NCT03803007

Acute Ischemic Stroke Interventional Study

Randomized, Double Blind, Multi Center, Multinational, Placebo Controlled, Single Parallel Escalating Dose Safety and Efficacy Study of ACT017 Used as an Add on Therapy on Top of Standard of Care of Acute Ischemic Stroke

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 160 (actual)
• Sponsor: Acticor Biotech · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

To assess safety of single IV (bolus + infusion) doses of ACT017 in patients with an acute ischemic stroke in addition to best emergency standard of care (including fibrinolysis by rtPA with or without added thrombectomy), with a specific focus on hemorrhage, whether clinically symptomatic (NIHSS score + 4 points or death, without other explanation), or seen (excluding other diagnoses) on 24-hour (hr) CT scan, serious adverse events (SAEs), suspected unexpected serious adverse reactions (SUSARs), and medically important events and other safety items including biological and immunological tolerability.

Detailed description

This first in-patient randomized, double blind, multicenter, multinational, placebo-controlled, parallel-dose 2-phase study combines a dose-escalation phase (1b) and a consolidation phase (2a). Dose Escalation (Phase 1b): Phase 1b was designed to (I) assess the dose- related safety and potential efficacy of glenzocimab administered as soon as possible and no later than 3 hours after the start of thrombolysis with tPA (itself administered within 4.5 hrs of the onset of acute ischemic stroke symptoms), and (II) identify the recommended phase 2 dose (RP2D). During this phase, patients were unevenly randomized between groups, to obtain a total of 60 patients, 12 at each dose level. At the starting level, 8 patients received either glenzocimab at the lowest pharmacologically active dose of 125 mg (n=4) or the matching placebo(n=4). After real-time review by the DSMB of clinical safety and a CT scan (and where available MRI) and giving a favorable opinion, the next patients were randomized in the second cohort (n=8) with 4 patients under a higher dose of 250 mg, 2 patients remaining at the initial starting dose (125 mg), and 2 patients under placebo. Following the same process, and after favorable opinion from the DSMB, patients were randomized in the third cohort (n=10) and received glenzocimab 500 mg (n=4), randomized versus 250 mg (n=2), 125 mg (n=2) or placebo (n=2). Similarly, the fourth cohort (n=12) randomized patients between ahigher dose of 1000 mg (n=4), versus 500 mg (n=2), 250 mg (n=2), 125 mg (n=2), or placebo (n=2). Once this fourth cohort completed, the DSMB issued a further positive opinion and the fifth cohort (n=22) randomized patients to 1000 mg (n=8), versus 500 mg (n=6), 250 mg (n=4), 125 mg (n=2), or placebo (n=2). Consolidation Phase with Final Dose (Phase 2a): After having reviewed patient's safety data included in the first part of the study, the DSMB confirmed that the study can continue with the glenzocimab recommended dose of 1000 mg. During this phase, a group of 100 patients will be treated, 50 with glenzocimab and 50 with matching placebo to complete the group of 160 patients planned to participate in this study. In addition, patients in each treatment arm will be stratified by type of Standard of Care (SOC) administered: * Thrombolysis with tPA only; * Thrombolysis with tPA AND mechanical thrombectomy Each treatment arm will contain 25 patients with one SOC, and 25 with the other SOC. The active glenzocimab dose will be that recommended after the last safety analysis has been performed.

Conditions

• Acute Ischemic Stroke

Interventions

Type	Name	Description
DRUG	Intravenous ACT017 1000 mg	Add-on therapy to the standard of Care in the treatment of the acute ischemic stroke symptoms
OTHER	Intravenous Placebo	Add-on therapy to the standard of Care in the treatment of the acute ischemic stroke symptoms

Timeline

• Start date: 2019-03-06
• Primary completion: 2021-09-27
• Completion: 2021-09-27
• First posted: 2019-01-14
• Last updated: 2021-10-06

Locations

1 site across 1 country: France