A Phase 2b Dose Finding Study of RMC-035 in Participants Undergoing Open-chest Cardiac Surgery (POINTER)

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

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

Study Overview

• Status: Completed
• Conditions: Kidney Injury Following Open-Chest Cardiac Surgery
• Intervention / Treatment: Drug: RMC-035; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 170
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Montreal, Canada
    • Research Site 4
  • Montreal, Canada
    • Research Site 5
  • Québec, Canada
    • Research Site 2
  • Saint John, Canada
    • Research Site 3
  • Toronto, Canada
    • Research Site 1
• Czechia
  • Hradec Králové, Czechia
    • Research Site 1
  • Prague, Czechia
    • Research Site 2
• Germany
  • Dresden, Germany
    • Research Site 5
  • Essen, Germany
    • Research Site 3
  • Giessen, Germany
    • Research Site 6
  • Halle, Germany
    • Research Site 4
  • München, Germany
    • Research Site 2
  • Münster, Germany
    • Research Site 1
• Spain
  • Barcelona, Spain
    • Research Site 3
  • Córdoba, Spain
    • Research Site 4
  • Madrid, Spain
    • Research Site 2
  • Madrid, Spain
    • Research Site 1
  • Pamplona, Spain
    • Research Site 6
  • Santiago de Compostela, Spain
    • Research Site 5

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RMC-035 high-dose; RMC-035 60 mg	Drug: RMC-035; Protein, a recombinant variant of A1M. Concentrate for solution for infusion.
Experimental: RMC-035 low-dose; RMC-035 30 mg	Drug: RMC-035; Protein, a recombinant variant of A1M. Concentrate for solution for infusion.
Placebo Comparator: Placebo; Placebo (tris-buffer)	Drug: Placebo; Identical to RMC-035 intervention devoid of the active substance.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in eGFR at Day 90 (the two arms of RMC-035 pooled compared against placebo)	Difference in estimated glomerular filtration rate (eGFR) at Day 90 (end of study) compared to baseline.	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Occurrence of MAKE (and each MAKE component) at Day 90	Occurrence of major adverse kidney events (MAKE), consisting of the following components: death, any new renal replacement therapy (RRT) after surgery, or sustained loss of kidney function, defined as a 25% or greater decline in eGFR, until Day 90.	90 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in eGFR at Day 90 (the two arms of RMC-035 compared separately against placebo)	Difference in eGFR at Day 90 compared to baseline	90 days
Occurrence of MAKE (and each MAKE component) at Day 60	Occurrence of MAKE, ie death, new any renal replacement therapy (RRT) after surgery, or sustained loss of kidney function, defined as a 25% or greater decline in eGFR, until Day 60.	60 days
Change from baseline in eGFR at Day 7 (the two arms of RMC-035 compared pooled and separately against placebo)	Difference in eGFR at Day 7 compared to baseline	7 days
Change from baseline in eGFR at Day 60 (the two arms of RMC-035 compared pooled and separately against placebo)	Difference in eGFR at Day 60 compared to baseline	60 days
Change from baseline in SCr until Day 7	Difference in serum creatinine results at Day 7 compared to baseline	7 days
Change from baseline in Cystatin C until Day 7	Difference in Cystatin C results at Day 7 compared to baseline	7 days
Occurrence of AKI	Occurrence of acute kidney injury (AKI), based on SCr, until Day 4	72 hours
Stage of AKI	Stage of any AKI occurring until Day 4	72 hours
Presence and titer of ADAs at Day 60	Presence of anti-drug antibodies (ADAs) and titer of ADAs where they occur	60 days
Presence and titer of ADAs at Day 90	Presence of anti-drug antibodies (ADAs) and titer of ADAs where they occur	90 days
ADA activity of neutralizing native A1M	Characteristics of any possible ADAs with regards to neutralizing A1M activity	90 days
ADA isotype	Characteristics of any possible ADAs with regards to immunoglobulin isotype	90 days

Collaborators and Investigators

• Sponsor: Guard Therapeutics AB
• Investigators: Study Director: Michael Reusch, MD, Guard Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2024
• Primary Completion (Actual): September 11, 2025
• Study Completion (Actual): September 11, 2025

Study Registration Dates

• First Submitted: June 20, 2024
• First Submitted That Met QC Criteria: June 20, 2024
• First Posted (Actual): June 26, 2024

Study Record Updates

• Last Update Posted (Estimated): October 2, 2025
• Last Update Submitted That Met QC Criteria: October 1, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: 24-ROS-07

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