SPT-07A Injection in Patients With Acute Ischemic Stroke (AIS): A Phase III Clinical Trial

Study Overview
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Brief Summary
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This is a multicenter, randomized, double-blind, placebo-controlled, parallel controlled clinical trial in Chinese patients with acute ischemic stroke. Objective to evaluate the efficacy and safety of SPT-07A injection compared with placebo in the treatment of patients with acute ischemic stroke.

Detailed Description
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The target population of this study is patients with acute ischemic stroke within 48 hours. All potential participants must provide informed consent, and those who provide informed consent will enter the screening (- 48   0h), and the screening qualification will be evaluated according to the inclusion criteria. The eligible subjects will enter the treatment period (day 1-7) and will be randomly assigned to the experimental group (SPT-07A injection group) or the control group (placebo group). During the treatment period, all subjects will receive SPT-07A injection or placebo by intravenous drip, twice a day for 7 consecutive days. During the treatment, all subjects need to receive basic treatment: citicoline sodium injection 0.25g, intravenous drip slowly, once a day, continuous administration for 7 days. According to the Chinese guidelines for the diagnosis and treatment of acute ischemic stroke (2018), the patients were given antihypertensive, hypoglycemic, lipid-lowering, anticoagulant or mannitol. All subjects were not allowed to receive interventional therapy (mechanical thrombectomy or stent implantation, etc.), thrombolysis (such as rtPA and urokinase), other cerebrovascular dilators (such as Butylphthalide, Flunarizine, Nicardipine and Nimodipine, etc.), other neuroprotective agents (such as Edaravone,etc., except citicoline) during the whole trial period. After the end of the treatment period (the 7th day), the subjects will enter the follow-up period (the 8th-90th day). During the follow-up period, subjects need to be followed up twice (30th day ± 3 days, 90th day ± 7 days).

Official Title
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Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Trial of the Efficacy and Safety of SPT-07A Injection in Patients With Acute Ischemic Stroke

Conditions
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Stroke, Acute

Intervention / Treatment
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* Drug: SPT-07A injection
* Other: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females aged 18 to 85 years; According to the Key points for diagnosis of various major cerebrovascular diseases in China 2019 and combined with the experience of clinicians, patients with ischemic stroke were diagnosed; From the last time that looks normal to the beginning of drug treatment ≤ 48 hours. When the onset time of symptoms can not be accurately obtained after awakening stroke or due to aphasia, disturbance of consciousness and other reasons, the final time of normal performance of patients should be taken as the criterion. First onset of ischemic stroke or prestroke with mRS of 0 or 1; A National Institutes of Health Stroke Scale (NIHSS) score between 6 and 20, and a total score of upper and lower limbs ≥2 on motor deficits; Capable of understanding the purpose and risk of the study and has signed, in writing, the informed consent form (ICF). If the subject is not capable of this at the time of enrollment, a legally authorized representative (LAR) will provide written informed consent in accordance with all regulations. Exclusion Criteria: Serious disturbance of consciousness (NIHSS 1a ≥2 score); Based on the opinion of the Investigator, the posterior circulation symptoms like ataxia in stroke patients are caused by posterior circulation ischemia, such as brainstem or cerebellum; Neuroimaging (CT/MRI) revealed intracranial hemorrhagic diseases (such as cerebral hemorrhage, epidural hematoma, subdural hematoma, subarachnoid hemorrhage, ventricular hemorrhage, traumatic cerebral hemorrhage, etc.); Rapidly improving or resolving symptoms, suggesting a possible transient ischemic attack (TIA) rather than a qualifying stroke; Subjects who are ready to undergo or have undergone intravenous thrombolysis, or endovascular therapy in 90 days from onset; Renal insufficiency: Serum creatinine > 2.5 times the upper limit of normal value, or other known serious renal insufficiency diseases; Liver function damage: ALT and AST > 2.5 times the upper limit of normal value, or other known liver diseases such as acute and chronic hepatitis, cirrhosis, etc.; Poorly controlled hypertension, with systolic blood pressure (≥ 180 mmHg) and/or diastolic blood pressure ( ≥110 mmHg); Subjects with heart rate < 40 beats/min and/or heart rate > 120 beats/min; 2-degree or 3-degree cardiac block without pacemaker or other malignant arrhythmia; acute myocardial infarction or interventional therapy in the past month, patients with heart failure (according to NYHA grade III-IV); Patients with status epilepticus who are unable to cooperate or unwilling to cooperate due to other organic mental disorders and moderate or severe cognitive impairment; Subjects with malignant tumors, serious diseases of the blood, digestive or other systems or hemophilia and the expected survival time is not more than 3 months; Female subjects who are pregnant, lactating/breast-feeding, or plan to become pregnant; Allergic constitution, or allergic to experimental drugs, analogous drugs or basic treatment drugs; Received treatment with any other investigational drug within 30 days before Baseline, or is currently participating in another clinical study; Any other reasons that, in the opinion of the investigator, make the subject unsuitable for enrollment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test group (SPT-07A injection group)<br> | Drug: SPT-07A injection<br>* 20mg (2), dissolved in 250ml of normal saline, and injected intravenously for 90±20min, twice a day, and administered for 7 days.<br>|
| Placebo Comparator: Control group (placebo group)<br> | Other: placebo<br>* 2 Injection simulants, dissolved in 250ml of normal saline, and injected intravenously for 90±20min, twice a day, and administered for 7 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Good outcome at 90 days | proportion of subjects with a modified Rankin Scale (mRS) ≤ 1 | at day 90 (±7) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of subjects with a modified Rankin Scale (mRS) ≤ 2 at day 90(±7) | proportion of subjects with a modified Rankin Scale (mRS) ≤ 2 | at day 90(±7) | 
| National Institute of Health stroke scale (NIHSS) at day 8(+1) | proportion of subjects with a National Institute of Health stroke scale (NIHSS) 0-1 or mean improvement value from baseline | at day 8(+1) | 
| Barthel Index (BI) at day 90(±7) | proportion of subjects with a Barthel Index (BI) ≥95 | at day 90(±7) | 
| modified Rankin Scale (mRS) at day 8(+1), 30(±3) and day 90(±7) | score of modified Rankin Scale (mRS) | at day 8(+1), 30(±3) and day 90(±7) | 
| National Institute of Health stroke scale (NIHSS) at day 8(+1), 30(±3) and day 90(±7) | score of National Institute of Health stroke scale (NIHSS) | at day 8(+1), 30(±3) and day 90(±7) | 
| Barthel Index (BI) at day 8(+1), 30(±3) and day 90(±7) | score of Barthel Index (BI) | at day 8(+1), 30(±3) and day 90(±7) |