Efficacy and Safety Evaluation of JX10 in Acute Ischemic Stroke Patients with Delayed Presentation: A Multicenter, Double-Blind, Placebo-Controlled, Randomized Study
- Trial ID
- 2024-519521-37-01
- Protocol
- JX10002
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to determine if **JX10** improves functional outcomes in patients with acute ischemic stroke (AIS) as measured by the modified Rankin Scale (mRS) when compared with placebo. Additionally, the study aims to evaluate the risk of symptomatic intracranial hemorrhage associated with JX10 in this patient population. These objectives are clinically relevant as they address both the potential therapeutic benefits and safety concerns of JX10, which are critical for its potential use in managing AIS.
Secondary objectives include evaluating the efficacy of JX10 on acute and 90-day clinical outcomes, as well as assessing the safety and tolerability of JX10 in participants with acute ischemic stroke. These secondary objectives provide further insights into the short-term and longer-term effects of JX10, contributing to a comprehensive understanding of its clinical profile.
Participants
The clinical trial involves a total of **671 participants** diagnosed with **acute ischemic stroke**. The study population includes both male and female subjects, aged between 18 and 90 years. Participants over the age of 85 must have a premorbid modified Rankin Scale (mRS) score of 0 to be eligible. The trial population was selected based on specific inclusion criteria, including the presence of acute ischemic stroke with compatible clinical presentation and radiographic evidence of salvageable tissue. Participants must have a pre-treatment National Institutes of Health Stroke Scale (NIHSS) score of 5 or higher and must have been functionally independent prior to stroke onset, as evidenced by a premorbid mRS score of less than 2. All women of childbearing potential and men are required to practice effective contraception during the study and for a specified period after the last dose of study treatment. The trial includes a vulnerable population, and informed consent is obtained in accordance with local and national regulations. Lifestyle considerations such as diet and physical activity are not specified in the available data.
Plans and Procedures
The clinical trial is designed to evaluate the **efficacy** and safety of JX10 in patients with **acute ischemic stroke**. This is a multicenter, double-blind, placebo-controlled, randomized, parallel-group study, categorized as a Phase 2/3 trial. The primary objective is to determine if JX10 improves functional outcomes as measured by the modified Rankin Scale (mRS) compared to placebo, and to assess the risk of symptomatic intracranial hemorrhage in participants. The trial is expected to commence recruitment in July 2025 and conclude by October 2029.
Participants will be randomly assigned to receive either JX10 or a placebo, both administered as a sterile, lyophilized powder for intravenous infusion. The maximum daily dose of JX10 is 300 mg, with a total treatment period of one day. The study includes several key visits: an initial screening visit to confirm eligibility, follow-up visits to monitor safety and efficacy, and an end-of-study visit to assess final outcomes. The inclusion criteria require participants to be aged 18 to 90 years, with specific conditions for those over 85, and to have a pre-treatment National Institutes of Health Stroke Scale (NIHSS) score of 5 or higher. Radiographic evidence of salvageable tissue and presentation within specific time frames post-stroke are also required.
Participant involvement is expected to last up to 90 days, with the primary endpoint being the proportion of participants with no or minimal symptoms at this time. Safety will be assessed by the incidence of symptomatic intracranial hemorrhage within 36 hours post-randomization. Conditions that may lead to early termination from the study include significant adverse events, withdrawal of consent, or protocol violations. The trial is conducted in compliance with all applicable regulations and ethical guidelines, ensuring the safety and rights of participants are prioritized throughout the study duration.
Treatment
The clinical trial involves the administration of **JX10**, an investigational medication developed by Corxel Pharmaceuticals Co. Ltd. JX10 is formulated as a **powder for concentrate for solution for infusion**. The active substance, also named JX10, is of chemical origin. The medication is administered via **intravenous infusion**. The maximum daily dose is 300 mg, with a total dose not exceeding 300 mg over the treatment period. The treatment duration is limited to one day. The study aims to evaluate the efficacy and safety of JX10 in patients with acute ischemic stroke, focusing on functional outcomes and the risk of symptomatic intracranial hemorrhage.
The trial also includes a **placebo** group for comparison. The placebo is prepared as a sterile, lyophilized white to light yellow cake or powder for infusion, mimicking the appearance of the active drug product. The placebo is administered in the same manner as JX10, ensuring blinding and maintaining the integrity of the double-blind study design. The placebo serves as a control to assess the true efficacy and safety profile of JX10 in the study population.
