Acute ischemic stroke MedDRA version: 22.1 Level: LLT Classification code 10055221 Term: Ischemic stroke System Organ Class: 100000004852
Conditions
Sponsors
ACTICOR BIOTECH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adult male or female patients = 18 years (i.e., at least 18 years old at time of randomization), 2. Having given their own written consent, or legal representative consent, or emergency consent, and in any case, in strict accordance with country-specific legal requirements, 3. 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, 4. Presenting with a pre-IVT NIHSS = 6, 5. In whom IVT is or has been initiated, whether or not patients are additionally eligible to mechanical thrombectomy (MT + IVT), according to the last recommendations of the last guidelines (ASA and ESO recommendations) 6. Women of childbearing potential (WOCBP) must have a negative serum/urine pregnancy test at baseline. Women of childbearing potential, i.e., fertile, are defined as women following menarche and until becoming post-menopausal unless permanently sterile, i.e., having undergone hysterectomy, bilateral salpingectomy and bilateral oophorectomy. 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 WOCBP 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. Patients affiliated to a health insurance – modality depending on country legal requirement Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 133 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 267
Exclusion criteria
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 on Baseline 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 hrs after cessation of glenzocimab or placebo infusion for e.g., carotid stenting, 10. Known renal insufficiency (Grades 4-5 – severe or terminal), with a creatinine clearance < 30 mL/Mn using Cockroft formula) 11. Known allergic reaction to contrast agents, 12. Patients under anti-coagulant therapy, except preventative doses of injectable low molecular 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 experimental drug
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To show the efficacy of glenzocimab vs. placebo, on the "poor outcome" defined as a mRS score of 4-6 (vs 0-3) assessed at Day 90;Secondary Objective: Key Secondary Obj:To show the efficacy of glenzocimab vs. placebo on the "favorable outcome" defined as an mRS score of 0-2 (vs 3-6) assessed at Day 90. Other Secondary Obj:To assess the efficacy of glenzocimab vs. placebo on the: •mRS 5-6 at Day 90 •mRS 0-1 at Day 90 •Ordinal mRS at Day 90 •Utility weighted mRS (UW-mRS) at Day90 •Change from baseline in the National Institute of Health Stroke Scale (NIHSS) score at Day 1 •All-cause mortality within 72 hours •All-cause mortality at Day 90 •Symptomatic and non-symptomatic ICHs •To assess recanalization in patients undergoing thrombectomy •To assess cerebral tissue reperfusion •To assess the impact on follow up imaging (follow up infarct volume, infarct growth and volume of hemorrhagic transformation) To assess the efficacy of glenzocimab vs. placebo of all endpoints (primary,key secondary and secondary) in specific subgroups:subjects who will receive thrombectomy vs who will not,by age level and baseline NIHSS level. ;Primary end point(s): Binary "Poor Outcome" on the mRS defined by a score of 4-6 (versus 0-3) assessed at Day 90 ;Timepoint(s) of evaluation of this end point: Day 90 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Efficacy Endpoint: Binary "Favorable Outcome" on the mRS defined by a score of 0-2 (versus 3-6) assessed at Day 90 Other secondary Efficacy Endpoints: •All-cause mortality at Day 90 •mRS 0-1 •mRS 5-6 at Day 90 •Ordinal mRS at Day 90 •Utility-Weighted mRS •All-cause mortality within 72 hours •Symptomatic and non-symptomatic ICHs • Neurological Status Change as assessed by: - Response defined by a relative decrease (%) in NIHSS value at 24 hrs compared to pre-IVT value higher than 30%. - Relative change (%) in NIHSS value at 24 hrs compared to pre-IVT value • Recanalization rate as centrally measured by eTICI score in those patients having a post-thrombectomy angiography with a focus on successful recanalization • Infarct volume progression: - Follow-up infarct volume (FIV) at 24 hrs on non-contrast CT or diffusion weighted MRI - Infarct growth (FIV minus baseline infarct volume on non-contrast CT or diffusion-weighted MRI) • Volume of hemorrhagic transformation • Quality of Life, as assessed at Day 90 by the EuroQol-5 Dimensions (EQ-5D-5L);Timepoint(s) of evaluation of this end point: T15min 6 hrs 24 hrs 7 Days 30 Days 60 Days 90 Days | — |
Countries
Belgium, Czechia, Czech Republic, Denmark, France, Germany, Israel, Slovakia, Spain, United Kingdom, United States
Contacts
Public ContactRegulatory Affairs Manager
ACTICOR BIOTECH
Outcome results
None listed