Safety and Efficacy of SHPL-49 Injection in Participants With Acute Ischemic Stroke

A Multicenter, Randomized, Double Blind, Placebo Controlled Phase II Clinical Study to Evaluate the Safety and Efficacy of SHPL-49 Injection in the Treatment of Acute Ischemic Stroke

This study is designed to determine the safety and efficacy of SHPL-49 intravenous infusion for 7 consecutive days in the treatment of acute ischemic stroke subjects.

Study Overview

• Status: Completed
• Conditions: Acute Ischemic Stroke
• Intervention / Treatment: Drug: 3 ampoules of SHPL-49 Injection; Drug: 6 ampoules of SHPL-49 Injection; Drug: 0.9% Sodium Chloride Injection

Detailed Description

Trial Objectives:

The primary objective of this study is to determine the effectiveness of different doses of SHPL-49 intravenous infusion for 7 consecutive days in the treatment of acute ischemic stroke subjects within 8h after onset.

The secondary objective is to determine the safety of different doses of SHPL-49 intravenous infusion for 7 consecutive days in the treatment of acute ischemic stroke subjects within 8h after onset.

Trial Design:

This study is a Phase II, multicenter, randomized, double Blind, placebo-Controlled design. Participants receive twice daily dosing for 7 consecutive days, or once on Days 1 and Day 8 and twice daily on Days 2 to Day 7, with each subject scheduled to receive 14 doses throughout the clinical trial. 270 Participants will be randomized 1:1:1 to SHPL-49 injection treated group (3 ampoules of SHPL-49 injections, Bis in die（BID）), SHPL-49 injection treated group (6 ampoules of SHPL-49 injections , BID) and placebo group (BID).

• Study Type: Interventional
• Enrollment (Actual): 270
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100070
      • Beijing Tiantan Hosptial，Capital Medical University
  • Guangdong
    • Shaoguan, Guangdong, China, 512026
      • Yuebei People's Hospital
  • Hebei
    • Hengshui, Hebei, China, 053099
      • Hengshui People's Hospital
    • Tangshan, Hebei, China, 063099
      • Tangshan Workers' Hospital
  • Henan
    • Nanyang, Henan, China, 473010
      • Nanshi Hospital of Nanyang
    • Pingdingshan, Henan, China, 467099
      • General Hospital of Pingmei Shenma Group
  • Inner Mongolia
    • Chifeng, Inner Mongolia, China, 025350
      • Keshiketeng Banner Traditional Chinese Medicine and Mongolian Medicine Hospital
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
  • Liaoning
    • Beipiao, Liaoning, China, 122199
      • Beipiao Central Hospital
    • Shenyang, Liaoning, China, 110024
      • Shenyang Medical College Affiliated Central Hospital
    • Shenyang, Liaoning, China, 110041
      • The first people's hospital of Shenyang
  • Shandong
    • Linyi, Shandong, China, 276100
      • Linyi People's Hospital
    • Linyi, Shandong, China, 276100
      • The First People's Hospital of Tancheng
  • Shanxi
    • Datong, Shanxi, China, 037001
      • Sinopharm Tongmei General Hospital
    • Linfen, Shanxi, China, 041000
      • Linfen People's Hospital
    • Linfen, Shanxi, China, 041000
      • Linfen Central Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age 18-80 years old (including upper and lower limits);
2. Clinically diagnosed as acute ischemic stroke according to the latest guidelines;
3. Patients with acute ischemic stroke who plan to receive or have received standard intravenous thrombolysis in hospital (this research center) within 8h after the onset of the disease;
4. Participants who have NIHSS ≥5 and ≤ 22 before thrombolysis;
5. Pre-stroke mRS Score ≤1;
6. Participants or legally authorized representatives who are able and willing to sign informed consent.

Exclusion Criteria:

1. Complicated with intracranial hemorrhagic diseases, including hemorrhagic stroke, epidural hematoma, intracranial hematoma, ventricular hemorrhage, subarachnoid hemorrhage, etc.;
2. Severe disturbance of consciousness: patients with NIHSS 1a consciousness level item score ≥2;
3. Cerebral Computed tomography (CT) or Magnetic resonance imaging (MRI) indicated a large anterior circulation cerebral infarction (ASPECT score < 6 or infarct area greater than 1/3 of the middle cerebral artery blood supply area);
4. Stroke with rapid improvement of symptoms before intravenous thrombolysis, or acute ischemic symptoms suspected to be caused by other causes;
5. Patients who are ready to receive or have receive intravascular therapy;
6. After the onset of the disease, drugs with neuroprotective effects have been applied in the instructions. Such as commercially available Edaravone, Edaravone and Dexborneol Concentrated Solution for Injection, Butylphthalide, Nimodipine, Ganglioside, Citicoline, Piracetam, Oxiracetam, Human Urinary Kallidinogenase, Cinepazide, Mouse Nerve Growth Factor For Injection, Cerebrolysin, Deproteinised Calf Blood Serum Injection, Deproteinised Calf Blood Extractives Injection, etc.;
7. Severe hypertension: systolic blood pressure ≥185mmHg or diastolic blood pressure ≥110mmHg after taking antihypertensive drugs before thrombolysis;
8. Severe renal insufficiency: serum creatinine >2 times the upper limit of normal or creatinine clearance (CLcr)< 30mL/min (Cockcroft-Gault formula), or other known severe renal insufficiency; (Note: Cockcroft-Gault formula: ① Male: CLcr (mL/min) = [140 - age (yrs)]× body weight (kg) / [0.814 × serum creatinine (μmol/L)]; (2) female: CLcr (mL/min) = {[140 - age (years old)] by weight (kg) / [0.814 x serum creatinine (μmol/L)]} x 0.85)
9. Severe liver function impairment: Alanine aminotransferase (ALT) or Aspartate aminotransferase(AST)>3 times the upper limit of normal, or other known liver diseases such as acute and chronic hepatitis, cirrhosis, etc.;
10. Patients with a heart function rating above Class II (according to the New York Heart Association (NYHA) heart function rating) or a history of congestive heart failure;
11. Patients with concurrent malignant tumors or undergoing anti-tumor therapy;
12. Allergic to experimental drugs or similar ingredients or materials used in imaging examinations;
13. Patients during pregnancy, breastfeeding or planning pregnancy;
14. Patients who have a history of epilepsy or have had seizure-like symptoms at the onset of stroke, or suffer from serious mental disorders, intellectual disabilities or dementia;
15. Suspected or confirmed alcohol dependence, or drinking more than 3 units (male) or 2 units (female) of alcohol within 24 hours prior to onset (1 unit =360 mL beer or 45 mL liquor with 40% alcohol or 150 mL wine);
16. Patients have participated in or are participating in another clinical study within the 3 months before singing informed consent;
17. Patients who are judged unsuitable for participation by the investigators in the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SHPL-49 Injection，3 ampoules; 1mL/ampoule	Drug: 3 ampoules of SHPL-49 Injection; 3 ampoules of SHPL-49 Injection in 100 mL 0.9% sodium chloride will be administered as a 30-minute intravenous infusion and applied twice daily for 7 days.
Experimental: SHPL-49 Injection，6 ampoules; 1mL/ampoule	Drug: 6 ampoules of SHPL-49 Injection; 6 ampoules of SHPL-49 Injection in 100 mL 0.9% sodium chloride will be administered as a 30-minute intravenous infusion and applied twice daily for 7 days.
Placebo Comparator: Placebo; 1mL/ampoule	Drug: 0.9% Sodium Chloride Injection; 100 mL 0.9% sodium chloride will be administered as a 30-minute intravenous infusion and applied twice daily for 7 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Modified Rankin Scale (mRS), with scores of 0-1 at Day 90	Proportion of participants with mRS scores of 0-1 at Day 90	90±7 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Shift analysis/ Ordinal analysis	A shift of one or more categories to reduced functional dependence analyzed across the whole distribution of outcomes on the mRS at Day 90	90±7 days
Modified Rankin Scale (mRS), with scores of 0-1 at Day 30	Proportion of participants with mRS Scores of 0-1 at Day 30	30±3 days
Modified Rankin Scale (mRS), with scores of 0-2 at Day 30	Proportion of participants with mRS Scores of 0-2 at Day 30	30±3 days
Modified Rankin Scale (mRS), with scores of 0-2 at Day 90	Proportion of participants with mRS Scores of 0-2 at Day 90	90±7 days
National Institute of Health stroke scale (NIHSS) on day 7or 8	The proportion of participants with NIHSS scores of 0-1 or with ≥4 point reduction from baseline on day 7 or 8 (after the completion of the final dose)	7 days or 8 days
National Institute of Health stroke scale (NIHSS) at Day 14 or at discharge	The proportion of participants with NIHSS scores of 0 to 1 or with 4 points reduction from baseline on day 14 or at discharge	14±2 days
Barthel index (BI) at Day 30	Proportion of participants with Barthel index ≥95 at Day 30	30±3 days
Barthel inde (BI) at Day 90	Proportion of participants with BI ≥95 at Day 90	90±7 days
National Institute of Health stroke scale (NIHSS) at Day 14 or at discharge	Changes in NIHSS scores from baseline at Day 14 or at discharge	14±2 days or at discharge
Mortality	Mortality over the 90-day study period	90±7 days
Serious adverse events	Serious adverse events over the 90-day study period	90±7 days
Adverse events	Adverse events over the 90-day study period	90±7 days
12-lead electrocardiogram	Abnormal 12-lead electrocardiogram over the 90-day study period	90±7 days
Vital signs	Abnormal vital signs over the 90-day study period	90±7 days
Physical examination	Abnormal results of physical examination over the 90-day study period	90±7 days
Laboratory test indicators	Abnormal laboratory test indicators over the 90-day study period	90±7 days
Symptomatic intracranial hemorrhage	Symptomatic intracranial hemorrhage within 36h after thrombolysis (Safe Implementation of Thrombolysis in Stroke-Monitoring Study Criteria)	22-36h after thrombolysis
Changes in laboratory test indicators	Changes in laboratory test indicators on day 7 or 8(at the end of the last dose), at Day 14 or at discharge, and at Day 90	7 days or 8 days，14±2 days，90±7 days
Changes in vital signs before and after administration	Changes in vital signs on day 7 or 8 (at the end of the last dose), at Day14 or at discharge , and at Day 90	7 days or 8 days，14±2 days，90±7 days

Collaborators and Investigators

• Sponsor: Shanghai Hutchison Pharmaceuticals Limited
• Collaborators: Beijing Tiantan Hospital
• Investigators: Principal Investigator: Yongjun Wang, Master, Beijing Tiantan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 29, 2023
• Primary Completion (Actual): November 26, 2024
• Study Completion (Actual): December 16, 2024

Study Registration Dates

• First Submitted: December 28, 2023
• First Submitted That Met QC Criteria: January 1, 2024
• First Posted (Actual): January 11, 2024

Study Record Updates

• Last Update Posted (Estimated): October 28, 2025
• Last Update Submitted That Met QC Criteria: October 24, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Ischemic Stroke; Inorganic Chemicals; Chlorine Compounds; Sodium Compounds; Chlorides; Hydrochloric Acid; Sodium Chloride
• Other Study ID Numbers: SHPL-Z003-201

Drug and device information, study documents

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