A Multi-center Study to Evaluate the Safety, Tolerability and Efficacy of TIN816 in Patients at Risk for Acute Kidney Injury Following Cardiac Surgery.

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.

This was 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.

Study Overview

• Status: Terminated
• Conditions: Acute Kidney Injury Following Cardiac Surgery
• Intervention / Treatment: Drug: TIN816; Other: Placebo

Detailed Description

The study consisted of a pre-operative period (screening visit), a treatment period (Day 1), and a post-treatment follow-up period (Day 2 to Day 90 (EOS)). Participants were followed daily in the hospital from Day 2 to Day 8 as in-patients or at home/nearby accommodation (e.g., hotel or rehabilitation unit if discharged earlier than Day 8), and then as out-patients until the end of the study (Day 30 and Day 90 (EOS) visits).

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1428DCO
    • Novartis Investigative Site
  • CABA, Argentina, C1181ACH
    • Novartis Investigative Site
  • Buenos Aires
    • CABA, Buenos Aires, Argentina, C1118AAT
      • Novartis Investigative Site
• Belgium
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
  • Limburg
    • Genk, Limburg, Belgium, 3600
      • Novartis Investigative Site
• Brazil
  • Estado de Bahia
    • Salvador, Estado de Bahia, Brazil, 40323-010
      • Novartis Investigative Site
  • São Paulo
    • São Paulo, São Paulo, Brazil, 05403 000
      • Novartis Investigative Site
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H1T 1C8
      • Novartis Investigative Site
    • Montreal, Quebec, Canada, H4J 1C5
      • Novartis Investigative Site
    • Montreal, Quebec, Canada, H2X 0A9
      • Novartis Investigative Site
    • Québec, Quebec, Canada, GIV 4G5
      • Novartis Investigative Site
• Czechia
  • Poruba
    • Ostrava, Poruba, Czechia, 708 52
      • Novartis Investigative Site
• Estonia
  • Estonia
    • Tartu, Estonia, Estonia, 50406
      • Novartis Investigative Site
• France
  • Nantes, France, 44093
    • Novartis Investigative Site
  • Neuilly-sur-Seine, France, 92200
    • Novartis Investigative Site
  • Paris, France, 75013
    • Novartis Investigative Site
  • Poitiers, France, 86021
    • Novartis Investigative Site
  • Rennes, France, 35033
    • Novartis Investigative Site
• Germany
  • Essen, Germany, 45147
    • Novartis Investigative Site
  • Bavaria
    • Regensburg, Bavaria, Germany, 93053
      • Novartis Investigative Site
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • Novartis Investigative Site
    • Leipzig, Saxony, Germany, 04289
      • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, H 1096
    • Novartis Investigative Site
  • Budapest, Hungary, H-1083
    • Novartis Investigative Site
  • Baranya
    • Pécs, Baranya, Hungary, 7623
      • Novartis Investigative Site
  • Hajdu Bihar Megye
    • Debrecen, Hajdu Bihar Megye, Hungary, 4032
      • Novartis Investigative Site
• India
  • Gujarat
    • Ahmedabad, Gujarat, India, 380054
      • Novartis Investigative Site
  • Uttar Pradesh
    • Lucknow, Uttar Pradesh, India, 226003
      • Novartis Investigative Site
• Lithuania
  • Vilnius, Lithuania, LT-08406
    • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 119074
    • Novartis Investigative Site
• Spain
  • Madrid, Spain, 28006
    • Novartis Investigative Site
  • A Coruna
    • Santiago Compostela, A Coruna, Spain, 15706
      • Novartis Investigative Site
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Novartis Investigative Site
  • Catalonia
    • Barcelona, Catalonia, Spain, 08907
      • Novartis Investigative Site
• Taiwan
  • Taipei, Taiwan, 10002
    • Novartis Investigative Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic Phoenix
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Univ Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 following ranges:

  1. body temperature between 35.0-37.5 °C
  2. blood pressure (systolic 100-160 mmHg, diastolic < 100 mmHg)
  3. 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.
• Non-emergent open chest cavity major cardiopulmonary bypass (CPB) surgery with expected CPB time ≥1 hour

