A Multi-center, Randomized, Double-blind, Placebo-controlled, Phase II Clinical Trial to Assess the Efficacy and to Evaluate Safety of HT047 in Patients With Acute Ischemic Stroke
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 78
- 试验地点
- 8
- 主要终点
- Change at Week 12 of treatment with HT047 Tab. from baseline in Korean version of Fugl-Meyer Assessment (FMA) motor function score
研究概览
简要总结
To assess the efficacy and to evaluate safety of HT047 in patients with acute ischemic stroke
详细描述
This clinical study is designed to initiate treatment with high or low dose HT047 or placebo in subjects with acute ischemic stroke within 2 weeks of onset of the disease and evaluate neurological function recovery in these subjects as measured by the extent of motor function recovery at Week 12 of treatment.
Subjects must have had a recent onset of acute ischemic stroke as confirmed by brain imaging. In terms of symptoms of ischemic stroke, patients who have motor function impairment with FMA motor score ≤ 55 as well as neurological function impairment with K-NIHSS score ≥ 4 and ≤ 15 are eligible for study participation. A subject who is considered by the investigator to be appropriate for study participation and provides informed consent will participate in this study.
At baseline, subjects will be randomized to HT047 high dose group (2250 mg/day), HT047 low dose group (1500 mg/day), or placebo group in a 1:1:1 ratio in a double blind fashion and be treated with the investigational product for 12 weeks starting from the next morning of baseline with a three times a day dosing schedule, 3 tablets per dose.
Since this is a first-in-human trial for HT047, subjects will have a study visit at Week 1 (Day 7) of participation for laboratory tests, ECG, and chest x-ray. A one-month portion of the investigational product will be supplied. During study treatment, subjects will visit the hospital at Weeks 1, 4, 8, and 12.
During the Week 1 visit, the above tests will be performed and the subject's physical status will be checked before he/she is sent home. In the subsequent visits, neurological function assessment and drug exchange will be carried out. At each visit, the study staff should carefully check the subject's medication compliance and verify the accurate number of remaining doses to be countered.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult at the age of ≥ 19
- •Diagnosis of acute ischemic stroke by brain imaging within 14 days of screening
- •FMA motor score ≤ 55 with arm or leg weakness at screening
- •K-NIHSS score ≥ 4 and ≤ 15 at screening
- •Individuals who have visual and hearing abilities to perform the trial; who are able to understand the words and sentences necessary to evaluate the efficacy and safety, as well as the investigator's instructions; and who are able to communicate (such as gestures, writing, speaking, etc.)
- •Voluntary written informed consent to study participation
排除标准
- •Presence of motor function impairment, which is caused by previous stroke except acute ischemic stroke occurring within 14 days of screening (A subject with previous history of stroke may participate if he/she showed no motor function impairment and the K-mRS score was ≤1 (0-1))
- •Diagnosis of and current treatment for degenerative neurological diseases, e.g., Parkinson's disease and Alzheimer's disease
- •Current treatment with amphetamines, selective serotonin reuptake inhibitors, or antipsychotics
- •Presence of brain diseases, such as brain tumor, traumatic brain damage, arteriovenous malformation, or moyamoya disease, or ischemic stroke caused by these diseases
- •Impaired ability to walk upright due to other illness prior to screening
- •Unstable vital signs at screening based on the judgment of the investigator e.g., systolic blood pressure ≥ 170mmHg despite antihypertensive treatment or other symptoms such as hyperthermia, tachycardia, or hyperventilation
- •Diagnosis of liver diseases prior to screening, such as hepatitis and liver cirrhosis, or current treatment for these diseases
- •Continuous treatment with potentially hepatotoxic drugs e.g., current treatment with propylthiouracil, ketoconazole, isoniazid, valproic acid, phenytoin, etc. that may induce acute hepatotoxicity
- •Severe, New York Heart Association (NYHA) Class III or higher heart failure at screening [NYHA Classes of heart failure] Class I: patients with no limitation of activities; they suffer no symptoms from ordinary activities.
