Mingfule (recombinant human TNK tissue-type plasminogen activator) / CSPC Pharma - LARVOL DELTA

Effect of Baseline ASPECTS on Tenecteplase Efficacy Before Thrombectomy in Acute Large-Vessel Occlusion Stroke: A Post Hoc Analysis of the BRIDGE-TNK Randomized Trial. (PubMed, Neurology) - P2/3 | "In this exploratory post hoc analysis, a signal of benefit was observed in patients with ASPECTS <8 who received intravenous tenecteplase before thrombectomy, whereas no functional improvement and possible safety concerns were seen in those with ASPECTS 8-10. Prospective confirmation in randomized trials is required before practice change."

Clinical • Journal • Retrospective data • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders

Tenecteplase (TNK) and other TNK formulations lose PAI-1 resistance in their two-chain form: Comparison with alteplase. (PubMed, Blood Adv) - "Alteplase and four TNK formulations: Metalyse (Boehringer Ingelheim), Tenectase (Gennova, India), GenetPA (BioApower, China) and Mingfule (CSPC, China) were compared in their native state and after two-chain conversion. However, after two-chain conversion, all TNK formulations showed similar fibrinolytic activity albeit with substantially reduced PAI-1 resistance. Metalyse and all new TNK formulations display similar fibrinolytic activity in their fully active two-chain states, but this is associated with substantial loss of PAI-1 resistance, challenging the view that the fully active two-chain form of TNK maintains PAI-1 resistance during thrombolysis."

Journal

Observational Study to Assess the Safety of rhTNK-tPA (Mingfule®) vs. Rt-PA (Actilyse®) in Treating Acute Ischemic Stroke (clinicaltrials.gov) - P=N/A | N=4500 | Not yet recruiting | Sponsor: CSPC Mingfule Pharmaceutical (Guangzhou) Co., Ltd.

New trial • Cardiovascular • Ischemic stroke

Phase III Clinical Trial of rhTNK-tPA in Treating Acute Ischemic Stroke With Extended Time Window. (clinicaltrials.gov) - P3 | N=890 | Recruiting | Sponsor: CSPC Mingfule Pharmaceutical (Guangzhou) Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Ischemic stroke

Cost-Effectiveness of rhTNK-tPA vs. rt-PA for Acute Ischemic Stroke Patients Within 4.5H of Symptom Onset in China (ISPOR-EU 2025) - "OBJECTIVES: To assess the cost-effectiveness of recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) compared to alteplase (rt-PA) for intravenous thrombolysis in acute ischemic stroke (AIS) patients within 4.5 hours of symptom onset, from the perspective of the healthcare system. A decision tree-Markov model was developed to estimate quality-adjusted life years (QALYs), direct medical costs, and incremental cost-effectiveness ratios (ICERs) for AIS patients receiving thrombolytic agent. From the perspective of Chinese healthcare system, we conclude that compared to the rt-PA regimen, rhTNK-tPA is a cost-effective option for acute ischemic stroke patients."

Clinical • Cost effectiveness • HEOR • Cardiovascular • Ischemic stroke

A multicenter, prospective, randomized, open-label, blinded endpoint trial of intravenous thrombolysis with tenecteplase for acute non-large vessel occlusion in extended time window (OPTION): Rationale and design. (PubMed, J Transl Int Med) - P4 | "Recombinant human tenecteplase (TNK) tissue-type plasminogen activator (rhTNK-tPA, also named tenecteplase) is non-inferior to alteplase when given up to 4.5 hours after acute ischemic stroke (AIS) within 4.5 hours. Safety outcomes include symptomatic intracranial hemorrhage within 36 hours, systemic bleeding within 90 days, and mortality within 90 days. The OPTION trial (NCT05752916) will provide evidence regarding the efficacy and safety of tenecteplase 4.5 to 24 hours in patients with AIS due to non-LVO."

Journal • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Ischemic stroke

Phase III Clinical Trial of rhTNK-tPA in Treating Acute Ischemic Stroke With Extended Time Window. (clinicaltrials.gov) - P3 | N=890 | Not yet recruiting | Sponsor: CSPC Mingfule Pharmaceutical (Guangzhou) Co., Ltd.

New P3 trial • Cardiovascular • Ischemic stroke

TRACE-5: Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-5 (clinicaltrials.gov) - P3 | N=452 | Completed | Sponsor: Beijing Tiantan Hospital | Recruiting ➔ Completed | Trial completion date: May 2026 ➔ Sep 2025 | Trial primary completion date: Feb 2026 ➔ Sep 2025

Trial completion • Trial completion date • Trial primary completion date • Cardiovascular • Ischemic stroke

Teneteplase Reperfusion Therapy in Acute Ischemic Cerebrovascular Events-Ⅳ (clinicaltrials.gov) - P3 | N=1386 | Not yet recruiting | Sponsor: Beijing Tiantan Hospital | Trial completion date: Dec 2025 ➔ Oct 2026 | Trial primary completion date: Jul 2025 ➔ Jul 2026

Trial completion date • Trial primary completion date • Cardiovascular • Ischemic stroke

A MULTICENTER, PROSPECTIVE, RANDOMIZED, OPEN-LABEL, BLINDED-ENDPOINT TRIAL OF TENECTEPLASE FOR ACUTE NON-LARGE VESSEL OCCLUSION IN EXTENDED TIME WINDOW (OPTION): RATIONALE AND DESIGN (ESOC 2025) - P4 | "Background and Aims: Intravenous thrombolysis, the standard of care for acute ischemic stroke (AIS) within 4.5 hours of symptom onset, is generally not offered to patients presenting beyond this time window. This pivotal trial will provide evidence in support of the concept that AIS due to non-LVO and a salvageable brain pattern selected with advanced imaging, benefit from intravenous rhTNK-tPA in the extended time window. (Trial registration: NCT05752916) Figure. Study Flow Chart"

Clinical • Cardiovascular • Ischemic stroke

BRIDGE TNK: A RANDOMIZED TRIAL OF INTRAVENOUS TENECTEPLASE PLUS ENDOVASCULAR THROMBECTOMY VERSUS ENDOVASCULAR THROMBECTOMY ALONE FOR ACUTE ISCHEMIC STROKE (ESOC 2025) - "Tenecteplase (TNK), a recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA), is a genetically modified variant of alteplase. BRIDGE TNK randomized 554 patients between May 9, 2022, and September 8, 2024. We expect that the statistical results will be completed in February 2025."

Clinical • Late-breaking abstract • Cardiovascular • Ischemic stroke

Intravenous rhTNK-tPA Before Stroke Thrombectomy in the Extended Time Window (clinicaltrials.gov) - P3 | N=820 | Not yet recruiting | Sponsor: Xinqiao Hospital of Chongqing

New P3 trial • Cardiovascular • Ischemic stroke

H2-THROMBUS: Intracoronary rhTNK-tPA Versus Tirofiban in Patients With STEMI and High Thrombus Burden (clinicaltrials.gov) - P4 | N=300 | Recruiting | Sponsor: Henan Institute of Cardiovascular Epidemiology | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Congestive Heart Failure • Myocardial Infarction • Thrombosis

BRIDGE-TNK: Endovascular Treatment With Versus Without Intravenous rhTNK-tPA in Stroke (clinicaltrials.gov) - P2/3 | N=550 | Completed | Sponsor: Xinqiao Hospital of Chongqing | Recruiting ➔ Completed | Trial completion date: Mar 2026 ➔ Feb 2025 | Trial primary completion date: Dec 2025 ➔ Dec 2024

Trial completion • Trial completion date • Trial primary completion date • Cardiovascular • Ischemic stroke

Minimally Invasive Surgery and RhTNK-tPA for Intracerebral Hemorrhage Evacuation (clinicaltrials.gov) - P1 | N=12 | Completed | Sponsor: Beijing Tiantan Hospital | Not yet recruiting ➔ Completed | N=18 ➔ 12

Enrollment change • Trial completion • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Hypertension • Vascular Neurology

