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

ST Elevation Myocardial Infarction Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05601999
• Other study ID #: TNP-STEMI-III
• Secondary ID: ? 142 eff. date
• Status: Recruiting
• Phase: Phase 3
• Start date: September 3, 2021
• Est. completion date: October 2024

Study information

• Verified date: March 2024
• Source: AO GENERIUM
• Contact: Rusava O. Matyushina, MD, PhD
• Phone: +7 (495) 988-47-94
• Email: romatyushina[@]generium.ru
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 244
• Est. completion date: October 2024
• Est. primary completion date: October 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction
• ST Elevation Myocardial Infarction

Intervention

Biological:
• GNR-060
GNR-060 will be administered in an individual dose depending on body weight as a single intravenous bolus
• Metalyse
Metalyse will be administered in an individual dose depending on body weight as a single intravenous bolus

Locations

Country	Name	City	State
Russian Federation	State Budgetary Institution of Health Care of the Arkhangelsk Region "First City Clinical Hospital named after E.E. Volosevich"	Arkhangel'sk	Arkhangelsk Region
Russian Federation	Regional State Budgetary Health Institution "Regional Clinical Emergency Hospital"	Barnaul	Altai Territory
Russian Federation	Regional State Budgetary Institution of Health Care "Altai Territorial Cardiology Dispensary"	Barnaul	Altai Territory
Russian Federation	Regional State Budgetary Health Institution "Belgorod Regional Clinical Hospital of St. Joasaph"	Belgorod	Belgorod Region
Russian Federation	State budgetary health care institution of the Sverdlovsk region "Scientific and practical center for specialized types of medical care" Ural Institute of Cardiology "	Ekaterinburg	Sverdlovsk Region
Russian Federation	State Autonomous Healthcare Institution "Interregional Clinical and Diagnostic Center"	Kazan	Republic Of Tatarstan
Russian Federation	State Autonomous Healthcare Institution of the Perm Territory "City Clinical Hospital No. 4"	Perm	Perm Territory
Russian Federation	Municipal budgetary health care institution "City emergency hospital of the city of Rostov-on-Don"	Rostov-on-Don	Rostov Region
Russian Federation	State Budgetary Institution of the Ryazan Region "Regional Clinical Hospital"	Ryazan'	Ryazan Region
Russian Federation	State Health Institution "City Clinical Emergency Hospital No. 25"	Volgograd	Volgograd Region
Russian Federation	State Budgetary Health Institution of the Yaroslavl Region "Regional Clinical Hospital"	Yaroslavl	Yaroslavl Region

Sponsors (1)

Lead Sponsor	Collaborator
AO GENERIUM

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Frequency and severity of hemorrhagic complications	Hemorragies will be classified based on BARC, ISTH and TIMI definitions	up to 30 days
Other	Incidence of the hemorrhagic stroke	Any case of treatment-related hemorrhagic stroke	up to 30 days
Other	Frequency and severity of the adverse drug reactions	Any adverse events related to the trombolisis	up to 30 days
Other	Proportion of patients with the antidrug antibodies	Anti-tenecteplaze antibody will be measured before trombolisis and 7 days after.	7 days
Primary	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	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
Secondary	Frequency of myocardial reperfusion based on ECG data	Resolution of the ST segment by 30%, 50%, 70% or more	after 90 minutes
Secondary	Changes in troponin T and creatine kinase MB levels		7 days
Secondary	90-Day mortality	Mortality within 90 days after myocardial infarction	90 days
Secondary	30-Day and 90-Day cardiovascular mortality	Cardiovascular mortality up to 30 and 90 days after myocardial infarction	30 and 90 days
Secondary	Frequency of the postinfarction complications	Frequency of any postifarction complication except for arrythmias	up to 30 days
Secondary	Frequency of the combined events "cardiovascular death + recurrent myocardial infarction + stroke" and "cardiovascular death + recurrent myocardial infarction + stroke + heart failure"		30 days