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

NCT07201688 | Recruiting Phase 3 DMC

• 1 other identifier: MK02-003
• Study Type: interventional
• Target: 890
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Ischemic Stroke

Outcome Measures

Primary Outcomes (1)

• The proportion of participants with a score of 0-1 on the modified Rankin Scale (mRS)

  The modified Rankin Scale (mRS) is used to assess the status of neurological function recovery in patients after stroke. By evaluating the independence of patients in daily activities, it classifies functional levels into grades 0-6 (Grade 0 indicates no symptoms at all, Grades 1-5 correspond to functional impairments ranging from mild to severe, and Grade 6 indicates death).

  At Day90.

Secondary Outcomes (12)

• Incidence of symptomatic intracerebral hemorrhage within 36 hours after randomization

  36 Hours after Randomization

• Overall mortality rate at Day 90.

  At Day90.

• Incidence of significant systemic hemorrhage (moderate to severe per GUSTO classification) at Day 90.

  At Day90.

• Proportion of adverse events (AEs)/serious adverse events (SAEs) at Day 90.

  At Day90.

• Modified Rankin Scale (mRS) score at Day 90 (shift analysis).

  At Day90.

Study Arms (2)

Experimental Group

EXPERIMENTAL

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

Drug: rhTNK-tPA

Placebo Group

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

rhTNK-tPA 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.

Experimental Group

Placebo 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.

Placebo Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥ 18 years, regardless of gender;
• 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";
• Modified Rankin Scale (mRS) score ≤ 1 before stroke onset;
• Baseline National Institutes of Health Stroke Scale (NIHSS) score ≥ 6;
• 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);
• Voluntary signing of the informed consent form by the participant or their legal guardian.

You may not qualify if:

• Patients with known allergy to recombinant human tissue plasminogen activator (rhTNK-tPA);
• Patients with an expected life expectancy of less than 1 year;
• Patients with rapidly improving symptoms (which may indicate spontaneous recanalization), as determined by the investigator;
• 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;
• Severe and persistent hypertension uncontrolled by medication ;
• Blood glucose \< 2.8 mmol/L or \> 22.2 mmol/L;
• Active internal bleeding with a high risk of hemorrhage;
• Any known coagulation disorder;
• Known platelet function defect or platelet count less than 100×10⁹/L;

Sponsors & Collaborators

• CSPC Mingfule Pharmaceutical (Guangzhou) Co., Ltd.: lead

Study Sites (1)

Puyang Oilfield General Hospital

Puyang, Henan, 457001, China

RECRUITING

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Central Study Contacts

Clinical Trials Information Group officer

CONTACT

031169085587; ctr-contact@cspc.cn

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Eligible subjects were centrally randomized at a 1:1 ratio to receive either rhTNK-Tpa or placebo treatment, with the two groups proceeding simultaneously and without mutual interference.

Study Record Dates

• First Submitted: September 22, 2025
• First Posted: October 1, 2025
• Study Start: November 30, 2025
• Primary Completion (Estimated): September 30, 2027
• Study Completion (Estimated): September 30, 2027
• Last Updated: December 16, 2025

Record last verified: 2025-11

Locations

CN (1)