Clinical trial NCT06475274: A Phase 2b Dose Finding Study of RMC-035 in Participants Undergoing Open-chest Cardiac Surgery
Official title: A Phase 2b, Randomized, Placebo-Controlled, Double-Blind, Parallel Group Dose-Finding Study to Evaluate the Efficacy on Renal Function and Safety of RMC-035 in Participants at High Risk for Kidney Injury Following Open-Chest Cardiac Surgery
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Kidney Injury Following Open-Chest Cardiac Surgery
Lead sponsor: Guard Therapeutics AB
Sponsor class: INDUSTRY
First posted: 2024-06-26
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Maximum age (years): 84
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The goal of this clinical trial is to identify the optimal dose of RMC-035 for protection of long-term renal function in adult patients undergoing cardiac surgery who are at high risk of kidney injury. It will also learn about the safety of RMC-035. The main question it aims to answer is:

* Does RMC-035 protect the function of kidneys after surgery?
* Is RMC-035 safe?

Researchers will compare RMC-035 in high dose, RMC-035 in low dose and placebo to see if

* Kidney function better for participants treated with any of the RMC-035 doses?
* What medical problems do participants have when receiving RMC-035?

Participants will

* Receive 3 doses of RMC-035 or placebo: at the beginning of surgery, end of surgery and 24h after surgery
* Have extra checkups and tests during their hospital stay
* Visit the clinic at two extra occasions at 60 days and 90 days after surgery for checkups and tests


Eligibility criteria: Inclusion Criteria:

* eGFR ≥30 ml/min/1.73m2
* Scheduled for non-emergent surgery of any of the following types, with use of cardiopulmonary bypass (CPB): coronary artery bypass grafting (CABG), valve surgery, ascending aorta aneurysm surgery
* Risk factors for acute kidney injury are present
* Participant capable of providing written informed consent
* Participant agrees to study restrictions such as not to take part in another interventional study, use contraception and not donate ova or sperm

Exclusion Criteria:

* Any medical condition that makes the participant unsuitable
* Scheduled for emergent surgeries
* Scheduled for CABG and/or valve surgery and/or ascending aorta aneurysm surgery combined with additional non-emergent cardiac surgeries
* 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
* Experiences a cardiogenic shock or hemodynamic instability which require inotropes or vasopressors or other mechanical devices such as intraaortic balloon pumping (IABP) within 24 hours prior to surgery
* Requires any of the following within one week prior to surgery: defibrillator or permanent pacemaker, mechanical ventilation, IABP, LVAD, other forms of mechanical circulatory support.
* Diagnosed with AKI prior to surgery
* Requires cardiopulmonary resuscitation prior to surgery
* Ongoing sepsis or an untreated diagnosed clinically significant infection
* Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥3.0 times the upper limit of normal (ULN).
* Total bilirubin ≥2.0 time ULN
* History of solid organ transplantation
* History of renal replacement therapy
* Severe allergic asthma
* Chronic immunosuppressive treatment that may have an impact on kidney function
* Ongoing chemotherapy or radiation therapy for malignancy that may have an impact on kidney function
* Current enrolment or past recent participation in any other clinical study involving an investigational study treatment
* Previously treatment of RMC-035
* Sensitivity to any of the study interventions, or components thereof

Primary outcomes:
measure: Change from baseline in eGFR at Day 90 (the two arms of RMC-035 pooled compared against placebo)
timeFrame: 90 days
Secondary outcomes:
measure: Occurrence of MAKE (and each MAKE component) at Day 90
timeFrame: 90 days
Other outcomes:
measure: Change from baseline in eGFR at Day 90 (the two arms of RMC-035 compared separately against placebo)
timeFrame: 90 days
measure: Occurrence of MAKE (and each MAKE component) at Day 60
timeFrame: 60 days
measure: Change from baseline in eGFR at Day 7 (the two arms of RMC-035 compared pooled and separately against placebo)
timeFrame: 7 days
measure: Change from baseline in eGFR at Day 60 (the two arms of RMC-035 compared pooled and separately against placebo)
timeFrame: 60 days
measure: Change from baseline in SCr until Day 7
timeFrame: 7 days
measure: Change from baseline in Cystatin C until Day 7
timeFrame: 7 days
measure: Occurrence of AKI
timeFrame: 72 hours
measure: Stage of AKI
timeFrame: 72 hours
measure: Presence and titer of ADAs at Day 60
timeFrame: 60 days
measure: Presence and titer of ADAs at Day 90
timeFrame: 90 days
measure: ADA activity of neutralizing native A1M
timeFrame: 90 days
measure: ADA isotype
timeFrame: 90 days
Locations:
city: Montreal
country: Canada
facility: Research site 4
city: Montreal
country: Canada
facility: Research site 5
city: Quebec
country: Canada
facility: Research site 2
city: Saint John
country: Canada
facility: Research site 3
city: Toronto
country: Canada
facility: Research site 1
city: Hradec Kralove
country: Czechia
facility: Research site 1
city: Prague
country: Czechia
facility: Research site 2
city: Dresden
country: Germany
facility: Research site 5
city: Essen
country: Germany
facility: Research site 3
city: Giessen
country: Germany
facility: Research site 6
city: Halle
country: Germany
facility: Research site 4
city: Muenchen
country: Germany
facility: Research site 2
city: Muenster
country: Germany
facility: Research site 1
city: Barcelona
country: Spain
facility: Research site 3
city: Cordoba
country: Spain
facility: Research site 4
city: Madrid
country: Spain
facility: Research site 1
city: Madrid
country: Spain
facility: Research site 2
city: Pamplona
country: Spain
facility: Research site 6
city: Santiago de Compostela
country: Spain
facility: Research site 5
Study officials:
affiliation: Guard Therapeutics
name: Michael Reusch, MD
role: STUDY_DIRECTOR
References: