Study of Efficacy and Safety of GNR-060 vs Metalyse in Patients With ST Elevation Myocardial Infarction

Study Overview
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Brief Summary
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GNR-060(JSC GENERIUM, Russia) is a proposed biosimilar to the referent product Metalyse. This study is to compare the clinical efficacy and safety of GNR-060 vs Metalyse as a thrombolitic agent in patients with with ST Elevation Myocardial Infarction (STEMI).

Detailed Description
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The trial is designed as a multicenter randomized single blinded study with the centralized blinded outcome assessment. The patients with diagnosed STEMI will be randomly assigned with one of the treatment options within 4 hours after the symptoms onset. The effectiveness of the tested product GNR-060 or reference product Metalyze will be assessed by the coronarography within 24 hours after the thrombolysis with the following PCI in case of ineffectiveness. The patients will then be followed up for survival and cardiac events for 90 days. The safety assessment will also include any related hemorrhagic complication. The pharmacokinetic parameters and immunogenicity will be also assessed.

Official Title
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Multicenter Randomized Single Blind Study of the Clinical Efficacy and Safety of GNR-060 (JSC GENERIUM, Russia) Compared to Metalyse (Boehringer Ingelheim Pharma GmbH & Co.KG, Germany) in Patients With ST Elevation Myocardial Infarction

Conditions
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ST Elevation Myocardial Infarction

Intervention / Treatment
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* Biological: GNR-060
* Biological: Metalyse


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Myocardial infarction with elevation of the ST segment of the ECG (at point J) in 2 adjacent leads after no more than 6 hours from the onset of pain (lasting at least 20 minutes) in the chest (at the time of screening): ≥ 2.5 mm in male ˂ 40 years, ≥ 2 mm in male ≥ 40 years, or ≥ 1.5 mm in female in leads V2-V3 and/or ≥ 1 mm in other leads in the absence of left ventricular hypertrophy or left bundle branch block. Exclusion Criteria: Diseases accompanied by significant bleeding, currently or within the last 6 months, hemorrhagic diathesis. Current oral anticoagulant therapy with INR > 1.3. Diseases of the central nervous system at present or in history (neoplasm, aneurysm, surgery on the brain or spinal cord). Severe uncontrolled arterial hypertension. Major surgical interventions, biopsy of a parenchymal organ or significant trauma within the last 2 months (including trauma in combination with AMI at the present time), recent (within the last 3 months) traumatic brain injury. Prolonged or traumatic cardiopulmonary resuscitation (> 2 minutes) within the last 2 weeks. Severe liver dysfunction, including liver failure, cirrhosis, portal hypertension (including esophageal varicose veins), active hepatitis. Peptic ulcer of the stomach or duodenum in the acute stage. Chronic kidney disease or other significant kidney disease with a decrease in glomerular filtration rate ≤30 ml / min / 1.73 m2. Arterial aneurysm or presence of arterial/venous vascular malformation. Neoplasm with an increased risk of bleeding. Acute pericarditis and/or subacute bacterial endocarditis. Acute pancreatitis. Hypersensitivity to the active substance (tenecteplase), gentamicin (residual traces of the manufacturing process) or any excipient. Hemorrhagic stroke or stroke of unknown etiology at present or in history. Intracranial (including subarachnoid) hemorrhage at present or in history. Ischemic stroke or transient ischemic attack (TIA) within the last 6 months. Recent bleeding from the gastrointestinal or genitourinary tract or childbirth (within the last 10 days). A recent (before 24 hours) puncture of an incompressible blood vessel (eg, subclavian or jugular vein). Congenital and hereditary hemorrhagic coagulopathy (hemophilia, etc.) in history. Pregnancy or breastfeeding. Body mass index (BMI) less than 18.5 or more than 40 kg/m2. Participation in another clinical trial currently or within 30 days prior to screening; use of any investigational drug within 30 days or 5 half-lives prior to screening.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GNR-060<br>Main group (122 patients) - GNR-060 | Biological: GNR-060<br>* GNR-060 will be administered in an individual dose depending on body weight as a single intravenous bolus<br>* Other names: Tenecteplase;|
| Active Comparator: Metalyse<br>Control group (122 patients) - Metalyse | Biological: Metalyse<br>* Metalyse will be administered in an individual dose depending on body weight as a single intravenous bolus<br>* Other names: Tenecteplase;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of the complete myocardial reperfusion based on the independent assessment of coronary angiography | TIMI Grade 3 coronary blood flow after the trombolisis | up to 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of the complete+partial myocardial reperfusion based on the independent assessment of coronary angiography | TIMI Grade 2 or 3 coronary blood flow after the trombolisis | up to 24 hours | 
| Frequency of myocardial reperfusion based on ECG data | Resolution of the ST segment by 30%, 50%, 70% or more | after 90 minutes | 
| Changes in troponin T and creatine kinase MB levels |  | 7 days | 
| 90-Day mortality | Mortality within 90 days after myocardial infarction | 90 days | 
| 30-Day and 90-Day cardiovascular mortality | Cardiovascular mortality up to 30 and 90 days after myocardial infarction | 30 and 90 days | 
| Frequency of the postinfarction complications | Frequency of any postifarction complication except for arrythmias | up to 30 days | 
| Frequency of the combined events cardiovascular death + recurrent myocardial infarction + stroke and cardiovascular death + recurrent myocardial infarction + stroke + heart failure |  | 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AMI, ECG, Hemorrhagic stroke, Coronary angiography, Revascularization, Tenecteplase, Metalyse, Metalise, TNK-tPA, Fibrin-specific plasminogen activator, Recombinant DNA technology, Myocardial Infarction, ST Elevation, STEMI, Myocardial Ischemia, Coronary Thrombosis, Thrombolysis, Thrombolytic, Thrombolytic therapy, Fibrinolytic therapy, Fibrinolysis, Bleeding, Hemorrhagic syndrome, Haemorrhage, Reperfusion