Clinical trial NCT04028518: A PhaseⅡ of Injection for Recombinant Human Tissue Plasminogen Kinase Derivative in Treatment of Acute Ischemic Stroke.
Official title: A PhaseⅡ, Multicenter, Prospective Randomised, Open Blinded Endpoint Study to Evaluate Safety and Efficacy of Injection for Recombinant Human Tissue Plasminogen Kinase Derivative in Treatment of Acute Ischemic Stroke.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Acute Ischemic Stroke
Lead sponsor: Angde Biotech Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
Collaborators: name: Beijing Tiantan Hospital
First posted: 2019-07-22
Enrollment: 180
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: 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 .

Detailed description: 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).

Eligibility criteria: 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.

Primary outcomes:
measure: The proportion of subjects with NIHSS score ≤1 or the decrease of 4 points or more from the baseline on the 14th day after treatment;
timeFrame: on the 14th day after treatment
Secondary outcomes:
measure: The proportion of subjects with NIHSS score ≤1 or the decrease of 4 points or more from the baseline at 72 hours after treatment;
timeFrame: at 72 hours after treatment;
measure: The proportion of subjects with mRS score of 0-1 on the 30th day and 90th day after treatment;
timeFrame: on the 30th day and 90th day after treatment;
measure: The proportion of subjects with mRS score of 0-2 on the 30th day and 90th day after treatment;
timeFrame: on the 30th day and 90th day after treatment;
measure: Continuous changes of mRS scores on the 30th and 90th days after treatment;
timeFrame: on the 30th and 90th days after treatment;
measure: The proportion of subjects with Barthel index score≥95 on the 30th day and 90th day after treatment;
timeFrame: on the 30th day and 90th day after treatment;
Other outcomes:
measure: Percentage of subjects with symptomatic intracranial hemorrhage (sICH);
timeFrame: within 36h after thrombolysis
measure: Mortality within 90 days after treatment;
timeFrame: within 90 days after treatment;
measure: The Proportion of subjects with adverse events/serious adverse events within 90 days after treatment.
timeFrame: within 90 days after treatment
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hospital, Capital Medical University
state: Beijing
Study officials:
References: