Clinical trial NCT06648304: Evaluate the Efficacy and Safety of TTYP01 Tablets in the Treatment of Acute Ischemic Stroke
Official title: A Randomized, Double-blind, Placebo-controlled, Multicenter Phase III Clinical Trial to Evaluate the Efficacy and Safety of TTYP01 Tablets in the Treatment of Acute Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Acute Ischemic Stroke
Lead sponsor: Shanghai Auzone Biological Technology Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-10-18
Enrollment: 614
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study is designed as a multi-center, randomized, double-blind, parallel, placebo-controlled trial to evaluate the efficacy and safety of TTYP01 tablets in the treatment of acute ischemic stroke.

Detailed description: A multicenter, randomized, double-blind, parallel, placebo-controlled trial design is used to evaluate the efficacy and safety of TTYP01 tablets in the treatment of patients with acute ischemic stroke.

It is estimated that 618 patients will be enrolled and randomly assigned to the treatment group and the placebo control group in a 1:1 ratio, with 309 patients in each group. Normally, the duration of this study is approximately 90 days. This study will be divided into 2 periods, with a total of five visits: Treatment observation period: D1 \~ D28 (the minimum length of in-hospital observation will be not less than 7 days), including 3 visits (V1- V3); follow-up period: D29 \~ D90, including 2 visits (V4: D60 ± 5 for telephone follow-up; V5: D90 ± 5, returning to hospital for end-of-study visit).

Eligibility criteria: Inclusion Criteria:

Subjects eligible for enrollment in the study must meet all of the following inclusion criteria:

1. Patients aged 18 \~ 80 years (both inclusive);
2. Patients diagnosed with acute ischemic stroke according to the 2019AHA/ASA guidelines for ischemic stroke;
3. Patients who do not accept suggestions of thrombolysis or thrombectomy or who do not meet the indications for these treatments;
4. Patients with symptom onset within ≤ 24 hours; for wake-up strokes or when the exact time of symptom onset cannot be determined due to aphasia or disturbance of consciousness, the last time the patient is seen to be normal shall prevail;
5. Patients who are having their first stroke or those who are experiencing a recurrence of stoke after a good recovery (mRS score of 0-1) from their most recent stroke;
6. There are clear signs of neurological deficit: 6≤NIHSS score≤20, and also, the sum of NIHSS score for the 5th upper limb and the 6th lower limb is greater than or equal to 2.
7. Subjects or their guardians are informed about the study, voluntarily agree to the participation, and provide written informed consent.

Exclusion Criteria:

Subjects who meet any of the following criteria will be excluded from the study:

1. Patients with any contraindications (such as metal implants like cardiac pacemakers, claustrophobia, etc.) that prevent them from undergoing CT or MRI examinations;
2. Cranial CT or MRI confirmed intracranial hemorrhagic conditions, including but not limited to cerebral hemorrhage, epidural hematoma, subdural hematoma, intracranial hematoma, ventricular hemorrhage, subarachnoid hemorrhage, and traumatic cerebral hemorrhage; or cases of cerebral infarction with post-infarction hemorrhagic transformation. In cases of minor oozing, the investigator will determine eligibility for enrollment;
3. Patients with massive cerebral infarction (low density \> 1/3 of the cerebral hemisphere) as indicated by imaging examinations such as CT or MRI;
4. Patients with cerebral infarction accompanied by disturbance of consciousness (NIHSS score Ia \> 1 point), posterior circulation infarction, or transient ischemic attack (TIA);
5. Patients with severe mental disorders, depression, or comorbid conditions affecting cognitive function, such as Alzheimer's disease, Parkinson's dementia, or Lewy body dementia, making them unable or unwilling to cooperate with the study;
6. Patients who are scheduled for or have received intravenous thrombolysis, or who require endovascular treatment in the immediate or recent future (within 90 days);
7. Patients with a history of brain malignant tumors or brain parasitic diseases;
8. Patients with a history of severe craniocerebral injury or intracranial infection and an mRS score \> 1 prior to this episode;
9. Patients with severe hypertension (systolic blood pressure ≥ 220 mmHg or diastolic blood pressure ≥ 120 mmHg) that is uncontrolled by treatment before the first dose;
10. Patients with blood glucose levels below 2.7 mmol/L without correction or above 22.2 mmol/L at the time of admission;
11. Patients with dysphagia;
12. Patients with a history of rheumatic heart disease or atrial fibrillation; those with a heart rate of less than 40 beats per minute or greater than 120 beats per minute; patients with second or third-degree heart block without a pacemaker or other malignant arrhythmias; and patients who have experienced acute myocardial infarction, cardiac intervention, or heart failure within the past 6 months (classified by the New York Heart Association \[NYHA\] as III-IV).
13. Patients with other serious systemic or organ diseases that the investigators believe may hinder the evaluation of efficacy or make it unlikely for the patient to complete the expected course of treatment and follow-up (such as malignant tumors with a life expectancy of less than 3 months, etc.).;
14. Patients with severe liver and kidney diseases or abnormal renal and liver function tests (alanine aminotransferase \[ALT\] or aspartate aminotransferase \[AST\] ≥ 3.0 times the upper limit of normal \[ULN\]; serum creatinine \[Cr\] \> 2.0 times the ULN);
15. Patients with a bleeding tendency, including platelet count (PLT) less than 75.0×10\^9/L, or severe bleeding within the 3 months prior to the onset of the disease.
16. Patients with contraindications to antiplatelet therapy or statin therapy;
17. Patients with allergic constitution, hypersensitivity to Edaravone or its excipients;
18. Patients with suspected or confirmed history of alcohol or drug abuse;
19. Patients who are pregnant, lactating or have a recent pregnancy plan and are unwilling to use contraception;
20. Patients who have participated in other clinical trials within 3 months or are participating in other clinical studies prior to this study;
21. Patients who are deemed unsuitable by the investigator for participation in the clinical trial.

Primary outcomes:
measure: Proportion of subjects with mRS score ≤1 on Day 90 of treatment.
timeFrame: 90 days after treatment initiation
Secondary outcomes:
measure: mRS score on Day 90 of treatment
timeFrame: 90 days after treatment initiation
measure: Proportion of subjects with mRS score ≤2 on D90 of treatment
timeFrame: 90 days after treatment initiation
measure: Change from baseline in mRS score on D7, D28, D60 and D90 of treatment
timeFrame: Baseline and 7, 28, 60, 90 days after treatment initiation
measure: Change in NIHSS score from baseline on D7, D28 and D90 of treatment
timeFrame: Baseline and 7, 28, 90 days after treatment initiation
measure: Proportion of patients with NIHSS score improvement ≥ 4 points on D7, D28, and D90 of treatment
timeFrame: 7, 28 and 90 days after treatment initiation
measure: Proportion of subjects with NIHSS score of 0-1 on D7, D28 and D90 of treatment
timeFrame: 7, 28 and 90 days after treatment initiation
measure: Change in BI score from baseline on D7, D28 and D90 of treatment
timeFrame: Baseline and 7, 28, 90 days after treatment initiation
measure: Proportion of subjects with BI score ≥ 95 points on D7, D28 and D90 of treatment
timeFrame: 7, 28 and 90 days after treatment initiation
measure: MoCA score and comparison on D7, D28 and D90 of treatment
timeFrame: 7, 28 and 90 days after treatment initiation
measure: HDRS score and comparison on D7, D28 and D90 of treatment
timeFrame: 7, 28 and 90 days after treatment initiation
measure: Proportion of subjects with recurrent stroke within 90 days of treatment
timeFrame: within 90 days of treatment
measure: Changes in cranial MRI findings (infarct volume) relative to baseline
timeFrame: Baseline and 5, 28 days after treatment initiation
measure: Changes in cranial MRI findings (infarct area) relative to baseline
timeFrame: Baseline and 5, 28 days after treatment initiation
Other outcomes:
Locations:
city: Chongqing
country: China
facility: Daping Hospital
state: Chongqing
Study officials:
affiliation: Daping Hospital and the Research Institute of Surgery of the Third Military Medical University
name: Yan-Jiang Wang, MD & PhD
role: PRINCIPAL_INVESTIGATOR
References: