Glenzocimab in Anterior stroke with Large Ischemic Core eligible for Endovascular therapy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Hopital Fondation Adolphe De Rothschild

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Trial duration

completed 2 Sep 2024

Decision date (initial)

2024-05-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety, Pharmacoeconomic

To assess, in AIS patients with baseline large ischemic core eligible for EVT, the efficacy of intravenous infusion of glenzocimab versus placebo on the proportion of good functional outcome at 3 months.

Secondary objectives 18

1. To assess the rate of no-reflow (NR) phenomenon on post EVT perfusion imaging
2. To assess the symptomatic intracranial hemorrhage rate at 24-36 hours
3. To assess any intracranial hemorrhage at 24-36 hours
4. To assess the all-cause mortality rate at 3 months
5. To assess the distribution of mRS score at 3 months
6. To assess the favorable functional outcome at 3 months
7. To assess the cognitive outcome at 3 months
8. To assess the final post-EVT complete recanalization
9. To assess the final post-EVT successful recanalization
10. To assess the decompressive hemicraniectomy surgery
11. To assess the neurological improvement at 24 hours
12. To assess the infarct growth at 24 hours
13. To assess the number of EVT passes
14. To assess the duration of the EVT procedure
15. To assess the occurrence, nature and severity of adverse events
16. To assess the cost effectiveness of IV glenzocimab compared to placebo over 12 months follow-up period.
17. To assess the favorable functional outcome at 12 months
18. To assesse the cognitive outcome at 12 months

Conditions and MedDRA coding

Ischemic stroke with Large Core

Regulatory references

Scientific advice from competent authorities

Ministry Of Social Affairs And Health

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Age >18 years old
2. Acute ischemic stroke due to an isolated proximal anterior large vessel occlusion (M1 and M2 segment of the middle cerebral artery, terminal internal carotid artery (TICA)
3. Indication of EVT within the time window of 0 to 24 hours in participants treated with or without intravenous thrombolysis
4. Presenting with a baseline infarct core volume assessed on the MRI (DWI sequence) or CT scan with an ASPECTS<6
5. All women in age of procreating must have a negative serum/urine pregnancy test at baseline
6. Affiliation to social security or any health insurance
7. Informed consent signed : By the patient; Or informed consent signed by a family member/ trustworthy person if his condition does not allow him to express his consent by written (L1111-6); In a situation urgently and in 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.

Exclusion criteria 18

1. Possible tandem occlusion on the baseline imaging requiring an eventual stenting
2. Significant mass effect with midline shift as confirmed on CT/MRI
3. Gastrointestinal or urinary tract haemorrhage in previous 21 days
4. Patient with intracranial haemorrhage
5. Platelet count <100 000 mm3
6. Known hypersensitivity to glenzocimab or to any of the excipients
7. Known hypersensitivity to the gadolinium used for the brain MRI perfusion, or one of its excipients
8. Known Severe renal insufficiency (Grades 4-5) with a glomerular filtration rate < 30mL/Min/1.73m2
9. Pregnant or breastfeeding woman
10. Adults subject to a legal protection measure (L1121-8)
11. Persons deprived of their liberty by a judicial or administrative decision, persons subject to psychiatric care under sections L3212-1 and L3123-1 and persons admitted to a health or social institution for purposes other than research (L1121-6).
12. Participation in another interventional clinical investigational drug or medical device trial within 30 days prior to the inclusion
13. Patients receiving anticoagulants within the last 24 hours and: For heparin, an elevated aPTT -greater than upper limit of normal for laboratory; For vitamin K antagonists (ex: warfarin), an INR >1.7; For direct thrombin inhibitors or direct factor Xa inhibitors, a plasmatic dosage of the drug greater than upper limit of normal for laboratory
14. Significant pre-stroke disability (mRS>2)
15. Patients under or needing immediate dual anti-platelet therapy (DAPT) within the first 24 hours after the cessation of glenzocimab or placebo infusion
16. Patients known to have already received other humanized fragment of monoclonal antibody (risk of anaphylaxis)
17. Patients known to be under ongoing anti-cancer treatment (radiotherapy, chemotherapy, immunotherapy)
18. Patients known to be under ongoing immunosuppressive therapy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Functional outcome at 3 months will be assessed with the modified Rankin Scale (mRS) score dichotomized 0 to 3 versus 4 to 6, collected by phone by trained professionals blinded to the treatment allocation.

Secondary endpoints 18

1. Proportion of patients with No-reflow (NR) phenomenon on post EVT perfusion imaging (visually demonstrable persistent hypoperfusion on rCBV or rCBF within the infarct lesion on qualitative maps processed according to validated software)
2. Proportion of patients with symptomatic intracranial hemorrhage assessed according to the Heidelberg classification, on a brain CT scan performed between 24-36 hours after EVT
3. Proportion of patients with any intracranial hemorrhage assessed according to the Heidelberg classification on a brain CT scan performed between 24-36 hours after EVT
4. All-cause death rate at 3 months
5. The distribution of mRS score at 3 months (Annex 1)
6. Proportion of patients with favorable functional outcome defined by a modified Rankin Scale score 0-2 at 3 months
7. Score of the MoCA 5-minutes at 3 months
8. Incidence of complete recanalization defined by a mTICI score of 2c or 3 on the post-EVT cerebral angiography
9. Incidence of successful recanalization defined by a mTICI score of 2b, 2c or 3 on the post-EVT cerebral angiography
10. Proportion of patients with decompressive hemicraniectomy surgery
11. Proportion of patients with neurological improvement defined by a decrease in NIHSS score > 8 points between the baseline score and the score at 24-36h after EVT
12. Cerebral infarct volume growth between baseline and 24h brain MRI
13. The number of EVT passes
14. Time (in minutes) between the arterial puncture and recanalization occurrence
15. Incidence of Serious/Non-Serious Adverse Events including bleeding-related events.
16. Cost per additional patient with a mRS 0-3 with glenzocimab use and cost per QALY (Quality adjusted Life Year) gained at 12 months.
17. Proportion of patients with favorable functional outcome defined by a modified Rankin Scale score 0-2 at 12 months
18. Score of the MoCA 5-minutes at 12 months

Investigational products

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

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Hopital Fondation Adolphe De Rothschild

Sponsor organisation

Hopital Fondation Adolphe De Rothschild

Address

29 Rue Manin

City

Paris

Postcode

75019

Country

France

Scientific contact point

Organisation

Hopital Fondation Adolphe De Rothschild

Contact name

Jean-Philippe Desilles

Public contact point

Organisation

Hopital Fondation Adolphe De Rothschild

Contact name

Amélie Yavchitz

Locations

1 EU/EEA country · 14 investigational sites

By country

Investigational sites

Application history

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