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).
• 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 and 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 of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TIN816 2 mg/kg; TIN816 2 mg/kg was administered as a single intravenous (i.v.) infusion over 2 hours.	Drug: TIN816; TIN816 was administered as a single intravenous (i.v.) infusion over 2 hours.
Experimental: TIN816 4 mg/kg; TIN816 4 mg/kg was administered as a single intravenous (i.v.) infusion over 2 hours.	Drug: TIN816; TIN816 was administered as a single intravenous (i.v.) infusion over 2 hours.
Placebo Comparator: Placebo; Placebo was administered as a single intravenous (i.v.) infusion over 2 hours.	Other: Placebo; Placebo was administered as a single intravenous (i.v.) infusion over 2 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ratio of the Highest Serum Creatinine Value up to and Including Study Day 6 Versus Baseline	The log-transformed ratio of the highest serum creatinine value up to and including Study Day 6 vs baseline was analysed by a linear model. The estimated mean and 90% confidence interval of the difference in log-transformed ratios vs baseline between each TIN816 treatment group and placebo were then back-transformed to obtain the geometric mean ratio. The geometric mean ratio (GMR) represents the ratio between TIN816 and placebo geometric mean estimates for the serum creatinine Day 6 to baseline geometric mean estimates.	Baseline, Day 1 - Day 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Maximum Acute Kidney Injury (AKI) Incidence Stages 1, 2 and 3 as Defined by Modified AKI Network Criteria	AKI incidence over the first week after surgery (Day 1 to Day 8) was measured using the modified AKIN classification system, based on changes in serum creatinine compared to pre-operative value. Severity of AKI was assessed using three stages, with stage 1 being mild or least severe and stage 3 the most severe. Stage 1: Serum creatinine (SCr) ≥1.5 - <2.0 x baseline within 7 days post-surgery Or ↑ SCr by ≥26.5 μmol/L (≥0.3 mg/dL) within 2 days post-surgery Stage 2: SCr ≥2.0 - <3.0 x baseline within 7 days post-surgery Stage 3: SCr ≥3.0x baseline within 7 days post-surgery Or ↑ SCr to ≥353.6 μmol/L (4.0 mg/dL) AND by ≥44.2 μmol/L (0.5 mg/dL) within 7 days post-surgery Or Initiation of RRT within 7 days post-surgery	Baseline, Day 8
Number of Participants With Anti-TIN816 Antibodies	Immunogenicity (IG) serum samples were collected to evaluate production of anti-TIN816 antibodies (anti-drug antibodies, ADAs).	Day 1 pre-dose, Day 8, Day 30 and Day 90
Number of Participants and Occurrence of Individual Components of Major Adverse Kidney Event at Day 30 (MAKE30)	The number of participants having major adverse kidney event at Day 30 (MAKE30) was assessed using the following components: death through day 30,; initiation of renal replacement therapy (RRT) through day 30, and; ≥25% reduction in eGFR from baseline to 30 days after surgery.	Baseline, Day 30
Number of Participants and Occurrence of Individual Components of Major Adverse Kidney Event at Day 90 (MAKE90)	The number of participants having major adverse kidney event at Day 90 (MAKE90) was assessed using the following components: death through day 90,; initiation of renal replacement therapy (RRT) through day 90, and; ≥25% reduction in eGFR from baseline to 90 days after surgery.	Baseline, Day 90

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticasl

Publications and helpful links

Helpful Links

• A Plain Language Trial Summary is available on www.novctrd.com

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2023
• Primary Completion (Actual): March 26, 2025
• Study Completion (Actual): June 23, 2025

Study Registration Dates

• First Submitted: August 30, 2022
• First Submitted That Met QC Criteria: August 30, 2022
• First Posted (Actual): September 1, 2022

Study Record Updates

• Last Update Posted (Actual): July 9, 2026
• Last Update Submitted That Met QC Criteria: July 7, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: cardiac surgery; acute kidney injury
• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Renal Insufficiency; Acute Kidney Injury
• Other Study ID Numbers: CTIN816A12201; 2024-511621-64-00 (Other Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No