E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Subjects with documented STEMI, presenting with persistent ischemic chest pain (>10 minutes) and new ≥2 mm ST-segment elevation in 2 adjacent ECG leads, in whom the total duration of symptoms to diagnostic ECG is anticipated to be within 4 hours. |
|
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). |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 the clinical outcome at 30-day follow-up after administration of a single subcutaneous injection of zalunfiban versus placebo in STEMI subjects in the 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, for information only, according to the Bleeding Academic Research Consortium [BARC] Types 3C and 5 criteria for information only) after a single subcutaneous injection of zalunfiban versus placebo at 30 days follow-up.
|
|
E.2.2 | Secondary objectives of the trial |
To assess after a single s.c. injection of zalunfiban vs placebo: Efficacy: -Restoration of the culprit coronary artery blood flow of the Culprit before intended PCI (or post-CAG in case no PCI performed) -Resolution of ST-segment deviation post-PCI/CAG - Blinded bail-out use of IV αIIbβ3 receptor antagonists or IV P2Y12 antagonist at 24 hours post-PCI/angiography
Safety: -Safety throughout study -Platelet count pre-PCI/CAG, post-PCI/CAG, 6hr post-PCI/CAG, 24hr post-PCI/CAG and at discharge/72hr post-PCI/s (whichever occurs first) - Bleeding events at 30 day FU: - According to ISTH Major - According to GUSTO mild and moderate criteria, BARC Types 2, 3, and 5 criteria, ISTH minor and/or major bleeding, and TIMI minor and major criteria) -The injection site reactions of a single s.c. injection of zalunfiban versus placebo at baseline, 1hr post-PCI/CAG, hospital discharge/72hr post- PCI/CAG, and at 30-day FU |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Planned transport to participating clinical site - Males aged ≥18 years or post-menopausal or surgically sterile females ≥50 years or ≥55 years (for Czech Republic study sites only). - Weight (by history) between 52 and 130 kg (115 and 287 lb). - Subjects with documented STEMI, presenting with persistent ischemic chest pain (>10 minutes) and new ≥2 mm ST-segment elevation in 2 adjacent ECG leads, in whom the total duration of symptoms to diagnostic ECG is 4 hours maximum. - Enrollment by EFIC process, verbal witnessed/short written informed consent, or written informed consent will be obtained in the acute phase by (para)medics [Romania and other select sites with the sponsor's approval: clinical site personnel, if greater than 30 minutes of delay is anticipated for door-to-balloon time]. Subject is willing and able to give informed consent. Written informed consent will be obtained as soon as the subject's clinical condition allows it. |
|
E.4 | Principal exclusion criteria |
- Cardio Pulmonary Resuscitation (CPR) for current Out of Hospital Cardiac Arrest (OHCA). - Cardiogenic shock 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 or direct oral anticoagulants **) and thrombolytic agents***. For example.. * acenocoumarol or phenprocoumon, fluindione, and Coumadin (warfarin) ** dabigatran, apixaban, edoxaban, rivaroxaban and betrixaban *** tenecteplase, alteplase, reteplase, streptokinase, and urokinase - 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). - Previously enrolled in this study. - Participation in another clinical study with an investigational product or device within the past month. - Life expectancy less than one year. |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy: To assess after a single subcutaneous injection of zalunfiban versus placebo: Clinical outcome as assessed by a 7-point scale. The 7 outcomes, ranking from worst to best, are: a. Death (all cause) at 30-day follow-up b. Stroke at 30-day follow-up c. Recurrent MI (Types 1 to 4 MI) at 30-day follow-up d. Acute stent thrombosis at 24 hours post-PCI/angiography e. New onset HF or rehospitalization for HF at 30-day follow-up f. MI with hs-cTnT levels ≥10x ULN at 24 hours post-PCI/angiography g. None of the above
Safety: To assess after a single subcutaneous injection of zalunfiban versus placebo: - Subject incidence of bleeding events (according to GUSTO severe or life-threatening criterion for safety assessment and, for information only, according to the BARC Types 3C and 5 criteria) at 30 days follow-up |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
see primary end points (E.5.1)
|
|
E.5.2 | Secondary end point(s) |
Efficacy: To assess after a single subcutaneous injection of zalunfiban versus placebo: - As assessed by an independent Core Laboratory: Corrected TIMI Frame Count of the Infarct-Related Artery (Culprit) before PCI/angiography - As assessed by an independent Core Laboratory: ST-segment deviation resolution 1-hour post-PCI/angiography - Blinded bail-out use of IV αIIbβ3 receptor antagonists or IV P2Y12 antagonists at 24 hours post-PCI/angiography
Safety To assess after a single subcutaneous injection of zalunfiban versus placebo: - Recording of AEs and SAEs: AEs up to 30-day follow-up; SAEs up to resolution/stabilization, the SAEs mortality and hospitalization for heart failure and atrial fibrillation up to 12-months follow-up - Platelet count before PCI/angiography, at the end of the PCI/angiography, 6 and 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, for information only, TIMI Major) at 30 days follow-up - Subject incidence of bleeding events according to GUSTO mild and moderate criteria, BARC Types 2, 3, and 5 criteria, ISTH minor and/or major bleeding, and TIMI minor and major criteria at 30 days follow-up - Subject incidence of injection site reactions at baseline, 1-hour post-PCI/angiography, hospital discharge/72-hours post- PCI/angiography, and at 30 days follow-up |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
see secondary end points (E.5.2) |
|
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) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 48 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Canada |
United States |
Czechia |
France |
Hungary |
Netherlands |
Romania |
|
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
|
A subject is considered to have completed the study if he/she has completed the 30-day FU visit. After Day 30 FU visit, subjects will continue to long-term assessment at Month 12. The end of the study is met when all patients have completed all assessments, all data have been cleaned and study site has been closed. A possible reason for early study termination includes that the SRC makes a decision for the early termination of the study per recommendation.
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 1 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 3 |