[Translation] A multicenter, randomized, open-label, endpoint-blind, active-drug parallel-controlled phase IIIc clinical trial of intravenous thrombolysis with recombinant human prourokinase for injection (rhPro-UK) for the treatment of acute ischemic stroke within 0-4.5 hours of onset

以注射用阿替普酶（rt-PA）作为对照，评价注射用rhPro-UK静脉溶栓治疗发病0-4.5小时急性缺血性脑卒中的有效性及安全性。

[Translation]

To evaluate the efficacy and safety of rhPro-UK intravenous thrombolytic therapy for acute ischemic stroke within 0-4.5 hours of onset, using alteplase for injection (rt-PA) as a control.

Start Date29 Jan 2023

Sponsor / Collaborator

Shanghai Tasly Pharmaceutical Co. Ltd.

NCT05700591

/ CompletedPhase 3

A Phase III Trial to Assess the Efficacy and Safety of Recombinant Human Prourokinase in the Treatment of Acute Acute Ischaemic Stroke in 4.5 Hours After Stroke Onset

Intravenous thrombolysis is the first-line therapy in patients with acute ischemic stroke within 4·5 hours of symptom onset, and recombinant tissue plasminogen activator (alteplase) is the preferred thrombolytic agent for this purpose.
RhPro-UK is a specific plasminogen activator. rhPro-UK only acts on occlusive thrombus and has little effect on hemostatic thrombus. In addition, rhPro-UK does not form covalent complexes with protease inhibitors in plasma, so the concentrations of rhpro-UK and protease inhibitors in the blood do not decrease compared with alteplase. Therefore, rhPro-UK therapies have a potential advantage of less systemic bleeding in treated subjects. Data from several previous studies suggest that rhPro-UK is efficacious when used to treat patients with acute myocardial infarction. On April 2, 2011, rhPro-UK injection was approved by the National Medical Products Administration to treat acute myocardial infarction. Since then, rhPro-UK has been widely used to treat myocardial infarction in China.
Since 2016, a phase 2 clinical trial was carried to explore the dosing of rhPro-UK in patients with acute ischemic stroke, followed by another study with a sample size of 680 patients to initially validate the efficacy and safety of the proposed dose of 35mg. The results of these studies suggested that rhPro-UK was effective, and there were no safety concerns. To further prove the efficacy and safety of rhPro-UK in patients with acute ischemic stroke, investigators conducted this phase 3 study (PROST-2).

Start Date29 Jan 2023

Sponsor / Collaborator

Shanghai Tasly Pharmaceutical Co. Ltd.

NCT05507645

/ CompletedPhase 3IIT

Recombinant Human Prourokinase（rhPro-UK）for Injection Versus Standard Medical Treatment for Acute Mild Ischemic Stroke (NIHSS≤5) Within 4.5 Hours After Symptom Onset

The purpose of this study is to investigate the safety and efficacy of rhPro-UK (35mg) versus standard medical treatment in acute mild ischemic stroke within 4.5 hours of symptom onset.

Start Date15 Nov 2022

Sponsor / Collaborator

Beijing Tiantan Hospital

100 Clinical Results associated with Recombinant human prourokinase

100 Translational Medicine associated with Recombinant human prourokinase

100 Patents (Medical) associated with Recombinant human prourokinase

Literatures (Medical) associated with Recombinant human prourokinase

01 Mar 2025·CLINICAL AND APPLIED THROMBOSIS-HEMOSTASIS

Efficacy and Safety of Recombinant Human Prourokinase in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis

Review

Author: Rifai, Mohamed ; Mansour, Zeyad T. ; Alzahrani, Abdulaziz A. ; Osman Ahmed, Abubaker ; Alzabidi, Hadeel A. ; Maiz, Ahmed A. ; Sanad Alotibi, Suhaiyh ; Mansour Alshehri, Sarah ; Salem, Leena ; Fahad Almazyad, Yara ; Ibrahim, Ahmed A.

