Effect of RBT-1 on Preconditioning Response Biomarkers in Subjects Undergoing CABG and/or Cardiac Valve Surgery (START)

A Phase 2, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Effect of RBT-1 on Preconditioning Response Biomarkers in Subjects Undergoing Coronary Artery Bypass Graft (CABG) and/or Cardiac Valve Surgery (The START Study)

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.

Study Overview

• Status: Completed
• Conditions: AKI
• Intervention / Treatment: Drug: Low Dose RBT-1; Drug: High Dose RBT-1; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 152
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ayla Rasmussen; Phone Number: 443-569-9228; Email: arasmussen@renibus.com

Study Locations

• Australia
  • Queensland
    • Southport, Queensland, Australia, 4215
      • Gold Cost University Hospital & Health Services
  • South Australia
    • Bedford Park, South Australia, Australia
      • Flinders Medical Centre
  • Victoria
    • Clayton, Victoria, Australia
      • Monash Medical Centre
    • Melbourne, Victoria, Australia, 3004
      • The Alfred Hospital
• Canada
  • New Brunswick
    • Saint John, New Brunswick, Canada, E2L 4L2
      • St-John Regional Hospital
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton Health Sciences Corporation
  • Quebec
    • Québec, Quebec, Canada, G1V 4G5
      • Institut Universitaire De Cardiologie Et De Pneumologie De Québec
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35801
      • Heart Center Research, LLC
  • California
    • Los Angeles, California, United States, 90033
      • Keck Hospital of USC
    • Santa Barbara, California, United States, 93102
      • Santa Barbara Cottage Hospital
    • Stanford, California, United States, 94305
      • Stanford University Medical Center
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Yale University School of Medicine
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • MedStar Health Research Institute, Inc.
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Hospital Anesthesia and Critical Care
  • Indiana
    • Bloomington, Indiana, United States, 47403
      • Indiana University Health Southern Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Lutheran Medical Group
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Michigan
    • Lansing, Michigan, United States, 48910
      • Mclaren Greater Lansing
    • Midland, Michigan, United States, 48670
      • MyMichigan Medical Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic Rochester
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth-Hitchcock Medical Center
  • New York
    • Flushing, New York, United States, 11355
      • New York Presbyterian-Queens
    • New York, New York, United States, 10032
      • Columbia University Irving Medical Center
    • Rochester, New York, United States, 14621
      • Rochester General Hospital Center for Clinical Research
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low Dose RBT-1; Single IV infusion prior to cardiac surgery	Drug: Low Dose RBT-1; intravenous administration
Experimental: High Dose RBT-1; Single IV infusion prior to cardiac surgery	Drug: High Dose RBT-1; intravenous administration
Placebo Comparator: Placebo; Single IV infusion prior to cardiac surgery	Drug: Placebo; intravenous administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the Efficacy of RBT-1 in Generating a Preconditioning Response as Measured by a Composite of Biomarkers	Composite of the geometric mean of the ratios of the maximum PreOp value over Baseline for plasma heme oxygenase-1 (HO-1), ferritin, and interleukin-10 (IL-10)	Baseline through Pre-Surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Renal Tubular Injury Biomarkers	Geometric mean of the ratios of the maximum PostOp value over Baseline for urine KIM-1, NGAL, and cystatin C.	Baseline through Day 3 post-cardiac surgery
Number of Subjects With Reduction in Urine Output	Documented AE of sustained reduction in urine output, oliguria, or anuria post-cardiac surgery through Day 5	Baseline through post-cardiac surgery through Day 5
Number of Subjects With Acute Kidney Injury (AKI)	AKI is defined using the KDIGO criteria (ie, an absolute increase in serum creatinine of ≥1.5 × Baseline; or documented AE of sustained reduction in urine output, oliguria, or anuria; or initiation of dialysis).	Baseline through Day 5 post-cardiac surgery

Collaborators and Investigators

• Sponsor: Renibus Therapeutics, Inc.

Publications and helpful links

General Publications

• Lamy A, Chertow GM, Jessen M, Collar A, Brown CD, Mack CA, Marzouk M, Scavo V, Washburn TB, Savage D, Smith J, Bennetts J, Assi R, Shults C, Arghami A, Butler J, Devereaux PJ, Zager R, Wang C, Snapinn S, Browne A, Rodriguez J, Ruiz S, Singh B; of START Investigators. Effects of RBT-1 on preconditioning response biomarkers in patients undergoing coronary artery bypass graft or heart valve surgery: a multicentre, double-blind, randomised, placebo-controlled phase 2 trial. EClinicalMedicine. 2024 Jan 8;68:102364. doi: 10.1016/j.eclinm.2023.102364. eCollection 2024 Feb.

Helpful Links

• Effects of RBT-1 on preconditioning response biomarkers in patients undergoing coronary artery bypass graft or heart valve surgery: a multicentre, double-blind, randomised, placebo-controlled phase 2 trial

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2021
• Primary Completion (Actual): November 9, 2022
• Study Completion (Actual): February 3, 2023

Study Registration Dates

• First Submitted: September 21, 2020
• First Submitted That Met QC Criteria: September 21, 2020
• First Posted (Actual): September 25, 2020

Study Record Updates

• Last Update Posted (Estimated): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 11, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: REN-004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No