Study to Evaluate the Efficacy of ASP1128 (MA-0217) in Subjects at Risk for Acute Kidney Injury (AKI) Following Coronary Artery Bypass Graft (CABG) and/or Valve Surgery

The study comprised of a screening visit, followed by CABG and/or valve surgery on Day 1, double-blind treatment period and a follow-up period up to Day 90 in subjects with moderate/severe risk of AKI at 2-22 hours post-surgery.

Subjects with low risk of AKI at 2-22 hours post-surgery assessment were enrolled in the observational cohort to evaluate subject characteristics and biomarkers for exploratory objectives.

Inclusion criteria

• Subject agrees not to participate in another interventional study after signing the informed consent form and until the end of study (EoS) visit has been completed.
• Subject is ≥ 35 years of age at the time of screening (visit 1).
• Subject undergoing non-emergent open chest cardiovascular surgery with the use of cardiopulmonary bypass pump (CPB) (i.e., coronary artery bypass graft (CABG) and/or valve surgery [including aortic root and ascending aorta surgery without circulatory arrest]) within 4 weeks of screening (visit 1).
• Subject is at risk of developing acute kidney injury (AKI) following cardiovascular surgery, i.e., has 1 or more of the following AKI risk factors:

• Age at screening of ≥ 70 years
• Documented history of eGFR < 60 mL/min per 1.73 m^2 as per Modification of Diet in Renal Disease Study (MDRD) or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (or documented measured glomerular filtration rate assessment) (history needs to be present for at least 90 days prior to screening, and eGFR at screening or baseline needs to be < 60 mL/min per 1.73 m^2, as well as per CKD-EPI equation.)
• Documented history of congestive heart failure requiring hospitalization. This condition should exist for ≥ 90 days prior to screening.
• Documented history of diabetes mellitus (type 1 or 2) of ≥ 90 days prior to screening, and subject is on active antidiabetic medication treatment for ≥ 90 days.
• Documented history of proteinuria/albuminuria at any time point before screening (urinary dipstick result of ≥ 2+, documented urinary albumin creatinine ratio measurement of ≥ 300 mg/g, or documented total quantity of protein in a 24-hour urine collection test ≥ 0.3 g/day)
• Subject must have the ability and willingness to return for all scheduled visits and perform all assessments.
• Female subject is eligible to participate if she is not pregnant and at least 1 of the following conditions applies:

• Not a woman of childbearing potential (WOCBP), OR
• WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least 30 days after the final study drug administration.
• Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 30 days after the final study drug administration.
• Female subject must not donate ova starting at screening and throughout the study period, and for 30 days after the final study drug administration.
• Male subject with female partner(s) of child-bearing potential must agree to use contraception during the treatment period and for at least 30 days after the final study drug administration.
• Male subject must not donate sperm during the treatment period and for at least 30 days after the final study drug administration.
• Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study period and for 30 days after the final study drug administration.

Exclusion criteria

At Screening:

• Subject has received investigational drug within 30 days or 5 half-lives, whichever is longer, prior to screening.
• Subject has received RRT within 30 days prior to screening.
• Subject has CKD stage 4 or 5, or stage 3 (i.e., eGFR 30-59 mL/min per 1.73m^2) with a known history of eGFR < 30 mL/min per 1.73 m^2 as per CKD-EPI or MDRD equation within 6 months prior to screening.
• Subject has a prior kidney transplantation.
• Subject has a known or suspected glomerulonephritis (other than Diabetic Kidney Disease).
• Subject has confirmed or treated endocarditis or other current active infection requiring antibiotic treatment within 30 days prior to screening.
• Subject is using prohibited.
• Subject has a prior history of intravenous drug abuse within 1 year prior to screening.
• Subject has a known chronic liver disorder with Child-Pugh B or C classification.
• Subject has any of the following abnormal liver or kidney function parameters:

• Alanine aminotransferase (ALT), aspartate aminotransferase (AST) > 2 times the upper limit of normal (ULN) or bilirubin increased to > 1.5 times the ULN.
• eGFR < 30 mL/min per 1.73 m^2 as per CKD-EPI equation.
• Subject has use of left ventricular assist device, intra-aortic balloon pump or other cardiac devices, or catecholamines within 7 days prior to screening.
• Subject has surgery scheduled to be performed without CPB (i.e., "Off-Pump" surgery).
• Subject has surgery scheduled to be performed under conditions of circulatory arrest, including planned deep hypothermic circulatory arrest.
• Subject has surgery scheduled for aortic dissection.
• Subject has surgery for a condition that is immediately life-threatening.
• Subject has surgery scheduled to correct major congenital heart defect.
• Subject has current or previous malignant disease. Subjects with a history of cancer are considered eligible if the subject has undergone therapy and the subject has been considered disease free or progression free for at least 5 years. Subject with completely excised basal cell carcinoma or squamous cell carcinoma of the skin and completely excised cervical cancer in situ are also considered eligible.

Preoperatively on the Day of Surgery:

• Exclusion criteria 1 to 17 are applicable at this time.
• Subject has AKI (any stage) present at presurgery baseline.
• Subject has known or suspected infection/sepsis at time of presurgery baseline.

Perioperative Exclusion Criteria:

• Subject requires Extracorporeal Membrane Oxygenation during or after completion of surgery.
• Subject requires ventricular assist device during or after completion of surgery.
• Subject has surgery performed "Off-Pump" at any time during surgery.

General:

• Subject has other condition, which makes the subject unsuitable for study participation.
• Female subject who is pregnant or lactating or has a positive pregnancy test within 72 hours prior to screening and/or randomization, has been pregnant within 6 months before screening assessment or breastfeeding within 3 months before screening or who is planning to become pregnant within the total study period.
• Subject has a known or suspected hypersensitivity to ASP1128 or any components of the formulation used.