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

Acute Kidney Injury Clinical Trial

— AKITA  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05126303
• Other study ID #: 21-ROS-05
• Status: Terminated
• Phase: Phase 2
• Start date: March 31, 2022
• Est. completion date: July 12, 2023

Study information

• Verified date: May 2024
• Source: Guard Therapeutics AB
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 177
• Est. completion date: July 12, 2023
• Est. primary completion date: April 15, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 84 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Kidney Injury
• Wounds and Injuries

Intervention

Drug:
• RMC-035
Concentrate for Solution for Infusion
• Placebo
Concentrate for Solution for Infusion

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Guard Therapeutics AB

Countries where clinical trial is conducted

United States,  Canada,  Czechia,  Germany,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Subjects Developing AKI, as Defined Per Kidney Disease Improving Global Outcomes (KDIGO) Criteria	Percentage of subjects developing AKI based on Serum Creatinine and/or Urine Output per KDIGO definition	72 hours
Secondary	Area Under the Curve (AUC) of Serum Creatinine (SCr)	Time-corrected area under the curve (AUC) of serum creatinine calculated as follows: The area under the SCr concentration versus time curve following drug administration were calculated using timepoints at Day 1 (12 hour), Day 2 (24 hour), Day 3 (48 hour) and Day 4 (72 hour). The individual log-transformed SCr values were determined, and the AUC (utilizing planned times) were calculated using the right Riemann sum: AUC = 0.5 x SCr(12h) + 0.5 x SCr(24h) + 1 x SCr(48h) + 1 x SCr(72h) The time-corrected AUC (log-scale) was then calculated as AUC/3	72 hours
Secondary	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
Secondary	Change in SCr Values Over Time	SCr at 12, 24, 48, and 72 hours, respectively, and at Day 7/discharge, Day 30 and Day 90	90 days
Secondary	Peak Cystatin C Value	Change from baseline of peak cystatin C from baseline to Day 7	7 days
Secondary	AUC of Cystatin C	Time-corrected AUC of cystatin C for Day 1 to Day 4 (72 hours after first dose of IMP) calculated as follows: The area under the cystatin C concentration versus time curve following drug administration were calculated using timepoints at Day 1 (12 hour), Day 2 (24 hour), Day 3 (48 hour) and Day 4 (72 hour). The individual log-transformed cystatin C values were determined, and the AUC (utilizing planned times) were calculated using the right Riemann sum: AUC = 0.5 x cystatin C(12h) + 0.5 x cystatin C(24h) + 1 x cystatin C(48h) + 1 x cystatin C(72h) The time-corrected AUC (log-scale) was then calculated as AUC/3	72 hours
Secondary	Number of Participants Requiring Renal Replacement Therapy (Dialysis)	Renal replacement therapy (dialysis treatment) required by any participant for any reason	7 days
Secondary	Number of Days Without Need for Dialysis	Number of days that participants were not requiring dialysis	90 days
Secondary	Major Adverse Kidney Event (MAKE) - SCr	MAKE at Day 30 and Day 90, defined as death, any dialysis, or =25% reduction of eGFR compared to baseline.; eGFR calculated based on Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation using SCr.	90 days
Secondary	AKI Within 72 Hours Based on Cystatin C and UO	AKI based on cystatin C and/or urine output (UO)	72 hours
Secondary	AKI Within 7 Days	AKI based on SCr and/or UO criteria, or cystatin C and/or UO criteria	7 days
Secondary	Persistence of AKI	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
Secondary	Severity of AKI	AKI severity stage 1, 2 or 3 per KDIGO criteria, with 1 being mildest stage and 3 being most severe stage.; Reference: KDIGO (2012). "Clinical Practice Guideline for Acute Kidney Injury." JOURNAL OF THE INTERNATIONAL SOCIETY OF NEPHROLOGY 2(1).	7 days
Secondary	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
Secondary	Pharmacokinetics of RMC-035 (AUC)	AUC(0-24) of RMC-035 concentrations in plasma (Day 3)	4 days
Secondary	Pharmacokinetics of RMC-035 (Cmax)	Cmax of RMC-035 concentrations in plasma Day 3	7 days
Secondary	Presence of Anti-drug Antibodies (ADA)	Presence of ADA at Day 1 (pre-surgery), Day 30, and Day 90; positive samples	90 days
Secondary	Characteristics of ADA (Cross-reactivity)	Characteristics of ADA developed at Day 30 and Day 90 with regards cross-reactivity with endogenous alpha-1-microglobulin (A1M)	90 days
Secondary	Peak SCr Value	Change from baseline of peak SCr from baseline to Day 7	7 days
Secondary	Major Adverse Kidney Event (MAKE) - Cystatin C	MAKE at Day 30 and Day 90, defined as death, any dialysis, or =25% reduction of eGFR compared to baseline.; eGFR calculated based on Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation using Cystatin C.	90 days
Secondary	Major Adverse Kidney Event (MAKE) - SCr and Cystatin C	MAKE at Day 30 and Day 90, defined as death, any dialysis, or =25% reduction of eGFR compared to baseline.; eGFR calculated based on Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation using SCr and Cystatin C.	90 days
Secondary	Change in Serum Cystatin C Values Over Time	Cystatin C measurement in serum at 12, 24, 48, and 72 hours, respectively, and at Day 7/discharge, Day 30 and Day 90	90 days