RhTNK-tPA Thrombolytic Removal of Intraventricular Hemorrhage (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: Beijing Tiantan Hospital

New P1 trial • Hematological Disorders

the efficacy and satety of Recombinant human TNK tissue type plasminogen activator injection for acte ischemic stroke patient within time window: a multi-center, real-world clinical trial . (ChiCTR) - P4 | N=1000 | Recruiting | Sponsor: China-Japan Union Hospital of Jilin Universtiy; China-Japan Union Hospital of Jilin Universtiy

New P4 trial • Cardiovascular • Ischemic stroke

H2-THROMBUS: Intracoronary rhTNK-tPA Versus Tirofiban in Patients With STEMI and High Thrombus Burden (clinicaltrials.gov) - P4 | N=300 | Not yet recruiting | Sponsor: Henan Institute of Cardiovascular Epidemiology

New P4 trial • Cardiovascular • Congestive Heart Failure • Myocardial Infarction • Thrombosis

Efficacy and Safety of Intravenous Tenecteplase Before Endovascular Thrombectomy for Acute Ischemic Stroke: The Multicenter, Randomized, BRIDGE-TNK Trial Protocol. (PubMed, J Am Heart Assoc) - P2/3 | "BRIDGE-TNK will provide important data on the role of intravenous tenecteplase before endovascular thrombectomy in patients with acute ischemic stroke with large-vessel occlusion who can be treated within 4.5 hours of last known well."

Journal • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Ischemic stroke

Tenecteplase vs Alteplase in Acute Ischemic Stroke Within 4.5 Hours: A Systematic Review and Meta-Analysis of Randomized Trials. (PubMed, Neurology) - "The updated meta-analysis confirms similar safety between TNK 0.25 mg/kg and TPA, while showing that TNK is superior to TPA regarding excellent functional outcome and reduced disability at 3 months. These findings support transitioning to TNK in clinical practice."

Clinical • Journal • Retrospective data • Review • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Ischemic stroke

The efficacy and safety of intra-arterial recombinant human TNK tissue-type plasminogen activator (rhTNK-tPA) thrombolysis for acute medium vessel occlusion: a pilot randomized controlled trial (ChiCTR) - P=N/A | N=60 | Not yet recruiting | Sponsor: Tongji Medical College, Huazhong University of Science and Technology; Tongji Hospital, Tongji Medical College, Huazhong University of Science and Tec

New trial • Cardiovascular

Cost-Effectiveness of rhTNK-tPA Versus rt-PA for Acute Ischemic Stroke Patients With 4.5H of Symptom Onset in China (ISPOR-EU 2024) - "From the perspective of Chinese national healthcare system, we conclude that compared to the rt-PA regimen, rhTNK-tPA is a cost-effective option for acute ischemic stroke patients."

Clinical • Cost effectiveness • HEOR • Cardiovascular • Ischemic stroke

Minimally Invasive Surgery and RhTNK-tPA for Intracerebral Hemorrhage Evacuation (clinicaltrials.gov) - P1 | N=18 | Not yet recruiting | Sponsor: Beijing Tiantan Hospital

New P1 trial • Surgery • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Hypertension • Vascular Neurology

Intravenous Tenecteplase Plus EVT Versus EVT Alone on 4.5 to 24 Hours After Basilar Artery Occlusion (clinicaltrials.gov) - P3 | N=332 | Recruiting | Sponsor: The First Affiliated Hospital of University of Science and Technology of China | Trial completion date: Mar 2025 ➔ Mar 2026 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial completion date • Trial primary completion date • Cardiovascular

A multicenter, prospective, post market "real-world" clinical study on the safety and efficacy of recombinant human TNK tissue type plasminogen activator for injection (rhTNK tPA) in the treatment of hyperacute ischemic stroke (onset<4.5 hours) (ChiCTR) - P4 | N=12000 | Recruiting | Sponsor: Linyi People's Hospital (Shandong Provincial Clinical Research Center for Geriatric Diseases); Linyi People's Hospital | Not yet recruiting ➔ Recruiting

Enrollment open • Real-world • Real-world evidence • Cardiovascular • Ischemic stroke