Glenzocimab for REperfusion in the setting of Endovascular therapy for brain infarctioN

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

3 Jan 2023 → 30 Jul 2025

Decision date (initial)

2024-10-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

ANR

External identifiers

EU CT number

2024-514352-32-00

EudraCT number

2021-000889-16

ClinicalTrials.gov

NCT05559398

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Therapy

To evaluate the efficacy of glenzocimab in addition to EVT and compared to EVT plus placebo, whether or not associated with IVT, on functional outcome at day 90.

Secondary objectives 3

1. • To evaluate the impact of glenzocimab in addition to EVT compared to EVT, whether or not associated with IVT, plus placebo on overall survival at day 90 and 1 year
2. • To evaluate the impact of glenzocimab in addition to EVT compared to EVT, whether or not associated with IVT, plus placebo on: 1. reperfusion at the end of EVT 2. early clinical improvement at 24 hrs 3. symptomatic intracranial haemorrhage at 24 hrs 4. overall intracranial haemorrhage at 24 hrs 5. serious adverse events (SAEs) 6. suspected unexpected serious adverse reactions (SUSARs) at 24 hrs and at day 90 7. bleeding-related events (BREs) at 24 hrs and at day 90 8. quality of life at day 90 and 1 year
3. • To evaluate the cost effectiveness of glenzocimab in addition to EVT compared to EVT plus placebo

Conditions and MedDRA coding

Acute ischemic stroke

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. 1. Age 18 years or older (Age≥18 years)
2. 2. No significant pre-stroke disability (pre-stroke mRS must be equal to 0 or 1);
3. 3.Indication of EVT within the time-window of 0 to 24 hrs in participants, treated with or without intravenous thrombolysis, and presenting with a clinico-radiological mismatch (defined by a NIHSS≥10 and an ASPECT score≥6)
4. 4. Occlusion of the cervical or intracranial internal carotid artery (ICA) or the proximal middle cerebral artery (MCA - M1 and/or M2), on magnetic resonance angiography (MRA) or, when this is not possible, on CT angiography (CTA);
5. 5. 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.
6. 6. 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.
7. 7. Women of child-bearing 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.
8. 8. Affiliation to social security or any health insurance

Exclusion criteria 18

1. 1. Contraindications to EVT;
2. 2. Contraindication to contrast agents
3. 3. Pre-existing neurologic and psychiatric disease with mRS ≥ 2;
4. 4. Unknown symptom’s onset or last seem well > 24 hours;
5. 5. Patients under or needing immediate DAPT administration;
6. 6. Significant mass effect with midline shift as confirmed on CT/MRI;
7. 7. Gastrointestinal or urinary tract hemorrhage in previous 21 days;
8. 8. Patient with intracranial haemorrhage
9. 9. Known Platelet count <100 000 mm3
10. 10. Pregnant or breastfeeding woman;
11. 11. Known hypersensitivity to glenzocimab or to any of the excipients;
12. 12. Known Severe renal insufficiency (Grades 4-5) with a glomerular filtration rate < 30mL/Min/1.73m2;
13. 13. Participation in another interventional clinical trial within 30 days prior to the inclusion.
14. 14. 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)
15. 15. Adults subject to a legal protection measure (L.1121-8)
16. 16. The patient or his/her family (if the patient is unable to give his/her opinion) expresses an inability to return for protocol visits
17. 17. patients receiving anticoagulants (i.e. heparin within 48 hours and an elevated aPTT -greater than upper limit of normal for laboratory-; (current use of oral anticoagulants (ex: warfarin) and INR >1.7; Current use of direct thrombin inhibitors or direct factor Xa inhibitors, as already mentioned in the non-authorized concomitant treatments
18. 18. patients who have already received another humanized fragment of monoclonal antibody with a suspicion of hypersensitivity

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary efficacy endpoint is the functional outcome at day 90 assessed by the modified mRS at day 90 +/- 15 days.

Secondary endpoints 3

1. Efficacy : • Favourable functional outcome defined by a mRS score ≤ 2 at day 90 • Proportion of patient with severe handicap (mRS 4-6) at Day 90 • Overall Survival at day-90 and 1 year • Early reperfusion outcomes: o Stroke volume by brain imaging at 24 hrs o Reperfusion at the end of MT procedure assessed by eTICI score o Early neurological improvement by NIHSS at 24 hrs • EQ-5D-5L at day 90 and 1 year
2. Safety: • Incidence of symptomatic or non-symptomatic ICH at 24 hrs • Incidence of symptomatic IntraCranial Hemorrhages (ICH) at 24 hrs • Incidence of non-symptomatic IntraCranial Hemorrhages (ICH) at 24 hrs • Incidence, nature and severity of Adverse Events, SAEs, SUSARs, Bleeding-Related Events (BREs) and Treatment-Emergent Adverse Events (TEAEs), at 24 hrs, at D7/discharge, 30 days and 90 days • Incidence of bleeding-related events at 90 days • Anti-glenzocimab
3. Cost -effectiveness • Cost per QALY (Quality adjusted Life Year) gained with the use of glenzocimab in addition to EVT • Cost per patient with a mRS score ≤ 2 gained with the use of glenzocimab in addition to EVT

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Mikaël MAZIGHI

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Mikaël MAZIGHI

Locations

1 EU/EEA country · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications