Clinical trial NCT05524051: 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
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Acute Kidney Injury Following Cardiac Surgery
Keywords: acute kidney injury
cardiac surgery
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2022-09-01
Enrollment: 98
Sex: ALL
Minimum age (years): 45
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Ratio of the highest serum creatinine value up to and including Study Day 6 versus baseline
timeFrame: from baseline to Day 6
Secondary outcomes:
measure: AKI stages 1, 2 and 3 as defined by modified AKI Network criteria
timeFrame: from baseline to Day 6
measure: Anti-drug antibodies against TIN816
timeFrame: from baseline to 90 Days
measure: Occurrence of major adverse kidney event at Day 90 (MAKE90)
timeFrame: 90 Days
measure: Occurrence of MAKE30
timeFrame: 30 Days
measure: Occurrence of individual components of the MAKE criteria at Days 30 or 90.
timeFrame: 30 or 90 Days
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic Phoenix
state: Arizona
city: Durham
country: United States
facility: Duke Univ Medical Center
state: North Carolina
city: Dallas
country: United States
facility: Univ of Texas Southwest Med Center
state: Texas
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Caba
country: Argentina
facility: Novartis Investigative Site
state: Buenos Aires
city: Buenos Aires
country: Argentina
facility: Novartis Investigative Site
city: Genk
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Curitiba
country: Brazil
facility: Novartis Investigative Site
state: Parana
city: Santo Andre
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Salvador
country: Brazil
facility: Novartis Investigative Site
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Montreal
country: Canada
facility: Novartis Investigative Site
state: Quebec
city: Quebec
country: Canada
facility: Novartis Investigative Site
city: Ostrava
country: Czechia
facility: Novartis Investigative Site
state: Poruba
city: Tartu
country: Estonia
facility: Novartis Investigative Site
city: Nantes Cedex 1
country: France
facility: Novartis Investigative Site
city: Neuilly Sur Seine
country: France
facility: Novartis Investigative Site
city: Paris
country: France
facility: Novartis Investigative Site
city: Poitiers
country: France
facility: Novartis Investigative Site
city: Rennes
country: France
facility: Novartis Investigative Site
city: Regensburg
country: Germany
facility: Novartis Investigative Site
state: Bavaria
city: Frankfurt am Main
country: Germany
facility: Novartis Investigative Site
state: Hessen
city: Bad Oeynhausen
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Pecs
country: Hungary
facility: Novartis Investigative Site
city: Ahmedabad
country: India
facility: Novartis Investigative Site
state: Gujarat
city: Ahmedabad
country: India
facility: Novartis Investigative Site
state: Gujarat
city: Bangalore
country: India
facility: Novartis Investigative Site
state: Karnataka
city: Lucknow
country: India
facility: Novartis Investigative Site
state: Uttar Pradesh
city: Vilnius
country: Lithuania
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Hospitalet de Llobregat
country: Spain
facility: Novartis Investigative Site
state: Barcelona
city: Badalona
country: Spain
facility: Novartis Investigative Site
state: Catalunya
city: Santiago De Compostela
country: Spain
facility: Novartis Investigative Site
state: Galicia
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticasl
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: