Phase IIa Randomized, Placebo-Controlled Trial Evaluating ApTOLL in ST Elevation Myocardial Infarction Patients Undergoing Emergency Angioplasty

The primary objective of this clinical trial is to evaluate the **safety** of ApTOLL at two different doses (0.2 mg/kg and 0.4 mg/kg) administered via intravenous bolus in patients with ST Elevation Myocardial Infarction (STEMI) who are candidates for emergency angioplasty and have not received thrombolytics. This is clinically relevant as ensuring the safety of ApTOLL is crucial before considering its broader application in the management of STEMI, a condition characterized by a significant risk of morbidity and mortality.

Secondary objectives include:

• Assessing the biological effect of ApTOLL on early infarct volume using late gadolinium enhancement-magnetic resonance imaging (LGE-MRI) at 5 (±2) days and 90 (±14) days post-randomization.
• Evaluating the impact of ApTOLL on cardiac parameters and functional index via echocardiography (ECHO) at 72 hours (±24 hours) and 90 (±14) days after randomization.
• Providing an initial estimate of the biological effect of ApTOLL on blood pro-inflammatory biomarkers associated with STEMI at baseline and at 24, 48, and 72 hours following randomization.

The clinical trial involves participants diagnosed with **STEMI (ST Elevation Myocardial Infarct)**, specifically those who are candidates for emergency angioplasty and have not received thrombolytics. The study population includes both male and female subjects aged 18 years and older. The trial does not specify the total number of participants, as this information was not provided by the sponsor. Participants were selected based on their admission with primary acute coronary syndrome and a final diagnosis of first STEMI, as defined by the 2017 European Society of Cardiology guidelines. The trial includes a vulnerable population, and informed consent is required from the subject or an acceptable surrogate. Women of childbearing potential must confirm a negative pregnancy test and adhere to effective birth control methods for a specified period post-dose. The trial does not provide specific details on lifestyle considerations such as diet or physical activity.

The clinical trial is a **randomized**, **double-blind**, placebo-controlled Phase IIa study designed to evaluate the safety and efficacy of ApTOLL in patients with **ST Elevation Myocardial Infarct (STEMI)**. The trial involves the administration of ApTOLL at two different doses (0.2 mg/kg and 0.4 mg/kg) via **intravenous bolus** to patients who are candidates for emergency angioplasty and have not received thrombolytics. The study is expected to commence on October 1, 2023, and conclude by January 1, 2025, with an estimated duration of participant involvement of up to 90 days.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, informed consent, and diagnosis of STEMI. Following randomization, participants will receive the investigational product or placebo and will be monitored for adverse events and safety outcomes, including all-cause mortality and specific adverse events like severe hypotension and cardiogenic shock, during the first 72 hours post-administration or until discharge. Follow-up visits will include assessments at 5 days, 72 hours, and 90 days post-randomization, utilizing LGE-MRI and echocardiography to evaluate the biological effects of ApTOLL on infarct volume and cardiac parameters. Biomarker analysis will also be conducted at baseline and at specified intervals post-randomization.

The primary endpoint focuses on the safety of ApTOLL, while secondary endpoints assess its biological effects on infarct volume, cardiac function, and pro-inflammatory biomarkers. Participants may be withdrawn from the study if they experience significant adverse events or if they withdraw consent. The trial is conducted under strict adherence to ethical guidelines, ensuring the safety and well-being of all participants throughout the study duration.

The clinical trial involves the investigation of **ApTOLL**, an experimental medication, in patients with ST Elevation Myocardial Infarction (STEMI). **ApTOLL** is formulated as a **concentrate for solution for injection/infusion** and is administered via **intravenous bolus use**. The active substance in **ApTOLL** is **APTAMER-4FT**, a nucleic acid-based compound. The trial evaluates two dosing regimens: 0.2 mg/kg and 0.4 mg/kg, with a maximum treatment period of one day. The primary objective is to assess the safety of **ApTOLL** in patients who are candidates for emergency angioplasty and have not received thrombolytics.

In addition to the experimental treatment, the study includes the use of a **placebo** control, referred to as **APTOLL PLACEBO**. The placebo is administered in the same manner as the experimental drug, via **intravenous bolus use**. The placebo is designed to match the experimental treatment in appearance and administration to ensure blinding in this randomized, placebo-controlled trial. The use of a placebo allows for the assessment of the efficacy and safety of **ApTOLL** by providing a baseline for comparison.

The efficacy of ApTOLL in patients with **ST Elevation Myocardial Infarction (STEMI)** will be assessed through several secondary endpoints. The biological effect of ApTOLL on early infarct volume will be evaluated using Late Gadolinium Enhancement Magnetic Resonance Imaging (LGE-MRI) at 5 days (±48 hours) post-randomization, and late changes in infarct volume will be assessed at 90 (±14) days post-randomization. MRI parameters will include infarct mass, infarct size as a percentage of total left ventricular mass, and left ventricular ejection fraction (LVEF). These MRI assessments will be conducted by local radiologists and reviewed by a central reader.

Additionally, the impact of ApTOLL on cardiac parameters will be determined through echocardiography at 72 (±24 hours) and 90 (±14) days post-randomization. Measurements will include left ventricular end-diastolic volume (LVEDV), LVEF, E-e’ ratio, trans-mitral pattern, estimated pulmonary artery pressure, inferior vena cava diameter, and the presence or absence of intracavitary thrombi.

Furthermore, the effect of ApTOLL on pro-inflammatory biomarkers will be analyzed by measuring levels of interleukin-6 (IL-6), interleukin-1b (IL-1b), interleukin-4 (IL-4), interleukin-10 (IL-10), CXCL-10, serum amyloid A (SAA), Toll-like receptor 4 (TLR4), cardiac troponin T, and high-sensitivity C-reactive protein (hsCRP) at baseline, 24 hours, 48 hours, and 72 hours post-randomization. These comprehensive assessments will provide insights into the efficacy of ApTOLL in the specified patient population.