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Background <p>Cardiac surgery with cardiopulmonary bypass invariably induces renal stress and risk of irreversible kidney function loss, with no approved drug treatments. RMC-035, a recombinant human alpha-1-microglobulin with potent heme-binding and antioxidant capacity, has shown promising long-term kidney-protective effects in a phase 2a trial of patients undergoing cardiac surgery. The primary objective of this phase 2b dose-optimisation trial is to demonstrate that RMC-035 (pooled dose groups) is superior to placebo in preserving renal function at 90&#xa0;days after surgery.</p> Methods <p>This randomised, blinded, placebo-controlled, multicentre study evaluates the efficacy and safety of RMC-035 among approximately 161 high-risk patients undergoing cardiac surgery who are randomised into one of three treatment groups in a 2:2:3 ratio: RMC-035 (30&#xa0;mg or 60&#xa0;mg) or placebo. The study drug is administered via three intravenous infusions, with the first dose given intraoperatively, followed by additional doses at 6 and 24&#xa0;h, respectively. The primary endpoint is the change in estimated glomerular filtration rate (eGFR) from baseline (pre-surgery) to Day 90. Important secondary endpoints include the incidence of major adverse kidney events at Day 90 and short-term outcomes reflecting changes in renal filtration markers up to Day 7. Safety assessments encompass adverse events, vital signs, electrocardiograms and routine safety laboratory tests. Additional evaluations include pharmacokinetics, anti-drug antibodies and immunological biomarkers.</p> Discussion <p>This multicentre, multinational phase 2b trial, will assess the change in eGFR within 90&#xa0;days of the first dose, providing additional evidence of the long-term kidney-protective potential of RMC-035 in patients undergoing cardiac surgery at high risk for kidney injury. Trial outcomes will inform the preferred dose, dosing regimen, and benefit-risk profile related to cardiac surgery for a future pivotal phase 3 trial.</p> Trial registration <p>The trial was registered June 20, 2024, at Clinicaltrials.gov (NCT06475274 <a href="https://clinicaltrials.gov/study/NCT06475274">https://clinicaltrials.gov/study/NCT06475274</a>). The trial including the participating EU countries is also registered with the EUCT number 2024–510658-28 under <a href="https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&amp;EUCT=2024-510658-28-00">https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&amp;EUCT=2024-510658-28-00</a>.</p> <p>The first patient was enrolled August 26, 2024.</p>

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POINTER: study protocol for a phase 2b, randomised, placebo-controlled, double-blind, parallel group dose-finding clinical study to evaluate the efficacy of RMC-035 on renal function and safety, in participants at high risk for kidney injury, following open-chest cardiac surgery

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月28日

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  • Alexander Zarbock,
  • Christian Strauss,
  • Maxime Laflamme,
  • Andrej Myjavec,
  • Johannes Böhm,
  • Jan Burkert,
  • C. David Mazer,
  • Benoit de Varennes,
  • Antonino Ginel Iglesias,
  • Klaus Matschke,
  • Tobias E. Larsson,
  • Michael Reusch

摘要

Background

Cardiac surgery with cardiopulmonary bypass invariably induces renal stress and risk of irreversible kidney function loss, with no approved drug treatments. RMC-035, a recombinant human alpha-1-microglobulin with potent heme-binding and antioxidant capacity, has shown promising long-term kidney-protective effects in a phase 2a trial of patients undergoing cardiac surgery. The primary objective of this phase 2b dose-optimisation trial is to demonstrate that RMC-035 (pooled dose groups) is superior to placebo in preserving renal function at 90 days after surgery.

Methods

This randomised, blinded, placebo-controlled, multicentre study evaluates the efficacy and safety of RMC-035 among approximately 161 high-risk patients undergoing cardiac surgery who are randomised into one of three treatment groups in a 2:2:3 ratio: RMC-035 (30 mg or 60 mg) or placebo. The study drug is administered via three intravenous infusions, with the first dose given intraoperatively, followed by additional doses at 6 and 24 h, respectively. The primary endpoint is the change in estimated glomerular filtration rate (eGFR) from baseline (pre-surgery) to Day 90. Important secondary endpoints include the incidence of major adverse kidney events at Day 90 and short-term outcomes reflecting changes in renal filtration markers up to Day 7. Safety assessments encompass adverse events, vital signs, electrocardiograms and routine safety laboratory tests. Additional evaluations include pharmacokinetics, anti-drug antibodies and immunological biomarkers.

Discussion

This multicentre, multinational phase 2b trial, will assess the change in eGFR within 90 days of the first dose, providing additional evidence of the long-term kidney-protective potential of RMC-035 in patients undergoing cardiac surgery at high risk for kidney injury. Trial outcomes will inform the preferred dose, dosing regimen, and benefit-risk profile related to cardiac surgery for a future pivotal phase 3 trial.

Trial registration

The trial was registered June 20, 2024, at Clinicaltrials.gov (NCT06475274 https://clinicaltrials.gov/study/NCT06475274). The trial including the participating EU countries is also registered with the EUCT number 2024–510658-28 under https://euclinicaltrials.eu/search-for-clinical-trials/?lang=en&EUCT=2024-510658-28-00.

The first patient was enrolled August 26, 2024.