A Phase II, Randomized, Placebo-Controlled, Double-Blind, Adaptive Study to Assess the Safety and Efficacy of Intravenous J147 Combined With Endovascular Therapy in Patients With Acute Ischemic Stroke
The goal of this clinical trial is to find out if the drug J147 improves outcomes for persons who have had an ischemic stroke. It also will learn about the safety of J147 when given by injection to stroke patients. Researchers will compare the outcomes of those who receive J147 after therapy to clear the blood clot to those who don't receive J147. Participants will be asked to undergo a series of three to four magnetic resonance imaging (MRI) brain scans, and blood samples will be collected at several time points. Participants will also be evaluated to measure several aspects of brain function.
• 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.