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
Condition: Acute Kidney Injury (AKI)
MeSH terms: Acute Kidney Injury; Wounds and Injuries
Intervention: ASP1128; Placebo
Intervention description: Intravenous Infusion; Intravenous Infusion
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 351.0
Sex: All
Minimum age: 35 Years
Healthy volunteers: No

Summary:

      The purpose of this study was to evaluate the efficacy of postsurgery treatment with ASP1128
      in subjects at risk for AKI following CABG and/or valve surgery.

      This study also investigated the safety and tolerability of postsurgery treatment with
      ASP1128, and pharmacokinetic characteristics of ASP1128 in subjects at risk for AKI following
      CABG and/or valve surgery.
    

Eligibility criteria:

        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.