rhTNK-tPA for large-vessel ischemic stroke treated 4.5–24 hours after last seen normal

Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase III Clinical Trial of Recombinant Human TNK Tissue-Type Plasminogen Activator for Injection (rhTNK-tPA, Mingfule) in Intravenous Thrombolysis for Acute Ischemic Stroke With Extended Time Window (4.5-24 Hours After Onset).

This study will try whether a single IV dose of rhTNK-tPA helps adults with large-vessel ischemic stroke who present 4.5 to 24 hours after they were last seen normal, compared with a placebo.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 890 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: CSPC Mingfule Pharmaceutical (Guangzhou) Co., Ltd. (Industry-sponsored)
• Locations: 1 site (Puyang, Henan)
• Trial ID: NCT07201688 on ClinicalTrials.gov

What this trial studies

This is a multicenter, randomized, double-blind, placebo-controlled Phase III trial comparing a single IV dose of rhTNK-tPA (0.25 mg/kg, max 25 mg) to placebo in adults with acute large-vessel occlusive ischemic stroke presenting 4.5–24 hours after last known normal, including wake-up strokes. Eligible patients must have ICA or M1/M2 MCA occlusion on CTA/MRA and a target perfusion mismatch on CTP or MR perfusion (core < 70 mL, mismatch ratio ≥ 1.8, mismatch volume ≥ 15 mL), with baseline NIHSS ≥ 6 and premorbid mRS ≤ 1. Participants are centrally randomized 1:1 and the trial planned enrollment was 890 patients with a possible increase to 1,300 after an unblinded interim sample-size re-estimation. The primary goal is to compare clinical outcomes between rhTNK-tPA and placebo in this extended treatment window.

Who should consider this trial

Good fit: Adults aged 18 or older with acute large-vessel occlusive ischemic stroke (ICA or M1/M2) who present 4.5–24 hours after last seen normal, have NIHSS ≥ 6, premorbid mRS ≤ 1, and a target perfusion mismatch on CTP or MR perfusion are ideal candidates.

Not a fit: Patients outside the 4.5–24 hour window, without a confirmed large-vessel occlusion or target perfusion mismatch, with ischemic core > 70 mL, significant pre-stroke disability, or a known allergy to rhTNK-tPA are unlikely to benefit from this treatment.

Why it matters

Potential benefit: If successful, this approach could allow effective thrombolytic treatment for some large-vessel stroke patients presenting beyond the conventional 4.5-hour window and improve functional outcomes.

How similar studies have performed: Prior studies of tenecteplase and perfusion-selected interventions have suggested benefit in some acute stroke populations, but using rhTNK-tPA in a 4.5–24 hour perfusion-selected large-vessel cohort is a relatively novel application building on that evidence base.

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;

Where this trial is running

Puyang, Henan

• Puyang Oilfield General Hospital — Puyang, Henan, China (Recruiting)

Study contacts

• Study coordinator: Clinical Trials Information Group officer

Conditions Acute Ischemic Stroke