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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Acute Kidney Injury (AKI)

Intervention / Treatment
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* Drug: RMC-035
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RMC-035<br>Participants will receive RMC-035 intravenously | Drug: RMC-035<br>* Multiple dosing during 48 hours following cardiac surgery<br>* Other names: Solution for injection;|
| Placebo Comparator: Placebo<br>Participants will receive matching placebo solution intravenously | Drug: Placebo<br>* Multiple dosing during 48 hours following cardiac surgery<br>* Other names: Solution for injection;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of Adverse Events (AEs) | number (%) of subjects with at least one AE number (%) of subjects with at least one SAE number (%) of subjects with at least one Treatment-Emergent AE (TEAE) number (%) of subjects with at least one serious TEAE number (%) of subjects with at least one non-serious TEAE number (%) of subjects with at least one TEAE of special interest number (%) of subjects with at least one TEAEs reported as related (possible/probable) to IMP number (%) of subjects with at least one TEAEs leading to withdrawal of IMP | Baseline through day 30 | 
| Severity of AEs | - Number of TEAEs per category (mild, moderate, severe life-threatening, death) | Within 4 days from first dose of IMP | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Observed Concentration (Cmax) | Analysis of RMC-035 concentration in plasma (AUC + t1/2) after fourth infusion. | Blood samples taken from pre-dose and up to two hours after start of Dose 5 | 
| Area Under the Curve (AUC) 0-24h | Analysis of RMC-035 concentrations in plasma following the fourth infusion. | Blood samples taken from pre-dose and up to two hours after start of Dose 5 | 
| Elimination Half-life (T1/2) | Analysis of RMC-035 concentration in plasma following the fourth infusion | Blood samples taken from pre-dose and up to two hours after start of Dose 5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AKI