E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 12.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10011085 |
E.1.2 | Term | Ischaemic coronary artery 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 |
To evaluate the safety and efficacy of the REG1 Anticoagulation System in Acute Coronary Syndrome patients undergoing cardiac catheterization by determination of the clinically acceptable dose range of RB007, which can be used to reliably reverse the anticoagulant effect of RB006. |
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E.2.2 | Secondary objectives of the trial |
1. Estimate the efficacy of the REG1 System in suppressing ischemic events (death, nonfatal myocardial infarction, recurrent ischemia in target vessel distribution, or urgent target vessel revascularization) compared to heparin (UFH or LMWH);
2. Confirm the anti-Factor IXa activity of RB006 by pharmacodynamic coagulation measurements;
3. Determine if the target doses of RB007 yield the predicted pharmacodynamic observed responses;
4. Compare the time required to achieve anticoagulation and time to reverse anticoagulation for both the REG1
System and heparin;
5. Compare the length of hospitalization for subjects receiving the REG1 System to subjects receiving heparin;
6. Determine the feasibility of early sheath removal using the REG1 System; and
7. Determine the effect of different RB007 dose ranges on the reversal of RB006 anticoagulation as it relates to
clinical and laboratory markers of anticoagulation |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. An Institutional Review Board (IRB/EC) approved informed consent is signed and dated prior to any studyrelated activities; 2. Subject is male or female between the ages of 18–85 years (inclusive); 3. Chest pain or other ischemic symptoms a minimum of 10 minutes in duration within 72 hours of randomization and anticipated cardiac catheterization within 24 hours of randomization 4. At least one of the following criteria are met: − New or presumably new ST-segment depression of at least 1 mm or transient (30 minutes) ST-segment elevation of at least 1 mm in 2 contiguous leads; − Elevated troponin I, T, or creatine phosphokinase-MB isoenzyme level within 24 hours of signing consent as defined by the universal MI definition1 − Documented coronary artery disease as evidenced on prior angiography, or by prior angioplasty, bypass graft surgery, or myocardial infarction; 5. Subject is a female with a negative urine or serum pregnancy test orpost-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 Subject has adequate birth control for study participation 6. Subject is able and willing to comply with the protocol and all study procedures. |
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E.4 | Principal exclusion criteria |
1. Acute ST-segment elevation myocardial infarction; of the following criteria apply: 2. Subject has significant medical or psychiatric condition or other risk factor that in the opinion of the Investigator precludes participation in the study; 3. Subject weighs >120 kg; 4. Subject has evidence of clinical instability including the following: a. Sustained systolic blood pressure <90 mm Hg or cardiogenic shock; b. Acute pulmonary edema or severe congestive heart failure; c. Suspected acute myocarditis, pericarditis, endocarditis, or cardiac tamponade; d. Suspected dissecting aortic aneurysm; e. Hemodynamically significant valvular heart disease, hypertrophic cardiomyopathy, restrictive cardiomyopathy, or congenital heart disease; 5. Subject has evidence of a contraindication to anticoagulation or increased risk of bleeding such as: a. Any evidence or history of intracranial bleeding or aneurysm or known structural central nervous system abnormality that predisposes the subject to intracranial hemorrhage; b. Any history of hemorrhagic stroke; c. Known hypercoagulable state, including treatment for malignancy (excluding basal cell skin carcinoma) in the past year, or coagulopathy, or abnormal bleeding tendency; d. Any history of intraocular hemorrhage; e. History of thrombocytopenia associated with abnormal bleeding; f. History of thrombocytosis associated with a thrombotic event; g. Family history of a coagulopathy or bleeding diathesis (1st h. Severe trauma, fracture, major surgery, or biopsy of a parenchymal organ within the 3 months prior to signing consent; degree); i. Prolonged cardiopulmonary resuscitation within the 2 weeks prior to signing consent; j. Peptic ulcer disease documented by endoscopy in the past 3 years or major gastrointestinal bleeding within 3 months of signing consent; k. Genitourinary bleeding within the past 3 months; l. Severe hypertension at the time of screening or randomization (systolic pressure >180 mm Hg or diastolic >110 mm Hg); 6. Use of the following medications before the study: a. Use of any investigational drug or device within 30 days of signing consent or the planned use of an investigational drug or device through the EOS visit (Day 31); b. Use of low-molecular-weight heparin within 3 days of signing consent; c. Use of warfarin, bivalirudin, fibrinolytic agents or glycoprotein IIb/IIIa inhibitors within 7 days of signing consent; 7. Subject has clinically significant abnormal laboratory findings (from local clinical laboratory) that would preclude safe administration of study drug. Specifically, subject will be excluded if they meet the following: a. Baseline hemoglobin (Hgb) <10 g/dL; b. Liver function tests [AST (SGOT) and/or ALT (SGPT)] > 2.5 times the upper limit of normal range; c. Platelet count <100,000/mm3 8. Planned use of femoral arterial sheath size greater than 7 French or Intra Aortic Balloon Pump or other support device, and/or any non-femoral vascular access approaches for index procedure; ; 9. Subject has known allergy or intolerance to aspirin, clopidogrel, and/or prasugrel or any other agent mandated by the study; 10. Subject has a history of illicit drug abuse in the past year or current evidence of such abuse in the opinion of the Investigator and; 11. Subject is pregnant or lactating.
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E.5 End points |
E.5.1 | Primary end point(s) |
The composite incidence of major and minor bleeding (not related to CABG) through 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 | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
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 | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
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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.8.2.3.1 | Comparator description |
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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 | 15 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 55 |
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 | Information not present in EudraCT |
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 |
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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 visit of the last subject undergoing the trial |
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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 | 4 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
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 | 0 |