Clinical trial NCT06447415: Safety, Tolerability, and Preliminary Efficacy of HRS-7450 Injection in the Treatment of Acute Ischemic Stroke: a Multi-center, Randomized, Double-blind, Double-dummy, Placebo-controlled Clinical Trial
Official title: Safety, Tolerability, and Preliminary Efficacy of HRS-7450 Injection in the Treatment of Acute Ischemic Stroke: a Multi-center, Randomized, Double-blind, Double-dummy, Placebo-controlled, Single Dose Incremental Phase Ib Clinical Trial
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Acute Ischemic Stroke
Lead sponsor: Fujian Shengdi Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-06-07
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Multi-center, randomized, double-blind and double simulated, placebo controlled, single dose escalation
Primary purpose: TREATMENT

Brief summary: This study is a multi-center, randomized, double-blind, double-dummy, placebo-controlled, single dose escalation study aimed at evaluating the overall safety, tolerability, and preliminary efficacy of HRS-7450 in patients with acute ischemic stroke.


Eligibility criteria: Inclusion Criteria:

1. Fully understand and voluntarily participate in this study, and sign an informed consent form (the informed consent form can be voluntarily signed by the individual or legal representative);
2. 18 ≤ Age ≤ 80 years old;
3. The onset time is within 4.5 to 24 hours, and medication can be completed within 24 hours of onset (onset time is defined as the patient's last normal time);
4. Clinically diagnosed as acute ischemic stroke (diagnosis follows the Chinese Guidelines for the Diagnosis and Treatment of Acute Ischemic Stroke 2023);
5. mRS score ≤ 2 before the first episode;
6. When screening, the National Institutes of Health Stroke Scale (NIHSS) scores from 3 to 25 (including both ends);
7. Female and male participants with fertility must agree to use efficient contraception measures from the signing of the informed consent form until one month after the last administration of the investigational drug, without a birth plan, and without donating sperm/eggs. (See "Contraceptive methods" in the attachment for details).

Exclusion Criteria:

1. Treatment with ateplase, teneplase, or other thrombolytic drugs;
2. Proposed endovascular treatment;
3. Intracranial hemorrhagic diseases;
4. Aortic arch dissection;
5. NIHSS awareness score 1a\>2 points;
6. Epileptic seizures or neurological dysfunction after seizures, or combined with other neurological/psychiatric disorders leading to uncooperative or non cooperative physical examinations;
7. Non enhanced CT shows a low-density shadow greater than one-third of the blood supply area of the middle cerebral artery or an ASPECT score of less than 6 points in the anterior circulation;
8. Previous history of intracranial hemorrhage;
9. Intracranial tumors, arteriovenous malformations, and giant aneurysms;
10. Acute occlusion of the internal carotid artery due to carotid artery dissection;
11. Multiple infarcts in areas supplied by multiple large blood vessels;
12. Have a history of ischemic stroke, severe traumatic brain injury, or intracranial or spinal surgery in the past month;
13. Gastrointestinal or urinary system bleeding within the past 2 weeks;
14. Major surgical procedures or severe injuries within the past 2 weeks;
15. Arterial puncture that is difficult to compress and stop bleeding within the past week;
16. Active visceral bleeding;
17. After actively reducing blood pressure, systolic blood pressure ≥ 180mmHg and/or diastolic blood pressure ≥ 100mmHg;
18. Screening period examination: Blood glucose\<2.8 or\>22.2mmol/L, platelet\<100 \* 109/L, other findings suggestive of a high risk of bleeding;
19. Within the past 3 months, acute ST segment elevation myocardial infarction (MI) and/or acute decompensated heart failure occurred, and/or QTc\>520 milliseconds, and/or due to acute coronary syndrome MI、 Hospitalization or involuntary coronary intervention for cardiac arrest; Or New York Heart Association Grade III/IV heart failure; Or known to have ventricular tachycardia;
20. History of severe liver disease, or aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) and/or glutamyltransferase (GGT) ≥ 3 x ULN and/or total bilirubin (TBIL) ≥ 2 x ULN.
21. Severe kidney disease with clinical significance, or eGFR\<45mL/min/1.73 m2;
22. Subjects with known potential bleeding constitution or coagulation dysfunction;
23. Subjects with a known history of glucose-6-phosphate dehydrogenase deficiency or a family history;
24. Known to be allergic to any component of HRS-7450 or its formulations or placebo;
25. Received therapeutic or prophylactic doses of heparin treatment within 24 hours;
26. Oral coumarin anticoagulants with an international standardized ratio INR\>2.7;
27. Use thrombin inhibitors, Xa factor inhibitors, or other anticoagulant drugs under study within48 hours;
28. Use platelet IIb/IIIa receptor inhibitors within 48 hours;
29. Pregnant women, or women of childbearing age who test positive for pregnancy, or those who are breastfeeding;
30. Participate in clinical studies of other drugs or devices within the first three months of the screening period (sign an informed consent form and receive treatment with the trial drug/device);
31. The terminal state of the disease, with an expected survival period of no more than 1 year;
32. Other situations where the researcher deems it inappropriate to participate in this experiment.

Primary outcomes:
measure: Symptomatic Intracranial Hemorrhage within 36 hours after the start of administration, The incidence of sICH
timeFrame: within 36 hours after the start of administration
Secondary outcomes:
measure: 7 day mortality rate after administration
timeFrame: within 7days after the start of administration
measure: The incidence of sICH 7 days after administration
timeFrame: within 7days after the start of administration
measure: The incidence of ICH 7 days after administration
timeFrame: within 7days after the start of administration
measure: The incidence of systemic bleeding 7 days after administration
timeFrame: within 7days after the start of administration
measure: Effective reperfusion rate measured by 24-hour PWI or CTP
timeFrame: within 24 hours after the start of administration
measure: 24-hour MRA or CTA measurement of vascular reperfusion rate
timeFrame: within 24 hours after the start of administration
measure: Infarct core volume measured by CT or MRI at 5-7 days
timeFrame: within 5-7days after the start of administration
measure: 24-hour NIHSS score change
timeFrame: within 24 hours after the start of administration
measure: 24-hour good response rate (NIHSS score reduction greater than 8 points, or NIHSS score 0-1)
timeFrame: within 24 hours after the start of administration
measure: 7 day NIHSS score change
timeFrame: within 7days after the start of administration
measure: 7 day good response rate (NIHSS score reduction greater than 8 points, or NIHSS score 0-1)
timeFrame: within 7days after the start of administration
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: The First Affiliated Hospital of Sun Yat sen University
state: Guangdong
Study officials:
References: