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

Phase 1

Completed

Brief Summary: 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: 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.

Recruitment & Eligibility

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)

Arm && Interventions

Group	Intervention	Description
RMC-035	RMC-035	Participants will receive RMC-035 intravenously
Placebo	Placebo	Participants will receive matching placebo solution intravenously

Primary Outcome Measures

Name	Time	Method
Frequency of Adverse Events (AEs)	Baseline through day 30	* 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
Severity of AEs	Within 4 days from first dose of IMP	- Number of TEAEs per category (mild, moderate, severe life-threatening, death)

Secondary Outcome Measures

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