Phase III Clinical Trial of Y-2 Sublingual Tablets in the Treatment of Acute Ischemic Stroke

Phase III Clinical Trial of Y-2 Sublingual Tablet in the Treatment of Acute Ischemic Stroke - a Multicenter, Randomized, Double-blind, Parallel, Placebo-controlled Phase III Clinical Trial

At present, the treatment of acute ischemic stroke includes intravenous thrombolysis, intravascular interventional therapy (including arterial thrombolysis, mechanical thrombectomy, angioplasty and stent implantation), antiplatelet therapy, anticoagulant therapy, defibrasion therapy, volume expansion therapy, and neuroprotective therapy. Y-2 sublingual tablet is an innovative drug developed by Yantai yinuoyi Biomedical Technology Co., Ltd. with independent intellectual property rights. This product is a free radical scavenger and inflammatory protein expression inhibitor. It can clear hydroxyl free radical (COH), nitric oxide free radical (no) and peroxynitrite ion (onoa), and inhibit the expression of tumor necrosis factor-A (TNF-a), interleukin IP (IL-1 (3), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) and other inflammatory related proteins induced by cerebral ischemia. By clearing the excessive free radicals produced in the brain tissue during ischemia and reperfusion and inhibiting the secondary inflammatory reaction, we can reduce the damage of free radicals and inflammatory reaction to the brain tissue, block the pathological change process caused by cerebral ischemia from two ways, and play a synergistic therapeutic role in cerebral ischemia injury.

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Drug: Y-2 sublingual tablets; Drug: d-borneol

Detailed Description

At present, the treatment of acute ischemic stroke includes intravenous thrombolysis, intravascular interventional therapy (including arterial thrombolysis, mechanical thrombectomy, angioplasty and stent implantation), antiplatelet therapy, anticoagulant therapy, defibrasion therapy, volume expansion therapy, and neuroprotective therapy. Y-2 sublingual tablet is an innovative drug developed by Yantai Yinuoyi Biomedical Technology Co., Ltd. with independent intellectual property rights. This product is a free radical scavenger and inflammatory protein expression inhibitor. It can clear hydroxyl free radical (COH), nitric oxide free radical (no) and peroxynitrite ion (onoa), and inhibit the expression of tumor necrosis factor-A (TNF-a), interleukin IP (IL-1 (3), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) and other inflammatory related proteins induced by cerebral ischemia. By clearing the excessive free radicals produced in the brain tissue during ischemia and reperfusion and inhibiting the secondary inflammatory reaction, we can reduce the damage of free radicals and inflammatory reaction to the brain tissue, block the pathological change process caused by cerebral ischemia from two ways, and play a synergistic therapeutic role in cerebral ischemia injury.

• Study Type: Interventional
• Enrollment (Actual): 914
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijin, China
    • Peking University Third Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Study Population

Stroke patients

Description

Inclusion Criteria:

-

Those who meet all of the following requirements:

1. Age ≥ 18 years old and ≤ 80 years old, regardless of gender;
2. After the onset of the disease, the National Institutes of Stroke Scale score: 6 ≤ NIHSS ≤ 20, and the sum of the fifth upper limb score and the sixth lower limb score was ≥2;
3. The onset time is within 48 hours (including 48 hours);
4. Patients diagnosed as ischemic stroke according to "key points for diagnosis of all kinds of major cerebrovascular diseases in China 2019", with good prognosis after the first attack or the last attack (MRS score ≤ 1 before this attack);
5. The informed consent approved by the ethics committee was voluntarily signed by the patient or his legal representative.

Exclusion Criteria:

-

Those who meet any of the following items:

1. Intracranial hemorrhagic diseases seen in head imaging: hemorrhagic stroke, epidural hematoma, intracranial hematoma, intraventricular hemorrhage, subarachnoid hemorrhage, etc; If it is only oozing blood, the researcher can judge whether it is suitable for inclusion;
2. Severe disturbance of consciousness: the item score of La consciousness level of NIHSS was more than 1;
3. Transient ischemic attack (TIA);
4. Systolic blood pressure was still higher than 220mmhg or diastolic blood pressure was higher than 120mmhg after blood pressure control;
5. Patients with severe mental disorders and dementia;
6. Severe active liver diseases have been diagnosed, such as acute hepatitis, chronic active hepatitis, cirrhosis, etc; Or ALT or AST > 2.0 × ULN;
7. Severe active kidney disease and renal insufficiency have been diagnosed; Or serum creatinine > 1.5 × ULN;
8. After the onset of the disease, the drugs with neuroprotective effect in the manual have been used;
9. Embolectomy or interventional therapy has been used or planned after the onset of the disease;
10. Complicated with malignant tumor or undergoing anti-tumor treatment; For the subjects diagnosed with malignant tumor after enrollment, whether to continue to participate in the study can be judged by the researcher and the willingness of the subjects;
11. Suffering from severe systemic diseases, the estimated survival time is less than 90 days;
12. Allergic to d-borneol or edaravone or excipients;
13. Patients during pregnancy, lactation and planned pregnancy;
14. Major operation history within 4 weeks before enrollment;
15. Have participated in other clinical studies or are participating in other clinical studies within 30 days before randomization;
16. The researcher thinks 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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Y-2 sublingual test group; Y-2 sublingual tablets: Edaravone 30mg and d-borneol 6mg.	Drug: Y-2 sublingual tablets; 30mg Edaravone+6mg d-borneo OR， Bid
Sham Comparator: placebo group; 60 μg d-borneol	Drug: d-borneol; 60 μg d-borneol OR， Bid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mRS score ≤ 1	Whether patients with mRS(Modified Rankin Scale) score ≤ 1. Used to calculate the proportion of patients with mRS score ≤ 1.	90 days after treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
patients' mRS score	patients' modified Rankin score	90 days after treatment initiation
Good functional outcome	Whether patients with mRS score ≤ 2. Used to calculate the proportion of good functional outcome (mRS ≤2)	90 days after treatment initiation
change of NIHSS score	Change of NIHSS (National Institute of Health stroke scale) score from baseline to day 14 after randomization	14 after treatment initiation
NIHSS score≤1 on 14 day	Whether NIHSS (National Institute of Health stroke scale) score≤1 on 14 day. Used to calculate the proportion of NIHSS score≤1 on 14 day.	14 after treatment initiation
NIHSS score≤1 on 30 day	Whether NIHSS (National Institute of Health stroke scale) score≤1 on 30 day. Used to calculate the proportion of NIHSS score≤1 on 30 day.	30 after treatment initiation
NIHSS score≤1 on 90 day	Whether NIHSS (National Institute of Health stroke scale) score≤1 on 90 day. Used to calculate the proportion of NIHSS score≤1 on 90 day.	90 after treatment initiation

Collaborators and Investigators

• Sponsor: Peking University Third Hospital
• Investigators: Principal Investigator: Dongsheng Fan, PhD, Peking University Third Hospital

Study record dates

Study Major Dates

• Study Start (Actual): June 28, 2021
• Primary Completion (Actual): August 10, 2022
• Study Completion (Actual): November 14, 2022

Study Registration Dates

• First Submitted: June 27, 2021
• First Submitted That Met QC Criteria: June 27, 2021
• First Posted (Actual): July 6, 2021

Study Record Updates

• Last Update Posted (Actual): August 22, 2023
• Last Update Submitted That Met QC Criteria: August 19, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke
• Other Study ID Numbers: D2020185

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