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

Phase 2

Active, not recruiting

• Conditions: Acute Ischemic Stroke
• Interventions: Drug: 3 ampoules of SHPL-49 Injection; Drug: 0.9% Sodium Chloride Injection; Drug: 6 ampoules of SHPL-49 Injection

• Registration Number: NCT06202378
• Lead Sponsor: Shanghai Hutchison Pharmaceuticals Limited

Brief Summary

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.

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, BID), SHPL-49 injection treated group (6 ampoules of SHPL-49 injections , BID) and placebo group (BID).

Study Timeline

• Study First Submitted: 2023-12-28
• Study Start: 2023-12-29
• Study First Submitted QC: 2024-01-01
• Study First Posted: 2024-01-11
• Status Verified: 2024-10
• Primary Completion: 2024-12-16
• Last Update Submitted: 2025-05-12
• Last Update Posted: 2025-05-14
• Study Completion: 2025-12-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 270

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 CT or 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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SHPL-49 Injection，3 ampoules	3 ampoules of SHPL-49 Injection	1mL/ampoule
Placebo	0.9% Sodium Chloride Injection	1mL/ampoule
SHPL-49 Injection，6 ampoules	6 ampoules of SHPL-49 Injection	1mL/ampoule

Primary Outcome Measures

Name	Time	Method
Modified Rankin Scale (mRS), with scores of 0-1 at Day 90	90±7 days	Proportion of participants with mRS scores of 0-1 at Day 90

Secondary Outcome Measures

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

Trial Locations

Locations (16)

Yuebei People's Hospital; 🇨🇳 Shaoguan, Guangdong, China

Hengshui People's Hospital; 🇨🇳 Hengshui, Hebei, China

Tangshan Workers' Hospital; 🇨🇳 Tangshan, Hebei, China

Nanshi Hospital of Nanyang; 🇨🇳 Nanyang, Henan, China

General Hospital of Pingmei Shenma Group; 🇨🇳 Pingdingshan, Henan, China

Keshiketeng Banner Traditional Chinese Medicine and Mongolian Medicine Hospital; 🇨🇳 Chifeng, Inner Mongolia Autonomous Region, China

The First Hospital of Jilin University; 🇨🇳 Changchun, Jilin, China

Beipiao Central Hospital; 🇨🇳 Beipiao, Liaoning, China

Shenyang Medical College Affiliated Central Hospital; 🇨🇳 Shenyang, Liaoning, China

The First People's Hospital of Shenyang; 🇨🇳 Shenyang, Liaoning, China

Linyi People's Hospital; 🇨🇳 Linyi, Shandong, China

The First People's Hospital of Tancheng; 🇨🇳 Linyi, Shandong, China

Sinopharm Tongmei General Hospital; 🇨🇳 Datong, Shanxi, China

Linfen People's Hospital; 🇨🇳 Linfen, Shanxi, China

Beijing Tiantan Hosptial，Capital Medical University; 🇨🇳 Beijing, Beijing, China

Linfen Central Hospital; 🇨🇳 Linfen, Shanxi, China