A randomized placebo-controlled double-blind trial phase II two-arm study to investigate infarct growth over 72 hours assessed with diffusion weighted imaging on MRI after treatment with intravenous tocilizumab or placebo in patients above 18 years of age with acute ischemic stroke undergoing endovascular thrombectomy.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Oslo University Hospital HF

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nervous System Diseases [C10]

Decision date (initial)

2026-03-12

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: Therapy

To assess the efficacy of tocilizumab given before/during EVT, on infarct growth in acute ischemic stroke patients at 72 hours after EVT.

Secondary objectives 23

1. To assess the efficacy of tocilizumab given before/during EVT, on mean infarct volume in acute ischemic stroke patients at 72 hours after EVT
2. To assess the efficacy of tocilizumab given before/during EVT, on lesion growth in acute ischemic stroke patients at 72 hours after EVT
3. To assess the efficacy of tocilizumab given before/during EVT, on mean lesion volume in acute ischemic stroke patients at 72 hours after EVT
4. To assess the change in levels of brain derived (BD)-Tau from baseline to post-EVT in the two treatment groups
5. To assess the change in levels of high-sensitivity C-reactive protein (hsCRP) from baseline to post-EVT in the two treatment groups
6. To assess the efficacy of tocilizumab compared to placebo measured by median National Institutes of Health Stroke Scale score (NIHSS)
7. To assess the efficacy of tocilizumab compared to placebo measured by median modified Rankin Scale score (mRS) at discharge, 30 and 90 days.
8. To assess the efficacy of tocilizumab compared to placebo measured by mean score on EQ-5D-5L after 90 days
9. To assess the efficacy of tocilizumab compared to placebo with respect to the proportion of all-cause death and stroke-related death
10. To compare the proportion of patients with any symptomatic intracranial haemorrhage until 72 hours in the two treatment groups
11. To compare the proportion of patients with any intracranial haemorrhage until 72 hours in the two treatment groups
12. To compare the proportion of patients with any infections until discharge in the two treatment groups
13. To compare the proportion of stroke-associated pneumonia until discharge in the two treatment groups
14. To compare the proportion of patients with serious adverse events in the two treatment groups
15. To compare the proportion of patients with adverse events in the two treatment groups
16. To describe circulating surrogate markers of axonal and cellular injury including neurofilament light chain (NfL), APP and S100b) and markers of immune activation in the relation to primary and secondary endpoints
17. To explore the mechanisms by which tocilizumab modulated the primary and secondary endpoints
18. To assess the efficacy of tocilizumab compared to placebo measured by the proportion of participants exhibiting a worsening of their index stroke defined as (A) progression of infarct core, or haemorrhagic transformation of the index stroke, as documented by medical imaging that is (a) life-threatening requiring intervention and/or (b) results in increased disability as gauged by a ≥4-point increase from lowest NIHSS during hospitalization or (B) results in death from the index stroke
19. To assess the proportion of participants with good neurological outcome, as defined by a score of 0-2 on NIHSS at 90 days in the treatment groups
20. To assess sex differences in outcomes and effects of tocilizumab in the treatment groups
21. To assess the role of cerebral hyperperfusion on transcranial doppler ultrasound as a risk factor for developing any intracranial haemorrhage
22. To assess the efficacy of tocilizumab given before/during EVT, on infarct growth in acute ischemic stroke patients with cerebral hyperperfusion on transcranial doppler upto 72 hours
23. To assess long-term outcomes after 5 years in the treatment groups

Conditions and MedDRA coding

Acute ischemic stroke

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Participant must be above 18 years of age at the time of signing the informed consent.
2. Participants who have acute ischemic stroke selected for emergency endovascular treatment according to treatment guidelines.
3. Onset of stroke symptoms (last-known-well) time to randomization time within 12 hours.
4. Large vessel occlusion in the anterior circulation (terminal internal carotid artery, M1 or M2 segment of MCA. Tandem extracranial carotid and intracranial occlusions are permitted).
5. Women of childbearing potential (WOCBP) can only be included if they use a highly effective contraception method as defined in Appendix 4 of the protocol.
6. Capable of giving signed informed consent or given by legal representative as described in Appendix I, section 10.1.2., including compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion criteria 13

