Clinical trial NCT05601999: Study of Efficacy and Safety of GNR-060 vs Metalyse in Patients With ST Elevation Myocardial Infarction
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: ST Elevation Myocardial Infarction
Keywords: Myocardial Infarction
ST Elevation
ECG
STEMI
Myocardial Ischemia
Coronary Thrombosis
Thrombolysis
Thrombolytic
Thrombolytic therapy
Fibrinolytic therapy
Fibrinolysis
Bleeding
Hemorrhagic syndrome
Haemorrhage
Hemorrhagic stroke
Coronary angiography
Revascularization
Reperfusion
Tenecteplase
Metalyse
Metalise
TNK-tPA
Fibrin-specific plasminogen activator
Recombinant DNA technology
AMI
Lead sponsor: AO GENERIUM
Sponsor class: INDUSTRY
First posted: 2022-11-01
Enrollment: 244
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Frequency of the complete myocardial reperfusion based on the independent assessment of coronary angiography
timeFrame: up to 24 hours
Secondary outcomes:
measure: Frequency of the complete+partial myocardial reperfusion based on the independent assessment of coronary angiography
timeFrame: up to 24 hours
measure: Frequency of myocardial reperfusion based on ECG data
timeFrame: after 90 minutes
measure: Changes in troponin T and creatine kinase MB levels
timeFrame: 7 days
measure: 90-Day mortality
timeFrame: 90 days
measure: 30-Day and 90-Day cardiovascular mortality
timeFrame: 30 and 90 days
measure: Frequency of the postinfarction complications
timeFrame: up to 30 days
measure: Frequency of the combined events "cardiovascular death + recurrent myocardial infarction + stroke" and "cardiovascular death + recurrent myocardial infarction + stroke + heart failure"
timeFrame: 30 days
Other outcomes:
measure: Frequency and severity of hemorrhagic complications
timeFrame: up to 30 days
measure: Incidence of the hemorrhagic stroke
timeFrame: up to 30 days
measure: Frequency and severity of the adverse drug reactions
timeFrame: up to 30 days
measure: Proportion of patients with the antidrug antibodies
timeFrame: 7 days
Locations:
city: Barnaul
country: Russian Federation
facility: Regional State Budgetary Health Institution "Regional Clinical Emergency Hospital"
state: Altai Territory
city: Barnaul
country: Russian Federation
facility: Regional State Budgetary Institution of Health Care "Altai Territorial Cardiology Dispensary"
state: Altai Territory
city: Arkhangel'sk
country: Russian Federation
facility: State Budgetary Institution of Health Care of the Arkhangelsk Region "First City Clinical Hospital named after E.E. Volosevich"
state: Arkhangelsk Region
city: Belgorod
country: Russian Federation
facility: Regional State Budgetary Health Institution "Belgorod Regional Clinical Hospital of St. Joasaph"
state: Belgorod Region
city: Perm
country: Russian Federation
facility: State Autonomous Healthcare Institution of the Perm Territory "City Clinical Hospital No. 4"
state: Perm Territory
city: Kazan
country: Russian Federation
facility: State Autonomous Healthcare Institution "Interregional Clinical and Diagnostic Center"
state: Republic Of Tatarstan
city: Rostov-on-Don
country: Russian Federation
facility: Municipal budgetary health care institution "City emergency hospital of the city of Rostov-on-Don"
state: Rostov Region
city: Ryazan'
country: Russian Federation
facility: State Budgetary Institution of the Ryazan Region "Regional Clinical Hospital"
state: Ryazan Region
city: Ekaterinburg
country: Russian Federation
facility: State budgetary health care institution of the Sverdlovsk region "Scientific and practical center for specialized types of medical care" Ural Institute of Cardiology "
state: Sverdlovsk Region
city: Volgograd
country: Russian Federation
facility: State Health Institution "City Clinical Emergency Hospital No. 25"
state: Volgograd Region
city: Yaroslavl
country: Russian Federation
facility: State Budgetary Health Institution of the Yaroslavl Region "Regional Clinical Hospital"
state: Yaroslavl Region
Study officials:
affiliation: AO GENERIUM
name: Oksana A. Markova, MD, MSc
role: STUDY_CHAIR
References: