg)
•pulse rate (50-100/min) stable with or without medication(s) as per Investigator assessment.
•No known increase in SCr of ≥25% at screening visit compared to a previous value obtained within the last 6 months as documented by a local laboratory using standard assay methodology.

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.
•Patients with bleeding risk at screening. 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 %
•History of coagulation factor deficiency: including, but not limited to fibrinogen ≤ 2.5 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.
•Scheduled 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).

Arms & Interventions

TIN816

Intervention: TIN816

Placebo

Intervention: Placebo

Outcomes

Primary Outcomes

Ratio of the highest serum creatinine value up to and including Study Day 6 versus baseline

Time Frame: from baseline to Day 6

To assess the effect of TIN816 on serum creatinine level in high-risk patients undergoing major cardio-vascular surgery, versus placebo

Secondary Outcomes

AKI stages 1, 2 and 3 as defined by modified AKI Network criteria(from baseline to Day 6)
Occurrence of individual components of the MAKE criteria at Days 30 or 90.(30 or 90 Days)
Anti-drug antibodies against TIN816(from baseline to 90 Days)
Occurrence of major adverse kidney event at Day 90 (MAKE90)(90 Days)
Occurrence of MAKE30(30 Days)