SY007 in Patients With Acute Ischemic Stroke

Study Overview
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Brief Summary
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This Phase 1b multiple center, randomized, double-blind, placebo-controlled study is a dose escalation trial evaluating the safety, tolerability, PK characteristics and efficacy of SY-007 after injection in acute ischemicstroke patients. The immunogenicity of SY-007 will be evaluated and this study will provide the recommended dosage for subsequent clinical trials.

Official Title
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Phase Ib Clinical Study to Evaluate Safety, Tolerance，Pharmacokinetics and Efficacy of SY-007 After Intravenous Injection in Acute Ischemic Stroke Subjects

Conditions
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Acute Ischemic Stroke

Intervention / Treatment
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* Drug: SY-007/ Placebo 15mg
* Drug: SY-007/ Placebo 30mg
* Drug: SY-007/ Placebo 60mg


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Aged from18 Years to 80 Years Within 24h after the onset of stroke symptoms (time the patient was last seen well) Score range from 4 to 20 points, inclusive, on the NIHSS at randomization Prior to index stroke, patient was able to perform basic activities of daily living without assistance, mRS score≤1 Absence of intracranial hemorrhage on brain CT or MRI Patients or legal representatives can give informed consent Key Exclusion Criteria: Venous thrombolytic therapy or endovascular treatments have been applied for patients; or Patients plan to conduct these kind of treatments. Glasgow score of Patients ≤8 Patients are receiving oral anticoagulants or INR>3.0 Baseline blood platelet counts <80*109/L NIHSS score could not been obtained at baseline FPG levels < 50mg/dL or >400mg/dL Patients with Kidney disorder eGFR <30 mL/min or patients need dialysis Patients with Acute and Chronic hepatitis, or Liver diseases (AST or/and ALT >2 × ULN(upper limit normal)) systolic blood pressure≥220mmHg or/and diastolic blood pressure≥120mmHg ; or Blood pressure under 90/60mmHg.

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 15mg SY-007/ Placebo Repeat Dose<br>Intravenous infusion of 15mg SY-007 or placebo twice a day for seven consecutive days. | Drug: SY-007/ Placebo 15mg<br>* 15 mg SY-007/ Placebo, the dosing interval is 12 hours ±2 hours for 7 consecutive days.<br>|
| Experimental: 30mg SY-007/ Placebo Repeat Dose<br>Intravenous infusion of 30mg SY-007 or placebo twice a day for seven consecutive days. | Drug: SY-007/ Placebo 30mg<br>* 30 mg SY-007/ Placebo, the dosing interval is 12 hours ±2 hours for 7 consecutive days.<br>|
| Experimental: 60mg SY-007/ Placebo Repeat Dose<br>Intravenous infusion of 60mg SY-007 or placebo twice a day for seven consecutive days. | Drug: SY-007/ Placebo 60mg<br>* 60 mg SY-007/ Placebo, the dosing interval is 12 hours ±2 hours for 7 consecutive days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerance of SY-007 | Number of patients with treatment-emergent adverse events and number of patients who died over 90 days | From Day 0 to Day 90 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetics of SY-007 | Peak Plasma Concentration (Cmax) | From Day 0 to Day 7 | 
| Pharmacokinetics of SY-007 | Area under the plasma concentration versus time curve (AUC) | From Day 0 to Day 7 | 
| Pharmacokinetics of SY-007 | Time to Cmax (Tmax) | From Day 0 to Day 7 | 
| Pharmacokinetics of SY-007 | Terminal half life (T½) | From Day 0 to Day 7 | 
| Pharmacokinetics of SY-007 | Clearance (CL) | From Day 0 to Day 7 | 
| Pharmacokinetics of SY-007 | Volume of distribution | From Day 0 to Day 7 | 
| Percentage of Participants With Excellent Outcome in Modified Rankin Scale（mRS) Score at Day 8, Day30, Day60, Day90 | Excellent mRS is defined as mRS score of 0 or 1 | Day 8, Day30, Day60, Day90 | 
| Modified Rankin Scale Score at Day 8, Day30, Day60, Day90 | Modified Rankin Scale Score range from 0 to 5，higher score mean a worse outcome. | Day 8, Day30, Day60, Day90 | 
| Percentage of Participants With National Institute of Health Stroke Scale (NIHSS) range from 0 to 1 at Day 8, Day30 |  | Day 8, Day30 | 
| Change From Baseline in NIHSS Score at Day 8, Day30 range from 0 to 1 at Day 8, Day30 |  | Day 8, Day30 | 
| Percentage of Participants With Excellent Outcome in Barthel index (BI) Score at Day 8, Day30, Day60, Day 90 | Excellent BI outcome is defined as a score of >=95. BI consists of 10 items that measure a participant's daily functioning, specifically the activities of daily living and mobility. | Day 8, Day30, Day60, Day 90 | 
| Change of Cerebral infarction volume before and after treatment |  | Baseline, Day 8, Day30 | 
| Immunogenicity of SY-007 | Anti-Drug antibody evaluation | From Day 0 to Day 30 |