E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with STEMI, presenting with persistent ischemic chest pain (>10 minutes) and new ≥2 mm ST-segment elevation in two adjacent ECG leads, in whom the total duration of symptoms is anticipated to be within 4 hours. |
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E.1.1.1 | Medical condition in easily understood language |
Patients with an Acute Myocardial Infarction presenting with specific abnormalities on their electrocardiogram. These patients are scheduled to undergo PCI (dotter treatment). |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | HLGT |
E.1.2 | Classification code | 10028593 |
E.1.2 | Term | Myocardial disorders |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10000891 |
E.1.2 | Term | Acute myocardial infarction |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028600 |
E.1.2 | Term | Myocardial ischaemia |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10081099 |
E.1.2 | Term | Acute cardiac event |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 23.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10062084 |
E.1.2 | Term | Platelet aggregation |
E.1.2 | System Organ Class | 100000004848 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10050661 |
E.1.2 | Term | Platelet aggregation inhibition |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Efficacy: - To assess restoration of the coronary artery blood flow (corrected Thrombolysis in Myocardial Infarction [TIMI] Frame Count) before intended PCI (or post coronary angiography in case no PCI is performed) after a single subcutaneous injection of RUC-4 versus placebo in STEMI subjects in the ambulance (pre-hospital setting). - To assess resolution of ST segment deviation post-PCI/angiography after a single subcutaneous injection of RUC-4 versus placebo in STEMI subjects in the ambulance (pre-hospital setting).
Safety: - To assess bleeding events (according to Global Use of Strategies to Open Occluded Coronary Arteries [GUSTO] severe or life threatening criterion for safety assessment and according to the Bleeding Academic Research Consortium [BARC] 3C and 5 criteria for information only) after a single subcutaneous injection of RUC-4 versus placebo up to 1 month post-PCI/angiography
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E.2.2 | Secondary objectives of the trial |
Safety: -To assess platelet count after a single s.c. injection RUC-4 vs placebo before PCI/angiography, at the end of the PCI/angiography, 6-hrs and 24-hrs post-PCI/angiography and at hospital discharge/72-hrs post-PCI/angiography - To assess bleeding events (according to ISTH Major and TIMI Major) after a single s.c. injection RUC-4 vs placebo up to 1 month post-PCI/angiography -To assess the injection site reactions of a single s.c. injection RUC-4 vs placebo at baseline, 1-hr post-PCI/angiography, hospital discharge/72-hrs post-PCI/angiography, and at 1-month FU.
Efficacy: -To assess a composite of all cause death, recurrent MI, urgent target vessel revascularization (TVR) or blinded bail-out use of intravenous (IV) αIIbβ3 antagonists or IV P2Y12 antagonist after a single s.c. injection of RUC-4 versus placebo up to 1 month post-PCI/angiography -To assess acute stent thrombosis after a single s.c. injection of RUC-4 versus placebo up to 24 hrs post-PCI. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Males aged ≥18 years or post-menopausal or surgically sterile females ≥50 years. Weight (by history) between 52 and 130 kg. Subjects with STEMI, presenting with persistent ischemic chest pain (>10 minutes) and new ≥2 mm ST-segment elevation in two adjacent ECG leads, in whom the total duration of symptoms is anticipated to be within 4 hours. Verbal witnessed / short written informed consent will be obtained in the acute phase by highly trained paramedics. After the PCI/angiography procedure written informed consent will be obtained. |
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E.4 | Principal exclusion criteria |
Cardio Pulmonary Resuscitation (CPR) for current Out of Hospital Cardiac Arrest (OHCA), except successful intervention for Ventricular Fibrillation (VF) with return of consciousness. Presenting with systolic blood pressure <90 mmHg confirmed on repeat testing and heart rate >100 beats per minute (bpm). Current known active coronavirus disease 2019 (COVID-19) infection (criteria according to local guidelines. Currently treated with renal dialysis. Current treatment with oral anticoagulation (Vitamin K antagonists [VKA] or direct oral anticoagulants [DOACs]). Major surgery, or trauma or bleeding leading to hospitalization, within the past month. Known history of ischemic or hemorrhagic stroke. Known severe anemia (regular blood transfusion needed). Participation in another clinical study with an investigational product or device within the past month. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy: As assessed by an independent Core Laboratory: - Corrected TIMI Frame Count before PCI/angiography - ST segment deviation resolution 1-hour post-PCI/angiography
Safety: - Subject incidence of bleeding events (according to GUSTO severe criterion for safety assessment and according to the BARC 3C and 5 criteria for information only) at baseline and up to 1 month post-PCI/angiography |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
see primary end points (E.5.1)
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E.5.2 | Secondary end point(s) |
Safety: - Platelet count before PCI/angiography, at the end of the PCI/angiography, 24 hours post-PCI/angiography and at hospital discharge/72-hours post-PCI/angiography (whichever occurs first) - Subject incidence of bleeding events (according to ISTH Major and TIMI Major for information only) at baseline and up to 1 month post-PCI/angiography - Subject incidence of injection site reactions at baseline, 1-hour post-PCI/angiography, hospital discharge/72-hours post-PCI/angiography, and at 1-month follow-up
Efficacy: - Time in days to a composite of all cause death, recurrent MI, urgent TVR or bail-out use of IV αIIbβ3 antagonists up to 1 month post-PCI/angiography - Subject incidence of acute stent thrombosis up to 24 hours post-PCI (according to the Academic Research Consortium [ARC] definition) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
see secondary end points (E.5.2) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Standard care will be performed from time of consent through last study visit. The end of study for a given subject is reached when follow-up at month 12 has been completed. The end of the whole study is met when all patients have completed all assessments, all data have been cleaned and study site has been closed. Premature termination of the study: a possible reason for early study termination includes that the SRC makes a decision for the early termination of the study per recommendation.
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 7 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 4 |
E.8.9.2 | In all countries concerned by the trial days | 15 |