A Prospective, Randomized, Double-blind Phase 2b Clinical Trial to Investigate the Efficacy and Safety of SP-8203 in Patients With Acute Ischemic Stroke Requiring Recombinant Tissue Plasminogen Activator (rtPA) Standard of Care
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 178
- 试验地点
- 1
- 主要终点
- The neurological improvement evaluated by the National Institute of Health Stroke Scale (NIHSS)
研究概览
简要总结
This clinical trial is designed to evaluate the efficacy and safety of the combination therapy of SP-8203 (Otaplimastat) and recombinant tissue Plasminogen Activator (rtPA) standard of care. In this clinical trial, rtPA will be injected intravenously using an infusion device. If reperfusion is not occur in spite of rtPA therapy, endovascular therapy can be performed.
详细描述
This clinical trial is designed to evaluate the efficacy and safety of the combination therapy of SP-8203 and rtPA in patients with acute ischemic stroke receiving rtPA standard of care.
As the standard procedure of rtPA therapy, rtPA will be injected intravenously using an infusion device. When reperfusion is not achieved in spite of rtPA therapy, endovascular therapy can be performed according to the judgment of a site investigator.
A total of 178 subjects will be enrolled in double-blind, randomized and parallel design with 89 subjects assigned to 80 mg/day SP-8203 group or placebo group, respectively.
If a subject, who is able to be enrolled, has neurologic deficit of ≥4 point on the National Institute of Health Stroke Scale (NIHSS) score and give his/her consent to participate in the trial, each treatment is administered after the investigational product is randomly assigned by institution after sequential allocation. The randomization number of patients is the same as the assigned number of the investigational product administered to the patients. The subject will receive the Investigational products a total of 6 times, with 12 hours intervals. Only for the patients who consent, blood sample will be taken after the sixth administration of the Investigational product for pharmacokinetic and pharmacodynamics analysis. For pharmacokinetic profile analysis, blood sample will be taken at 0~5, 30±5, and 120±5 minutes after the complete sixth administration of the investigational products. For pharmacodynamic profile analysis, blood sample will be taken at between 24 to 48 hours after the first administration, at 0 minute after the sixth administration and at 4th week visit. The first blood sampling time is set to after 24 hours because of the patient's stability, but it can be performed before the investigational product has been administered in accordance with the judgment of the investigators.
The subject will have brain initial Magnetic Resonance Imaging (MRI) and Magnetic Resonance Angiography (MRA) performed within 6 hours before and after the administration of investigational product, and brain Computed Tomography (CT) will be performed at 24±3 hours after completion of the first administration of investigational products.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 19 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with neurologic deficit of ≥ 4 points by NIHSS score
- •Adults aged ≥19 years and ≤85 years. (Pre-stroke mRS must be 0 or 1; No significant pre-stroke disability)
- •Subjects who can receive rtPA therapy within 4.5 hours after the onset of early symptoms of acute ischemic stroke.
- •Subjects available for brain MRI (DWI, GRE/Susceptibility Weighted Imaging (SWI), FLAIR, MRA) scanning
- •Subjects who consent to participate in this trial.
排除标准
- •Patients with systemic allergic diseases or hypersensitivity to specific drugs.
- •Patients who were diagnosed with myocardial infarction (MI) within the last 6 months.
- •Patients who had arrhythmia causing clinical symptoms such as dyspnea or palpitation within the last 6 months.
- •Patients showing the following abnormal ECG findings in stable condition at Emergency Room:
- •The range of pulse rate - under 55/min or exceed 120/min
- •2nd or 3rd degree Atrioventricular (AV) block indicated in ECG
- •Congenital or acquired QT syndrome indicated in ECG
- •Pre-excitation syndrome indicated in ECG
- •Patients with severe heart failure of New York Heart Association (NYHA) Class III or Class IV.
- •Patients with fever (≥ 38℃) or infection signs which require antibiotic therapy at screening.
- •Patients with pulmonary diseases (asthma, Chronic Obstruction Pulmonary disease, and active tuberculosis etc.) who have being recently been treated more than 1 month at screening.
- •Patients with decreased hemoglobin (Hb< 10g/dL), decreased platelet count (PLT< 100,000/mm3) or hematocrit of <25% in complete blood count.
- •Patients who have undergone hemodialysis and/or treatments due to nephropathies, acute or chronic renal failure at screening.
- •Patients with a cancer in following conditions: diagnosed within 6 months before the screening time, or any treatment for cancer within the previous 6 months, or with recurrent/ metastatic cancer.
- •Pregnant and lactating women. However, women of childbearing age can participate in the trial only when non-pregnancy is confirmed. Woman of childbearing age is defined as woman who is not definitely menopause and did not receive a surgical contraception.
- •Patients who do not consent to use double barrier contraception during the trial period.
- •Patients who have participated in other clinical trials of other drugs within the past 3 months. However, if they participated in observational studies and did not take drugs, they can participate in this trial.
- •Patients who cannot participate in the trial according to the judgment of investigators.
- •Those who cannot be administered with rtPA.
研究组 & 干预措施
SP-8203
SP-8203 80 mg (40 mg/dose twice a day for three days)
干预措施: SP-8203 (Drug)
Placebo
Placebo group: twice a day for three days
干预措施: Placebo (Drug)
结局指标
主要结局
The neurological improvement evaluated by the National Institute of Health Stroke Scale (NIHSS)
时间窗: Change from 0 day at 28 days
The neurological improvement evaluated by the National Institute of Health Stroke Scale (NIHSS) until 28 day in subjects with acute ischemic stroke requiring rtPA (recombinant tissue Plasminogen Activator) standard of care. The maximum total score is 42 points, which indicates the most critical condition and the minimum total score is 0, which indicates no neurologic deficit.
次要结局
- Incidence of parenchymal hematoma observed on brain Computed Tomography (CT) scan(Day 1)
- The number of occurrence and volume of intracranial hemorrhage classified by mTICI grade within 5 days(Day 5)
- The Incidence of major systemic bleeding(within 5 days of administration)
- The fold change of infarct growth classified by modified Treatment in Cerebral Ischemia (mTICI) grade within 5 days(Day 5)
- The incidence of serious adverse events(follow-up to 30 days after the last visit)
- The difference in the distribution of modified Rankin Scale (mRS) scores(Day 90)
- The change in the National Institute of Health Stroke Scale (NIHSS) scores(Change from 0 day at 90 days)
- The change in Barthel index(Change from 0 day at 90 days)
- The rate of death(follow-up to 30 days after the last visit)
- The incidence rate of adverse events, and adverse drug reaction(follow-up to 30 days after the last visit)
- The incidence of symptomatic Intracranial Hemorrhage (sICH)(within 5 days of administration)