Efficacy and Safety Evaluation of Subcutaneous Selatogrel in Preventing Recurrent Acute Myocardial Infarction in Post-AMI Patients

The primary objective of this study is to evaluate the **clinical efficacy** of selatogrel when self-administered upon the occurrence of symptoms suggestive of an **acute myocardial infarction** (AMI) in subjects at risk of having a recurrent AMI. This is clinically relevant as it aims to provide a potential intervention for reducing the risk of recurrent AMI, which is a critical concern in patients with a history of this condition.

The secondary objective is to assess the safety of self-administration of selatogrel. Evaluating the safety profile is essential to ensure that the self-administration of this medication does not pose additional risks to patients, thereby supporting its potential use in clinical practice.

The clinical trial involves a total of **7500 participants** who are at risk of having a recurrent **acute myocardial infarction (AMI)**. The study population includes both male and female subjects aged 18 years and older. Participants were selected based on a confirmed diagnosis of symptomatic Type 1 AMI, either ST-elevation myocardial infarction (STEMI) or Non-ST-elevation myocardial infarction (NSTEMI), diagnosed no longer than four weeks prior to randomization. The trial population also includes individuals with multivessel coronary artery disease, defined as having 50% or greater stenosis in two or more coronary artery territories or the left main artery. Additionally, participants must have at least two of the following risk factors: a second prior AMI, diabetes mellitus requiring glucose-lowering treatment, chronic kidney disease with an estimated glomerular filtration rate less than 60 mL/min/1.73 m², peripheral artery disease, or absence of successful coronary revascularization of the qualifying AMI. The study includes a vulnerable population, and participants must have successfully self-administered a placebo using an autoinjector during screening. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled**, parallel-group study to evaluate the efficacy and safety of self-administered subcutaneous **selatogrel** for the prevention of all-cause death and treatment of **acute myocardial infarction** (AMI) in subjects with a recent history of AMI. The trial aims to assess the clinical efficacy of selatogrel when self-administered upon the occurrence of symptoms suggestive of an AMI in subjects at risk of having a recurrent AMI. The study is expected to run from November 2021 to August 2025, with participant involvement lasting until the end of the study or until early termination conditions are met.

Participants will undergo a sequence of study visits, beginning with an inclusion (screening) visit where eligibility is confirmed based on criteria such as age, prior AMI diagnosis, and successful self-administration of a placebo. Follow-up visits will be scheduled to monitor the occurrence of death or non-fatal AMI after any study treatment self-administration, as well as to assess safety endpoints such as treatment-emergent bleeding events. The end-of-study visit will conclude the participant's involvement, unless early termination is warranted due to adverse events or withdrawal of consent.

The expected length of participant involvement is contingent upon the study's duration, with conditions for early termination including the occurrence of severe adverse events or non-compliance with study protocols. The primary endpoints focus on the efficacy and safety of the treatment, with secondary endpoints including the occurrence of death, non-fatal AMI, and hospitalization or unplanned emergency department visits for heart failure within 30 days after any treatment administration. The study is conducted under strict adherence to ethical guidelines, ensuring informed consent and participant safety throughout the trial.

The clinical trial involves the administration of **Selatogrel**, an investigational medication developed by Idorsia Pharmaceuticals Ltd. Selatogrel is provided as a **solution for injection in a pre-filled injector**. The active substance, selatogrel, is of chemical origin. The medication is administered via the **subcutaneous route**. The maximum daily dose is 16 mg, with a total dose not exceeding 16 mg per treatment period. The treatment period is limited to a single day. Participants are instructed to self-administer the medication upon experiencing symptoms suggestive of an acute myocardial infarction. Compliance with the dosing schedule is monitored throughout the study.

The study also includes a **Selatogrel matching placebo** to maintain the double-blind design. The placebo is used as a comparator treatment to evaluate the efficacy and safety of selatogrel. The placebo is designed to match the investigational product in appearance and administration method, ensuring that neither the participants nor the investigators are aware of the treatment allocation. The placebo is administered under the same conditions as the active treatment, with the same dosing schedule and route of administration.

The efficacy of the clinical trial will be assessed by evaluating the occurrence of death or non-fatal **acute myocardial infarction (AMI)** following any self-administration of the study treatment. The primary endpoint will be ranked based on severity, with the outcomes categorized as follows: 1) Death from all causes, 2) AMI with compromised electro-hemodynamics, 3) ST-elevation myocardial infarction (STEMI), 4) High-risk non-ST-elevation myocardial infarction (NSTEMI), 5) NSTEMI with peak cardiac troponin levels exceeding 10 times the upper limit of normal, and 6) None of the aforementioned outcomes within 7 or 2 days after each treatment administration. Only the most severe outcome will be considered as the primary endpoint.

Secondary efficacy endpoints include the composite occurrence of death, non-fatal AMI, hospitalization, or unplanned emergency department visits for heart failure within 30 days after any treatment administration. The efficacy parameters will be collected and analyzed according to the predefined schedule and criteria, ensuring a comprehensive assessment of the treatment's impact on the specified outcomes.