Clinical trial NCT05126303: Efficacy and Safety of RMC-035 in Subjects at High Risk for Acute Kidney Injury Following Open-Chest Cardiac Surgery
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Acute Kidney Injury
Lead sponsor: Guard Therapeutics AB
Sponsor class: INDUSTRY
First posted: 2021-11-19
Enrollment: 177
Sex: ALL
Minimum age (years): 18
Maximum age (years): 84
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, adaptive, parallel group
Primary purpose: PREVENTION

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Subjects Developing AKI, as Defined Per Kidney Disease Improving Global Outcomes (KDIGO) Criteria
timeFrame: 72 hours
Secondary outcomes:
measure: Area Under the Curve (AUC) of Serum Creatinine (SCr)
timeFrame: 72 hours
measure: Duration of AKI
timeFrame: 90 days
measure: Change in SCr Values Over Time
timeFrame: 90 days
measure: Peak Cystatin C Value
timeFrame: 7 days
measure: AUC of Cystatin C
timeFrame: 72 hours
measure: Number of Participants Requiring Renal Replacement Therapy (Dialysis)
timeFrame: 7 days
measure: Number of Days Without Need for Dialysis
timeFrame: 90 days
measure: Major Adverse Kidney Event (MAKE) - SCr
timeFrame: 90 days
measure: AKI Within 72 Hours Based on Cystatin C and UO
timeFrame: 72 hours
measure: AKI Within 7 Days
timeFrame: 7 days
measure: Persistence of AKI
timeFrame: 7 days
measure: Severity of AKI
timeFrame: 7 days
measure: Change in Urine Albumin to Creatinine Ratio (UACR) and Urine Protein to Creatinine Ratio (UPCR)
timeFrame: 90 days
measure: Pharmacokinetics of RMC-035 (AUC)
timeFrame: 4 days
measure: Pharmacokinetics of RMC-035 (Cmax)
timeFrame: 7 days
measure: Presence of Anti-drug Antibodies (ADA)
timeFrame: 90 days
measure: Characteristics of ADA (Cross-reactivity)
timeFrame: 90 days
measure: Peak SCr Value
timeFrame: 7 days
measure: Major Adverse Kidney Event (MAKE) - Cystatin C
timeFrame: 90 days
measure: Major Adverse Kidney Event (MAKE) - SCr and Cystatin C
timeFrame: 90 days
measure: Change in Serum Cystatin C Values Over Time
timeFrame: 90 days
Other outcomes:
Locations:
city: Fort Wayne
country: United States
facility: Indiana Ohio Heart
state: Indiana
city: Lincoln
country: United States
facility: Bryan Heart
state: Nebraska
city: Rochester
country: United States
facility: Rochester Regional Health - Rochester General Hospital
state: New York
city: Durham
country: United States
facility: Duke University Hospital
state: North Carolina
city: Dallas
country: United States
facility: Baylor Scott and White Research Institute - Dallas
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia (UVA) Health - University Hospital
state: Virginia
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Milwaukee
country: United States
facility: Aurora Health Care - Aurora St. Luke's Medical Center
state: Wisconsin
city: Hamilton
country: Canada
facility: Hamilton Health Sciences
city: Montréal
country: Canada
facility: CHUM
city: Montréal
country: Canada
facility: MUHC - Royal Victoria Hospital
city: Québec
country: Canada
facility: Institut Universitaire de Cardiologie et de Pneumologie de Québec
city: Saint John
country: Canada
facility: St. John Regional Hospital
city: Toronto
country: Canada
facility: Saint Michael's Hospital
city: Hradec Kralove
country: Czechia
facility: University Hospital Hradec Kralove
city: Praha 5
country: Czechia
facility: University Hospital Motol - Charles University Prague
city: Bad Oeynhausen
country: Germany
facility: Herz- und Diabeteszentrum Nordrhein-Westfalen (NRW)
city: Dresden
country: Germany
facility: Herzzentrum Dresden GmbH
city: Essen
country: Germany
facility: Westdeutsches Herzzentrum Essen
city: Gießen
country: Germany
facility: Universitätsklinikum Giessen und Marburg - Standort Giessen
city: Halle
country: Germany
facility: Universitätsklinikum Halle (Saale)
city: Köln
country: Germany
facility: Universitätsklinikum Köln
city: München
country: Germany
facility: Deutsches Herzzentrum München
city: Münster
country: Germany
facility: Münster University Hospital
city: Barcelona
country: Spain
facility: Hospital Sant Pau
city: Córdoba
country: Spain
facility: Reina Sofia University Hospital
city: Madrid
country: Spain
facility: Hospital de La Princesa
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago (CHUS)
Study officials:
affiliation: Guard Therapeutics
name: Tobias Agervald, MD
role: STUDY_DIRECTOR
affiliation: Muenster University Hospital
name: Alexander Zarbock, MD
role: PRINCIPAL_INVESTIGATOR
References: