Phase 3 Randomized, Placebo-Controlled Study on the Efficacy and Safety of Zalunfiban in Pre-Hospital ST-Elevation Myocardial Infarction Patients

The primary objective of this study is to evaluate the **efficacy** and **safety** of a single subcutaneous injection of zalunfiban compared to placebo in subjects with ST-elevation myocardial infarction (STEMI) in a pre-hospital setting. Clinically, this is significant as it aims to improve outcomes in STEMI patients by potentially offering a new therapeutic option that can be administered before hospital arrival. The primary efficacy endpoint is the clinical outcome at a 30-day follow-up, while the primary safety endpoint involves assessing bleeding events according to the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) severe or life-threatening criterion and, for information only, the BARC Type 3C and 5 criteria.

Secondary objectives include:

• Assessing the restoration of blood flow in the infarct-related artery before percutaneous coronary intervention (PCI) or post-coronary angiography if no PCI is performed.
• Evaluating the resolution of ST-segment deviation post-PCI/angiography.
• Determining the blinded bail-out use of intravenous αIIbβ3 receptor antagonists or P2Y12 antagonist at 24 hours post-PCI/angiography.
• Monitoring safety through adverse event reporting throughout the study.
• Measuring platelet count at various time points relative to PCI/angiography.
• Assessing bleeding events according to multiple criteria at a 30-day follow-up.
• Evaluating injection site reactions at baseline, 1-hour post-PCI/angiography, hospital discharge/72-hours post-PCI/angiography, and at 30-day follow-up.

The clinical trial involves a total of **57 participants** who are being studied to assess the efficacy and safety of a single subcutaneous injection of zalunfiban versus placebo in subjects with documented **ST-elevation myocardial infarction (STEMI)**. The study population includes both male and female subjects, with males aged 18 years and older, and females who are post-menopausal or surgically sterile aged 50 years and older, or 55 years and older for Czech Republic study sites. Participants are required to have a weight between 52 and 130 kg. The trial population was selected based on the presence of persistent ischemic chest pain lasting more than 10 minutes and new ST-segment elevation of at least 2 mm in two adjacent ECG leads, with the total duration of symptoms to diagnostic ECG anticipated to be within 4 hours. The study includes a vulnerable population, and informed consent is obtained in the acute phase by paramedics or at clinical sites, according to local legal regulations. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is a **Phase 3** prospective, blinded, randomized, placebo-controlled, international multicenter study designed to evaluate the safety and efficacy of a single subcutaneous injection of **zalunfiban** in subjects with ST-elevation myocardial infarction (STEMI) in a pre-hospital setting. The trial aims to assess the clinical outcome at a 30-day follow-up and monitor bleeding events according to established criteria. The study involves a comparison between zalunfiban and a placebo, with the primary endpoints focusing on clinical outcomes and safety assessments.

The trial is structured to include several key visits: an initial screening visit, follow-up visits, and an end-of-study visit. During the screening visit, eligibility criteria are confirmed, including age, weight, and documented STEMI presentation. Participants are required to have persistent ischemic chest pain and specific ECG changes, with symptom onset to diagnostic ECG anticipated within four hours. Follow-up visits are scheduled to monitor clinical outcomes, adverse events, and safety parameters, including bleeding events and platelet counts. The end-of-study visit marks the conclusion of the participant's involvement, with a final assessment of clinical outcomes and safety data.

Participants are expected to be involved in the study for a duration of up to 30 days, with the possibility of extended follow-up for serious adverse events up to 12 months. Conditions that may lead to early termination from the study include withdrawal of consent, significant protocol deviations, or adverse events that compromise participant safety. The trial is anticipated to conclude by June 2026, with recruitment having commenced in April 2021. The study is conducted under strict adherence to ethical guidelines, with informed consent obtained in accordance with local regulations.

The clinical trial involves the administration of **Zalunfiban**, an investigational medication, which is a **solution for injection**. Zalunfiban is chemically synthesized and is provided by Celecor Therapeutics, Inc. The active substance in Zalunfiban is also known by its chemical name, 2-amino-N-{5-[5-oxo-7-(piperazin-1-yl)-5H-[1,3,4]thiadiazolo[3,2-a]pyrimidin-2-yl]pyridin-3-yl} acetamide, and is referred to by the synonyms RUC-4 or RUC 4. The medication is administered as a single **subcutaneous injection** with a maximum dose of 0.13 mg/kg. The treatment period is limited to a single day, and the administration is conducted in a pre-hospital setting for subjects with ST-elevation myocardial infarction (STEMI). Participant compliance with the dosing regimen is monitored throughout the study.

The study also includes a **placebo** group, which receives a placebo for Zalunfiban. The placebo is designed to match the investigational product in appearance but contains no active pharmaceutical ingredient. The placebo is administered in the same manner as Zalunfiban, as a single subcutaneous injection, to maintain the study's blinded and randomized design. The use of a placebo allows for the assessment of the safety and efficacy of Zalunfiban by providing a comparator group within the trial. Compliance with the placebo administration is similarly monitored to ensure the integrity of the study results.

The efficacy of the clinical trial will be assessed by evaluating the clinical outcomes at a 30-day follow-up after the administration of a single subcutaneous injection of **zalunfiban** compared to a placebo in subjects with ST-elevation myocardial infarction (STEMI) in a pre-hospital setting. The primary efficacy endpoint will be measured using a 7-point scale, ranking outcomes from worst to best, including death (all cause) within 30 days, stroke, recurrent myocardial infarction (MI), acute stent thrombosis, new onset heart failure (HF) or re-hospitalization for HF, MI with high-sensitivity cardiac troponin T (hs-cTnT) levels ≥10 times the upper limit of normal (ULN), and none of the above.

Secondary efficacy endpoints will include assessments conducted by an independent Core Laboratory, such as the Corrected TIMI Frame Count of the Infarct-Related Artery before percutaneous coronary intervention (PCI)/angiography, ST-segment deviation resolution 1-hour post-PCI/angiography, and the blinded bail-out use of intravenous αIIbβ3 receptor antagonists or intravenous P2Y12 antagonists at 24 hours post-PCI/angiography. These assessments will provide a comprehensive evaluation of the therapeutic impact of **zalunfiban** on the clinical outcomes of STEMI patients.