Acute Ischemic Stroke Interventional Study

Inclusion Criteria:

1. Adult male or female patients ≥ 18 years (i.e., at least 18 years old at time ofrandomization). Extreme caution should be exercised in patients over 80 years of agewith regards their general health, neurological status and any concomitant diseasesand treatments that are likely to be more common;
2. Patients who have given written consent, legal representative consent or emergencyconsent (including e-consent) in accordance with local legal and IECs/IRBsrequirements;
3. Patients presenting with an acute disabling ischemic stroke in either the anterior orposterior circulation.The time of onset is known or if unknown, the last time thepatient was seen well, was at most 4.5 hrs before confirmation of the diagnosisenabling the initiation of alteplase administration within this time-frame;
4. Patients presenting at least a NIHSS ≥ 6 prior to thrombolysis with tPA;
5. Patients eligible for, or administered thrombolysis treatment with tPA;
6. Patients who can undergo mechanical thrombectomy if eligible;
7. Patients affiliated to social security insurance (if applicable, in accordance tolocal regulations);
8. Effective birth control method should be used for at least the next 2 months by women,and 4 months by men after IMP administration; birth control methods considered to behighly effective include:

• intrauterine device
• intrauterine hormone-releasing system
• bilateral tubal occlusion
• vasectomized partner
• sexual abstinence (if applicable in accordance to local regulations)

9. Women of child-bearing potential must undergo a urinary or plasma pregnancy test withnegative results;

Exclusion Criteria:

1. Coma, and/or NIHSS >25;
2. Patients < 18 years of age;
3. Prior ischemic stroke within the past 3 months with pre-stroke mRS known to be > 2;
4. Baseline CT-scan evaluation: more than 1/3 of the middle cerebral artery) regions ofclear hypodensity on the baseline imaging;
5. Significant mass effect with midline shift;
6. Stroke of hemorrhagic origin;
7. Contra-indications to thrombolysis with tPA:
8. Patients with known hypersensitivity to the active substance alteplase or to anyof its excipients;
9. Patients with a high risk of hemorrhages:

• significant bleeding disorder at present or within the past 6 months;
• known haemorrhagic diathesis (episodes within past 6 months);
• patients receiving effective oral anticoagulant treatment, e.g. warfarinsodium;
• manifest or recent severe or dangerous bleeding;
• known history of or suspected intra-cranial haemorrhage;
• any history of central nervous system lesion (i.e. trauma, intra-parenchymalneoplasm, unsecured aneurysm, intracranial or spinal surgery, vascularmalformation etc..);
• recent (< 10 days) traumatic external heart massage, obstetrical delivery,or puncture of a non-compressible blood-vessel (e.g. subclavian or jugularvein puncture);
• bacterial endocarditis, pericarditis;
• acute pancreatitis;
• documented ulcerative gastrointestinal disease during the past 3 months,oesophageal varices, arterial-aneurysm, arterial/venous malformations;
• neoplasm involving an increased risk of bleeding;
• severe liver disease, including hepatic failure, cirrhosis, portalhypertension (esophageal varices) and active hepatitis;
• major surgery or significant trauma during the past 3 months;
• patients receiving anti-coagulants prior to study: the inclusion may howeverbe considered when the dose or time since the last intake of anticoagulanttreatment makes residual efficacy unlikely. This should be confirmed by theappropriate tests of anticoagulant activity for the product(s) concerned toshow no clinically relevant activity on the coagulation system defined asfollows :
• INR ≤ 1.5 for vitamin K antagonists; .
• Low Molecular Weight Heparin (LMWH) and Unfractionated Heparin (UFH):aPPT/ACT/KCT ≤ 39 sec or their patient/witness ratio ≤ 1.2 and/or PT ≤ 16 sec (heparin at sub-therapeutic doses (≤ 50 IU/kg) during themechanical thrombectomy procedure is authorized);
• Non-Vitamin-K or Direct Oral Anti-Coagulants (NOACs- DOACs) ≤ 50 ng/mLin patients with normal renal function;
• need for carotid stenting together with a dual anti-platelet treatment (ontop of glenzocimab); this can be carried out 24 hrs after the initiation oftreatment with glenzocimab;
• platelets count <100 × 103/μL (<100 000/ mm3)
• prior hemorrhagic stroke.

3. Systolic blood pressure ≥ 185 mm Hg despite appropriate acute therapy to lowerblood pressure therapy;
4. Diastolic blood pressure ≥ 110 mm Hg; despite appropriate acute therapy to lowerblood pressure therapy;
5. Glucose >400 mg/dL (>4 g/L) despite treatment;
6. Glycemia <50 mg/dL (<0,5 g/L);
7. Patients receiving a dual antiplatelet treatment;
8. Cardiopulmonary resuscitation within the past 10 days;
9. Childbirth within the past 10 days,
10. Epileptic seizure at the onset of symptoms;
11. Life expectancy < 3 months
12. Pregnant or breastfeeding;
13. Females of childbearing potential not using effective birth control methods;
14. Known severe (grade 3 and above) renal impairment or Glomerular Filtration Rate < 30ml/min/1.73 m2 or Serum Creatinine > 2X ULN (1.2 mg/dL for men and 1.0 mg/dL forwomen) at screening;
15. Known current participation