ACTISAVE: ACuTe Ischemic Stroke Study Evaluating Glenzocimab Used as Add-on Therapy Versus placEbo

NCT05070260 | Completed Phase 2 DMC FDA Drug

• 1 other identifier: ACT-CS-005
• Study Type: interventional
• Target: 438
• Locations: 2 countries
• Sites: 10

Brief Summary

A randomized, double blind, multicenter, multinational, placebo controlled, parallel group, single dose, adaptive phase II/III study. The study evaluates the efficacy and safety of a fixed dose of glenzocimab (1000 mg IV over 6 hrs including initial bolus of 15 minutes) on top of the best standard of care.

Conditions

Acute Ischemic Stroke

Keywords

Haemorrhages GPVI; Thrombolysis; Thrombectomy; Anti-platelet; glenzocimab; ACT017; stroke; GPVI

Outcome Measures

Primary Outcomes (1)

• Binary Poor Outcome on the mRS defined by a score of 4-6 (versions 0-3)

  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

  Day 90

Secondary Outcomes (74)

• Key Secondary Efficacy Endpoint - mRS

  Day 90

• Mortality

  Day 90

• mRS

  Day 90

• mRS

  Day 90

• Ordinal mRS

  Day 90

Other Outcomes (2)

• Imaging for exploratory endpoints

  Baseline

• Imaging for exploratory endpoints

  24 hours

Study Arms (2)

Intravenous glenzocimab (ACT017) 1000 mg

EXPERIMENTAL

Intravenous glenzocimab (ACT017) 1000 mg to be added to thrombolysis +/- mechanical thrombectomy

Drug: Intravenous glenzocimab (ACT017) 1000 mg

Intravenous Placebo

PLACEBO COMPARATOR

Intravenous Placebo to be added to thrombolysis +/- mechanical thrombectomy

Drug: Intravenous Placebo

Interventions

Intravenous glenzocimab (ACT017) 1000 mg DRUG

Add-on therapy to the standard of Care in the treatment of the acute ischemic stroke symptoms

Also known as: Thrombolysis +/- thrombectomy

Intravenous glenzocimab (ACT017) 1000 mg

Intravenous Placebo DRUG

Add-on therapy to the standard of Care in the treatment of the acute ischemic stroke symptoms

Also known as: Thrombolysis +/- thrombectomy

Intravenous Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult male or female patients ≥ 18 years (i.e., at least 18 years old at time of randomization)
• Having given their own written consent, or legal representative consent, and in any case, in strict accordance with country-specific legal requirements,
• 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
• Presenting with a pre-IVT NIHSS ≥ 6
• In whom IVT is or has been initiated, whether or not patients are additionally eligible to mechanical thrombectomy (MT+ IVT), according to the recommendation of the last guidelines (ASA and ESO recommandations),
• 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
• 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:

You may not qualify if:

• Coma, or NIHSS \>25,
• Patients \< 18 years,
• Protected adults under guardianship or curatorship,
• Prior ischemic stroke within the past 3 months,
• mRS pre-stroke known to be ≥ 2,
• 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),
• Significant mass effect with midline shift,
• Stroke of hemorrhagic origin,
• 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,
• Known renal insufficiency (Grades 4-5 - severe or terminal with a creatinine clearance \< 30 mL/min using Cockroft formula),
• Known allergic reaction to contrast agents,
• Patients under anti-coagulant therapy, except preventative doses of injectable low molecular weight heparin (LMWH),
• Known ongoing treatment with a mAb,
• Prior cardiopulmonary resuscitation \< 10 days,
• Childbirth within \< 10 days,

Sponsors & Collaborators

• Acticor Biotech: lead

Study Sites (10)

Black Medical center

Bradenton, Florida, 34209, United States

Location

Nova Clinical Research

Bradenton, Florida, 34209, United States

Location

Northside hospital

St. Petersburg, Florida, 30342, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Washington university

St Louis, Missouri, 63130, United States

Location

Miami Valley hospital

Dayton, Ohio, 45409, United States

Location

Chattanooga center for neurological research

Chattanooga, Tennessee, 37403, United States

Location

Houston Methodist hospital

Houston, Texas, 77030, United States

Location

Memorial Hermann Hospital

Houston, Texas, 77030, United States

Location

University Clinic Essen

Essen, 45147, Germany

Location

Related Publications (3)

• Voors-Pette C, Lebozec K, Dogterom P, Jullien L, Billiald P, Ferlan P, Renaud L, Favre-Bulle O, Avenard G, Machacek M, Pletan Y, Jandrot-Perrus M. Safety and Tolerability, Pharmacokinetics, and Pharmacodynamics of ACT017, an Antiplatelet GPVI (Glycoprotein VI) Fab. Arterioscler Thromb Vasc Biol. 2019 May;39(5):956-964. doi: 10.1161/ATVBAHA.118.312314.

  PMID: 31017822 BACKGROUND

• Renaud L, Lebozec K, Voors-Pette C, Dogterom P, Billiald P, Jandrot Perrus M, Pletan Y, Machacek M. Population Pharmacokinetic/Pharmacodynamic Modeling of Glenzocimab (ACT017) a Glycoprotein VI Inhibitor of Collagen-Induced Platelet Aggregation. J Clin Pharmacol. 2020 Sep;60(9):1198-1208. doi: 10.1002/jcph.1616. Epub 2020 Jun 4.

  PMID: 32500636 BACKGROUND

• Pottecher J, Raffi F, Jandrot-Perrus M, Binay S, Comenducci A, Desort-Henin V, Francois D, Gharakhanian S, Labart M, Meilhoc A, Toledano E, Pletan Y, Avenard G, Sato VH; GARDEN Investigators. Targeting GPVI with glenzocimab in COVID-19 patients: Results from a randomized clinical trial. PLoS One. 2024 Jun 17;19(6):e0302897. doi: 10.1371/journal.pone.0302897. eCollection 2024.

  PMID: 38885234 DERIVED

MeSH Terms

Conditions

Ischemic Stroke; Stroke

Interventions

glenzocimab

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Andrea Comenducci, MD

  Acticor Biotech

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A randomized, double blind, multicenter, multinational, placebo controlled, parallel group, single dose, adaptive phase II/III study (respectively Part 1 and 2).

Study Record Dates

• First Submitted: July 30, 2021
• First Posted: October 7, 2021
• Study Start: September 23, 2021
• Primary Completion: April 30, 2024
• Study Completion: April 30, 2024
• Last Updated: July 3, 2024

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1); US (9)