Inclusion Criteria:  Adult male or female patients ≥ 18 years (i.e., at least 18 years old at time of randomization) Having given their own written consent or legal representative consent or emergency consent in accordance with local legal requirements Presenting with an acute disabling ischemic stroke either in the anterior or in posterior circulation, with or without visible occlusion, with a known time of onset, that is ≤ 4.5 hrs Presenting with a pre-IVT NIHSS ≥ 4 In whom thrombolysis with tPA is or has been initiated, whether or not patients are additionally eligible to mechanical thrombectomy (MT)  With an effective birth control method (if relevant) that should last for at least 2 months for non-menopausal women, and 4 months for men after IMP administration if applicable according to local regulatory requirement; birth control methods which may be considered as highly effective include:  intrauterine device intrauterine hormone-releasing system bilateral tubal occlusion vasectomized partner sexual abstinence Women of childbearing potential must have a negative pregnancy test Patients affiliated to social security insurance (if applicable, in accordance to local regulations)  Exclusion Criteria:  Coma, or NIHSS >25. Patients < 18 years. Prior ischemic stroke within the past 3 months. 4. mRS pre-stroke known to be ≥ 2.  5. Large (more than 1/3 of the middle cerebral artery) regions of clear hypodensity on Baseline Computed Tomography or Computed Tomography Angiography (CT/CTA) or Magnetic Resonance Imaging with/without vascular injection (MRA/MRI).  6. Significant mass effect with midline shift. 7. Stroke of hemorrhagic origin. 8. Patients likely to require dual antiplatelet therapy within the 12 hrs after cessation of glenzocimab or placebo infusion for e.g., carotid stenting.  9. Known renal insufficiency (Grades 4-5 - severe or terminal). 10. Known allergic reaction to contrast agents.  11. Known ongoing anti-coagulant therapy. 12. Known ongoing treatment with a mAb. 13. Prior cardiopulmonary resuscitation < 10 days. 14. Childbirth within < 10 days.  15. Epileptic seizure at symptom onset. 16. Life expectancy (except for stroke) < 3 months. 17. Pregnancy or breastfeeding.  18. Females of childbearing potential not using effective birth control methods.  19. Known current participation in another clinical investigation with experimental drug.