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

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

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).

Study Overview

• Status: Recruiting
• Conditions: ST Elevation Myocardial Infarction
• Intervention / Treatment: Biological: GNR-060; Biological: Metalyse

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 244
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Rusava O. Matyushina, MD, PhD; Phone Number: 7109 +7 (495) 988-47-94; Email: romatyushina@generium.ru
• Study Contact Backup: Name: Oksana A. Markova, MD, MSc; Phone Number: 7077 +7 (495) 988-47-94; Email: oamarkova@generium.ru

Study Locations

• Russian Federation
  • Altai Territory
    • Barnaul, Altai Territory, Russian Federation, 656038
      • Not yet recruiting
      • Regional State Budgetary Health Institution "Regional Clinical Emergency Hospital"
    • Barnaul, Altai Territory, Russian Federation, 656055
      • Recruiting
      • Regional State Budgetary Institution of Health Care "Altai Territorial Cardiology Dispensary"
  • Arkhangelsk Region
    • Arkhangel'sk, Arkhangelsk Region, Russian Federation, 163001
      • Recruiting
      • State Budgetary Institution of Health Care of the Arkhangelsk Region "First City Clinical Hospital named after E.E. Volosevich"
  • Belgorod Region
    • Belgorod, Belgorod Region, Russian Federation, 308007
      • Recruiting
      • Regional State Budgetary Health Institution "Belgorod Regional Clinical Hospital of St. Joasaph"
  • Perm Territory
    • Perm, Perm Territory, Russian Federation, 614107
      • Recruiting
      • State Autonomous Healthcare Institution of the Perm Territory "City Clinical Hospital No. 4"
  • Republic Of Tatarstan
    • Kazan, Republic Of Tatarstan, Russian Federation, 420101
      • Not yet recruiting
      • State Autonomous Healthcare Institution "Interregional Clinical and Diagnostic Center"
  • Rostov Region
    • Rostov-on-Don, Rostov Region, Russian Federation, 344068
      • Recruiting
      • Municipal budgetary health care institution "City emergency hospital of the city of Rostov-on-Don"
  • Ryazan Region
    • Ryazan', Ryazan Region, Russian Federation, 390039
      • Not yet recruiting
      • State Budgetary Institution of the Ryazan Region "Regional Clinical Hospital"
  • Sverdlovsk Region
    • Ekaterinburg, Sverdlovsk Region, Russian Federation, 620144
      • Recruiting
      • State budgetary health care institution of the Sverdlovsk region "Scientific and practical center for specialized types of medical care" Ural Institute of Cardiology "
  • Volgograd Region
    • Volgograd, Volgograd Region, Russian Federation, 400138
      • Not yet recruiting
      • State Health Institution "City Clinical Emergency Hospital No. 25"
  • Yaroslavl Region
    • Yaroslavl, Yaroslavl Region, Russian Federation, 150062
      • Not yet recruiting
      • State Budgetary Health Institution of the Yaroslavl Region "Regional Clinical Hospital"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency and severity of hemorrhagic complications	Hemorragies will be classified based on BARC, ISTH and TIMI definitions	up to 30 days
Incidence of the hemorrhagic stroke	Any case of treatment-related hemorrhagic stroke	up to 30 days
Frequency and severity of the adverse drug reactions	Any adverse events related to the trombolisis	up to 30 days
Proportion of patients with the antidrug antibodies	Anti-tenecteplaze antibody will be measured before trombolisis and 7 days after.	7 days

Collaborators and Investigators

• Sponsor: AO GENERIUM
• Investigators: Study Chair: Oksana A. Markova, MD, MSc, AO GENERIUM

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2021
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2024

Study Registration Dates

• First Submitted: October 26, 2022
• First Submitted That Met QC Criteria: October 31, 2022
• First Posted (Actual): November 1, 2022

Study Record Updates

• Last Update Posted (Actual): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Coronary angiography; STEMI; Thrombolytic therapy; Revascularization; AMI; Bleeding; Haemorrhage; Myocardial Infarction; Hemorrhagic stroke; Myocardial Ischemia; ECG; Fibrinolysis; Reperfusion; Hemorrhagic syndrome; Recombinant DNA technology; Thrombolysis; TNK-tPA; Fibrinolytic therapy; Coronary Thrombosis; Tenecteplase; Thrombolytic; ST Elevation; Metalyse; Metalise; Fibrin-specific plasminogen activator
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; ST Elevation Myocardial Infarction; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Tenecteplase
• Other Study ID Numbers: TNP-STEMI-III; № 142 eff. date 17 March 2021 (Other Identifier: Ministry of Health of the Russian Federation)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No