Clinical trial NCT06202378: Safety and Efficacy of SHPL-49 Injection in Participants With Acute Ischemic Stroke
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Acute Ischemic Stroke
Lead sponsor: Shanghai Hutchison Pharmaceuticals Limited
Sponsor class: INDUSTRY
Collaborators: name: Beijing Tiantan Hospital
First posted: 2024-01-11
Enrollment: 270
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Modified Rankin Scale (mRS), with scores of 0-1 at Day 90
timeFrame: 90±7 days
Secondary outcomes:
measure: Shift analysis/ Ordinal analysis
timeFrame: 90±7 days
measure: Modified Rankin Scale (mRS), with scores of 0-1 at Day 30
timeFrame: 30±3 days
measure: Modified Rankin Scale (mRS), with scores of 0-2 at Day 30
timeFrame: 30±3 days
measure: Modified Rankin Scale (mRS), with scores of 0-2 at Day 90
timeFrame: 90±7 days
measure: National Institute of Health stroke scale (NIHSS) on day 7or 8
timeFrame: 7 days or 8 days
measure: National Institute of Health stroke scale (NIHSS) at Day 14 or at discharge
timeFrame: 14±2 days
measure: Barthel index (BI) at Day 30
timeFrame: 30±3 days
measure: Barthel inde (BI) at Day 90
timeFrame: 90±7 days
measure: National Institute of Health stroke scale (NIHSS) at Day 14 or at discharge
timeFrame: 14±2 days or at discharge
measure: Symptomatic intracranial hemorrhage
timeFrame: 22-36h after thrombolysis
measure: Mortality
timeFrame: 90±7 days
measure: Serious adverse events
timeFrame: 90±7 days
measure: Adverse events
timeFrame: 90±7 days
measure: Changes in laboratory test indicators
timeFrame: 7 days or 8 days，14±2 days，90±7 days
measure: Changes in vital signs before and after administration
timeFrame: 7 days or 8 days，14±2 days，90±7 days
measure: 12-lead electrocardiogram
timeFrame: 90±7 days
measure: Vital signs
timeFrame: 90±7 days
measure: Physical examination
timeFrame: 90±7 days
measure: Laboratory test indicators
timeFrame: 90±7 days
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Tiantan Hosptial，Capital Medical University
state: Beijing
city: Shaoguan
country: China
facility: Yuebei People's Hospital
state: Guangdong
city: Hengshui
country: China
facility: Hengshui People's Hospital
state: Hebei
city: Tangshan
country: China
facility: Tangshan Workers' Hospital
state: Hebei
city: Nanyang
country: China
facility: Nanshi Hospital of Nanyang
state: Henan
city: Pingdingshan
country: China
facility: General Hospital of Pingmei Shenma Group
state: Henan
city: Chifeng
country: China
facility: Keshiketeng Banner Traditional Chinese Medicine and Mongolian Medicine Hospital
state: Inner Mongolia Autonomous Region
city: Changchun
country: China
facility: The First Hospital of Jilin University
state: Jilin
city: Beipiao
country: China
facility: Beipiao Central Hospital
state: Liaoning
city: Shenyang
country: China
facility: Shenyang Medical College Affiliated Central Hospital
state: Liaoning
city: Shenyang
country: China
facility: The First People's Hospital of Shenyang
state: Liaoning
city: Linyi
country: China
facility: Linyi People's Hospital
state: Shandong
city: Linyi
country: China
facility: The First People's Hospital of Tancheng
state: Shandong
city: Datong
country: China
facility: Sinopharm Tongmei General Hospital
state: Shanxi
city: Linfen
country: China
facility: Linfen Central Hospital
state: Shanxi
city: Linfen
country: China
facility: Linfen People's Hospital
state: Shanxi
Study officials:
affiliation: Beijing Tiantan Hospital
name: Yongjun Wang, master
role: PRINCIPAL_INVESTIGATOR
References: