Phase III Clinical Trial of rhTNK-tPA in Treating Acute Ischemic Stroke With Extended Time Window.

NCT ID: NCT07201688

Last Updated: 2025-12-16

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 890 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-11-30
• Study Completion Date: 2027-09-30

Brief Summary

This is a multicenter, randomized, double-blind, placebo-controlled Phase III clinical study designed to evaluate the efficacy of recombinant human tissue-type plasminogen activator variant (rhTNK-tPA) (0.25 mg/kg, maximum dose 25 mg) compared with placebo in patients with acute large vessel occlusive stroke who present within 4.5 to 24 hours of symptom onset. The study plans to enroll patients with acute large vessel occlusive stroke who present within 4.5 to 24 hours of symptom onset (including wake-up strokes and strokes without witnesses). A centralized 1:1 randomization will be adopted, and eligible participants will be randomly assigned to two groups: the experimental group will receive rhTNK-tPA at a dose of 0.25 mg/kg, while the placebo group will receive rhTNK-tPA placebo.

Detailed Description

This multicenter, randomized, double-blind, placebo-controlled Phase III clinical study aims to evaluate the efficacy of recombinant human tissue-type plasminogen activator variant (rhTNK-tPA) (0.25 mg/kg, maximum dose 25 mg) compared with placebo in patients with acute large vessel occlusive stroke who present within 4.5 to 24 hours of symptom onset. The study initially planned to enroll 890 patients, who would be randomly assigned to the experimental group (rhTNK-tPA group) or the control group (placebo group) at a 1:1 ratio. After an unblinded sample size re-estimation during the interim analysis, the maximum sample size could be adjusted to 1,300 patients.

Key characteristics of the primary study population include: age ≥ 18 years; time from symptom onset to treatment ranging from 4.5 hours to 24 hours; occlusion of the internal carotid artery, M1 or M2 segment of the middle cerebral artery confirmed by computed tomography angiography (CTA)/magnetic resonance angiography (MRA), which is the responsible vessel for the signs and symptoms of acute ischemic stroke; modified Rankin Scale (mRS) score ≤ 1 before symptom onset; baseline National Institutes of Health Stroke Scale (NIHSS) score ≥ 6; and presence of target mismatch on computed tomography perfusion (CTP) or magnetic resonance imaging (MRI) combined with magnetic resonance perfusion (MRP) (ischemic core volume < 70 mL, mismatch ratio ≥ 1.8, and mismatch volume ≥ 15 mL). Patients with a known allergy to rhTNK-tPA and those with contraindications to thrombolysis were excluded.

The entire study duration is approximately 90 days, including the screening period, treatment period, and follow-up period. The primary study endpoint is the proportion of participants with a modified Rankin Scale (mRS) score of 0-1 at the 90-day follow-up.

Conditions

Acute Ischemic Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Experimental Group

Receive rhTNK-tPA administration at 0.25mg/kg, with the maximum dose not exceeding 25mg.

Group Type: EXPERIMENTAL

rhTNK-tPA

Intervention Type: DRUG

Each vial should be dissolved in 3mL of sterile water for injection to prepare a drug solution with a concentration of 5.33mg/mL. Calculate the total drug amount based on the participant's actual body weight, measure the required volume of the drug solution, and ensure the maximum dose does not exceed 25mg. Administer as a single bolus intravenous injection, completing the injection within 5-10 seconds.

Placebo Group

Receive placebo treatment, administration method and dosage same as rhTNK-tPA

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

One vial is dissolved in 3mL of sterile water for injection. Calculate the total drug amount based on the participant's actual body weight, then measure the required volume of the drug solution. Administer as a single bolus intravenous injection, completing the injection within 5-10 seconds.

Interventions

rhTNK-tPA

Each vial should be dissolved in 3mL of sterile water for injection to prepare a drug solution with a concentration of 5.33mg/mL. Calculate the total drug amount based on the participant's actual body weight, measure the required volume of the drug solution, and ensure the maximum dose does not exceed 25mg. Administer as a single bolus intravenous injection, completing the injection within 5-10 seconds.

Intervention Type: DRUG

Placebo

One vial is dissolved in 3mL of sterile water for injection. Calculate the total drug amount based on the participant's actual body weight, then measure the required volume of the drug solution. Administer as a single bolus intravenous injection, completing the injection within 5-10 seconds.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Aged ≥ 18 years, regardless of gender;

2. Time from symptom onset to treatment is 4.5 - 24 hours(Including the boundary values.), including patients with wake-up stroke or stroke without witnesses; the time of symptom onset is defined as the "last known normal time";

3. Modified Rankin Scale (mRS) score ≤ 1 before stroke onset;

4. Baseline National Institutes of Health Stroke Scale (NIHSS) score ≥ 6;

5. Neuroimaging findings: occlusion of the internal carotid artery (ICA), M1 or M2 segment of the middle cerebral artery (MCA) confirmed by computed tomography angiography (CTA)/magnetic resonance angiography (MRA), which is the responsible vessel for the signs and symptoms of acute ischemic stroke; presence of target mismatch on computed tomography perfusion (CTP) or magnetic resonance imaging (MRI) + magnetic resonance perfusion (MRP) (ischemic core volume < 70 mL, mismatch ratio ≥ 1.8, mismatch volume ≥ 15 mL);

6. Voluntary signing of the informed consent form by the participant or their legal guardian.

Exclusion Criteria

1. Patients with known allergy to recombinant human tissue plasminogen activator (rhTNK-tPA);

2. Patients with an expected life expectancy of less than 1 year;

3. Patients with rapidly improving symptoms (which may indicate spontaneous recanalization), as determined by the investigator;

4. Patients with a score of > 2 on Item 1a (Level of Consciousness) of the National Institutes of Health Stroke Scale (NIHSS), or those who had a seizure at stroke onset, or had hemiplegia after seizure, or had other neurological/psychiatric disorders that rendered them unable or unwilling to cooperate;

5. Severe and persistent hypertension uncontrolled by medication ;

6. Blood glucose < 2.8 mmol/L or > 22.2 mmol/L;

7. Active internal bleeding with a high risk of hemorrhage;

8. Any known coagulation disorder;

9. Known platelet function defect or platelet count less than 100×10⁹/L;

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CSPC Mingfule Pharmaceutical (Guangzhou) Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Puyang Oilfield General Hospital

Puyang, Henan, China

Site Status: RECRUITING

Countries

China

Central Contacts

Clinical Trials Information Group officer

Role: CONTACT

ctr-contact@cspc.cn

031169085587

Facility Contacts

Yutie Zhao, Chief Physician

Role: primary

454981103@qq.com

13633935069

Other Identifiers

MK02-003

Identifier Type: -

Identifier Source: org_study_id