Y-3 Injection in the Treatment of Acute Ischemic Stroke Phase II Clinical Trial

Y-3 Injection in the Treatment of Acute Ischemic Stroke Phase II Clinical Trial -- Multicenter, Randomized, Double-blind, Parallel, Placebo-controlled Phase II Clinical Trial

The objective of this clinical trial was to explore the efficacy and safety of Y-3 injection at different doses in patients with acute ischemic stroke within 48 hours of onset.

A multicenter, randomized, double-blind, parallel, placebo-controlled trial design was designed to include 240 participants.

Subjects press 1:1:1: 1 ratio of patients were randomly divided into Y-3 low-dose group (20 mg/ time, qd), medium-dose group (40 mg/ time, qd), high-dose group (60mg/ time, qd) and placebo control group, with 60 cases in each group. Random stratification factors include:

Time of onset (≤24 hours, > 24 hours). The patients were treated for 10 consecutive days (10 times) and followed up to 90 days after the first dose.

The trial was divided into three phases: screening/baseline, treatment, and follow-up.

Screening/baseline period: Subjects enter the screening/baseline period for screening examination after signing the informed consent.

Treatment period: Eligible subjects were randomly assigned at a ratio of 1:1:1:1 to receive Y-3 injection low-dose group, medium-dose group, high-dose group and placebo control drug for 10 consecutive days (10 times), during which relevant examinations required by the protocol were conducted and safety was assessed.

Follow-up period: Participants who finished treatment were followed up until 90 days after the first dose.

Stroke-related scale scores were performed at 10, 30, and 90 days after first use of the investigational drug The scores of Montgomery Depression Rating Scale (MSAS) and Hamilton Anxiety Scale (HAMA) were performed on the 10th and 90th days after the use of experimental drugs. Adverse events were recorded during treatment and follow-up to further assess safety

Study Overview

• Status: Completed
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: Y-3 Injection/Y-3 blank injection

Detailed Description

A multicenter, randomized, double-blind, parallel, placebo-controlled trial design was designed to include 240 participants, who were randomly assigned to Y-3 low-dose group (20 mg/ time, qd), medium-dose group (40 mg/ time, qd), high-dose group (60 mg/ time, qd) and placebo control group in a ratio of 1:1:1:1. Each group had 60 cases.

Random stratification factors included: onset time (≤24 hours, > 24 hours).The patients were treated for 10 consecutive days (10 times) and followed up to 90 days after the first dose.

The trial was divided into three phases:screening/baseline, treatment, and follow-up.

Screening/baseline period: Subjects enter the screening/baseline period for screening examination after signing the informed consent.Treatment period: Eligible subjects were randomly assigned at a ratio of 1:1:1:1 to receive Y-3 injection low-dose group, medium-dose group, high-dose group and placebo control drug for 10 consecutive days (10 times), during which relevant examinations required by the protocol were conducted and safety was assessed.Follow-up period: Participants who finished treatment were followed up until 90 days after the first dose.Stroke-related scale scores were performed on the 10th, 30th and 90th days after the first use of the experimental drug, and Montgomery Depression Rating Scale (MADRS) and Hamilton Anxiety Scale (HAMA) scores were performed on the 10th and 90th days after the first use of the experimental drug. Adverse events were recorded during treatment and follow-up to further assess safety.

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100000
      • Beijing Tiantan Hospital, Capital Medical University Beijing
  • Guangxi
    • Liuzhou, Guangxi, China, 545000
      • Liuzhou Workers Hospital
  • Hebei
    • Cangzhou, Hebei, China, 061000
      • Cangzhou Central Hospital
    • Hengshui, Hebei, China, 053000
      • Harrison International Peace Hospital
  • Heilongjiang
    • Daqing, Heilongjiang, China, 163000
      • Daqing Oilfield General Hospital
    • Daqing, Heilongjiang, China, 163000
      • Daqing People's Hospital
  • Henan
    • Nanyang, Henan, China, 473000
      • The First Affiliated Hospital of Nanyang Medical College
    • Nanyang, Henan, China, 473000
      • Nanyang Second People's Hospital
    • Nanyang, Henan, China, 473000
      • Nanyang South Stone Hospital
  • Hunan
    • Changsha, Hunan, China, 410000
      • Hunan Provincial People's Hospital
  • Inner Mongolia Autonomous Region
    • Baotou, Inner Mongolia Autonomous Region, China, 014000
      • The First Affiliated Hospital of Baotou Medical College, Inner Mongolia University of Science and Technology
    • Baotou, Inner Mongolia Autonomous Region, China, 014100
      • Inner Mongolia Baotou Steel Hospital
    • Hohhot, Inner Mongolia Autonomous Region, China, 010000
      • Inner Mongolia International Mongolian Medicine Hospital
  • Jiangsu
    • Huai'an, Jiangsu, China, 223001
      • Huai 'an First People's Hospital
    • Lianyungang, Jiangsu, China, 222000
      • Lianyungang First People's Hospital
    • Lianyungang, Jiangsu, China, 222000
      • Lianyungang Second People's Hospital
    • Taizhou, Jiangsu, China, 225300
      • Taizhou Second People's Hospital
    • Xuzhou, Jiangsu, China, 221000
      • Xuzhou Central Hospital (Old Hospital Area)
    • Xuzhou, Jiangsu, China, 221000
      • Xuzhou Central Hospital（New compound）
    • Xuzhou, Jiangsu, China, 221000
      • Xuzhou First People's Hospital
  • Jiangxi
    • Pingxiang, Jiangxi, China, 337000
      • Pingxiang People's Hospital
  • Liaoning
    • Beipiao, Liaoning, China, 122100
      • Beipiao Central Hospital
    • Jinzhou, Liaoning, China, 121000
      • The First Affiliated Hospital of Jinzhou Medical University
    • Shenyang, Liaoning, China, 110000
      • Shenyang First People's Hospital
    • Shenyang, Liaoning, China, 110000
      • Chinese People's Liberation Army Northern Theater Command General Hospital
  • Shandong
    • Jinan, Shandong, China, 250000
      • Shandong Third Hospital
    • Liaocheng, Shandong, China, 252000
      • Liaocheng People's Hospital
    • Linyi, Shandong, China, 276100
      • Tancheng County First People's Hospital
    • Tengzhou, Shandong, China, 277500
      • Tengzhou Central People's Hospital
  • Zhejiang
    • Dongyang, Zhejiang, China, 322100
      • Dongyang City People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

-

Only those who meet all the following criteria can be included in the group:

1. Age ≥ 18 years old and<81 years old, regardless of gender;
2. After the onset of this disease, the National Institutes of Research Stroke Scale score was 6 ≤ NIHSS ≤ 20 points, and the sum of the 5th upper limb and 6th lower limb scores was ≥ 2 points. If patients receiving thrombolysis treatment were screened and evaluated based on the NIHSS score after thrombolysis;
3. Within 48 hours (including 48 hours) of onset;
4. Diagnosed as ischemic stroke according to the "Key Diagnostic Points for Various Major Cerebrovascular Diseases in China 2019", with good recovery after the first or last onset (mRS score ≤ 1 point before this onset);
5. Obtain informed consent from the patient or their legal representative voluntarily signed and approved by the ethics committee.

Exclusion Criteria:

-

Those who meet one of the following criteria during filtering cannot be included in the group:

1. Intracranial hemorrhagic diseases seen on cranial imaging: hemorrhagic stroke, epidural hematoma, intracranial hematoma, ventricular hemorrhage, subarachnoid hemorrhage, etc; If it is only oozing blood, the researcher can determine whether it is suitable for enrollment;
2. Severe consciousness disorder: The item score of NIHSS's 1a consciousness level is greater than 1 point;
3. Transient ischemic attack (TIA);
4. After controlling the patient's blood pressure, the systolic blood pressure remains ≥ 220mmHg or the diastolic blood pressure remains ≥ 120mmHg;
5. Previously diagnosed patients with severe mental disorders and severe dementia;
6. Patients previously diagnosed with depression or anxiety disorder;
7. Patients undergoing antidepressant or anti anxiety treatment;
8. Diagnosed with severe active liver diseases, such as acute hepatitis, chronic active hepatitis, liver cirrhosis, etc; Or ALT or AST>2.0 × ULN;
9. Diagnosed with severe active kidney disease or renal insufficiency; Or serum creatinine>1.5 × ULN;
10. After the onset of the disease, drugs with brain cytoprotection in the instructions have been used, such as edaravone, concentrated solution of edaravone and dextranol for injection, nimodipine, ganglioside, CDPC, piracetam, oxiracetam, butylphenylpeptide, human urinary kallidinogenase (Urinary Kallidinogenase), cinepazide, rat nerve growth factor, cerebrolysin (cerebroprotein hydrolysate), calf serum deproteinized injection Calf blood deproteinized extract injection, etc;
11. After the onset of this disease, thrombectomy or interventional therapy has been applied or planned to be applied;
12. Previously diagnosed with concurrent malignant tumors and undergoing anti-tumor treatment;
13. Previously diagnosed with severe systemic diseases, with an estimated survival period of<90 days;
14. The patient is in pregnancy, lactation, and there is a possibility of pregnancy in the patient/patient partner who plans to conceive during the trial period;
15. Previously known allergies to this product or any of its excipients (15-hydroxystearic acid polyethylene glycol ester, propylene glycol, sodium hydroxide);
16. A history of major surgeries within 4 weeks prior to enrollment and assessed by the researcher as affecting neurological function scores or affecting 90 day survival;
17. Have participated in other clinical studies or are currently participating in other clinical studies within the first 30 days of randomization;
18. The researcher believes that it is not suitable to participate in this clinical study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Y-3 low-dose group (20 mg/dose, qd); Y-3 injection 20mg diluted with about 250 ml normal saline, intravenous infusion, qd, continuous medication for 10 days.	Drug: Y-3 Injection/Y-3 blank injection; The first dose should be completed as soon as possible after randomization; The time from the second dose to the first dose shall not be less than 12h, but not more than 24h+1h; The time interval of each subsequent administration is 24h±1h;
Experimental: Y-3 medium dose group (40 mg/dose, qd); Y-3 injection 40mg diluted with about 250 ml normal saline, intravenous infusion, qd, continuous medication for 10 days.	Drug: Y-3 Injection/Y-3 blank injection; The first dose should be completed as soon as possible after randomization; The time from the second dose to the first dose shall not be less than 12h, but not more than 24h+1h; The time interval of each subsequent administration is 24h±1h;
Experimental: Y-3 high-dose group (60 mg/dose, qd); Y-3 injection 60mg diluted with about 250 ml normal saline, intravenous infusion, qd, continuous medication for 10 days.	Drug: Y-3 Injection/Y-3 blank injection; The first dose should be completed as soon as possible after randomization; The time from the second dose to the first dose shall not be less than 12h, but not more than 24h+1h; The time interval of each subsequent administration is 24h±1h;
Placebo Comparator: Blank control group; Y-3 blank injection 10ml was diluted with about 250 ml normal saline, intravenous infusion, qd, and continuous medication for 10 days.	Drug: Y-3 Injection/Y-3 blank injection; The first dose should be completed as soon as possible after randomization; The time from the second dose to the first dose shall not be less than 12h, but not more than 24h+1h; The time interval of each subsequent administration is 24h±1h;

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of subjects with mRS score ≤ 1 on the 90th day of treatment .	The proportion of subjects with mRS score ≤ 1 on the 90th day of treatment .	90th day of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Grade analysis of mRS Score on the 90th day of treatment;	Grade analysis of mRS Score on the 90th day of treatment;	90th day of treatment
The proportion of subjects with mRS Score ≤2 on the 90th day of treatment;	The proportion of subjects with mRS Score ≤2 on the 90th day of treatment;	90th day of treatment
Changes in NIH Stroke Scale from baseline on day 10 of treatment;	Changes in NIH Stroke Scale from baseline on day 10 of treatment;	10th day of treatment
Proportion of NIH Stroke of 0-1 or ≥4 reduction from baseline on day 10 and day 30 of treatment.	Proportion of NIH Stroke of 0-1 or ≥4 reduction from baseline on day 10 and day 30 of treatment.The content of NIHSS score included: consciousness level (consciousness level, consciousness level questioning, consciousness level command), gaze, visual field, facial paralysis, upper limb movement, lower limb movement, body aid movement, sensation, language, dysarthria, neglect. The score ranges from 0 to 42, with higher scores indicating more severe nerve damage.Score 0 to 1: normal or nearly normal Scores 1-4: mild stroke/minor stroke .5 to 15 points: moderate stroke .15-20 points: moderate to severe stroke Scores 21-42: severe stroke	On the 10th and 30th day of treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montgomery Depression Rating Scale scores on day 10 and day 90 were <, respectively; Proportion of patients with scores of 12, ≥12, and ≥22;	Montgomery Depression Rating Scale scores on day 10 and day 90 were <, respectively; Proportion of patients with scores of 12, ≥12, and ≥22.There are 10 items in the scale, with a total score of 60 points. The higher the score, the higher the degree of depression. MADRS < 12 indicates no depressive symptoms, 12≤MADRS < 22 indicates mild depression, 22≤MADRS < 30 indicates moderate depression, and MADRS≥30 indicates severe depression.	On the 10th and 90th day of treatment
Hamilton Anxiety Scale scores on day 10 and day 90 were <, respectively; Proportion of patients with scores of 7, ≥7, and ≥14.	Hamilton Anxiety Scale (HAMA) scores on day 10 and day 90 were <, respectively; Proportion of patients with scores of 7, ≥7, and ≥14.The scale used a 5-level scoring method, and the criteria for each level were: 0-asymptomatic; 1- Light; 2- Medium; 3- heavy; 4- Extremely heavy. The total score of Hamilton anxiety Scale is a very important basis to reflect the severity of patients' anxiety, that is, the less severe the disease, the lower the total score; The more severe the condition, the higher the total score. A total score of less than 7 is considered to have no symptoms of anxiety; A score of 7-13 is considered to be likely to have anxiety; A score of 14 to 20 is considered to be definitely anxious; 21 to 28 points, is considered to have significant anxiety; A score greater than 29 is considered likely to be severe anxiety.	On the 10th and 90th day of treatment
Incidence of adverse events (AE) in each group;	Incidence of adverse events (AE) in each group;	From the time the subject receives medication to the end of the 90th day of the treatment
The incidence of treatment-related adverse events (TEAEs) in each group;	The incidence of treatment-related adverse events (TEAEs) in each group;	From the time the subject receives medication to the end of the 90th day of the treatment
The occurrence of important adverse events in each group;	The occurrence of important adverse events in each group;	From the time the subject receives medication to the end of the 90th day of the treatment
The occurrence of serious adverse events (SAEs) in each group;	The occurrence of serious adverse events (SAEs) in each group;	From the time the subject receives medication to the end of the 90th day of the treatment
The occurrence of suspicious and unexpected serious adverse reactions (SUSAR) in each group;	The occurrence of suspicious and unexpected serious adverse reactions (SUSAR) in each group;	From the time the subject receives medication to the end of the 90th day of the treatment
Laboratory examination indicators: blood routine, urine routine, blood biochemistry, Laboratory examination indicators: blood routine, urine routine, blood biochemistry, coagulation function	Detect blood routine through a blood cell analyzer, including white blood cell count, neutrophil count, lymphocyte count, hemoglobin, and platelet count.Use a biochemical analyzer to detect blood biochemistry, including alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, direct bilirubin, creatinine, urea/urea nitrogen, uric acid, and so on. Detect coagulation function through a coagulation analyzer, including prothrombin time (PT), partially activated prothrombin time (APTT), international standardized ratio (INR), fibrinogen (FIB).Detect urine routine through a urine analyzer.These indicators are measured during the baseline period and post administration visit period to observe the impact of the drug on this indicator, whether the drug will cause AE and SAE，the occurrence of AE and SAE, the type and severity of AE and SAE, and ultimately to determine the safety of the drug.	Baseline period, on the 10th , 30th and 90th day
Vital signs: heart rate, blood pressure, body temperature, respiration	Detecting parameters such as heart rate, electrocardiogram, and QT interval through an electrocardiogram monitor.Detecting blood pressure through a blood pressure monitor.Detecting body temperature through a thermometer.Detect respiratory rate by observing changes in chest contour count of the subject.These indicators are measured during the baseline period and post administration visit period to observe the impact of the drug on this indicator, whether the drug will cause AE and SAE，the occurrence of AE and SAE, the type and severity of AE and SAE, and ultimately to determine the safety of the drug.	Baseline period, on the 10th , 30th and 90th day
Physical examination of the whole body: lungs, gastrointestinal tract, urinary system, musculoskeletal system, skin, lymph nodes, and other systems.	Detect systems such as lungs, gastrointestinal tract, urinary system, musculoskeletal, skin, lymph nodes, etc. through observation, auscultation, percussion, palpation, and other examination methods. These indicators are measured during the baseline period and post administration visit period to observe the impact of the drug on this indicator, whether the drug will cause AE and SAE，the occurrence of AE and SAE, the type and severity of AE and SAE, and ultimately to determine the safety of the drug.	Baseline period, on the 10th , 30th and 90th day
Clinical laboratory examination	Laboratory evaluation not specified in the protocol, including parameters such as hematology, biochemical tests, urine analysis, etc. These indicators are measured during the baseline period and post administration visit period to observe the impact of the drug on this indicator, whether the drug will cause AE and SAE，the occurrence of AE and SAE, the type and severity of AE and SAE, and ultimately to determine the safety of the drug.	From the baseline period to the end of the 90th day of the treatment
Discontinuation due to adverse events;	Discontinuation due to adverse events【AE includes abnormal laboratory test results (haematological, clinical biochemical, or urinalysis) or other safety assessments (e.g. electrocardiograms, radiological scans, vital signs measurements), including deterioration relative to baseline and deemed clinically significant in the medical and scientific judgment of the investigator; Exacerbation of pre-existing diseases; A new condition detected or diagnosed after the initiation of the investigational drug.】	From the beginning to the end caused by adverse events
Discontinuation due to any other non-adverse event.	Discontinuation due to any other non-adverse event(Any discontinuation other than an adverse event)	From the beginning to the end due to unexpected circumstances except for adverse events

Collaborators and Investigators

• Sponsor: Beijing Tiantan Hospital
• Collaborators: Neurodawn Pharmaceutical Co., Ltd.
• Investigators: Study Director: Shuya Li, IRB of Beijing Tiantan Hospital Capital Medical University Beijing

Publications and helpful links

General Publications

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Study record dates

Study Major Dates

• Study Start (Actual): June 4, 2023
• Primary Completion (Actual): November 18, 2023
• Study Completion (Actual): December 24, 2023

Study Registration Dates

• First Submitted: April 3, 2024
• First Submitted That Met QC Criteria: May 20, 2024
• First Posted (Actual): May 28, 2024

Study Record Updates

• Last Update Posted (Estimated): June 4, 2024
• Last Update Submitted That Met QC Criteria: June 3, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction
• Other Study ID Numbers: Y-3-LC-02

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No