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

Primary Purpose

Acute Kidney Injury Following Cardiac Surgery

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
TIN816
Placebo
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Kidney Injury Following Cardiac Surgery focused on measuring acute kidney injury, cardiac surgery

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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 position. Sitting vital signs should be within the following ranges:

    1. oral 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 not older than 6 weeks 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).
  • Currently receiving renal replacement therapy.
  • 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 < 2.5-2.8 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, ovulation, symptothermal, 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.

Sites / Locations

  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
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  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
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  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
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  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting
  • Novartis Investigative SiteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

TIN816

Placebo

Arm Description

TIN816

Placebo

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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
Anti-drug antibodies against TIN816
To assess immunogenicity (IG) of TIN816
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
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
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

Full Information

First Posted
August 30, 2022
Last Updated
October 23, 2023
Sponsor
Novartis Pharmaceuticals
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1. Study Identification

Unique Protocol Identification Number
NCT05524051
Brief Title
A Multi-center Study to Evaluate the Safety, Tolerability and Efficacy of TIN816 in Patients at Risk for Acute Kidney Injury Following Cardiac Surgery.
Official Title
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 Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 3, 2023 (Actual)
Primary Completion Date
October 17, 2024 (Anticipated)
Study Completion Date
October 17, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novartis Pharmaceuticals

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Kidney Injury Following Cardiac Surgery
Keywords
acute kidney injury, cardiac surgery

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model 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.
Masking
ParticipantInvestigator
Masking Description
Two arms: TIN816 and placebo. Randomization ratio is 1:1.
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
TIN816
Arm Type
Experimental
Arm Description
TIN816
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo
Intervention Type
Drug
Intervention Name(s)
TIN816
Intervention Description
TIN816
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Ratio of the highest serum creatinine value within 5 days post-dose versus baseline
Description
To assess the effect of TIN816 on serum creatinine level in high-risk patients undergoing major cardio-vascular surgery, versus placebo
Time Frame
from baseline to Day 6
Secondary Outcome Measure Information:
Title
AKI stages 1, 2 and 3 as defined by modified AKI Network criteria
Description
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
Time Frame
from baseline to Day 6
Title
Anti-drug antibodies against TIN816
Description
To assess immunogenicity (IG) of TIN816
Time Frame
from baseline to 90 Days
Title
Occurrence of major adverse kidney event at Day 90 (MAKE90)
Description
To assess the effect of TIN816 on the incidence of AKD in high-risk patients undergoing major cardio-vascular surgery, versus placebo
Time Frame
90 Days
Title
Occurrence of MAKE30
Description
To assess the effect of TIN816 on the incidence of AKD in high-risk patients undergoing major cardio-vascular surgery, versus placebo
Time Frame
30 Days
Title
Occurrence of individual components of the MAKE criteria at Days 30 or 90.
Description
To assess the effect of TIN816 on the incidence of AKD in high-risk patients undergoing major cardio-vascular surgery, versus placebo
Time Frame
30 or 90 Days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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 (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: 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 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
1-888-669-6682
Email
Novartis.email@novartis.com
First Name & Middle Initial & Last Name or Official Title & Degree
Novartis Pharmaceuticals
Phone
+41613241111
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Novartis Pharmaceuticals
Organizational Affiliation
Novartis Pharmaceuticasl
Official's Role
Study Director
Facility Information:
Facility Name
Novartis Investigative Site
City
Caba
State/Province
Buenos Aires
ZIP/Postal Code
C1181ACH
Country
Argentina
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Buenos Aires
ZIP/Postal Code
C1428DCO
Country
Argentina
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Curitiba
State/Province
PR
ZIP/Postal Code
80040-050
Country
Brazil
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Rio de Janeiro
State/Province
RJ
ZIP/Postal Code
22211 230
Country
Brazil
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Porto Alegre
State/Province
RS
ZIP/Postal Code
90560 030
Country
Brazil
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
01308-050
Country
Brazil
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Sao Paulo
State/Province
SP
ZIP/Postal Code
01327 001
Country
Brazil
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Ostrava
State/Province
Poruba
ZIP/Postal Code
708 52
Country
Czechia
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Praha 4
ZIP/Postal Code
140 00
Country
Czechia
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Tartu
ZIP/Postal Code
50406
Country
Estonia
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Nantes Cedex 1
ZIP/Postal Code
44093
Country
France
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Neuilly Sur Seine
ZIP/Postal Code
92200
Country
France
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Paris 13
ZIP/Postal Code
75651
Country
France
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Regensburg
State/Province
Bavaria
ZIP/Postal Code
93053
Country
Germany
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Bad Oeynhausen
ZIP/Postal Code
32545
Country
Germany
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Dresden
ZIP/Postal Code
01307
Country
Germany
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Giessen
ZIP/Postal Code
35392
Country
Germany
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Leipzig
ZIP/Postal Code
04289
Country
Germany
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Pecs
State/Province
Baranya
ZIP/Postal Code
7621
Country
Hungary
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Budapest
State/Province
Pest Megye
ZIP/Postal Code
1134
Country
Hungary
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Budapest
ZIP/Postal Code
1122
Country
Hungary
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Budapest
ZIP/Postal Code
H 1096
Country
Hungary
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Debrecen
ZIP/Postal Code
4032
Country
Hungary
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Kaunas
State/Province
LTU
ZIP/Postal Code
LT 50161
Country
Lithuania
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Vilnius
ZIP/Postal Code
LT 08661
Country
Lithuania
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Singapore
ZIP/Postal Code
119074
Country
Singapore
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Hospitalet de Llobregat
State/Province
Barcelona
ZIP/Postal Code
08907
Country
Spain
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Badalona
State/Province
Catalunya
ZIP/Postal Code
08916
Country
Spain
Individual Site Status
Recruiting
Facility Name
Novartis Investigative Site
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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

Learn more about this trial

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

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