Study of the KPCXM18 Injection for Treatment of Acute Ischemic Stroke

Study Overview
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Brief Summary
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This study is a multicenter, randomized, double-blind, parallel, placebo-controlled trial design to evaluate the efficacy and safety of the KPCXM18 injection at different doses for the treatment of acute ischemic stroke and its PK/PD characteristics in patients.

Official Title
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A Multicenter, Randomized, Double-blind, Parallel, Placebo-controlled Phase II Clinical Trial Evaluating the Efficacy and Safety of the KPCXM18 Injection in Patients With Acute Ischemic Stroke.

Conditions
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Acute Ischemic Stroke

Intervention / Treatment
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* Drug: The KPCXM18 injection
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18 to 80 years old (including 18 years old and 80 years old), male or female; Diagnosed with acute ischemic stroke according to the Chinese guidelines for the diagnosis and treatment of acute ischemic stroke 2018; The time from the last normal behavior to the time of initiation of the drug infusion ≤ 48 hours. For stroke after waking up or when the time of symptom onset cannot be accurately obtained due to aphasia, consciousness disorder, and other reasons, the time of onset should take the last time the patient showed normally as standard; The patients who first attacked, or the patients who had a good prognosis after the last attacked ( mRS score was ≤1 before the onset of the disease ); During the screening period, 4 points ≤ NIHSS score ≤ 24 points, and the sum of NIHSS fifth upper limb and sixth lower limb score ≥2 points; The subject or his guardian is aware of the study, and if the subject or his guardian is unable to read, the impartial witness reads the informed consent form and other written materials, witnesses the informed consent, voluntarily participates and signs the written informed consent. Exclusion Criteria: Patients with intracranial hemorrhagic diseases confirmed by head CT or MRI: hemorrhagic stroke, epidural hematoma, intracranial hematoma, ventricular hemorrhage, subarachnoid hemorrhage, etc; Patients with disturbance of consciousness (NIHSS score Ia ≥2 points); Patients who need or have undergone intravenous thrombolysis or endovascular interventional therapy (including endovascular mechanical thrombectomy, intravascular thrombus aspiration, arterial thrombolysis, angioplasty and stenting, etc.) or patients with arteriovenous bridging therapy after this onset; Patients with malignant tumors, serious diseases of blood, digestion or other systems or diseases with bleeding tendencies (such as hemophilia, etc.), and the expected survival time is not more than 3 months; Patients with a history of major surgery within 1 month before screening; Patients with severe hypertension (systolic blood pressure ≥ 200 mmHg or diastolic blood pressure ≥110 mmHg) that cannot be controlled after treatment; Patients with heart rate < 40 beats/min and/or ventricular rate > 120 beats/min; Patients with 2nd and 3rd degree heart blocks without pacemakers or other malignant arrhythmias; Patients with acute myocardial infarction, cardiac interventional therapy, or heart failure (grade III and IV according to NYHA) within the past 1 month; Patients with severe liver function impairment, or ALT, AST > 2.0 times the upper limit of normal value (ULN); Patients with severe renal impairment, or serum creatinine (Cr) > 1.5× ULN; Patients who have used neuroprotective drugs (including commercially available edaravone, edaravone and dexborneol, nimodipine, gangliosides, piracetam, oxiracetam, butylphthalide, etc.) after the onset of this illness, as well as other traditional Chinese medicine labels containing the effect of treating acute ischemic stroke (cerebral infarction); Patients with other psychiatric diseases and limb disorders, including severe mental disorders, dementia and other combined diseases that may affect neurological function tests; Patients with a history of alcohol or drug abuse; Patients with allergies, hypersensitivity to citicoline, KPCXM18 or excipients; Pregnancy, lactation. or patients who have a family plan within 3 months of the first dose and who are unwilling to use contraception; Patients who participated in or are currently participating in other clinical trials within 1 month prior to this study; The investigator considers that patients are not suitable for clinical trials

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: low-dose group （The KPCXM18 injection）<br>Intravenous infusion of 20 mg twice daily at intervals of 12±2 hours for 10 days. | Drug: The KPCXM18 injection<br>* Intravenous infusion<br>|
| Experimental: middle-dose group （The KPCXM18 injection）<br>Intravenous infusion of 60 mg twice daily at intervals of 12±2 hours for 10 days. | Drug: The KPCXM18 injection<br>* Intravenous infusion<br>|
| Experimental: high-dose group （The KPCXM18 injection）<br>Intravenous infusion of 100 mg twice daily at intervals of 12±2 hours for 10 days. | Drug: The KPCXM18 injection<br>* Intravenous infusion<br>|
| Placebo Comparator: Placebo<br>Intravenous infusion twice a day with an interval of 12±2 hours for 10 days. | Drug: Placebo<br>* Intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in NIHSS score from baseline at day 10 after administration | The National Institute of Health stroke scale(NIHSS) score ranging from 0-42. Higher score indicates worse function. | day 10 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with mRS score ≤ 1 at day 90±7 after administration | The Modified Rankin Scale(mRS) score ranging from 0-5. Higher score indicates worse function. | day 90±7 | 
| Change in BI score from baseline at day 90±7 after administration | The Barthel Index score ranges from 0 to 100, the higher scores mean a better outcome. | day 90±7 | 
| Change in EQ-5D score from baseline at day 90±7 after administration |  | day 90±7 | 
| Changes in NIHSS score from baseline on days 30±3 and 90±7 after administration | The National Institute of Health stroke scale(NIHSS) score ranging from 0-42. Higher score indicates worse function. | days 30±3 and 90±7 | 
| Changes in mRS score from baseline on days 30±3 and 90±7 after administration | The Modified Rankin Scale(mRS) score ranging from 0-5. Higher score indicates worse function. | days 30±3 and 90±7 | 
| The proportion of subjects whose NIHSS score improved by ≥4 points at days 10, 30±3 and 90±7 after administration | The National Institute of Health stroke scale(NIHSS) score ranging from 0-42. Higher score indicates worse function. | days 10, 30±3 and 90±7 | 
| Proportion of subjects with recurrence of stroke within 90±7 days after administration |  | within 90±7 days | 
| Changes in serum biomarkers (TNF-α, MMP9, CHE, IL-10, S100-β) from baseline on day 7 after administration |  | day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stroke