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

Acute Kidney Injury (AKI) Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04829916
• Other study ID #: 20-ROS-04
• Status: Completed
• Phase: Phase 1
• Start date: March 16, 2021
• Est. completion date: July 15, 2021

Study information

• Verified date: April 2024
• Source: Guard Therapeutics AB
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: July 15, 2021
• Est. primary completion date: July 15, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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)

Related Conditions & MeSH terms

• Acute Kidney Injury
• Acute Kidney Injury (AKI)

Intervention

Drug:
• RMC-035
Multiple dosing during 48 hours following cardiac surgery
• Placebo
Multiple dosing during 48 hours following cardiac surgery

Locations

Country	Name	City	State
Germany	Münster University Hospital	Münster

Sponsors (1)

Lead Sponsor	Collaborator
Guard Therapeutics AB

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Severity of AEs	- Number of TEAEs per category (mild, moderate, severe life-threatening, death)	Within 4 days from first dose of IMP
Secondary	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
Secondary	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
Secondary	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