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

Contact Information

Margaret Carlson
margaret.carlson@hsc.utah.edu
8015853752

Brief Summary

STUDY OBJECTIVE(S), DESIGN AND ENDPOINTS

Primary Objective

● To evaluate the efficacy of postsurgery treatment with ASP1128 in subjects at risk for AKI following CABG and/or valve surgery

Secondary Objectives

● 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

Exploratory Objectives

● 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

Inclusion Criteria

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

days.

● 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

Contraception Requirements]

OR

● 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.

Exclusion Criteria

Subject will be excluded from participation if any of the following apply:

At screening:

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

Disease).

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 5.1.3.1 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

randomization.):

● 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

investigator.

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.

General:

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

formulation used.

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.