|Principal Investigator: Craig Selzman|
|Keywords: Cardiac Surgery , Acute Kidney Injury||Department: Cardiothoracic Division|
|IRB Number: 00137758|
|Specialty: Cardiothoracic Surgery|
|Sub Specialties: Heart Failure|
|Recruitment Status: Recruiting|
STUDY OBJECTIVE(S), DESIGN AND ENDPOINTS
● To evaluate the efficacy of postsurgery treatment with ASP1128 in subjects at risk for AKI following CABG and/or valve surgery
● To investigate the safety and tolerability of postsurgery treatment with ASP1128 in subjects at risk for AKI following CABG and/or valve surgery
● To investigate the pharmacokinetic characteristics of ASP1128 in subjects at risk for AKI following CABG and/or valve surgery
● To investigate the pharmacodynamic characteristics of ASP1128 in subjects at risk for AKI following CABG and/or valve surgery
● To evaluate subject characteristics and biomarkers (including the NC device) for identifying subjects at risk for AKI following CABG and/or valve surgery
Subject is eligible for the study if all of the following apply:
1. Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved written
informed consent and privacy language as per national regulations (e.g., Health Insurance
Portability and Accountability Act [HIPAA] Authorization for US sites) must be obtained
from the subject prior to any study-related procedures
(including withdrawal of prohibited medication).
2. Subject agrees not to participate in another interventional study after signing the informed
consent form (ICF) and until the end of study (EoS) visit has been completed.
3. Subject is ≥ 35 years of age at time of screening (visit 1).
4. Subject undergoing non-emergent open chest cardiovascular surgery with use of CPB
(i.e., CABG and/or valve surgery [including aortic root and ascending aorta surgery,
without circulatory arrest]) within 4 weeks of screening (visit 1).
5. Subject is at risk of developing 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 m2 as per Modification of
Diet in Renal Disease Study (MDRD) or CKD-EPI equation (or documented
measured GFR assessment)
o History needs to be present for at least 90 days prior to screening. Both SCr
and eGFR need to be documented in the chart, and
o eGFR at screening or baseline needs to be < 60 mL/min per 1.73 m2, as well
as per CKD-EPI equation.
● Documented history of congestive heart failure requiring hospitalization. This
condition should exist for at least 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
● Documented history of proteinuria/albuminuria at any time point before screening
o Urinary dipstick result of ≥ 2+, OR
o Documented urinary albumin creatinine ratio measurement of ≥ 300 mg/g, or
o Documented total quantity of protein in a 24-hour urine collection test
≥ 0.3 g/day.
6. Subject must have the ability, in the opinion of the investigator, and willingness to return
for all scheduled visits and perform all assessments.
7. A female subject is eligible to participate if she is not pregnant see [Appendix 12.3
Contraception Requirements] and at least 1 of the following conditions applies:
● Not a woman of childbearing potential (WOCBP) as defined in [Appendix 12.3
● WOCBP who agrees to follow the contraceptive guidance as defined in
[Appendix 12.3 Contraception Requirements] throughout the treatment period and
for at least 30 days after the final study drug administration.
8. 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.
9. Female subject must not donate ova starting at screening and throughout the study period,
and for 30 days after the final study drug administration.
10. A male subject with female partner(s) of childbearing potential must agree to use
contraception as detailed in [Appendix 12.3 Contraception Requirements] during the
treatment period and for at least 30 days after the final study drug administration.
11. A male subject must not donate sperm during the treatment period and for at least 30 days
after the final study drug administration.
12. 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.
Subject will be excluded from participation if any of the following apply:
1. Subject has received investigational drug within 30 days or 5 half-lives, whichever is
longer, prior to screening.
2. Subject has use of RRT within 30 days prior to screening.
3. Subject has CKD stage 4 or 5, or stage 3 (i.e., eGFR 30-59 mL/min per 1.73m2) with a
known history of eGFR < 30 mL/min per 1.73 m2 as per CKD-EPI or MDRD equation
within 6 months prior to screening.
4. Subject has a prior kidney transplantation.
5. Subject has a known or suspected glomerulonephritis (other than Diabetic Kidney
6. Subject has confirmed or treated endocarditis, or other current active infection requiring
antibiotic treatment, within 30 days prior to screening.
7. Subject is using prohibited medications as specified in the concomitant medication section
of the protocol [Section 22.214.171.124 Prohibited and Restricted Treatment].
8. Subject has a prior history of intravenous drug abuse within 1 year prior to screening.
9. Subject has a known chronic liver disorder with Child-Pugh B or C classification.
10. Subject has any of the following abnormal liver or kidney function parameters as assessed
at screening. (If the results from the central laboratory are not yet available at time of
randomization, results from local laboratory within 7 days before the surgery can be used
for verifying this criterion. The subject will not be excluded from the study if central
laboratory results from screening are exclusionary and are available only after
● Alanine aminotransferase (ALT), aspartate aminotransferase (AST) to > 2 times the
upper limit of normal (ULN) or bilirubin increased to > 1.5 times the ULN (not due to
previously diagnosed Gilbert’s syndrome).
● eGFR < 30 mL/min per 1.73 m2 as per CKD-EPI equation.
11. Subject has use of left ventricular assist device (LVAD), intra-aortic balloon pump
(IABP) or other cardiac devices, or catecholamines within 7 days prior to screening.
12. Subject has surgery scheduled to be performed without CPB (i.e., “Off-Pump” surgery).
13. Subject has surgery scheduled to be performed under conditions of circulatory arrest,
including planned deep hypothermic circulatory arrest.
14. Subject has surgery scheduled for aortic dissection.
15. Subject has surgery for a condition that is immediately life-threatening as per the
discretion of the investigator.
16. Subject has surgery scheduled to correct major congenital heart defect.
17. 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 at the Day of Surgery:
18. Exclusion criteria 1 to 17 are applicable at this time.
19. Subject has AKI (any stage) present at presurgery baseline at the discretion of the
20. Subject has known or suspected infection/sepsis at time of presurgery baseline at the
discretion of investigator.
Perioperative Exclusion Criteria:
21. Subject requires Extracorporeal Membrane Oxygenation (ECMO) during or after
completion of surgery.
22. Subject requires ventricular assist device (VAD) during or after completion of surgery.
23. Subject has surgery performed “Off-Pump” at any time during surgery.
24. Subject has other condition, which, in the investigator’s opinion, makes the subject
unsuitable for study participation.
25. 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.
26. Subject has a known or suspected hypersensitivity to ASP1128 or any components of the
27. Subject is an employee of the Astellas Group or the contract research organization (CRO)
involved in the study.
Waivers to the inclusion and exclusion criteria will NOT be allowed.