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

NCT05524051 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: CTIN816A122012024-511621-64-00
• Study Type: interventional
• Target: 102
• Locations: 14 countries
• Sites: 33

Brief Summary

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.

Conditions

Acute Kidney Injury Following Cardiac Surgery

Keywords

acute kidney injury; cardiac surgery

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Number of Participants With Maximum Acute Kidney Injury (AKI) Incidence Stages 1, 2 and 3 as Defined by Modified AKI Network Criteria

  Baseline, Day 8

• Number of Participants With Anti-TIN816 Antibodies

  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)

  Baseline, Day 30

• Number of Participants and Occurrence of Individual Components of Major Adverse Kidney Event at Day 90 (MAKE90)

  Baseline, Day 90

Study Arms (3)

TIN816 2 mg/kg

EXPERIMENTAL

TIN816 2 mg/kg was administered as a single intravenous (i.v.) infusion over 2 hours.

Drug: TIN816

TIN816 4 mg/kg

EXPERIMENTAL

TIN816 4 mg/kg was administered as a single intravenous (i.v.) infusion over 2 hours.

Drug: TIN816

Placebo

PLACEBO COMPARATOR

Placebo was administered as a single intravenous (i.v.) infusion over 2 hours.

Other: Placebo

Interventions

TIN816 DRUG

TIN816 was administered as a single intravenous (i.v.) infusion over 2 hours.

TIN816 2 mg/kg; TIN816 4 mg/kg

Placebo OTHER

Placebo was administered as a single intravenous (i.v.) infusion over 2 hours.

Placebo

Eligibility Criteria

• Age: 45 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.
• Non-emergent open chest cavity major cardiopulmonary bypass (CPB) surgery with expected CPB time ≥1 hour

You may not qualify if:

• 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.).

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (37)

Mayo Clinic Phoenix

Phoenix, Arizona, 85054, United States

Location

Duke Univ Medical Center

Durham, North Carolina, 27710, United States

Location

Novartis Investigative Site

CABA, Buenos Aires, C1118AAT, Argentina

Location

Novartis Investigative Site

Buenos Aires, C1428DCO, Argentina

Location

Novartis Investigative Site

CABA, C1181ACH, Argentina

Location

Novartis Investigative Site

Genk, Limburg, 3600, Belgium

Location

Novartis Investigative Site

Leuven, 3000, Belgium

Location

Novartis Investigative Site

Salvador, Estado de Bahia, 40323-010, Brazil

Location

Novartis Investigative Site

São Paulo, São Paulo, 05403 000, Brazil

Location

Novartis Investigative Site

Montreal, Quebec, H1T 1C8, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H2X 0A9, Canada

Location

Novartis Investigative Site

Montreal, Quebec, H4J 1C5, Canada

Location

Novartis Investigative Site

Québec, Quebec, GIV 4G5, Canada

Location

Novartis Investigative Site

Ostrava, Poruba, 708 52, Czechia

Location

Novartis Investigative Site

Tartu, 50406, Estonia

Location

Novartis Investigative Site

Nantes, 44093, France

Location

Novartis Investigative Site

Neuilly-sur-Seine, 92200, France

Location

Novartis Investigative Site

Paris, 75013, France

Location

Novartis Investigative Site

Poitiers, 86021, France

Location

Novartis Investigative Site

Rennes, 35033, France

Location

Novartis Investigative Site

Regensburg, Bavaria, 93053, Germany

Location

Novartis Investigative Site

Dresden, Saxony, 01307, Germany

Location

Novartis Investigative Site

Leipzig, Saxony, 04289, Germany

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Pécs, Baranya, 7623, Hungary

Location

Novartis Investigative Site

Debrecen, Hajdu Bihar Megye, 4032, Hungary

Location

Novartis Investigative Site

Budapest, H 1096, Hungary

Location

Novartis Investigative Site

Budapest, H-1083, Hungary

Location

Novartis Investigative Site

Ahmedabad, Gujarat, 380054, India

Location

Novartis Investigative Site

Lucknow, Uttar Pradesh, 226003, India

Location

Novartis Investigative Site

Vilnius, LT-08406, Lithuania

Location

Novartis Investigative Site

Singapore, 119074, Singapore

Location

Novartis Investigative Site

Santiago Compostela, A Coruna, 15706, Spain

Location

Novartis Investigative Site

Badalona, Barcelona, 08916, Spain

Location

Novartis Investigative Site

Barcelona, Catalonia, 08907, Spain

Location

Novartis Investigative Site

Madrid, 28006, Spain

Location

Novartis Investigative Site

Taipei, 10002, Taiwan

Location

MeSH Terms

Conditions

Acute Kidney Injury

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticasl

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 30, 2022
• First Posted: September 1, 2022
• Study Start: March 3, 2023
• Primary Completion: March 26, 2025
• Study Completion: June 23, 2025
• Last Updated: April 2, 2026
• Results First Posted: April 2, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

FR (5); IN (2); SG (1); HU (4); US (2); TW (1); AR (3); BE (2); CZ (1); BR (2); DE (4); CA (4); LI (1); ES (1)