Evaluate the Efficacy and Safety of TTYP01 Tablets in the Treatment of Acute Ischemic Stroke

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: TTYP01 tablets; Drug: Placebo (Simulant TTYP01 Tablets)

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).

• Study Type: Interventional
• Enrollment (Actual): 614
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Chongqing
    • Chongqing, Chongqing, China, 400042
      • Daping Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TTYP01 tablets; 2 tablets (60 mg) of TTYP01, twice daily, administered 30~60 minutes before breakfast and dinner	Drug: TTYP01 tablets; Administered 30~60 minutes before breakfast and dinner (i.e., fasting state), bid. Subjects are given 2 tablets (60 mg) of investigational drug each time. The first administration should be administered within 1 hour after enrollment. If the subject is randomized in a fed state, the first administration may be administered in a non-fasting state. The interval between the first and second administration should be at least 6 hours, with continuous administration for 28 days (56 administrations).
Placebo Comparator: Placebo (Simulant TTYP01 Tablets); 2 tablets (0 mg) of placebo, twice daily, administered 30~60 minutes before breakfast and dinner	Drug: Placebo (Simulant TTYP01 Tablets); Administered 30~60 minutes before breakfast and dinner (i.e., fasting state), bid. Subjects are given 2 tablets (0 mg) of placebo each time. The first administration should be administered within 1 hour after enrollment. If the subject is randomized in a fed state, the first administration may be administered in a non-fasting state. The interval between the first and second administration should be at least 6 hours, with continuous administration for 28 days (56 administrations).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects with mRS score ≤1 on Day 90 of treatment.	The mRS (modified Rankin Scale) is a scoring system used to assess the ability of post-stroke patients in their daily lives. It assesses the degree of functional impairment of patients after stroke through a standardized questionnaire, and is one of the most widely used tools for assessing the sequelae of stroke internationally. The MRS scores range from 0 to 5, with higher scores indicating more severe disability in patients.	90 days after treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mRS score on Day 90 of treatment	The mRS (modified Rankin Scale) is a scoring system used to assess the ability of post-stroke patients in their daily lives. It assesses the degree of functional impairment of patients after stroke through a standardized questionnaire, and is one of the most widely used tools for assessing the sequelae of stroke internationally. The MRS scores range from 0 to 5, with higher scores indicating more severe disability in patients.	90 days after treatment initiation
Proportion of subjects with mRS score ≤2 on D90 of treatment	The mRS (modified Rankin Scale) is a scoring system used to assess the ability of post-stroke patients in their daily lives. It assesses the degree of functional impairment of patients after stroke through a standardized questionnaire, and is one of the most widely used tools for assessing the sequelae of stroke internationally. The MRS scores range from 0 to 5, with higher scores indicating more severe disability in patients.	90 days after treatment initiation
Change from baseline in mRS score on D7, D28, D60 and D90 of treatment	The mRS (modified Rankin Scale) is a scoring system used to assess the ability of post-stroke patients in their daily lives. It assesses the degree of functional impairment of patients after stroke through a standardized questionnaire, and is one of the most widely used tools for assessing the sequelae of stroke internationally. The MRS scores range from 0 to 5, with higher scores indicating more severe disability in patients.	Baseline and 7, 28, 60, 90 days after treatment initiation
Change in NIHSS score from baseline on D7, D28 and D90 of treatment	The NIHSS (National Institutes of Health Stroke Scale) is a standardized neurological examination tool used to assess neurological deficits in stroke patients. The scale consists of 15 tests and the total score is the sum of the individual scores ranges from 0 to 42, with lower scores indicating a better state of the patient.	Baseline and 7, 28, 90 days after treatment initiation
Proportion of patients with NIHSS score improvement ≥ 4 points on D7, D28, and D90 of treatment	The NIHSS (National Institutes of Health Stroke Scale) is a standardized neurological examination tool used to assess neurological deficits in stroke patients. The scale consists of 15 tests and the total score is the sum of the individual scores ranges from 0 to 42, with lower scores indicating a better state of the patient.	7, 28 and 90 days after treatment initiation
Proportion of subjects with NIHSS score of 0-1 on D7, D28 and D90 of treatment	The NIHSS (National Institutes of Health Stroke Scale) is a standardized neurological examination tool used to assess neurological deficits in stroke patients. The scale consists of 15 tests and the total score is the sum of the individual scores ranges from 0 to 42, with lower scores indicating a better state of the patient.	7, 28 and 90 days after treatment initiation
Change in BI score from baseline on D7, D28 and D90 of treatment	The BI (Barthel Index) is used to assess the patient's ability to perform activities of daily living and can be used to evaluate the patient's functional recovery before and after treatment, and it is one of the most widely used and researched methods of basic assessment of activities of daily living in clinical practice, with credible results. It is mainly based on the patient's actual daily performance and is not judged by the ability the patient may have. The BI scores range from 0 to 100, with higher scores indicating a better state of the patient.	Baseline and 7, 28, 90 days after treatment initiation
Proportion of subjects with BI score ≥ 95 points on D7, D28 and D90 of treatment	The BI (Barthel Index) is used to assess the patient's ability to perform activities of daily living and can be used to evaluate the patient's functional recovery before and after treatment, and it is one of the most widely used and researched methods of basic assessment of activities of daily living in clinical practice, with credible results. It is mainly based on the patient's actual daily performance and is not judged by the ability the patient may have. The BI scores range from 0 to 100, with higher scores indicating a better state of the patient.	7, 28 and 90 days after treatment initiation
MoCA score and comparison on D7, D28 and D90 of treatment	The MoCA (Montreal Cognitive Assessment) Scale is a rating tool used to provide rapid screening for cognitive dysfunction. It includes 11 screening items in 8 cognitive domains: attention and concentration, executive function, memory, language, visual structural skills, abstract thinking, calculation and orientation. The total score is 30, with ≥26 being normal; the lower the score, the more severe the cognitive impairment.	7, 28 and 90 days after treatment initiation
HDRS score and comparison on D7, D28 and D90 of treatment	The HDRS (Hamilton Depression Scale) was developed by Hamilton in 1960 and is the most commonly used scale for assessing depressive states in clinical settings. There are three versions of this scale: 17-item, 21-item and 24-item. The 21-item version was used for this Clinical Study, with a score range from 0 to 64. A score greater than 30 is severe depression, greater than 20 is moderate depression, and greater than 17 is mild depression.	7, 28 and 90 days after treatment initiation
Proportion of subjects with recurrent stroke within 90 days of treatment		within 90 days of treatment
Changes in cranial MRI findings (infarct volume) relative to baseline	Infarct volume will report in mm^3	Baseline and 5, 28 days after treatment initiation
Changes in cranial MRI findings (infarct area) relative to baseline	Infarct area will report in mm^2	Baseline and 5, 28 days after treatment initiation

Collaborators and Investigators

• Sponsor: Shanghai Auzone Biological Technology Co., Ltd.
• Investigators: Principal Investigator: Yan-Jiang Wang, MD & PhD, Daping Hospital and the Research Institute of Surgery of the Third Military Medical University

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2023
• Primary Completion (Actual): June 17, 2024
• Study Completion (Actual): June 17, 2024

Study Registration Dates

• First Submitted: October 15, 2024
• First Submitted That Met QC Criteria: October 16, 2024
• First Posted (Actual): October 18, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 30, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Brain Infarction; Brain Ischemia; Infarction; Necrosis; Ischemic Stroke; Stroke; Cerebral Infarction; Ischemia
• Other Study ID Numbers: TTYP01-III-AIS

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No