A Phase 2b Dose Finding Study of RMC-035 in Participants Undergoing Open-chest Cardiac Surgery
NCT Number: NCT06475274
Acronym: POINTER
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE2
Conditions: Kidney Injury Following Open-Chest Cardiac Surgery
Interventions: DRUG: RMC-035|DRUG: Placebo
Sponsor: Guard Therapeutics AB
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 161
Study Design: Allocation: RANDOMIZED|Intervention Model: PARALLEL|Masking: QUADRUPLE (PARTICIPANT, CARE_PROVIDER, INVESTIGATOR, OUTCOMES_ASSESSOR)|Primary Purpose: PREVENTION
Start Date: 2024-08-30
Completion Date: 2025-10-30
Locations: Centre Hospitalier de l Universite de Montreal (CHUM), Montréal, Canada|McGill University Health Center (MUHC), Montréal, Canada|Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ), Québec, Canada|St. John Regional Hospital, Saint John, Canada|St. Michael's Hospital, Toronto, Canada|University Hospital Hradec Kralove, Hradec Kralove, Czechia|University Hospital Motole, Prague, Czechia|Herzzentrum Dresden, Dresden, Germany|Universitätsklinikum Essen, Essen, Germany|Universitätsklinikum Giessen und Marburg - Standort Giessen, Gießen, Germany|Universitätsklinikum Halle (Saale), Halle, Germany|Deutsches Herzzentrum München, München, Germany|Universitätsklinikum Münster, Münster, Germany|Hospital de la Santa Creu i Sant Pau, Barcelona, Spain|Reina Sofia University Hospital, Córdoba, Spain|Hospital de La Princesa, Madrid, Spain|Hospital Universitario Ramon y Cajal, Madrid, Spain|Clinica Universidad de Navarra, Pamplona, Spain|Complejo Hospitalario Universitario de Santiago (CHUS), Santiago de Compostela, Spain

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

Primary Outcome Measures: 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: 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: 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