Emergent reperfusion is the main goal for acute ischemic stroke therapy (AIS). Endovascular therapy (EVT) is recommended within 6 hrs of stroke onset, and up to 24 hrs following perfusion imaging criteria.

Despite the major benefit associated with MT, more than 50% of the patients remain disabled at 3 months. Reperfusion rates after MT are critical to determine functional outcome. However, complete reperfusion is obtained in only 50 % of the patients, due to, at least in part, erratic emboli and/or no-reflow processes. The aim of this study is to evaluate the efficacy of glenzocimab in addition to EVT and compared to EVT plus placebo, whether or not associated with ntravenous thrombolysis (IVT), on functional outcome at day 90.

Inclusion Criteria:

1. Age 18 years or older (Age≥18 years)

2. No significant pre-stroke disability (pre-stroke mRS must be equal to 0 or 1);

3. Indication of EVT within the time-window of 0 to 24 hrs in participants treated with or without intravenous thrombolysis;

4. Participants presenting with a target mismatch defined by an initial infarct volume (ischemic core) of less than 70 ml, a ratio of volume of ischemic tissue to initial infarct volume of 1.8 or more, and an absolute volume of potentially reversible ischemia (penumbra) of 15 ml or more on magnetic resonance imaging (MRI) or, when this is not possible, on perfusion computed tomography (CTP);

5. Occlusion of the cervical or intracranial internal carotid artery (ICA) or the proximal middle cerebral artery (MCA - M1 and M2), on magnetic resonance angiography (MRA) or, when this is not possible, on CT angiography (CTA);

6. Informed consent signed:

   • By the patient
   • Or informed consent signed by a family members/trustworthy person if his condition does not allow him to express his consent by written as per L. 1111-6,
   • In a situation urgently and in the absence of family members/trustworthy person, the patient can be enrolled. The consent to participate to the research will be requested as soon as the condition of the patient will allow him to consent.

7. Post-menopausal women defined as not having menses for 12 months without an alternative medical cause. For WOCBP, a highly effective birth control method should be in place that can achieve a failure rate of less than 1% per year that should last 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 contraception associated 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 that should last for 4 months after IMP administration include:

   • vasectomy,
   • use of condom combined with a highly effective birth control method for their WOCB partner.

   Please note that hormonal contraception is a risk factor for thromboembolic events and attention should be called to reconsider it passed the acute stroke phase.

8. Women of child-bearing potential must have negative results of a plasma pregnancy test (serum betaHCG).

9. Affiliation to social security or any health insurance

Exclusion Criteria:

1. Contraindications to EVT;
2. Contraindication to contrast agents
3. Pre-existing neurologic and psychiatric disease with mRS ≥ 3;
4. Unknown symptom's onset;
5. Patients under or needing immediate DAPT administration;
6. Patients previously treated by tenecteplase within 24 hrs;
7. Significant mass effect with midline shift as confirmed on CT/MRI;
8. Gastrointestinal or urinary tract hemorrhage in previous 21 days;
9. Patient with intracranial haemorrhage
10. Platelet count <100 000 mm3;
11. Pregnant or breastfeeding woman;
12. Known hypersensitivity to glenzocimab or to any of the excipients;
13. Severe renal insufficiency (Grades 4-5) with a glomerular filtration rate < 30mL/Min/1.73m2;
14. Participation in another interventional clinical trial within 30 days prior to the inclusion.
15. Persons deprived of their liberty by a judicial or administrative decision, persons subject to psychiatric care under sections L.3212-1 et L.3213-1 and persons admitted to a health or social institution for purposes other than research (L.1121-6)
16. Adults subject to a legal protection measure (L.1121-8)
17. The patient or his/her family (if the patient is unable to give his/her opinion) expresses an inability to return for protocol visits
18. patients receiving anticoagulants, as already mentioned in the non-authorized concomitant treatments
19. patients who have already received another humanized fragment of monoclonal antibody with a suspicion of hypersensitivity