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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
108
Glenzocimab (ACT-017, Acticor Biotech) is formulated for IV administration as a sterile product with 20 mM sodium citrate and 130 mM sodium chloride buffer at pH of 5.0. It is supplied for clinical trial use in vials containing 50 mL of the drug product at a concentration of 10 mg/mL. Each vial contains 500 mg of glenzocimab. Two vials (2x500 mg) of glenzocimab should be administered concomitantly for eligible patients for a total daily dose of 1g. Glenzocimab is intended to be administered as an IV infusion over 6 hrs, with 1/4 of the dose administered by a 15-minute bolus and 3/4 of the dose administered by 5h45min-slow infusion.
Placebo of glenzocimab is 0.9%NaCl (Acticor Biotech) for IV administration. It is supplied for clinical trial use in vials of 50 mL. Two vials of placebo of glenzocimab should be administered concomitantly for eligible patients.
Hospices Civils de Lyon
Bron, France
CHU Dupuytren
Limoges, France
CHU Timone
Marseille, France
Hôpital Gui de Chauliac
Montpellier, France
CHRU Nancy Hopital central
Nancy, France
Hôpital fondation Adolphe de Rothschild
Paris, France
Hôpital Lariboisière AP-HP
Paris, France
Hôpital Sainte Anne
Paris, France
Hôpital de Hautepierre
Strasbourg, France
Hôpital Foch
Suresnes, France
...and 2 more locations
Efficacy mRS 90
The primary efficacy endpoint is the functional outcome assessed by the modified Rankin Scale (mRS) at day 90 +/- 15 days. The Modified Rankin Scale (mRS) is used to measure the degree of disability in patients who have had a stroke. The scale runs from 0-6, running from perfect health without symptoms to death. 0 - No symptoms. 1. \- No significant disability. Able to carry out all usual activities, despite some symptoms. 2. \- Slight disability. Able to look after own affairs without assistance, but unable to carry out all previous activities. 3. \- Moderate disability. Requires some help, but able to walk unassisted. 4. \- Moderately severe disability. Unable to attend to own bodily needs without assistance, and unable to walk unassisted. 5. \- Severe disability. Requires constant nursing care and attention, bedridden, incontinent. 6. \- Dead.
Time frame: 90 days
Favorable functional outcome
Favorable functional outcome defined by a mRS ≤ 2 at day 90 +/- 15 days
Time frame: 90 days
Severe handicap
Proportion of patients with a severe handicap: mRS equal to 4, 5 or 6 at day 90 +/- 15 days
Time frame: 90 days
Survival
Overall survival at 90 days and 1 year
Time frame: 90 days and 1 year
Early reperfusion outcomes : volume
Stroke volume by MRI at 24 hrs
Time frame: 24 hours
Early reperfusion outcomes : eTICI
Reperfusion at the end of procedure assessed by the expanded treatment in cerebral infarction (eTICI) score.The eTICI is defined as follows : grade 0: no perfusion noted (0% reperfusion) grade 1: reduction in thrombus but without any resultant filling of distal arterial branches grade 2a: reperfusion of 1-49% of the territory grade 2b50: reperfusion of 50-66% of the territory grade 2b67: reperfusion of 67-89% of the territory grade 2c: extensive reperfusion of 90-99% of the territory grade 3: complete or full reperfusion (100% reperfusion)
Time frame: 24 hours
Early reperfusion outcomes NIHSS
Early neurological improvement by National Institutes of Health Stroke Scale, or NIH Stroke Scale (NIHSS) at 24 hrs. The NIHSS is composed of 11 items, each of which scores a specific ability between a 0 and 4. For each item, a score of 0 typically indicates normal function in that specific ability, while a higher score is indicative of some level of impairment. The individual scores from each item are summed in order to calculate a patient's total NIHSS score. The maximum possible score is 42, with the minimum score being a 0.
Time frame: 24 hours
Quality of life
EQ5D-5L at day 90 and at 1 year. EQ-5D is a standardised measure of health-related quality of life. The EQ-5D-5L descriptive system uses five dimensions. The five levels in each dimension are worded as (1) 'not /no problems', (2) 'slight problems', (3) 'moderate problems', (4) 'severe problems', and (5) 'unable to' (mobility, self-care, usual activities), 'extreme' (pain/depression), or 'extremely' (anxiety/depression). EQ-5D-5L is the sum of the five dimensions.
Time frame: 90 days and 1 year
IntraCranial Hemorrhages
Incidence of symptomatic or non-symptomatic IntraCranial Hemorrhages (ICH) at 24 hrs
Time frame: 24 hours
Symptomatic IntraCranial Hemorrhages
Incidence of symptomatic IntraCranial Hemorrhages (ICH) at 24 hrs
Time frame: 24 hours
Non-Symptomatic IntraCranial Hemorrhages
Incidence of non-symptomatic IntraCranial Hemorrhages (ICH) at 24 hrs
Time frame: 24 hours
Adverse event
Incidence, nature and severity of Adverse Events, SAEs, SUSARs, Bleeding-Related Events (BREs) and/or Treatment-Emergent Adverse Events (TEAEs), at 24 hrs, at D7/discharge, 30 days and 90 days
Time frame: 24 hours, 7 days, 30 days, 90 days
Bleeding relating events
Incidence of bleeding-related events at 90 days
Time frame: 90 days
Anti-glenzocimab antibodies
Anti-glenzocimab antibodies (ADA) blood concentration at 3 months for 50 patients.
Time frame: 3 months
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