Guard Therapeutics has announced the dosing of the first European patient in the Phase 2b POINTER study, which is evaluating RMC-035 as a kidney-protective treatment during open-heart surgery. The patient was dosed at the University Hospital Carl Gustav Carus in Dresden, Germany, under the supervision of Professor Klaus Matschke, the principal investigator.
The POINTER study is a randomized, double-blind, and placebo-controlled trial designed to establish the optimal dosing regimen and identify the precise target patient population for a future pivotal Phase 3 study of RMC-035. The trial aims to enroll approximately 160 patients, with at least 30% having chronic kidney disease, defined as an estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73m2.
Study Design and Endpoints
Patients will be randomized into two different dose arms of RMC-035 (60 mg and 30 mg) and a placebo control arm in a 2:2:3 ratio. Renal function before surgery will serve as a stratification factor, ensuring even distribution of patients with and without chronic kidney disease across all treatment arms. The primary endpoint of the study is the change in eGFR from study entry to 90 days post-surgery, aligning with the study's planned follow-up duration.
A key secondary endpoint is the incidence of Major Adverse Kidney Events (MAKE) at 90 days post-surgery, defined as death, dialysis treatment, or a ≥ 25% loss of eGFR compared to pre-surgery. Data from the two RMC-035 dose arms will be pooled and compared against placebo in the primary efficacy analyses.
Safety Monitoring and Recruitment
An independent Data Safety Monitoring Committee (DSMC) will conduct interim safety reviews based on data from one-third and two-thirds of the planned number of patients. The results of these analyses will be blinded to Guard Therapeutics. Patient recruitment began in late August 2024 and is expected to continue for approximately one year. The overall study results are anticipated to be available about six months after completion of patient enrollment.
RMC-035: A Novel Kidney-Protective Agent
RMC-035 represents a first-in-class drug, consisting of a recombinant and modified variant of the endogenous protein alpha-1-microglobulin. This investigational drug is designed to protect cells and their mitochondria from damage caused by oxygen deprivation and elevated levels of heme, a toxic oxygen-binding protein. Preclinical studies have demonstrated favorable treatment effects of RMC-035 in various disease models. RMC-035 exhibits a natural affinity for the kidneys and is primarily being developed as an intravenous kidney-protective treatment for patients at high risk of developing acute kidney injury (AKI).
Clinical Context and Significance
Open-heart surgery, particularly coronary artery bypass grafting (CABG), often leads to significant kidney damage due to ischemia-reperfusion injury and hemolysis. This damage can result in irreversible loss of kidney function and future end-stage renal disease requiring dialysis or kidney transplantation. RMC-035 aims to counteract these injuries and reduce the risk of long-term renal complications.
Guard Therapeutics CEO, Tobias Agervald, stated, "After study initiation in Canada according to plan, we have now also started to enroll patients for the POINTER study in Europe. A total of 14 clinics in Germany, the Czech Republic and Spain will be involved in the patient recruitment to the study."
RMC-035 has received Investigational New Drug (IND) clearance from the U.S. Food and Drug Administration (FDA) for the treatment of AKI in open-heart surgery and has been granted Fast Track Designation by the FDA to reduce the risk of irreversible kidney damage, dialysis, or death following open-heart surgery in high-risk patients. Results from the Phase 2 AKITA study showed a statistically significant and clinically relevant favorable effect of RMC-035 on long-term kidney outcomes in this patient population.
