ACTISAVE: ACuTe Ischemic Stroke Study Evaluating Glenzocimab Used as Add-on Therapy Versus placEbo

Inclusion Criteria:

1. Adult male or female patients ≥ 18 years (i.e., at least 18 years old at time ofrandomization)

2. Having given their own written consent, or legal representative consent, and in anycase, in strict accordance with country-specific legal requirements,

3. Presenting with an acute disabling ischemic stroke either in the anterior or inposterior circulation, with or without visible occlusion, with a known time ofonset, that is ≤ 4.5 hrs

4. Presenting with a pre-IVT NIHSS ≥ 6

5. In whom IVT is or has been initiated, whether or not patients are additionallyeligible to mechanical thrombectomy (MT+ IVT), according to the recommendation ofthe last guidelines (ASA and ESO recommandations),

6. Women of childbearing potential (WOCBP) must have a negative serum/urine pregnancytest at baseline. Women of childbearing potential, i.e., fertile, are defined aswomen following menarche and until becoming post-menopausal unless permanentlysterile, i.e., having undergone hysterectomy, bilateral salpingectomy and bilateraloophorectomy

7. Post-menopausal women defined as not having menses for 12 months without analternative medical cause. For WOCBP, a highly effective birth control method shouldbe in place that can achieve a failure rate of less than 1% per year that shouldlast for at least 2 months after IMP administration. Birth control methods which may be considered as highly effective in WOCBP include:

• combined (estrogen and progestogen containing) hormonal contraceptionassociated with inhibition of ovulation (intravaginal, transdermal),

• progestogen-only hormonal contraception associated with inhibition of ovulation (injectable, implantable)

• intrauterine device (IUD),

• intrauterine hormone-releasing system (IUS),

• bilateral tubal occlusion,

• vasectomized partner, Birth control methods which may be considered as highly effective for men and thatshould last for 4 months after IMP administration include:

• vasectomy,

• use of condom combined with a highly effective birth control method for theirWOCBP partner. Please note that hormonal contraception is a risk factor for thromboembolic eventsand attention should be called to reconsider it passed the acute stroke phase.

8. Patients affiliated to a health insurance - modality depending on country legalrequirement

Exclusion Criteria:

1. Coma, or NIHSS >25,

2. Patients < 18 years,

3. Protected adults under guardianship or curatorship,

4. Prior ischemic stroke within the past 3 months,

5. mRS pre-stroke known to be ≥ 2,

6. Large (more than 1/3 of the middle cerebral artery) regions of clear hypodensity onBaseline Computed Tomography Angiography (CTA) or Magnetic Resonance Imaging (MRI)or with vascular injection (MRA),

7. Significant mass effect with midline shift,

8. Stroke of hemorrhagic origin,

9. Patients likely to require dual antiplatelet therapy (DAPT) within the first 24 hrsafter cessation of glenzocimab or placebo infusion for e.g., carotid stenting,

10. Known renal insufficiency (Grades 4-5 - severe or terminal with a creatinineclearance < 30 mL/min using Cockroft formula),

11. Known allergic reaction to contrast agents,

12. Patients under anti-coagulant therapy, except preventative doses of injectable lowmolecular weight heparin (LMWH),

13. Known ongoing treatment with a mAb,

14. Prior cardiopulmonary resuscitation < 10 days,

15. Childbirth within < 10 days,

16. Seizures at stroke onset if it precludes obtaining an accurate baseline (pre-IVT)NIHSS,

17. Life expectancy (except for stroke) < 3 months,

18. Pregnancy or breastfeeding,

19. Females of childbearing potential not using effective birth control methods,

20. Known current participation in another clinical investigation with experimentaldrug.