Efficacy and Safety of RMC-035 in Subjects at High Risk for Acute Kidney Injury Following Open-Chest Cardiac Surgery (AKITA)

A Phase 2, Randomized, Placebo-Controlled, Double-Blind, Adaptive, Parallel Group Clinical Study to Evaluate the Efficacy and Safety of RMC-035 in Subjects at High Risk for Acute Kidney Injury Following Open-Chest Cardiac Surgery

This study evaluates RMC-035 compared to placebo for the prevention of acute kidney injury (AKI) in subjects who are at high risk for AKI following cardiac surgery. Half of the subjects will receive RMC-035 and the other half will receive placebo.

Study Overview

• Status: Terminated
• Conditions: Acute Kidney Injury
• Intervention / Treatment: Drug: RMC-035; Drug: Placebo

Detailed Description

This is a Phase 2, randomized, double-blind, adaptive, parallel group clinical study that will evaluate RMC-035 compared to placebo in subjects at high risk for acute kidney injury (AKI) following cardiac surgery. Subjects are randomized in a 1:1 ratio.

• Study Type: Interventional
• Enrollment (Actual): 177
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Sara Thuresson; Phone Number: +46733319438; Email: trials@guardtherapeutics.com

Study Locations

• Canada
  • Hamilton, Canada
    • Hamilton Health Sciences
  • Montréal, Canada
    • CHUM
  • Montréal, Canada
    • MUHC - Royal Victoria Hospital
  • Québec, Canada
    • Institut universitaire de cardiologie et de pneumologie de Québec
  • Saint John, Canada
    • St. John Regional Hospital
  • Toronto, Canada
    • Saint Michael's Hospital
• Czechia
  • Hradec Kralove, Czechia
    • University Hospital Hradec Kralove
  • Praha 5, Czechia
    • University Hospital Motol - Charles University Prague
• Germany
  • Bad Oeynhausen, Germany
    • Herz- und Diabeteszentrum Nordrhein-Westfalen (NRW)
  • Dresden, Germany
    • Herzzentrum Dresden GmbH
  • Essen, Germany
    • Westdeutsches Herzzentrum Essen
  • Gießen, Germany
    • Universitätsklinikum Giessen und Marburg - Standort Giessen
  • Halle, Germany
    • Universitätsklinikum Halle (Saale)
  • Köln, Germany
    • Universitatsklinikum Koln
  • München, Germany
    • Deutsches Herzzentrum München
  • Münster, Germany, DE-481 49
    • Münster University Hospital
• Spain
  • Barcelona, Spain
    • Hospital Sant Pau
  • Córdoba, Spain
    • Reina Sofia University Hospital
  • Madrid, Spain
    • Hospital de la Princesa
  • Oviedo, Spain
    • Hospital Universitario Central de Asturias
  • Santiago de Compostela, Spain
    • Complejo Hospitalario Universitario de Santiago (CHUS)
• United States
  • Indiana
    • Fort Wayne, Indiana, United States, 48604
      • Indiana Ohio Heart
  • Nebraska
    • Lincoln, Nebraska, United States, 68506
      • Bryan Heart
  • New York
    • Rochester, New York, United States, 14621
      • Rochester Regional Health - Rochester General Hospital
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Hospital
  • Texas
    • Dallas, Texas, United States, 75226
      • Baylor Scott and White Research Institute - Dallas
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia (UVA) Health - University Hospital
  • Wisconsin
    • Madison, Wisconsin, United States, 53706
      • University of Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Aurora Health Care - Aurora St. Luke's Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 84 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Institutional Review Board/ International Ethics Committee approved Informed Consent obtained
2. Ability to understand and comply with the study requirements and able to provide written informed consent
3. Age ≥18 and <85 years
4. Estimated glomerular filtration rate (eGFR) is ≥30 mL/min/1.73 m2
5. Subject is scheduled for non-emergent coronary artery bypass grafting (CABG) surgery and/or valve surgery and/or ascending aorta aneurysm surgery with use of cardiopulmonary bypass (CPB), and AKI risk factors are present at screening
6. Female subject is not of child-bearing potential, or agreeing not to become pregnant
7. Female subject must not be breastfeeding
8. Female subject must not donate ova
9. Male subject and their female spouse/partner(s) who are of childbearing potential must be using a highly effective form of birth control
10. Male subjects must not donate sperm
11. Subject agrees not to participate in another interventional study

Exclusion Criteria:

