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 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.

Study Overview

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

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 one of the two arms: TIN816 or placebo. Efficacy will be evaluated 5 days after treatment. The randomization ratio is 1:1; TIN816 : placebo.

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: 1-888-669-6682; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals; Phone Number: +41613241111

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1428DCO
    • Recruiting
    • Novartis Investigative Site
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1181ACH
      • Recruiting
      • Novartis Investigative Site
• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • Novartis Investigative Site
• Brazil
  • PR
    • Curitiba, PR, Brazil, 80040-050
      • Recruiting
      • Novartis Investigative Site
  • RJ
    • Rio de Janeiro, RJ, Brazil, 22211 230
      • Recruiting
      • Novartis Investigative Site
  • RS
    • Porto Alegre, RS, Brazil, 90560 030
      • Recruiting
      • Novartis Investigative Site
  • SP
    • Sao Paulo, SP, Brazil, 01327 001
      • Recruiting
      • Novartis Investigative Site
    • Sao Paulo, SP, Brazil, 01308-050
      • Recruiting
      • Novartis Investigative Site
• Czechia
  • Praha 4, Czechia, 140 00
    • Recruiting
    • Novartis Investigative Site
  • Poruba
    • Ostrava, Poruba, Czechia, 708 52
      • Recruiting
      • Novartis Investigative Site
• Estonia
  • Tartu, Estonia, 50406
    • Recruiting
    • Novartis Investigative Site
• France
  • Nantes Cedex 1, France, 44093
    • Recruiting
    • Novartis Investigative Site
  • Neuilly Sur Seine, France, 92200
    • Recruiting
    • Novartis Investigative Site
  • Paris 13, France, 75651
    • Recruiting
    • Novartis Investigative Site
• Germany
  • Bad Oeynhausen, Germany, 32545
    • Recruiting
    • Novartis Investigative Site
  • Dresden, Germany, 01307
    • Recruiting
    • Novartis Investigative Site
  • Giessen, Germany, 35392
    • Recruiting
    • Novartis Investigative Site
  • Leipzig, Germany, 04289
    • Recruiting
    • Novartis Investigative Site
  • Bavaria
    • Regensburg, Bavaria, Germany, 93053
      • Recruiting
      • Novartis Investigative Site
• Hungary
  • Budapest, Hungary, 1122
    • Recruiting
    • Novartis Investigative Site
  • Budapest, Hungary, H 1096
    • Recruiting
    • Novartis Investigative Site
  • Debrecen, Hungary, 4032
    • Recruiting
    • Novartis Investigative Site
  • Baranya
    • Pecs, Baranya, Hungary, 7621
      • Recruiting
      • Novartis Investigative Site
  • Pest Megye
    • Budapest, Pest Megye, Hungary, 1134
      • Recruiting
      • Novartis Investigative Site
• Lithuania
  • Vilnius, Lithuania, LT 08661
    • Recruiting
    • Novartis Investigative Site
  • LTU
    • Kaunas, LTU, Lithuania, LT 50161
      • Recruiting
      • Novartis Investigative Site
• Singapore
  • Singapore, Singapore, 119074
    • Recruiting
    • Novartis Investigative Site
• Spain
  • Barcelona
    • Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Recruiting
      • Novartis Investigative Site
  • Catalunya
    • Badalona, Catalunya, Spain, 08916
      • Recruiting
      • Novartis Investigative Site
• Taiwan
  • Taipei, Taiwan, 10002
    • Recruiting
    • Novartis Investigative Site

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 (systolic and diastolic blood pressure and pulse rate) will be assessed in the sitting or supine position. Vital signs should 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 3 months (ideally obtained at least 3 weeks before the screening visit) 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 6 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
  • Platelet dysfunction: e.g., ADP induced platelet aggregation lower than 60 %
  • Pre-existing coagulation factor deficiency: including, but not limited to fibrinogen ≤ 2.5 g/L
• 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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Placebo; Placebo
Experimental: TIN816	Drug: TIN816; TIN816

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ratio of the highest serum creatinine value within 5 days post-dose versus baseline	To assess the effect of TIN816 on serum creatinine level in high-risk patients undergoing major cardio-vascular surgery, versus placebo	from baseline to Day 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AKI stages 1, 2 and 3 as defined by modified AKI Network criteria	To assess the effect of TIN816 on the incidence and severity of AKI in patients at high risk for AKI and undergoing major cardio-vascular surgery, versus placebo	from baseline to Day 6
Anti-drug antibodies against TIN816	To assess immunogenicity (IG) of TIN816	from baseline to 90 Days
Occurrence of major adverse kidney event at Day 90 (MAKE90)	To assess the effect of TIN816 on the incidence of AKD in high-risk patients undergoing major cardio-vascular surgery, versus placebo	90 Days
Occurrence of MAKE30	To assess the effect of TIN816 on the incidence of AKD in high-risk patients undergoing major cardio-vascular surgery, versus placebo	30 Days
Occurrence of individual components of the MAKE criteria at Days 30 or 90.	To assess the effect of TIN816 on the incidence of AKD in high-risk patients undergoing major cardio-vascular surgery, versus placebo	30 or 90 Days

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): March 3, 2023
• Primary Completion (Estimated): July 9, 2025
• Study Completion (Estimated): October 2, 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): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: cardiac surgery; acute kidney injury
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Wounds and Injuries; Acute Kidney Injury
• Other Study ID Numbers: CTIN816A12201

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