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

NCT ID: NCT05524051

Last Updated: 2025-12-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 98 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-03
• Study Completion Date: 2025-06-23

Brief Summary

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.

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.

Conditions

Acute Kidney Injury Following Cardiac Surgery

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

TIN816

TIN816

Group Type: EXPERIMENTAL

TIN816

Intervention Type: DRUG

TIN816

Placebo

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo

Interventions

TIN816

TIN816

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: OTHER

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 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.

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticasl

Locations

Mayo Clinic Phoenix

Phoenix, Arizona, United States

Duke Univ Medical Center

Durham, North Carolina, United States

Novartis Investigative Site

CABA, Buenos Aires, Argentina

Novartis Investigative Site

Buenos Aires, , Argentina

Novartis Investigative Site

CABA, , Argentina

Novartis Investigative Site

Genk, Limburg, Belgium

Novartis Investigative Site

Leuven, , Belgium

Novartis Investigative Site

São Paulo, São Paulo, Brazil

Novartis Investigative Site

Salvador, , Brazil

Novartis Investigative Site

Montreal, Quebec, Canada

Novartis Investigative Site

Montreal, Quebec, Canada

Novartis Investigative Site

Montreal, Quebec, Canada

Novartis Investigative Site

Québec, Quebec, Canada

Novartis Investigative Site

Ostrava, Poruba, Czechia

Novartis Investigative Site

Tartu, , Estonia

Novartis Investigative Site

Nantes, , France

Novartis Investigative Site

Neuilly-sur-Seine, , France

Novartis Investigative Site

Paris, , France

Novartis Investigative Site

Poitiers, , France

Novartis Investigative Site

Rennes, , France

Novartis Investigative Site

Regensburg, Bavaria, Germany

Novartis Investigative Site

Dresden, Saxony, Germany

Novartis Investigative Site

Leipzig, Saxony, Germany

Novartis Investigative Site

Essen, , Germany

Novartis Investigative Site

Pécs, Baranya, Hungary

Novartis Investigative Site

Debrecen, Hajdu Bihar Megye, Hungary

Novartis Investigative Site

Budapest, , Hungary

Novartis Investigative Site

Budapest, , Hungary

Novartis Investigative Site

Ahmedabad, Gujarat, India

Novartis Investigative Site

Lucknow, Uttar Pradesh, India

Novartis Investigative Site

Vilnius, , Lithuania

Novartis Investigative Site

Singapore, , Singapore

Novartis Investigative Site

Santiago Compostela, A Coruna, Spain

Novartis Investigative Site

Badalona, Barcelona, Spain

Novartis Investigative Site

L'Hospitalet de Llobregat, Barcelona, Spain

Novartis Investigative Site

Madrid, , Spain

Novartis Investigative Site

Taipei, , Taiwan

Countries

United States; Argentina; Belgium; Brazil; Canada; Czechia; Estonia; France; Germany; Hungary; India; Lithuania; Singapore; Spain; Taiwan

Other Identifiers

CTIN816A12201

Identifier Type: -

Identifier Source: org_study_id

2024-511621-64-00

Identifier Type: OTHER

Identifier Source: secondary_id