Safety and Efficacy of J147 in Acute Ischemic Stroke

Korábbi kezelés

• Patients that have received intravenous or intra-arterial thrombolytic for the current stroke prior to mechanical thrombectomy.
• Patients participating in a study involving an investigational drug or device.
• Patients previously enrolled in this clinical study. Specific Neuroimaging Exclusion Criteria

Más betegség

• Serious, advanced, or terminal illness with an anticipated life expectancy of <6 months.
• History of life-threatening allergy (more than rash) to contrast medium.
• Computed tomography (CT) or MRI evidence of acute intracranial hemorrhage (the presence of chronic microbleeds is allowed).
• Imaging evidence or history of intracranial neoplasms except for meningiomas.

Laborértékek

• Known renal insufficiency with creatinine ≥3 mg/dL or glomerular filtration rate (GFR) of <30 mL/min.
• Clinically significant hepatic impairment, defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3× upper level of normal (ULN) and/or total bilirubin >1.5× ULN, unless attributable to a known diagnosis of Gilbert's syndrome without other evidence of liver dysfunction.
• Any clinically significant medical history, physical examination finding, laboratory abnormality, vital sign abnormality, or 12-Lead ECG finding that, in the opinion of the investigator, may pose a risk to the patient's safety or well-being, interfere with the patient's ability to participate fully in the study, or confound the interpretation of study results.

Egyéb

• Absolute contraindication to MRI with gadolinium contrast.
• Patients that are unlikely to be available for a 90-day follow up.
• Female patients who are pregnant or lactating or are unwilling to use effective methods of contraception.
• Patients with known adverse reaction to J147 or its components.
• Significant mass effect with midline shift.

• Signed informed consent obtained from the patient or legally authorized representative.
• A new focal disabling neurologic deficit consistent with acute cerebral ischemia.
• Baseline NIHSS ≥5 and ≤25 points obtained prior to randomization with a disabling neurological deficit as determined by clinical judgement.
• Pre-stroke mRS score of 0-2.
• Availability to be treated within 24 hours of last known well.
• Candidates to receive EVT treatment without IV thrombolytic therapy. Such patients should be initiated as recommended by the local standard of care for the early management of patients with AIS.
• eTICI or better reperfusion achieved after completion of EVT.
• Females, unless they are permanently sterile (e.g., hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) or postmenopausal (defined as no menses for at least 12 consecutive months without an alternative medical cause and, when applicable, confirmed by serum follicle stimulating hormone [FSH] level) must agree to use highly effective methods of contraception during the study and for a minimum of 30 days after the last dose of study drug. In women aged <45 years who report being postmenopausal, postmenopausal status must be confirmed by a serum FSH level in the postmenopausal range according to the laboratory's reference values. Until postmenopausal status is confirmed, these participants must remain abstinent or use a highly effective method of contraception. Highly effective methods include:
  • Combined (estrogen- and progestogen-containing) hormonal contraception (oral, intravaginal, transdermal, or injectable).
  • Progestogen-only hormonal contraception (oral, injectable, or implantable).
  • Intrauterine device (IUD).
  • Intrauterine hormone-releasing system (IUS).
  • Bilateral tubal occlusion.
  • Sexual abstinence, if consistent with the participant's usual lifestyle.
  • Vasectomized partner, provided the partner is the sole sexual partner and the vasectomy has been confirmed with a negative sperm count.
  • Barrier methods (e.g., condoms with spermicide, diaphragms) are not considered highly effective and should only be used as additional protection.
• Women of childbearing potential (WOCBP) must have a negative urine pregnancy test before enrollment.
• Male participants with WOCBP partners must either:
  • Be vasectomized, or
  • Agree to use condoms with spermicide plus an additional highly effective method of contraception used by the female partner, during the study and for 30 days after the last dose of study drug.
• Men must also agree not to donate sperm during the study and for the same period post-treatment.
  • Specific Neuroimaging Inclusion Criteria
• Occlusion of an internal carotid, middle cerebral, anterior cerebral, posterior cerebral artery, suitable for mechanical embolectomy, confirmed on vascular imaging. Tandem extra-intracranial lesions may be included.
  • The following imaging criteria should also be met on admission neuroimaging:
• MRI criterion: volume of DWI ≥5 and ≤70 mL determined by any validated, automated artificial intelligence (AI) thresholding estimates of core and penumbra for participant selection and mismatch volume at least 25 mL, mismatch ratio at least 1.8 and a hypoperfusion intensity ratio 0.4 or higher.