Efficacy
The efficacy of the investigational product JX10 in the treatment of **acute ischemic stroke** will be assessed through a primary endpoint focused on the proportion of participants exhibiting no or minimal symptoms at 90 days post-treatment. This endpoint will be evaluated using the modified Rankin Scale (mRS), a widely recognized tool for measuring the degree of disability or dependence in daily activities of people who have suffered a stroke. The trial is designed as a multicenter, double-blind, placebo-controlled, randomized, parallel-group study, ensuring rigorous assessment of the treatment's efficacy compared to a placebo.
Data collection will occur at specified intervals, with the primary efficacy endpoint being assessed at the 90-day mark following randomization. The trial will also monitor safety endpoints, including the incidence of symptomatic intracranial hemorrhage within 36 hours post-randomization, which will be defined by specific criteria such as parenchymal hemorrhage type 2, subarachnoid hemorrhage, or intraventricular hemorrhage, combined with a neurological deterioration of 4 points or more on the National Institutes of Health Stroke Scale (NIHSS) from baseline or leading to death. These assessments will be conducted using validated clinical scales and imaging techniques to ensure accurate and reliable data collection.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Age ≥ 18 and ≤ 90 years old (Age > 85 must be mRS 0 at baseline (premorbid) to be eligible).
- Written informed consent by patient, his her legally authorized representative, or independent physician where local regulation allows (in accordance with all local and national regulations or according to the local ethics committee's guidelines or by another process compliant with applicable national laws and regulations and ethics committee requirements).
- Acute ischemic stroke with compatible clinical presentation and symptomatic high grade stenosis or complete intracranial internal carotid, M1, M2 or distal branches of the middle cerebral artery (MCA), anterior cerebral artery (ACA), or posterior cerebral artery (PCA), demonstrated by: a. Computer Tomography Angiography (CTA) or Magnetic Resonance Angiography (MRA) with high grade stenosis or occlusion of an eligible artery, or b. Computer Tomography or Magnetic Resonance Perfusion (CTP/MRP) with focal deficit in an eligible artery, or c. Non-contrast Computer Tomography (NCCT) with hyperdense artery sign in an eligible artery or Magnetic Resonance Imaging (MRI) with susceptibility vessel sign (defined as a hypointense signal exceeding the diameter of the contralateral artery at the thrombus site) in an eligible artery.
- Radiographic evidence of salvageable tissue* is present based on: a. A mismatch ratio (perfusion lesion (Tmax > 6 seconds) volume core estimate) > 1.2, b. Estimated core infarct volume < 70 mL, and c. Total mismatch volume ≥ 10 mL on CTP or magnetic resonance (MR) perfusion weighted imaging (PWI) MRI diffusion imaging. The perfusion criteria apply to all participants, including those who present within 4.5 to 6 hours of LKW, if perfusion imaging is obtained. Perfusion is mandatory for patients presenting beyond 6 hours, optional for patients < 6 hours. *The quantitative assessment of penumbra may include alternative methods (e.g., if the software uses different parameters in place of Tmax).
- Presentation with intended study treatment within 4.5 to 6 hours of Last Know Well (LKW) in the absence of radiographic assessment of perfusion or within 4.5 to 24 hours of LKW with radiographic evidence of penumbra meeting criterion
- Pre-treatment score of NIHSS ≥ 5.
- Functionally independent prior to stroke onset as evidenced by premorbid mRS < 2 (< 1 if age 86-90).
- All women of childbearing potential and all men must practice contraception as described in Section 8.3.5. For women of childbearing potential, a negative pregnancy test at screening is required. All women of childbearing potential must practice effective contraception for at least 30 days after their last dose of study treatment. All men must practice effective contraception during the study and for 90 days after their last dose of study treatment. In addition, participants should not donate sperm or eggs during the study and for at least 90 days after their dose of study treatment.
Exclusion Criteria
- Radiographic findings pre-randomization of any of the following: a. Large core infarction, evidenced by a core infarct volume > 70 mL, assessed on DWI or CTP; or extensive early ischemic change (hypodensity) on non-contrast CT estimated to be > 1 3 MCA territory, or significant hypodensity outside the Tmax > 6 seconds perfusion lesion that invalidates mismatch criteria, or b. Occlusion in more than 1 vascular territory confirmed on CTA MRA, or c. Significant mass effect or clinically significant cerebral edema per Investigator’s judgement, or d. Evidence of acute intracranial or extracranial hemorrhage, intracranial tumor (except small meningioma), neoplasm, or arteriovenous malformation, or e. Clinical history, past imaging, or clinical judgement suggests that the intracranial occlusion is chronic.
- Non-ischemic or non-thrombotic etiology of current stroke symptoms such as suspected cerebral vasospasm, infectious source (e.g., bacterial endocarditis, septic shock), complications from acute drug abuse (e.g., cocaine intoxication).
- Medical history or active clinically significant bleeding, lesions, or conditions (at the investigator’s judgement) considered to be of significant risk for major bleeding; (this may include but not limited to any history of intracranial hemorrhage or vascular aneurysm of the large arteries of major intraspinal or intracerebral abnormalities).
- Cerebral infarction within 90 days of screening.
- Arterial dissection involving any intracranial artery or the aortic arch. Confirmed acute coronary syndrome within 90 days of screening.
- Severe hepatic impairment as defined by decompensated liver disease (e.g., Child-Pugh Class C) or clinically significant hepatic condition associated with coagulopathy or bleeding risk.
- Medical history of chronic renal failure, any condition requiring dialysis or renal replacement therapy or evidence of acute kidney injury at the time of screening, an estimated glomerular filtration rate < 30 mLmin1.73m2.
- Severe, uncontrolled hypertension (systolic blood pressure ≥ 185 mmHg or diastolic blood pressure ≥ 110 mmHg) that cannot be controlled with antihypertensive therapy.
- Known bleeding diathesis (hereditary or acquired) or any significant coagulopathy. Specifically, platelet count < 100,000 microliter, international normalized ratio > 1.7, aPTT > 40 seconds, or prothrombin time > 15 seconds.
- Major trauma, surgery, or invasive procedures: a. Severe head trauma within 3 months of screening or acute head trauma. b. Major trauma not involving the head within 14 days of screening. c. Major surgery with 14 days of screening. d. Intracranial or intraspinal surgery within 90 days of screening. e. Dural puncture (e.g., lumbar puncture) or arterial puncture of a noncompressible blood vessel within 7 days of screening.
- Pre-existing medical, neurological, or psychiatric disease that would confound the neurological or functional evaluations of this study.
- Pre-treatment blood glucose > 400 mgdL (22.20 mmolL) or Pre-treatment blood glucose < 50 mgdL (2.78 mmolL) unless it is corrected prior to study treatment administration. Participants with subsequently normalized blood glucose levels may be considered for inclusion, per Investigator judgement.
- Known hereditary or acquired abnormality of UGT1A1 metabolism or deficiency such as Gilbert's syndrome (hereditary liver condition with elevated bilirubin), Crigler-Najjar syndrome (UGT1A1 gene defect associated with congenital non-hemolytic jaundice).
- Prolonged QT with QTc of > 450 ms for males and > 460 ms for females
- Life expectancy less than 6 months due to comorbid condition.
- Prior thrombolytic administration within 90 days of screening or planned thrombolytic administration for the AIS. (Co-administration with any other thrombolytic agent(s) within 48 hours is prohibited).
- Known or suspected use of any oral anticoagulant therapy, including but not limited to vitamin K antagonists, thrombin inhibitors, or factor Xa inhibitors, within 48 hours of screening unless blood testing confirms absence of drug substance in the system.
- Use of dual anti-platelet therapy, IV aspirin, or glycoprotein IIb/IIIa inhibitors within 24 hours of screening. Pre-screening use of oral antiplatelet monotherapy with aspirin at doses less than or equal to 325 mg daily OR clopidogrel 75 mg daily is permitted.
- Use of heparin or low molecular weight heparin at a therapeutic dose, excluding prescreening prophylactic dose low molecular weight heparin with a normal aPTT.
- Use of nephrotoxic medications or agents within 7 days of screening that would (in the investigator’s opinion) pose significant risk of acute kidney injury (e.g. aminoglycosides, cyclosporins, lactams, amphotericin B, cisplatin, indomethacin, etc.).
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Recruiting | 01 Jul 2025 | 16 |
 Bulgaria | Recruiting | 01 Jul 2025 | 43 |
 Finland | Not Recruiting | 01 Jul 2025 | 3 |
 France | Recruiting | 01 Jul 2025 | 45 |
 Germany | Recruiting | 01 Jul 2025 | 12 |
 Greece | Recruiting | 01 Jul 2025 | 20 |
 Hungary | Recruiting | 01 Jul 2025 | 6 |
 Italy | Recruiting | 01 Jul 2025 | 36 |
 Latvia | Recruiting | 01 Jul 2025 | 17 |
 Lithuania | Recruiting | 01 Jul 2025 | 16 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
JX10 | Test | POWDER FOR CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENIOUS INFUSION | 300 | 1 | PRD11798366 |
Jx10 placebo drug product is prepared as a sterile, lyophilized white to light yellow cake or powder for infusion. | Placebo | N/A | — | — | — | N/A |