A PhaseⅡ of Injection for Recombinant Human Tissue Plasminogen Kinase Derivative in Treatment of Acute Ischemic Stroke.
A PhaseⅡ of Injection for Recombinant Human Tissue Plasminogen Kinase Derivative in Treatment of Acute Ischemic Stroke.
The primary purpose of this trial is to compare the efficacy of different doses of
 investigator product and comparator product in patients with acute ischemic stroke in 4.5
 Hours after stroke onset, and provide a basis of drug administration for phase Ⅲ clinical
 trial.

 The secondary purpose of this trial is to compare the safety of different dose of
 investigational product and comparator product in patients with acute ischemic stroke in 4.5
 hours afterstroke onset .
This study is a multicenter, prospective randomised, open blinded endpoint study.

 Patients with acute ischemic stroke need to undergo CT or MRI to exclude intracranial
 hemorrhage and perform NIHSS score before enrollment. Subjects who have passed the screening
 criteria according to the inclusion and exclusion criteria will be randomly assigned to
 low-dose test drugs, high-dose test drugs or reference drugs for thrombolytic therapy at a
 ratio of 1:1:1. The random stratification factor is the thrombolysis time window ("≤3h" vs
 "3~4.5h").

 The start of administration of the study drug is recorded as 0h, CT or MRI and NIHSS score,
 laboratory test, and electrocardiogram were performed at 24 hours; NIHSS score was performed
 at 72 hours; NIHSS score，laboratory test and electrocardiogram were performed on the14th
 day(the start of administration is recorded as Day 1 ,then the 14th day after administration
 should be recorded as Day 15 ); mRS score and Barthel index score were performed on the 30th
 day (Day 31); mRS score and Barthel index score were performed on the 90th day (Day 91).
Inclusion Criteria:

 -  Diagnosis of acute ischemic stroke according to the WHO (World Health Organization)
 stroke diagnostic criteria, and symptoms of stroke have existed for at least 30mins,
 and there is no significant improvement before treatment；

 -  The symptoms of acute ischemic stroke are expected to be less than 4.5 hours after the
 time of acute ischemic stroke which is defined as the last time the patient function
 well;

 -  NIHSS score at the time of treatment: from 4 points to 24 points (including 4 points
 and 24 points);

 -  From the signing of informed consent form to 3 months of the last dose should be the
 absence of a birth plan and willing to take effective contraceptive measures;

 -  Understand and follow the research process, voluntarily participate, and sign an
 informed consent form (informed consent is voluntarily signed by the person or legal
 representative).

 Exclusion Criteria:

 -  Weight >120kg;

 -  Imaging shows multiple cerebral infarction (low density > 1/3 brain hemisphere);

 -  The timing of stroke symptoms is not known;

 -  mRS score before stroke≥ 2 points;

 -  NIHSS score 1a (level of consciousness) ≥ 2 points during screening;

 -  CT/MRI imaging examination showed signs of intracranial hemorrhage or suspected
 subarachnoid hemorrhage despite CT/MRI imaging findings did not show abnormalities.

 -  Subjects have an acute bleeding tendency, including a platelet count of less than 100
 × 109 / L, application of heparin or oral anticoagulant drugs (such as warfarin)
 within 24 hours before onset , and an INR > 1.6;

 -  Patients who are ready to go or have undergone endovascular treatment;

 -  Patients who had severe trauma or major surgery in the last 3 months (according to the
 investigator's assessment);

 -  A stroke has occurred in the last 3 months; or has a history of any stroke with
 diabetes;

 -  Severe liver damage, including liver failure, cirrhosis, portal hypertension
 (esophageal varices), and active hepatitis;

 -  Other diseases lead to patients with an expected survival time of no more than one
 year;

 -  Hypertension remains uncontrolled after active antihypertensive therapy. Uncontrolled
 hypertension refers to a systolic blood pressure >185 mmHg and/or a diastolic blood
 pressure >110 mmHg measured at intervals of at least 10mins, repeated 3 times;

 -  Blood glucose <50 mg/dl (equivalent to 2.78mmol/L) or >400 mg/dl (equivalent to
 22.2mmol/L);

 -  Patients who are unable to cooperate or are unwilling to cooperate with epileptic
 seizures, or other mental illnesses during stroke episodes;

 -  Known to be allergic to research drugs or similar ingredients, or materials used in
 imaging studies;

 -  The restricted drug specified in the protocol or any drug that may interfere with the
 test results must be ingested or desired to continue to be ingested;

 -  Participating in other trials or has been participated in other trials within 30 days
 before randomization;

 -  Pregnancy or lactation, or women who have a positive pregnancy test result;

 -  The Subject who is unsuitable for this study in the opinion of the investigators.