Evaluation of M2RLAB Mononuclear Cell Therapy for Acute Kidney Injury Post-Cardiac Surgery: A Randomized, Placebo-Controlled Clinical Trial

The primary objective of this study is to evaluate the **efficacy** of cell therapy compared to placebo by measuring the time to recovery of renal function in patients who develop **acute kidney injury (AKI)** within 48 hours after cardiac surgery. Additionally, the study aims to assess the safety and tolerability of cell therapy versus placebo in this patient population. These objectives are clinically relevant as they address the potential of cell therapy to improve renal recovery and patient safety following cardiac surgery, which is critical for reducing morbidity and improving outcomes in patients with AKI.

Secondary objectives include:

• Assessment of major adverse kidney events (MAKE) occurrence in patients receiving cell therapy versus placebo.
• Evaluation of the efficacy of cell therapy versus placebo by assessing the need for and duration of renal replacement therapy, length of ICU and hospital stay, and survival at 30 and 90 days in patients developing AKI post-surgery.
• Assessment of creatinine levels during admission and progression of renal injury in patients receiving cell therapy versus placebo.
• Evaluation of the safety and tolerability of cell therapy by assessing the incidence of infectious and surgery-related complications, as well as the evolution of ventricular function in patients developing AKI post-surgery.

The clinical trial focuses on patients who develop **acute kidney injury** (AKI) within 48 hours after cardiac surgery. The study population includes both male and female participants over the age of 18, who are capable of understanding and signing informed consent. Participants are those undergoing elective or emergent valvular and/or coronary heart surgery with extracorporeal circulation. The trial does not involve a vulnerable population. Participants must have a serum creatinine increase of more than 50% from baseline and a urine NGAL value exceeding 200 microgram/g creatinine within the first 48 hours post-surgery. The sponsor has not provided information regarding the total number of participants. Lifestyle considerations such as diet, physical activity, or habits are not specified. Key inclusion criteria include the ability to sign informed consent within 12 hours of AKI diagnosis and adherence to contraceptive measures for participants of childbearing age from hospital discharge until the end of the trial. The selection process for the trial population is not detailed in the provided data.

The clinical trial is designed to evaluate the efficacy and safety of **cell therapy** using **Mononuclear cells M2RLAB** for the treatment of **acute kidney injury** (AKI) following cardiac surgery. This is a Phase IV, randomized, double-blind, controlled trial comparing the investigational product to a placebo, **Suero fisiológico (NaCl 0.9%)**. The trial aims to assess the time to recovery of renal function and the safety profile of the cell therapy in patients who develop AKI within 48 hours post-surgery. The trial is expected to commence recruitment on July 1, 2024, and conclude by June 30, 2026.

Participants will be involved in the study for a maximum treatment period of one day, with the total duration of their involvement extending until the end of the study. The inclusion criteria require participants to be over 18 years of age, capable of providing informed consent, and having undergone elective or emergent valvular and/or coronary heart surgery with extracorporeal circulation. Participants must exhibit a serum creatinine increase of over 50% from baseline and a urine NGAL value exceeding 200 microgram/g creatinine within the first 48 hours post-surgery. Women and men of childbearing potential must adhere to contraceptive measures from hospital discharge until study completion.

The trial includes several key visits: an initial screening visit to confirm eligibility, followed by the administration of the investigational product or placebo. Follow-up visits will be conducted to monitor renal function recovery time, adverse events, and other secondary endpoints such as the incidence of major adverse kidney events (MAKE), duration of renal replacement therapy, and overall survival at 30 and 90 days. The end-of-study visit will assess the final outcomes and any long-term effects of the treatment. Participants may be withdrawn from the study if they experience serious adverse events or if they no longer meet the inclusion criteria.

The clinical trial involves the administration of **Mononuclear cells M2RLAB**, an experimental medication designed for the treatment of acute kidney injury following cardiac surgery. This investigational product is classified as a **biological** and is formulated for **injectable** use. The active substance, **M2RLAB**, is derived from structurally diverse substances used in **cell therapy**. The medication is administered via **intravenous use**. The dosing regimen specifies a maximum daily dose of 10 ml, with a total treatment period not exceeding one day. The trial aims to evaluate the efficacy and safety of this cell therapy in comparison to a placebo.

The comparator treatment in this study is **Suero fisiológico (NaCl 0,9%)**, which serves as the placebo. This solution is commonly used as a standard isotonic saline solution in clinical settings. Although the pharmaceutical form and route of administration are not explicitly detailed, it is typically administered intravenously in similar clinical trials. The use of this placebo allows for a controlled assessment of the investigational product's effects on renal function recovery in patients experiencing acute kidney injury post-cardiac surgery.

The efficacy of the investigational cell therapy in the clinical trial will be assessed by evaluating the **renal function recovery time** in patients who develop acute kidney injury (AKI) within 48 hours after cardiac surgery. Primary endpoints include the proportion of patients with no persistently altered creatinine values, defined as values greater than 31% of baseline, seven days after the AKI episode. Additionally, the occurrence of adverse events (AEs), serious AEs (SAEs), AEs resulting in discontinuation of study treatment, and AEs of special interest will be monitored.

Secondary endpoints will focus on reducing the incidence of major adverse kidney events (MAKE), which encompass death, dialysis, or a permanent reduction in estimated glomerular filtration rate (CKD-EPI) of more than 30% from baseline. Other secondary measures include the number of patients on renal replacement therapy and the duration of such therapy, duration of ICU admission, and overall hospital stay. Global survival rates at 30 and 90 days, the number of patients on dialysis at these time points, and maximum creatinine values recorded during hospitalization will also be evaluated. Improved levels of injury biomarkers in urine and the incidence of surgical wound infections, respiratory infections during ICU stay, and complications related to surgery will be assessed. Unexplained hemodynamic impairments, such as a drop in cardiac index or systemic systolic blood pressure, will be monitored as well.