Acute ischemic stroke (AIS) is a leading cause of mortality and disability worldwide. Recombinant human prourokinase (rhPro-UK) has emerged as a promising thrombolytic agent amid the global shortage of thrombolytics. We assessed the safety and efficacy of rhPro-UK in AIS patients within 4.5 h of stroke onset through a systematic review and meta-analysis of RCTs from PubMed, Web of Science, Scopus, and Cochrane until January 2024. Data were pooled using risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI) in R version 4.3. PROSPERO ID: CRD42025638980. Three RCTs (2289 patients) were included. rhPro-UK showed comparable efficacy to recombinant tissue plasminogen activator (r-tPA) in excellent neurological recovery (mRS 0–1: RR 1.04, 95% CI [0.98, 1.10], P = 0.19) and functional independence (mRS 0–2: RR 1.00, 95% CI [0.96, 1.05], P = 0.87). However, rhPro-UK significantly reduced NIHSS scores at 24 h (MD −0.43, 95% CI [−0.85, −0.02], P = 0.04) and seven days (MD −0.85, 95% CI [−1.39, −0.30], P < 0.01), and decreased systemic bleeding (RR 0.60, 95% CI [0.49, 0.75], P < 0.01). No significant differences were observed in 90-day mortality (RR 1.13, 95% CI [0.62, 2.05], P = 0.69) or intracerebral hemorrhage (RR 0.83, 95% CI [0.61, 1.13], P = 0.23). rhPro-UK demonstrates comparable efficacy to r-tPA with reduced NIHSS scores and systemic bleeding, supporting its role as a cost-effective and safer alternative for AIS treatment within 4.5 h. Further investigation in stroke management protocols is warranted.

01 Mar 2025·Brain and Behavior

Efficacy and Safety of Recombinant Human Prourokinase in Acute Ischemic Stroke Within 4.5 h: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

Review

Author: Tahir, Muhammad Fawad ; Alam, Umama ; Waseem, Muhammad Hassan ; Iqbal, Javed ; Abideen, Zain Ul ; Ali, Muhammad Abdullah ; Rasheed, Sanan ; Aimen, Sania ; Raja, Hafsa Arshad Azam ; Mukhlis, Muhammad ; Waheed, Aiman ; Farooq, Ubaid ; Khan, Marium

ABSTRACT:

Background:

Acute ischemic stroke (AIS) requires timely thrombolysis to restore perfusion and minimize neurological damage. Recombinant human prourokinase (rhPro‐UK) has emerged as a promising alternative to alteplase, with potential efficacy and safety benefits within the critical 4.5‐h treatment window.

Methods:

Electronic databases, including PubMed, ScienceDirect, and Cochrane Central, were comprehensively searched from inception until December 2024. Risk ratios (RRs) with 95% confidence intervals were pooled for the dichotomous outcomes using a random effects model in Review Manager software. The heterogeneity among the included trials was evaluated using the I2 statistics, and a sensitivity analysis was conducted to investigate the source of heterogeneity.

Results:

The final statistical analysis included 1179 participants in the rhPro‐UK and 1148 in the tPA group. Excellent functional outcome (modified Rankin Scale [mRS] 0‐1) (RR = 1.04, 95% CI: [0.98, 1.10]; p = 0.16) and good functional outcome (mRS 0‐2) (RR = 1.00, 95% CI: [0.96, 1.05]; p = 0.90; I2 = 0%) were comparable between the two groups. There was also no significant difference in mortality and major neurological improvement. However, there was a trend toward a lower risk of symptomatic intracranial hemorrhage (sICH) in the rhPro‐UK group (RR = 0.53, 95% CI: [0.18, 1.59]; p = 0.26).

Conclusion:

rhPro‐UK demonstrated comparable efficacy to alteplase in achieving functional outcomes in AIS within 4.5 h, with no significant differences in mortality or neurological improvement. Although not statistically significant, a trend toward lower sICH risk with rhPro‐UK highlights its potential safety advantage. More high‐quality randomized clinical trials are required to confirm these findings.

01 Jan 2025·LANCET NEUROLOGY

Safety and efficacy of intravenous recombinant human prourokinase for acute ischaemic stroke within 4·5 h after stroke onset (PROST-2): a phase 3, open-label, non-inferiority, randomised controlled trial

Article

Author: Wei, Yan ; Li, Zixiao ; Meng, Xia ; Li, Hao ; Wang, Xuechun ; Zhu, Suiqiang ; Fan, Dongsheng ; Liu, Liping ; Dong, Qiang ; Wang, Yilong ; Xu, Yun ; Li, Shuya ; Lu, Guozhi ; Gu, Hong-Qiu ; Wang, Ziran ; Feng, Baoyu ; Zhao, Xingquan ; Wang, Yongjun ; Ma, Yutong ; Dai, Hongguo

BACKGROUND:

Intra-arterial prourokinase has been shown to be a promising thrombolytic agent in patients with acute ischaemic stroke. Given the global shortage of thrombolytics, we aimed to assess the non-inferiority of intravenous recombinant human prourokinase compared with alteplase in patients with acute ischaemic stroke who were ineligible for or who refused endovascular thrombectomy.

