Study 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. 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.
Interventions
Placebo
TIN816
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.
Study Location
Novartis Investigative Site
Recruiting
Buenos Aires,C1428dco,Argentina
Novartis Investigative Site
Recruiting
Caba,Buenos Aires,C1118aat,Argentina
Novartis Investigative Site
Recruiting
Caba,Buenos Aires,C1181ach,Argentina
Novartis Investigative Site
Recruiting
Genk,3600,Belgium
Novartis Investigative Site
Recruiting
Leuven,3000,Belgium
Novartis Investigative Site
Recruiting
Sao Paulo,SP,01308-050,Brazil
Novartis Investigative Site
Recruiting
Sao Paulo,SP,01327 001,Brazil
Novartis Investigative Site
Recruiting
Montreal,Quebec,H2x 0a9,Canada
Novartis Investigative Site
Recruiting
Prague 4,146 24,Czechia
Novartis Investigative Site
Recruiting
Ostrava,Poruba,708 52,Czechia
Novartis Investigative Site
Recruiting
Tartu,50406,Estonia
Novartis Investigative Site
Recruiting
Nantes Cedex 1,44093,France
Novartis Investigative Site
Recruiting
Neuilly Sur Seine,92200,France
Novartis Investigative Site
Recruiting
Rennes,35043,France
Novartis Investigative Site
Recruiting
Paris 13,75651,France
Novartis Investigative Site
Recruiting
Poitiers,86021,France
Novartis Investigative Site
Recruiting
Regensburg,Bavaria,93053,Germany
Novartis Investigative Site
Recruiting
Leipzig,04289,Germany
Novartis Investigative Site
Recruiting
Bad Oeynhausen,32545,Germany
Novartis Investigative Site
Recruiting
Dresden,01307,Germany
Novartis Investigative Site
Recruiting
Frankfurt,60590,Germany
Novartis Investigative Site
Recruiting
Budapest,H 1096,Hungary
Novartis Investigative Site
Recruiting
Debrecen,4032,Hungary
Novartis Investigative Site
Recruiting
Pecs,Baranya,7621,Hungary
Novartis Investigative Site
Recruiting
Budapest,1122,Hungary
Novartis Investigative Site
Recruiting
Singapore,119074,Singapore
Novartis Investigative Site
Recruiting
Hospitalet de Llobregat,Barcelona,08907,Spain
Novartis Investigative Site
Recruiting
Santiago De Compostela,Galicia,15706,Spain
Novartis Investigative Site
Recruiting
Badalona,Catalunya,08916,Spain
Novartis Investigative Site
Recruiting
Madrid,28006,Spain
Novartis Investigative Site
Recruiting
Taipei,10002,Taiwan
Duke Univ Medical Center Department of Medicine
Recruiting
Durham,North Carolina,27710,United States
Anne Cherry
Mayo Clinic Phoenix
Recruiting
Phoenix,Arizona,85054,United States
Erica Boyd
Leslie Thomas
Univ of Texas Southwest Med Center Cardiovasc And Thoracic Surg
Recruiting
Dallas,Texas,75390-9034,United States
Michael Jessen
Worldwide Contacts
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