Clinical trial NCT04829916: A Study to Evaluate RMC-035 in Subjects Undergoing Cardiac Surgery
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Kidney Injury (AKI)
Keywords: AKI
Lead sponsor: Guard Therapeutics AB
Sponsor class: INDUSTRY
First posted: 2021-04-02
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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)

Primary outcomes:
measure: Frequency of Adverse Events (AEs)
timeFrame: Baseline through day 30
measure: Severity of AEs
timeFrame: Within 4 days from first dose of IMP
Secondary outcomes:
measure: Maximum Observed Concentration (Cmax)
timeFrame: Blood samples taken from pre-dose and up to two hours after start of Dose 5
measure: Area Under the Curve (AUC) 0-24h
timeFrame: Blood samples taken from pre-dose and up to two hours after start of Dose 5
measure: Elimination Half-life (T1/2)
timeFrame: Blood samples taken from pre-dose and up to two hours after start of Dose 5
Other outcomes:
Locations:
city: Münster
country: Germany
facility: Münster University Hospital
Study officials:
affiliation: Guard Therapeutics AB
name: Tobias Agervald, MD PhD
role: STUDY_DIRECTOR
References: