Glenzocimab for REperfusion in the Setting of Endovascular Therapy for Brain infarctioN: GREEN Study

NCT05559398 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: APHP 201028 / ACT-CS-0042021-000889-16
• Study Type: interventional
• Target: 260
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Stroke, Acute; Stroke, Ischemic

Keywords

Platelet glycoprotein VI; Endovascular therapy

Outcome Measures

Primary Outcomes (1)

• 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.

  90 days

Secondary Outcomes (13)

• Favorable functional outcome

  90 days

• Severe handicap

  90 days

• Survival

  90 days and 1 year

• Early reperfusion outcomes : volume

  24 hours

• Early reperfusion outcomes : eTICI

  24 hours

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Glenzocimab

EXPERIMENTAL

Drug: Glenzocimab

Interventions

Glenzocimab DRUG

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.

Glenzocimab

Placebo DRUG

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.

Placebo

Eligibility Criteria

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

You may qualify if:

• Age 18 years or older (Age≥18 years)
• No significant pre-stroke disability (pre-stroke mRS must be equal to 0 or 1);
• Indication of EVT within the time-window of 0 to 24 hrs in participants treated with or without intravenous thrombolysis;
• Participants presenting with a target mismatch defined by an initial infarct volume (ischemic core) of less than 70 ml, a ratio of volume of ischemic tissue to initial infarct volume of 1.8 or more, and an absolute volume of potentially reversible ischemia (penumbra) of 15 ml or more on magnetic resonance imaging (MRI) or, when this is not possible, on perfusion computed tomography (CTP);
• Occlusion of the cervical or intracranial internal carotid artery (ICA) or the proximal middle cerebral artery (MCA - M1 and M2), on magnetic resonance angiography (MRA) or, when this is not possible, on CT angiography (CTA);
• Informed consent signed:
• By the patient
• Or informed consent signed by a family members/trustworthy person if his condition does not allow him to express his consent by written as per L. 1111-6,
• In a situation urgently and in the absence of family members/trustworthy person, the patient can be enrolled. The consent to participate to the research will be requested as soon as the condition of the patient will allow him to consent.
• 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),

You may not qualify if:

• Contraindications to EVT;
• Contraindication to contrast agents
• Pre-existing neurologic and psychiatric disease with mRS ≥ 3;
• Unknown symptom's onset;
• Patients under or needing immediate DAPT administration;
• Patients previously treated by tenecteplase within 24 hrs;
• Significant mass effect with midline shift as confirmed on CT/MRI;
• Gastrointestinal or urinary tract hemorrhage in previous 21 days;
• Patient with intracranial haemorrhage
• Platelet count \<100 000 mm3;
• Pregnant or breastfeeding woman;
• Known hypersensitivity to glenzocimab or to any of the excipients;
• Severe renal insufficiency (Grades 4-5) with a glomerular filtration rate \< 30mL/Min/1.73m2;
• Persons deprived of their liberty by a judicial or administrative decision, persons subject to psychiatric care under sections L.3212-1 et L.3213-1 and persons admitted to a health or social institution for purposes other than research (L.1121-6)
• Adults subject to a legal protection measure (L.1121-8)

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Related Publications (1)

• Mazighi M, Lambert J, Gory B, Seners P, Calviere L, Cho TH, Aghetti A, Pasi M, Boulouis G, Lapergue B, Consoli A, Turc G, Rouchaud A, Wolff V, Pop R, Suissa L, Richard S, Cordonnier C, Arquizan C, Costalat V, Guedon A, Cognard C, Mameri L, Escalard S, Redjem H, Smajda S, Robichon E, Al Raaisi A, Boisseau W, Blanc R, Maier B, Boursin P, Dubus E, Desilles JP, Piotin M, Rigon MR, Olivot JM. Glenzocimab for reperfusion in the setting of endovascular therapy for brain infarction: GREEN study. J Neurointerv Surg. 2025 Aug 27:jnis-2025-023606. doi: 10.1136/jnis-2025-023606. Online ahead of print.

  PMID: 40866207 DERIVED

MeSH Terms

Conditions

Stroke; Ischemic Stroke

Interventions

glenzocimab

Condition Hierarchy (Ancestors)

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

Central Study Contacts

mikael Mazighi, MD PHD

CONTACT

1 49 95 25 97; mikael.mazighi@aphp.fr

matthieu resche-rigon, MDPHD

CONTACT

142499742; matthieu.resche-rigon@u-paris.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, double blinded, multicentre, placebo controlled study

Study Record Dates

• First Submitted: September 26, 2022
• First Posted: September 29, 2022
• Study Start: October 10, 2022
• Primary Completion: October 10, 2025
• Study Completion (Estimated): October 10, 2026
• Last Updated: September 29, 2022

Record last verified: 2022-09