Effect of RBT-1 on Preconditioning Response Biomarkers in Subjects Undergoing CABG and/or Cardiac Valve Surgery
Condition: AKI
Intervention: Low Dose RBT-1; High Dose RBT-1; Placebo
Intervention description: intravenous administration; intravenous administration; intravenous administration
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Subjects will be randomized 1:1:1 to low dose RBT-1, high dose RBT-1, and placebo
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 152.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the effect of RBT-1 (stannous protoporphyrin
      [SnPP]/iron sucrose [FeS]) on preconditioning response biomarkers in subjects who are at risk
      for AKI following cardiac surgery.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or female subjects ≥18 years of age at Screening.

          2. Able and willing to comply with all study procedures.

          3. Stable kidney function per Investigator assessment and no known episodes of AKI during
             the preceding 4 weeks.

          4. Scheduled to undergo non-emergent coronary and/or valve surgery(ies) requiring
             cardiopulmonary bypass, including:

               -  CABG alone;

               -  Combined CABG surgery/repair of 1 or more cardiac valves;

               -  Cardiac valve(s) replacement or repair alone.

          5. Females and males of childbearing potential must agree to use 2 forms of
             contraception, with at least 1 being a barrier method, or abstain from sexual activity
             for 30 days following study drug administration.

          6. Male subjects must agree not to donate or sell sperm for 30 days following study drug
             administration.

        Exclusion Criteria:

          1. Presence of AKI (KDIGO criteria) at the time of Screening.

          2. Surgery to be performed without cardiopulmonary bypass.

          3. Surgery to be performed under conditions of circulatory arrest or hypothermia with
             rectal temperature <28°C (82.4°F).

          4. eGFR ≤20 mL/min/1.73m2 or need for dialysis.

          5. Surgery for aortic dissection or to correct a major congenital heart defect.

          6. Administration of iodinated contrast media within 24 hours prior to cardiac surgery or
             evidence of contrast-induced nephropathy prior to cardiac surgery.

          7. Cardiogenic shock or hemodynamic instability within the 24 hours prior to surgery and
             requirement for inotropes or vasopressors or other mechanical devices, such as
             intra-aortic balloon counter-pulsation.

          8. Requirement for any of the following within 7 days prior to cardiac surgery:

               -  Defibrillator or permanent pacemaker;

               -  Mechanical ventilation;

               -  Intra-aortic balloon counter-pulsation;

               -  Left ventricular assist device;

               -  Other forms of mechanical circulatory support.

          9. Known history of cancer within the past 2 years, except for carcinoma in situ of the
             cervix or adequately treated basal cell carcinoma of the skin.

         10. Known or suspected sepsis at time of Screening or confirmed or treated endocarditis
             within 30 days prior to cardiac surgery.

         11. Other current active infection requiring systemic antibiotic treatment.

         12. Inadequate hepatic function, defined as total bilirubin or alanine aminotransferase or
             aspartate aminotransferase >2X the upper limit of normal at time of Screening or Child
             Pugh Class C liver disease or higher.

         13. Any congenital coagulation disorder.

         14. Asplenia (anatomic or functional).

         15. History of photosensitivity or active skin disease that, in the opinion of the
             Investigator, could be worsened by RBT-1.

         16. Known hypersensitivity or previous anaphylaxis to SnPP or any tin-based product.

         17. Serum ferritin >500 ng/mL or those who have received IV iron within 28 days of
             Screening.

         18. Pregnancy or lactation.

         19. Treatment with an investigational drug or participation in an interventional study
             within 30 days prior to administration of study drug.

         20. In the opinion of the Investigator, any disease processes or confounding variables
             that would inappropriately alter the outcome of the study.

         21. Inability to comply with the requirements of the study protocol.