METHODS:

PROST-2 was a phase 3, open-label, non-inferiority, randomised controlled trial conducted at 61 hospitals in China. Patients older than 18 years with acute ischaemic stroke, who were ineligible for or who refused endovascular thrombectomy, were randomly assigned in a 1:1 ratio within 4·5 h of stroke onset to receive intravenous recombinant human prourokinase (15 mg bolus followed by 20 mg infusion within 30 min) or intravenous alteplase (0·9 mg per kg, maximum dose 90 mg; 10% bolus followed by remainder as infusion over 60 min). The primary efficacy outcome was the proportion of patients with a modified Rankin Scale score of 0 or 1 at 90 days, assessed via masked review in the intention-to-treat population, with a non-inferiority margin for the risk ratio of 0·93. The primary safety outcome was the incidence of symptomatic intracranial haemorrhage within 36 h. This trial is registered with ClinicalTrials.gov (NCT05700591) and is now completed.

FINDINGS:

Between Jan 29, 2023, and March 14, 2024, 1552 patients were randomly assigned: 775 received recombinant human prourokinase and 777 received alteplase. The primary outcome of a modified Rankin Scale score of 0 or 1 at 90 days was reached by 558 (72·0%) of 775 patients in the recombinant human prourokinase group versus 534 (68·7%) of 777 in the alteplase group (risk ratio 1·04 [95% CI 0·98 to 1·10]; p<0·0001 for non-inferiority). The frequency of symptomatic intracranial haemorrhage within 36 h was lower in the recombinant human prourokinase group than in the alteplase group (two [0·3%] of 770 patients vs ten [1·3%] of 775, risk difference -1·0 percentage points [95% CI -2·1 to -0·1]; p=0·021), as was the incidence of major bleeding at 7 days (four [0·5%] vs 16 [2·1%]; -1·5 percentage points (-2·8 to -0·4); p=0·0072). All-cause mortality within 7 days did not differ between groups (five [0·6%] deaths in the recombinant human prourokinase group vs 13 [1·7%] in the alteplase group; risk difference -1·0 percentage points; 95% CI -2·3 to 0·1]; p=0·060).

INTERPRETATION:

In our trial, recombinant human prourokinase was shown to be non-inferior to alteplase for achieving excellent functional outcome, with no difference between groups in safety endpoints. These findings support the use of recombinant human prourokinase as a viable alternative to alteplase for patients with ischaemic stroke who are eligible for intravenous thrombolysis therapy but ineligible for or who have refused endovascular thrombectomy.

FUNDING:

Tasly Biopharmaceuticals, National Key R&D Program of China, National Natural Science Foundation of China, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and Beijing Municipal Science & Technology Commission.

TRANSLATION:

For the Chinese translation of the abstract see Supplementary Materials section.

100 Deals associated with Recombinant human prourokinase

External Link

KEGG	Wiki	ATC	Drug Bank
-	-	B01AD04	-

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Myocardial Infarction	China	Shanghai Tasly Pharmaceutical Co. Ltd.	02 Apr 2011

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Stroke	NDA/BLA	China	Shanghai Tasly Pharmaceutical Co. Ltd.	07 Aug 2024
Acute Ischemic Stroke	Phase 3	China	Shanghai Tasly Pharmaceutical Co. Ltd.	18 May 2018
Pulmonary Embolism	Phase 2	China	Shanghai Tasly Pharmaceutical Co. Ltd.	06 Jun 2017

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05700591 (PROST-2, Neurology) Manual	Phase 3	Acute Ischemic Stroke	1,552	recombinant human prourokinase	aoaxmajbde(exugtqerjx) = switdvckbm tmibvkxktg (rrdgbbqkut ) View more	Positive	11 Dec 2024
				alteplase	aoaxmajbde(exugtqerjx) = fazgzuivxa tmibvkxktg (rrdgbbqkut ) View more
rhpro-UK STROKEIIa (ISC2019)	Phase 2	Acute Ischemic Stroke	190	Intravenous rhpro-UK 50mg	xjuaiyxjdg(zeurmqnufo) = fnwrzeidwi tblouaeyfg (mglddpawit )	Positive	01 Feb 2019
				Intravenous rhpro-UK 35mg	xjuaiyxjdg(zeurmqnufo) = uzzprgnnzb tblouaeyfg (mglddpawit )

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