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.

Study Overview

• Status: Completed
• Conditions: Acute Kidney Injury (AKI)
• Intervention / Treatment: Drug: RMC-035; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Münster, Germany, DE-481 49
    • Münster University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 68 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Guard Therapeutics AB
• Investigators: Study Director: Tobias Agervald, MD PhD, Guard Therapeutics AB

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2021
• Primary Completion (Actual): July 15, 2021
• Study Completion (Actual): July 15, 2021

Study Registration Dates

• First Submitted: March 26, 2021
• First Submitted That Met QC Criteria: April 1, 2021
• First Posted (Actual): April 2, 2021

Study Record Updates

• Last Update Posted (Actual): April 23, 2024
• Last Update Submitted That Met QC Criteria: April 18, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: AKI
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Acute Kidney Injury; Pharmaceutical Solutions
• Other Study ID Numbers: 20-ROS-04

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No