The aim of the study is to determine if single-bolus recombinant nonimmunogenic staphylokinase is effective and save thrombolytic agent in with ischemic stroke in comparison to alteplase.
Experimental Drug Profile. The active substance of Fortelyzin is Forteplase. It`s recombinant protein which contains aminoacid sequence of staphylokinase. It is single chain molecula, consists of 138 aminoacids, weight 15.5 kDa. When staphylokinase is added to human plasma containing a fibrin clot, it preferentially reacts with plasmin at the clot surface, forming a plasmin-staphylokinase complex. This complex activates plasminogen trapped in the thrombus. The plasmin-staphylokinase complex and plasmin bound to fibrin are protected from inhibition by alpha2-antiplasmin. Once liberated from the clot (or generated in plasma), however, they are rapidly inhibited by alpha2-antiplasmin. This selectivity of action confines the process of plasminogen activation to the thrombus, preventing excessive plasmin generation, alpha2-antiplasmin depletion, and fibrinogen degradation in plasma. In rabbits anti forteplase antibodies are not produced. It was achieved by replacement of amino acids in immunogenic epitop of molecule staphylokinase. Blood fibrinogen decrease after i.v. injection of Fortelyzin less 10% within first 24 hours. Angiographic data suggests that restoration of coronary blood flow appears in up to 80% of patients with STEMI after i.v. injection of Fortelyzin.
Main goals of the study to prove an efficacy of the single-bolus intravenous injection of recombinant nonimmunogenic staphylokinase (Fortelyzin) in comparison with bolus infusion alteplase(Actilise) in patients with ischemic stroke.
Main goals of the study to prove an efficacy of the single-bolus intravenous injection of recombinant nonimmunogenic staphylokinase (Fortelyzin) in comparison with bolus infusion alteplase (Actilise) in patients with ischemic stroke.
to prove a safety and to assess possible adverse events in the single-bolus intravenous injection of recombinant nonimmunogenic staphylokinase (Fortelyzin) in comparison with bolus infusion alteplase (Actilise) in patients with ischemic stroke.
Study Design. All eligible patients will be randomized in two equal groups for administration recombinant nonimmunogenic staphylokinase (Fortelyzin) or alteplase (Actilise) by using "envelope method" of randomization. It is an open-lable study. Each of agents will be administered no longer then 4,5 hours from symptoms onset. Experimental and comparative agent will be administered as prescribed in its instructions.
Worsening of pre-existing conditions Expected fluctuations or expected deterioration of the underlying disease will not be recorded as an AE. Worsening of the disease under study will be recorded as an AE if one of the following criteria is met.
Worsening of disease meets the criteria for an SAE. Action is taken with investigational drug, i.e. dose is reduced or treatment discontinued or increased.
Treatment is required (concomitant medication is added or changed). The investigator believes a patient has shown a clear, unexpected deterioration from baseline symptoms.
The same criteria as above apply to recording of AEs resulting from worsening of other pre-existing conditions. Pre-existing conditions are not recorded as AEs if they do not meet the criteria above. Specifically, the following will not be recorded as an AE:
Pre-existing conditions present at baseline, which remain unchanged during the trial.
Vital Signs, ECG and Laboratory test results qualifying as AE Changes in safety tests including blood pressure, pulse rate, ECG and laboratory tests will be recorded as AEs, if:
they are not associated with an already reported AE, symptom or diagnosis and action is taken with the investigational drug, i.e. dose is reduced or treatment discontinued or treatment is required (concomitant medication is added or changed) An AE is defined as any untoward medical occurrence, including an exacerbation of a pre-existing condition, in a patient in a clinical investigation who received a pharmaceutical product. The event does not necessarily have to have a causal relationship with this treatment. All adverse events occurring during the course of the clinical trial (i.e., from signing the informed consent onwards through the observational phase) will be collected, documented and reported to the sponsor by the investigator. A SAE is defined as any AE which results in death, is immediately life-threatening, results in persistent or significant disability / incapacity, requires or prolongs patient hospitalisation, is a congenital anomaly / birth defect, or is to be deemed serious for any other reason representing a significant hazard, which is comparable to the aforementioned criteria. All serious adverse events and non-serious bleeds will be fully documented in the appropriate CRFs. For each adverse event, the investigator will provide the onset, end, intensity, treatment required, outcome, seriousness and action taken with the investigational drug. The investigator will determine the relationship of the investigational drug to all AE as defined in the 'Adverse Event Reporting' section of the Investigator Site File. The basis for judging the intensity of the AE as well as the causal relationship between the investigational product and the AE is described below. Intensity of event Mild: Awareness of sign(s) or symptom(s) which is/are easily tolerated Moderate: Enough discomfort to cause interference with usual activity Severe: Incapacitating or causing inability to work or to perform usual activities
- Alteplase Drug
Intervention Desc: Intravenous alteplase 0.9 mg/kg (10% bolus and 90% as IV infusion over 1 hour, maximum 90 mg) ARM 1: Kind: Experimental Label: Actilise Description: Intravenous alteplase 0.9 mg/kg (10% bolus and 90% as IV infusion over 1 hour, maximum 90 mg)
- Recombinant staphylokinase Drug
Other Names: Fortelyzin Intervention Desc: 15 mg of drug reconstituted in 15 ml of 0.9% solution of NaCl given as single i.v. bolus over 5 - 10 seconds ARM 1: Kind: Experimental Label: Recombinant staphylokinase Description: Lyophilizate for solution making for intravenous injection, 5 mg (745000 ME). 15 mg of drug reconstituted in 15 ml of 0.9% solution of NaCl given as single i.v. bolus over 5 - 10 seconds
|Type||Measure||Time Frame||Safety Issue|
|Primary||Good functional recovery||within 90 days after fibrinolysis|
|Secondary||Modified Rankin scale + NIHSS + Barthel||within 90 days after fibrinolysis|
|Secondary||NIHSS||after 24 hours|
|Secondary||All Cause Death||within 90 days after fibrinolysis|
|Secondary||Hemorrhagic transformation||within 90 days after fibrinolysis|
|Secondary||Symptomatic hemorrhagic transformation||within 90 days after fibrinolysis|
- Supergene, LLC Lead