A Study to Evaluate RMC-035 in Subjects Undergoing Cardiac Surgery

A Phase 1b, Randomised, Double-Blind, Parallel Treatment Group Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetics of RMC-035 in Subjects Undergoing Non-Emergent On-Pump Coronary Artery Bypass Graft and/or Valve Surgery

The purpose of the clinical study is to assess safety, tolerability and pharmacokinetics of RMC-035 for the prevention and treatment of acute kidney injury (AKI) in patients undergoing cardiac surgery.

This is a study with two parallel treatment groups where subjects are randomized to receive RMC-035 or a matching placebo in a double-blind fashion. The study will comprise of a screening visit, followed by CABG and/or valve replacement on Day 1, double-blind treatment period and a follow-up period up to Day 30.

Key Inclusion Criteria:

• Female and male subjects with an age ≥18 years

• Subject is scheduled for non-emergent (elective) CABG and/or valve surgery (single or multiple valves) with use of cardiopulmonary bypass (CPB)

• Subject has at least ONE of the following risk factors for AKI at screening:

  • History of LVEF <35% for at least 3 months prior to screening assessed by either echocardiography, cardiac MRI or nuclear scan.
  • History of previous open chest cavity cardiac surgery with or without CPB
  • Confirmed diagnosis of type 2 diabetes (T2DM) at least 3 months prior to screening AND ongoing treatment with an approved anti-diabetic drug
  • Age ≥70 years
  • Documented history of heart failure NYHA class II or higher for at least 3 months or longer at screening
  • Documented history of previous AKI before date of screening independent of the etiology of AKI
  • Documented history of anemia with hemoglobin ≤ 11 g/dL (≤6.8 mmol/L) for at least 3 months prior to screening
  • Documented history of albuminuria, defined as UACR >30 mg/g or > 30 mg/24 hour in a 24-hour urine collection.
  • eGFR is ≤ 60 mL/min/1.73 m2 using the Chronic Kidney Disease - Epidemiology Collaboration (CKD-EPI) equation

Key Exclusion Criteria:

• Estimated glomerular filtration rate (eGFR) is <30 mL/min/1.73 m2 using the Chronic Kidney Disease - Epidemiology Collaboration (CKD-EPI) equation at screening or at baseline
• Subject has surgery scheduled to be performed without CPB ("off-pump")
• Subject has surgery scheduled for aortic dissection
• Subject is scheduled for CABG and/or valve surgery combined with additional non-emergent cardiac surgeries, e.g. for atrial fibrillation ablation
• Subject is scheduled to undergo trans catheter aortic valve implantation (TAVI) or trans catheter aortic valve replacement (TAVR), or single vessel off-pump surgeries or left ventricular device (LVAD) implantation
• Subject has a requirement for any of the following within one week prior to surgery: defibrillator or permanent pacemaker, mechanical ventilation, IABP, LVAD, other forms of mechanical circulatory support (MCS) (Note: The prophylactic insertion of an IABP preoperatively for reasons not related to existing LV pump function is not exclusionary)