A Study to Evaluate the Efficacy and Safety of BX-001N in Preventing Cardiac Surgery-Associated Acute Kidney Injury (CSA-AKI) and Major Adverse Kidney Events (MAKE)

Official title

Randomized, Single-blind, Multi-center, Placebo-controlled, Phase 2a Clinical Trial of BX-001N to Prevent From Cardiac Surgery-Associated Acute Kidney Injury (CSA-AKI) and Subsequent Major Adverse Kidney Events (MAKE)

Overview

This is a Randomized, Single-blind, Multi-center, Placebo-controlled, Phase 2a clinical trial of BX-001N to prevent patients from Cardiac Surgery Associated Acute Kidney Injury (CSA-AKI) and subsequent Major Adverse Kidney Events (MAKE) in approximately 50 participants.

Detailed description

This study will enroll approximately 50 participants, with 16 participants randomized to Experimental Group 1 and 4 participants to the Placebo Group 1, 15 participants to Experimental Group 2 and 15 participants to the Placebo Group 2.

Randomized participants will be hospitalized from one day prior to surgery (Baseline, Day -1) through Day 7.

Investigational product (IP) (i.e., BX-001N) will be administered intravenously at a weight-based dose as follows: The test drug will be administered three times in total. Participants in the Placebo Group will receive placebo at the same time points and in the same manner.

Follow-up visits will be conducted up to Day 90 at the study site for scheduled efficacy and safety assessments.

Interventions

• Drug BX-001N Experimental group 1
  Each participant will receive BX-001N at a weight-based low dose via IV injection once daily for a total of three administrations.
• Drug BX-001N Experimental group 2
  Each participant will receive BX-001N at a weight-based high dose via IV injection once daily at the same time during hospitalization, for a total of three administrations.
• Drug Placebo group 1
  Each participant will receive Placebo at a weight-based dose via IV injection once daily at the same time during hospitalization, for a total of three administrations.
• Drug Placebo group 2
  Each participant will receive Placebo at a weight-based dose via IV injection once daily at the same time during hospitalization, for a total of three administrations.

Primary outcome measures

• Change from baseline in NGAL levels [Time frame: Baseline(Day -1) to Day 7]
• Change from baseline in sCr levels [Time frame: Baseline(Day -1) to Day 7]
• Change from baseline in eGFR [Time frame: Baseline(Day -1) to Day 30]

Secondary outcome measures (6)

• Change from baseline in CysC [Time frame: Baseline(Day -1) to Day 7]
• Change from baseline in TIMP-2 [Time frame: Baseline(Day -1) to Day 7]
• Change from baseline in IGFBP7 [Time frame: Baseline(Day -1) to Day 7]
• Collection of Major Adverse Renal Events [MAKE] [Time frame: Up to Day 90]
• Change from baseline in Incidence of AKI based on Kidney Disease: Improving Global Outcomes [KDIGO] criteria [Time frame: Baseline(Day -1) to Day 7]
• Change from baseline in BUN [Time frame: Baseline(Day -1) to Day 30]

Eligibility criteria

Inclusion criteria

• 19 to 90 years of age
• Participants with aortic disease scheduled for cardiac surgery via total circulatory arrest (TCA)
• Body weight ≥ 30 kg
• Participants with vital signs within the following ranges

• Temperature : 35.0\~37.5°C
• Blood pressure : Systolic blood pressure(SBP) 100\~160 mmHg, Diastolic blood pressure(DBP) < 100 mmHg
• Pulse : 50\~100 bpm (regardless of drug use)
• Willing to comply with the schedule and sign the informed consent
• Participants with moderate renal impairement

Exclusion criteria

• Participants scheduled for emergent or salvage cardiac surgery
• Use of kidney replacement therapy (KRT) or presence of acute kidney injury (AKI)
• Participants at risk of bleeding
• Participants who underwent cardiac surgery via mid-sternotomy or thoracotomy, including major congenital heart disease
• Participants who received cardiopulmonary resuscitation within 30 days prior to cardiac surgery
• Recipient of a solid organ or bone marrow transplantation
• Participants with cardiogenic shock or hemodynamics instability, or planned use of intra-aortic balloon pump, extracorporeal membrane oxygenation, or left ventricular assist device
• Active systemic bacterial, viral, or fungal infection
• History of HIV
• Positive serology test for HAV, HBV, HCV or Syphilis
• Participants with impaired liver function due to cirrhosis, or those with 2x UNR blood levels of ALP, AST, or ALT, or with total bilirubin levels outside the normal range
• Uncontrolled hypertension
• History of congenital immunodeficiency
• Genetic disorder with severe and abnormal bilirubin metabolism
• Participants deemed unsuitable for the study in the discretion of the investigator
• History of malignancy
• Planned use of any pharmacologic agent other than the IP assigned in this study for the prevention or treatment of acute kidney injury
• History of severe allergic or anaphylactic reactions, or sensitivity to the IP or its constituents
• History of participation in other clinical trials within 30 days
• Presence of a do-not-resuscitate order or life expectancy of < 3 months
• Female subjects of childbearing potential
• Male subjects and their spouse/partner are not willing to use appropriate contraception, or if their spouse/partner is pregnant, breastfeeding or has a plan
• Poorly controlled type 2 diabetes mellitus
• New York Heart Association (NYHA) Class IV heart failure

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Prevention

Study locations

South Korea · 8 centers

• Keimyung University Dongsan Medical Center — Daegu
• Seoul National University Bundang Hospital — Seongnam
• Korea University Anam Hospital — Seoul
• Seoul National University Hospital — Seoul
• Severance Hospital — Seoul
• Seoul Asan Medical center — Seoul
• Samsung Medical Center — Seoul
• Pusan National University Yangsan Hospital — Yangsan

Identifiers

NCT: NCT07164833 · BX-001N-002

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