Evaluation of RTP-026 Sodium in a Randomized, Double-Blind, Placebo-Controlled Trial for Safety and Efficacy in ST-Elevation Myocardial Infarction Patients

The primary objective of this exploratory, randomized, double-blind, multicentre, placebo-controlled study is to evaluate the **safety** and **tolerability** of RTP-026 in comparison to placebo in patients with ST-Elevation Myocardial Infarction (STEMI). This is clinically relevant as it aims to determine the potential adverse effects and overall acceptability of RTP-026 when administered in multiple doses, which is crucial for ensuring patient safety and guiding future therapeutic use. Additionally, the study seeks to assess the **efficacy** of RTP-026 against placebo, which is vital for understanding its therapeutic potential in improving clinical outcomes in STEMI patients.

The clinical trial involves a total of **10 participants** diagnosed with **ST-Elevation Myocardial Infarction (STEMI)**. The study population includes both male and female subjects, specifically men aged 18 to 85 years and post-menopausal women up to 85 years of age. Participants were selected based on the acute onset of chest pain lasting less than 12 hours and specific electrocardiogram (ECG) criteria indicative of STEMI. The trial does not involve a vulnerable population. Participants are required to be eligible for primary percutaneous coronary intervention (PCI) and must have a neutrophil-to-lymphocyte ratio (NLR) within a specified range at hospital admission. Lifestyle factors such as diet and physical activity are not specified as part of the selection criteria. The trial aims to evaluate the safety, tolerability, and efficacy of RTP-026 compared to a placebo in multiple doses.

The clinical trial is designed as an **exploratory, randomized, double-blind, multicentre, placebo-controlled** study to evaluate the safety, tolerability, and efficacy of RTP-026 in patients with **ST-Elevation Myocardial Infarction (STEMI)**. The trial will involve the administration of RTP-026 via **intravenous infusion** and will compare its effects against a placebo. The study is set to commence recruitment on May 1, 2024, with an estimated completion date of December 31, 2025. The trial will be conducted in a **Phase 4** setting, focusing on therapeutic exploratory and confirmatory objectives.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, acute onset of chest pain, and specific **ECG** characteristics. Following successful screening, participants will be randomized to receive either RTP-026 or placebo. The primary safety endpoint will involve monitoring adverse events, serious adverse events, vital signs, ECGs, and laboratory abnormalities. Efficacy will be assessed by measuring changes in cardiac biomarkers such as cTnT and CK-MB at baseline and at specified intervals post-**PCI**.

Follow-up visits will occur at multiple time points, including 6, 12, and 24 hours post-PCI, to evaluate both primary and secondary endpoints. Secondary endpoints will include assessments of myocardial salvage index, infarct size, myocardial oedema, and left ventricular ejection fraction, all determined by **CMR** within 48 hours and 90 days post-PCI. Additional evaluations will include changes in Pro-BNP, hsCRP, and NLR, as well as the composite of death and major adverse cardiac events up to 90 days post-PCI.

The expected duration of participant involvement is approximately 90 days, with conditions for early termination including withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The trial aims to provide comprehensive data on the safety and efficacy of RTP-026 in the specified patient population, contributing to the understanding of its therapeutic potential in the management of STEMI.

The clinical trial involves the administration of **RTP-026**, an investigational medication formulated as a **solution for infusion**. The active substance in RTP-026 is **RTP-026 sodium**, classified as a protein of other origin. The medication is administered via **intravenous infusion**. The dosing regimen specifies a maximum daily dose of 0.68 mg/kg, with the same amount as the maximum total dose. The treatment period is limited to a single day. The study aims to evaluate the safety, tolerability, and efficacy of RTP-026 in patients diagnosed with **ST-Elevation Myocardial Infarction (STEMI)**.

In addition to the experimental treatment, the study includes a **placebo** group. The placebo is referred to as **RTP-026 Placebo** and is used as a comparator to assess the effects of the investigational drug. The placebo does not contain any active substance and serves to maintain the double-blind nature of the trial. The administration details for the placebo are not specified, as it is intended to mimic the experimental treatment without providing therapeutic effects.

The efficacy of RTP-026 in patients with **ST-Elevation Myocardial Infarction (STEMI)** will be assessed through a series of primary and secondary endpoints. The primary efficacy endpoint involves comparing the effect of RTP-026 against placebo by evaluating changes in cardiac biomarkers, specifically cTnT and CK-MB, at baseline and at 6, 12, and 24 hours post-percutaneous coronary intervention (PCI). These biomarkers will be measured to determine the treatment's impact on myocardial injury.

Secondary efficacy endpoints will include a comprehensive assessment using cardiac magnetic resonance (CMR) imaging. This will involve measuring the Myocardial Salvage Index (MSI) and Infarct Size (IS) within 48 hours and 90 days post-PCI. Additionally, myocardial edema and changes in left ventricular ejection fraction (LVEF) will be evaluated using CMR at the same time points. Other secondary endpoints include changes in Pro-BNP, hsCRP, and Neutrophil-to-Lymphocyte Ratio (NLR) at baseline and at 6, 12, and 24 hours post-PCI. The study will also monitor the composite of death and major adverse cardiac events (MACE) up to 28 and 90 days post-PCI, as well as the duration of hospital stay until discharge.