1. Medical condition that makes the subject unsuitable for study participation
2. Scheduled for emergent surgeries (eg, aortic dissection)
3. Scheduled for CABG and/or valve surgery and/or ascending aorta aneurysm surgery combined with additional non-emergent cardiac surgeries (eg, congenital heart defects)
4. Scheduled to undergo transcatheter aortic valve implantation (TAVI) or transcatheter aortic valve replacement (TAVR), or off-pump surgeries or left ventricular assist device (LVAD) implantation
5. Experiences a cardiogenic shock or hemodynamic instability which require inotropes or vasopressors or other mechanical devices within 24 hours prior to surgery
6. Requirement for defibrillator or permanent pacemaker, mechanical ventilation, intraaortic balloon pumping (IABP), LVAD, or other forms of mechanical circulatory support (MCS)
7. Diagnosed with AKI (as defined by KDIGO criteria) within 3 months prior to surgery
8. Required cardiopulmonary resuscitation within 14 days prior to cardiac surgery
9. Ongoing sepsis or an untreated diagnosed clinically significant infection (viral or bacterial)
10. Total bilirubin or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 2 times the upper limit of normal (ULN)
11. History of solid organ transplantation
12. History of renal replacement therapy (RRT)
13. Medical condition which requires active immunosuppressive treatment
14. Severe allergic asthma
15. Ongoing chemotherapy or radiation therapy for malignancy that may have an impact on kidney function
16. Received an investigational medicinal product within the last 90 days (or within 5 half-lives of the investigational drug, whichever is longer)
17. Subject has a known allergy to RMC-035 or one of its constituents, or has previously received RMC-035

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RMC-035; RMC-035 is a concentrate (6.0 mg/mL) for solution for infusion for IV administration. Dosing will be based on renal function at Day -1: Subjects with eGFR ≥60 mL/min/1.73m2 will receive 1.3 mg/kg (per dose) for the first and second dose, followed by 0.65 mg/kg (per dose) for the third, fourth and fifth dose, while subjects with eGFR >30 and <60 mL/min/1.73m2 will receive 0.65 mg/kg (per dose) for all five doses Dosing occurs at time 0 and then after 6, 12, 24 and 48 hours.	Drug: RMC-035; Concentrate for Solution for Infusion; Other Names: ROSgard
Placebo Comparator: Placebo; Identical to RMC-035 arm except that the placebo contains no active ingredient.	Drug: Placebo; Concentrate for Solution for Infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects developing AKI, as defined per Kidney Disease Improving Global Outcomes (KDIGO) criteria	AKI based on Serum Creatinine and/or Urine Output per KDIGO definition	72 hours
Safety and Tolerability	Nature, frequency and severity of treatment-emergent adverse events	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve (AUC) of Serum creatinine (SCr)	Time-corrected area under the curve (AUC) of serum creatinine	72 hours
Duration of AKI	Duration of AKI defined as the number of days meeting the definition of AKI (KDIGO definition) starting within 72 hours after first dose of IMP until resolution	90 days
Post-baseline changes in renal function: SCr and cystatin C values	SCr and cystatin C (and corresponding eGFR values) at 12, 24, 48, and 72 hours, respectively, and at Day 7/discharge, Day 30 and Day 90	90 days
Post-baseline changes in renal function: Peak SCr and cystatin C values	Change from baseline of peak SCr and cystatin C	7 days
Post-baseline changes in renal function: AUC of cystatin C	Time-corrected AUC of cystatin C for Day 1 to Day 4 (72 hours after first dose of IMP)	72 hours
Need for renal replacement therapy: Dialysis treatment	Dialysis treatment (for any reason)	7 days
Need for renal replacement therapy: Dialysis free	Dialysis free days	90 days
Major adverse kidney event (MAKE)	MAKE at Day 30 and Day 90, defined as death, any dialysis, or ≥25% reduction of eGFR compared to baseline Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (either SCr, cystatin C, or both)	90 days
AKI Characteristics: AKI within 72 hours based on cystatin C and UO	AKI based on cystatin C and/or urine output (UO)	72 hours
AKI Characteristics: AKI within 7 days	AKI based on SCr and/or UO criteria, or cystatin C and/or UO criteria	7 days
AKI Characteristics: Persistence	AKI persistence, defined as an AKI (KDIGO definition) developing within 72 hours after first dose of IMP and with a duration of ≥72 hours	7 days
AKI Characteristics: Severity	AKI severity stage per KDIGO criteria	7 days
Change in urine albumin to creatinine ratio (UACR) and urine protein to creatinine ratio (UPCR)	Post-baseline changes in UACR and UPCR at Day 4, Day 30, and Day 90	90 days
Pharmacokinetics of RMC-035	AUC of RMC-035 concentrations in plasma	7 days
Pharmacokinetics of RMC-035	Cmax of RMC-035 concentrations in plasma	7 days
Presence and titers of anti-drug antibodies (ADA)	Presence and titers of ADA at Day 1 (pre-surgery), Day 30, and Day 90	90 days
Characteristics of ADA	Characteristics of ADA developed at Day 30 and Day 90 with regards to isotype, neutralizing capacity, and cross-reactivity with endogenous alpha-1-microglobulin (A1M)	90 days

Collaborators and Investigators

• Sponsor: Guard Therapeutics AB
• Investigators: Study Director: Tobias Agervald, MD, Guard Therapeutics; Principal Investigator: Alexander Zarbock, MD, Muenster University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2022
• Primary Completion (Actual): April 15, 2023
• Study Completion (Actual): July 12, 2023

Study Registration Dates

• First Submitted: November 8, 2021
• First Submitted That Met QC Criteria: November 8, 2021
• First Posted (Actual): November 19, 2021

Study Record Updates

• Last Update Posted (Estimated): July 24, 2023
• Last Update Submitted That Met QC Criteria: July 20, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Wounds and Injuries; Acute Kidney Injury
• Other Study ID Numbers: 21-ROS-05

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
• product manufactured in and exported from the U.S.: No