1. Any intracranial haemorrhage during the qualifying imaging.
2. Large core of established infarction (ASPECTS 0-2).
3. Systolic blood pressure > 185 mmHg or diastolic blood pressure > 110 mmHg at baseline, despite appropriate medical management.
4. 5. Known hypersensitivity to tocilizumab or any of the excipients listed in section 6.1 of the SmPC: Sucrose, Polysorbate 80 (E 433), Disodium phosphate dodecahydrate (for pH adjustment), Sodium dihydrogen phosphate dihydrate (for pH adjustment) and water for injections.
5. Pregnancy/Lactation; female, with positive urine or serum beta human chorionic gonadotropin (β-hCG) test, or breastfeeding.
6. Malignancies, ongoing infection, immunodeficiency, or any suspicion of acute infection.
7. Clinical history, past imaging or clinical judgment suggesting that the intracranial occlusion is chronic, or there is suspected intracranial dissection such that there is a predicted lack of success with endovascular intervention.
8. Endovascular thrombectomy procedure is completed as defined by the presence of TICI 2c/3 reperfusion or completion of groin / arterial closure
9. Patients receiving immunosuppressive drugs other than prednisolone ≤ 10 mg/day.
10. Known prior receipt of tocilizumab for any reason, including prior enrolment in this trial.
11. Contraindications to MRI.
12. Absent or poor collateral circulation during qualifying imaging.
13. Known thrombocytopenia (platelet count <100 × 10³/µL), neutropenia, or elevated liver enzymes (ALT or AST >1.5 × the upper limit of normal [ULN]).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. ΔDWI lesion volume

Secondary endpoints 30

1. DWI lesion volume
2. ΔFLAIR lesion volume
3. FLAIR lesion volume
4. Change in levels of brain derived (BD)-Tau
5. Change in levels of high-sensitivity C-reactive protein (hsCRP)
6. NIHSS
7. mRS score
8. EQ-5D-5L domains and VAS
9. Occurrence of death (all-cause and stroke-related)
10. Occurrence of symptomatic intracranial haemorrhage
11. Occurrence of any intracranial haemorrhage
12. Occurrence of any infection
13. Occurrence of pneumonia
14. Occurrence of serious adverse events
15. Occurrence of adverse events
16. Blood levels of circulating surrogate markers
17. Blood levels of immune activation -and inflammatory markers
18. Alterations in immune cell transcriptomics and genomic alterations in relation to primary and secondary endpoints.
19. Serum concentrations of tocilizumab
20. Worsening of index stroke defined as (A) progression of infarct core, or haemorrhagic transformation of the index stroke, as documented by medical imaging that is (a) life-threatening requiring intervention and/or (b) results in increased disability as gauged by a ≥4-point increase from lowest NIHSS during hospitalization or (B) results in death from the index stroke.
21. Occurence of NIHSS score 0-2
22. Sex difference in infarct growth, NIHSS, mRS, EQ-5D-5L domains and VAS
23. Mean MCA peak systolic velocity ratio
24. Median NIHSS
25. Median mRS
26. Rate of mortality
27. Mean score on EQ-5D-5L domains and VAS
28. Atrophy, infarct volume at MRI
29. Blood levels of immune activation and inflammatory markers
30. Rate of major cardiovascular events (MACE)

Investigational products

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

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Oslo University Hospital HF

Sponsor organisation

Oslo University Hospital HF

Address

Taarnbygget, Kirkeveien 166 Kirkeveien 166

City

Oslo

Postcode

0450

Country

Norway

Scientific contact point

Organisation

Oslo University Hospital HF

Contact name

Anne Hege Aamodt

Public contact point

Organisation

Oslo University Hospital HF

Contact name

Anne Hege Aamodt

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Results and documents

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

Documents 8 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