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

NCT04564833 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: REN-004
• Study Type: interventional
• Target: 152
• Locations: 3 countries
• Sites: 25

Brief 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.

Conditions

AKI

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Change in Renal Tubular Injury Biomarkers

  Baseline through Day 3 post-cardiac surgery

• Number of Subjects With Reduction in Urine Output

  Baseline through post-cardiac surgery through Day 5

• Number of Subjects With Acute Kidney Injury (AKI)

  Baseline through Day 5 post-cardiac surgery

Study Arms (3)

Low Dose RBT-1

EXPERIMENTAL

Single IV infusion prior to cardiac surgery

Drug: Low Dose RBT-1

High Dose RBT-1

EXPERIMENTAL

Single IV infusion prior to cardiac surgery

Drug: High Dose RBT-1

Placebo

PLACEBO COMPARATOR

Single IV infusion prior to cardiac surgery

Drug: Placebo

Interventions

Low Dose RBT-1 DRUG

intravenous administration

Low Dose RBT-1

High Dose RBT-1 DRUG

intravenous administration

High Dose RBT-1

Placebo DRUG

intravenous administration

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects ≥18 years of age at Screening.
• Able and willing to comply with all study procedures.
• Stable kidney function per Investigator assessment and no known episodes of AKI during the preceding 4 weeks.
• 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.
• 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.
• Male subjects must agree not to donate or sell sperm for 30 days following study drug administration.

You may not qualify if:

• Presence of AKI (KDIGO criteria) at the time of Screening.
• Surgery to be performed without cardiopulmonary bypass.
• Surgery to be performed under conditions of circulatory arrest or hypothermia with rectal temperature \<28°C (82.4°F).
• eGFR ≤20 mL/min/1.73m2 or need for dialysis.
• Surgery for aortic dissection or to correct a major congenital heart defect.
• Administration of iodinated contrast media within 24 hours prior to cardiac surgery or evidence of contrast-induced nephropathy prior to cardiac surgery.
• 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.
• 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.
• 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.
• Known or suspected sepsis at time of Screening or confirmed or treated endocarditis within 30 days prior to cardiac surgery.

Sponsors & Collaborators

• Renibus Therapeutics, Inc.: lead

Study Sites (25)

Heart Center Research, LLC

Huntsville, Alabama, 35801, United States

Location

Keck Hospital of USC

Los Angeles, California, 90033, United States

Location

Santa Barbara Cottage Hospital

Santa Barbara, California, 93102, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06519, United States

Location

MedStar Health Research Institute, Inc.

Washington D.C., District of Columbia, 20010, United States

Location

University of Chicago Hospital Anesthesia and Critical Care

Chicago, Illinois, 60637, United States

Location

Indiana University Health Southern Indiana

Bloomington, Indiana, 47403, United States

Location

Lutheran Medical Group

Fort Wayne, Indiana, 46804, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

McLaren Greater Lansing

Lansing, Michigan, 48910, United States

Location

MyMichigan Medical Center

Midland, Michigan, 48670, United States

Location

Mayo Clinic Rochester

Rochester, Minnesota, 55905, United States

Location

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

New York Presbyterian-Queens

Flushing, New York, 11355, United States

Location

Columbia University Irving Medical Center

New York, New York, 10032, United States

Location

Rochester General Hospital Center for Clinical Research

Rochester, New York, 14621, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Gold Cost University Hospital & Health Services

Southport, Queensland, 4215, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, Australia

Location

Monash Medical Centre

Clayton, Victoria, Australia

Location

The Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

St-John Regional Hospital

Saint John, New Brunswick, E2L 4L2, Canada

Location

Hamilton Health Sciences Corporation

Hamilton, Ontario, L8L 2X2, Canada

Location

Institut Universitaire de Cardiologie et de Pneumologie de Québec

Québec, Quebec, G1V 4G5, Canada

Location

Related Publications (1)

• 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.

  PMID: 38586479 RESULT

Related 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

Results Point of Contact

• Title: Stacey Ruiz, PhD / VP, Drug Development
• Organization: Renibus Therapeutics

sruiz@renibus.com

424-209-2734

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Subjects will be randomized 1:1:1 to low dose RBT-1, high dose RBT-1, and placebo

Study Record Dates

• First Submitted: September 21, 2020
• First Posted: September 25, 2020
• Study Start: August 4, 2021
• Primary Completion: November 9, 2022
• Study Completion: February 3, 2023
• Last Updated: April 15, 2024
• Results First Posted: January 16, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

CA (3); US (18); AU (4)