- •Class II: patients with slight, mild limitation of activity; they are comfortable with rest or with mild exertion.
- •Class III: patients with marked limitation of activity; they are comfortable only at rest.
- •Class IV: patients who should be at complete rest, confined to bed or chair; any physical activity brings on.
- •Diagnosis of or treatment for cancer within 6 months of screening or presence of recurrent or metastatic cancer
- •Treatment with or intake of traditional oriental medicine (herbal medicine) or health functional foods containing potentially hepatotoxic plants, such as Germander (Teucrium chamaedrys, Teucrium polium), toothed clubmoss (Lycopodium serratum), or celandine (Chelidonium majus), within 4 weeks prior to study participation
- •Treatment with or intake of traditional Korean medicine containing pueraria root and/or scutellaria root or other drugs or health functional foods containing their respective index components, i.e. puerarin and baicalin, within 4 weeks prior to study participation
- •Hematologic findings as follows
- •① Increased serum aspartate or alanine aminotransferase (AST/ALT) levels ≥ 1.5 x site specific upper limit of normal in laboratory test
- •② Decreased hemoglobin (Hb) level (Hb< 10 g/dl), decreased platelet (PLT) level (PLT< 100,000/mm3), or hematocrit (Hct) level < 25% in whole blood count test.
- •③ Increased serum creatinine (Cr) level (Cr > 2.0 mg/dl) in laboratory test or patient on dialysis
- •Pregnant or lactating women A woman of childbearing potential can participate in the study only if non-pregnancy is confirmed.
- •Subjects must use a double barrier method or must have been surgically sterilized.
- •Previous participation in a clinical study for another drug within 3 months of screening. A subject who participated in an observational study that did not involve drug treatment may participate in this study.
- •Individuals who are considered by the investigator to be inadequate for study participation due to other reasons.
研究组 & 干预措施
HT047 High-dose group
three times a day dosing schedule 3 tablets per dose
干预措施: HT047 High-dose group (Drug)
HT047 Low-dose group
three times a day dosing schedule 3 tablets per dose
干预措施: HT047 Low-dose group (Drug)
Placebo
three times a day dosing schedule 3 tablets per dose
干预措施: Placebo (Drug)
结局指标
主要结局
Change at Week 12 of treatment with HT047 Tab. from baseline in Korean version of Fugl-Meyer Assessment (FMA) motor function score
时间窗: 12 weeks
Total score of motor function test for upper extremity in 66 marks plus total score of motor function test for lower extremity in 34 marks is 100 marks.
次要结局
- Proportion of subjects with K-NIHSS score 0 - 2 at Week 12(12weeks)
- Proportion of subjects with K-mRS score 0, ≤ 1, and ≤ 2 at Week 12(12weeks)
- Change at Weeks 4, 8 and 12 from baseline in FMA motor function score(4weeks, 8weeks, 12 weeks)
- Change at Weeks 4, 8, and 12 from baseline in FMA motor function score according to the timing of treatment initiation after the onset of stroke.(4weeks, 8weeks, 12 weeks)
- Change at Weeks 4, 8, and 12 from baseline in FMA motor function score according to the presence of prognostic risk factors (hypertension, diabetes, dyslipidemia, etc.)(4weeks, 8weeks, 12 weeks)
- Change at Weeks 4 and 12 from baseline in Korean-National Institutes of Health Stroke Scale (K-NIHSS) scores(4weeks, 12 weeks)
- Change at Weeks 4 and 12 from baseline in Korean modified Rankin Scale (K-mRS) scores(4weeks, 12weeks)
- Change at Weeks 4 and 12 from baseline in Korean Modified Barthel Index (K-MBI) score(4weeks, 12weeks)
研究者
Hocheol Kim
Professor
Kyunghee University