E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Coronary Artery Disease (CAD) in patients undergoing Percutaneous Coronary Intervention (PCI) |
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E.1.1.1 | Medical condition in easily understood language |
Coronary Artery Disease (CAD) in patients undergoing Percutaneous Coronary Intervention (PCI) |
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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 | 16.1 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10011085 |
E.1.2 | Term | Ischaemic coronary artery disorders |
E.1.2 | System Organ Class | 100000004849 |
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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 |
To determine the efficacy of REG1 compared to bivalirudin in patients with coronary artery disease (CAD) undergoing Percutaneous Coronary Intervention (PCI) for preventing the composite of death, nonfatal myocardial infarction, nonfatal stroke and urgent target lesion revascularization (TLR) through Day 3. |
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E.2.2 | Secondary objectives of the trial |
1. Determine the efficacy of REG1 compared to bivalirudin for preventing the composite of death, nonfatal myocardial infarction, nonfatal stroke, urgent TLR and stent thrombosis (including intra-procedural) through Day 3.
2. Determine the safety of REG1 compared to bivalirudin on major hemorrhagic complications of PCI through Day 3 and Day 30.
3. Determine the efficacy of REG1 compared to bivalirudin for preventing the composite of death, nonfatal myocardial infarction, nonfatal stroke and urgent TLR through Day 30.
4. Determine the efficacy of REG1 compared to bivalirudin in cardiac biomarker-positive patients for preventing the composite of death, nonfatal myocardial infarction, nonfatal stroke and urgent TLR through Day 3.
5. Determine the efficacy of REG1 compared to bivalirudin in cardiac biomarker-negative patients for preventing the composite of death, nonfatal myocardial infarction, nonfatal stroke and urgent TLR through Day 3. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. The study population will consist of patients with CAD undergoing PCI. Three key subgroups will be included as follows:
a. Subgroup A: Patients with ischemic symptoms at rest and positive cardiac biomarkers (troponin I or T or creatine kinase-MB) related to an acute coronary syndrome event within 7 days;
b. Subgroup B: Patients not meeting criteria for Subgroup A with at least one of the following risk factors:
• Remote acute coronary syndrome (>7 days) with positive cardiac biomarkers
• Unstable angina (ACS without positive cardiac biomarkers)
• Age >70 years
• Diabetes
• Chronic kidney disease (estimated CrCl < 60 mL/min)
• Planned multivessel PCI
• Prior CABG surgery
• Peripheral vascular disease;
c. Subgroup C: Patients with negative cardiac biomarkers and no risk factor, thereby not meeting criteria for Subgroup A or B;
2. Willing and able to sign an Institutional Review Board/Ethics Committee (IRB/EC) approved informed consent prior to any study-related activities;
3. Male or female age 18 or greater;
4. If female of childbearing potential, must have a negative urine or serum pregnancy test or be post-menopausal for at least 1 year prior to randomization. Females of childbearing potential must be practicing adequate birth control to be eligible. It is the Investigator’s responsibility for determining whether the patient has adequate birth control for study participation;
5. Subject is able and willing to comply with the protocol and all study procedures, including the 20 + 4 hour blood draw, Endpoint Assessment (Day 3-10) and Day 30 follow-up assessment as outlined in the protocol. |
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E.4 | Principal exclusion criteria |
1. Acute ST-segment elevation myocardial infarction within 48 hours of randomization; of the following:
2. Evidence of current clinical instability including the following:
a. Sustained systolic blood pressure <90 mm Hg or cardiogenic shock;
b. Suspected acute myocarditis, pericarditis, endocarditis, or cardiac tamponade;
c. Suspected dissecting aortic aneurysm;
3. Evidence of a contraindication to anticoagulation or increased risk of bleeding such as:
a. Any evidence or history of intracranial bleeding or aneurysm;
b. Known hypercoagulable state, including treatment for malignancy (excluding basal cell skin carcinoma) in the past year, or coagulopathy with abnormal bleeding tendency;
c. History of intraocular hemorrhage other than due to diabetic retinopathy;
d. History of thrombocytopenia associated with abnormal bleeding;
e. History of thrombocytosis associated with a thrombotic event;
f. Severe trauma, fracture, major surgery, or biopsy of a parenchymal organ within 3 months;
g. Prolonged cardiopulmonary resuscitation within 3 months;
h. Major gastrointestinal bleeding within 3 months;
i. Spontaneous genitourinary bleeding within 3 months;
j. Any planned surgical procedure within 30 days after randomization;
4. Use of any investigational drug or device within 30 days of randomization or the planned use of an investigational drug or device through EOS (Day 30 follow-up);
5. Use of the following antithrombotic agents:
a. Fibrinolytic agents within 48 hours;
b. GP IIb/IIIa inhibitors within 24 hours;
c. Bivalirudin within 24 hours
d. Prior exposure to any component of REG1;
6. Baseline hemoglobin (Hgb) <9 g/dL or equivalent;
7. Renal impairment as determined by any one of the following:
a. Baseline estimated glomerular filtration rate (GFR) ≤ 10 mL/min/1.73m²;
b. Currently undergoing renal replacement therapy (hemodialysis or peritoneal dialysis);
c. Degree of renal impairment for which use of bivalirudin is prohibited or contraindicated per local label instructions;
8. Baseline platelet count <100,000/mm3
9. Known allergy or intolerance to aspirin, to all available ADP/P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor), or to bivalirudin or REG1 (or any of their respective components); ;
10. The following planned procedures:
a. Planned staged PCI procedure within 3 days after randomization;
b. Planned CABG or valve surgery within 30 days after randomization;
11. Any other medical or psychiatric condition that in the Investigator’s judgment precludes participation in the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The composite of death, nonfatal myocardial infarction, nonfatal stroke and urgent TLR through Day 3. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. The composite of death, nonfatal myocardial infarction, nonfatal stroke, urgent TLR and stent thrombosis (including intra-procedural) through Day 3;
2. Major non-CABG bleeding (Bleeding Academic Research Consortium [BARC] Types 3 and 5) through Day 3;
3. The composite of death, nonfatal myocardial infarction, nonfatal stroke and urgent TLR through Day 30;
4. The composite of death, nonfatal myocardial infarction, nonfatal stroke and urgent TLR in Subgroup A (cardiac biomarker-positive patients) through Day 3;
5. The composite of death, nonfatal myocardial infarction, nonfatal stroke and urgent TLR in Subgroups B and C (cardiac biomarker-negative patients) through Day 3.
6. Major non-CABG bleeding (BARC Types 3 and 5) through Day 30.
Safety Endpoints
1. Incidence of bleeding (not related to CABG);
2. Incidence and severity of allergic adverse events, as well as the following:
a. Immunologic biomarker analysis;
b. Evaluations associated with risk mitigations strategies for possible allergic reactions;
3. Incidence of treatment emergent adverse events. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Through Day 3 and Day 30. |
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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 | Yes |
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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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) | Yes |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 203 |
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 |
Belgium |
Canada |
Denmark |
France |
Israel |
Italy |
Austria |
Netherlands |
Norway |
Poland |
Portugal |
Russian Federation |
Slovakia |
Sweden |
United Kingdom |
United States |
Czech Republic |
Estonia |
Germany |
Hungary |
Spain |
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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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Last call to the last patient. |
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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 | 2 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 2 |
E.8.9.2 | In all countries concerned by the trial months | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |