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

Acute Ischemic Stroke Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06202378
• Other study ID #: SHPL-Z003-201
• Status: Recruiting
• Phase: Phase 2
• Start date: December 28, 2023
• Est. completion date: December 31, 2025

Study information

• Verified date: January 2024
• Source: Shanghai Hutchison Pharmaceuticals Limited
• Contact: Wenwen Xu, master
• Phone: 86-21-62506452
• Email: xuwenwen[@]shpl.com.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 270
• Est. completion date: December 31, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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: ? 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.

Related Conditions & MeSH terms

• Acute Ischemic Stroke
• Cerebral Infarction
• Ischemia
• Ischemic Stroke
• Stroke

Intervention

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 IV infusion and applied twice daily for 7 days.
• 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 IV infusion and applied twice daily for 7 days.
• 0.9% Sodium Chloride Injection
100 mL 0.9% sodium chloride will be administered as a 30-minute IV infusion and applied twice daily for 7 days.

Locations

Country	Name	City	State
China	Beijing Tiantan Hosptial,Capital Medical University	Beijing	Beijing
China	Linfen Central Hospital	Linfen	Shanxi

Sponsors (2)

Lead Sponsor	Collaborator
Shanghai Hutchison Pharmaceuticals Limited	Beijing Tiantan Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Barthel index (BI) at Day 30	Proportion of participants with Barthel index =95 at Day 30	30±3 days
Secondary	Barthel inde (BI) at Day 90	Proportion of participants with BI =95 at Day 90	90±7 days
Secondary	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
Secondary	Symptomatic intracranial hemorrhage	Symptomatic intracranial hemorrhage within 36h after thrombolysis (Safe Implementation of Thrombolysis in Stroke-Monitoring Study Criteria)	22-36h after thrombolysis
Secondary	Mortality	Mortality over the 90-day study period	90±7 days
Secondary	Serious adverse events	Serious adverse events over the 90-day study period	90±7 days
Secondary	Adverse events	Adverse events over the 90-day study period	90±7 days
Secondary	Changes in laboratory test indicators	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	7 days or 8 days,14±2 days,90±7 days
Secondary	Changes in vital signs before and after administration	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	7 days or 8 days,14±2 days,90±7 days
Secondary	12-lead electrocardiogram	Abnormal 12-lead electrocardiogram over the 90-day study period	90±7 days
Secondary	Vital signs	Abnormal vital signs over the 90-day study period	90±7 days
Secondary	Physical examination	Abnormal results of physical examination over the 90-day study period	90±7 days
Secondary	Laboratory test indicators	Abnormal laboratory test indicators over the 90-day study period	90±7 days