Interleukin-6 Receptor Inhibition for Symptomatic Intracranial Atherosclerosis

NCT ID: NCT06447701

Last Updated: 2025-07-28

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 486 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-10-30
• Study Completion Date: 2029-06-30

Brief Summary

IRIS-sICAS is a multicenter, randomized, double-blind, placebo-controlled clinical trialis a multicenter, randomized, double-blind, placebo-controlled clinical trial, to assess the safety and efficacy of tocilizumab injection in lowering the incidence of newly diagnosis ischemic stroke and improving prognosis in symptomatic intracranial atherosclerosis patients.

Detailed Description

Intracranial atherosclerosis (ICAS) is one of the most common causes of stroke worldwide, and the currently recommended intensive pharmacologic and surgical treatments show only modest efficacy, with approximately 20% of strokes still recurring, for which there is no targeted treatment. Tocilizumab is a recombinant humanized anti-human interleukin-6 receptor monoclonal antibody that exerts anti-inflammatory effects by specifically binding to the IL-6 receptor and blocking IL-6 signal transduction. Previous studies have shown that tocilizumab can effectively attenuate acute ischemic injury in the early stage of myocardial infarction and has potentially anti-atherosclerotic effects. However, application in ICAS not yet reported. This study is a multicenter, randomized, double-blind, placebo-controlled clinical trial, which enrolled patients with symptomatic ICAS occurring within 72 hours of ischemic stroke or high-risk transient ischemic attack. Patients who consented to participate in the study were randomly assigned in a 1:1 ratio to receive a single infusion of 320mg tocilizumab or placebo (saline injection), and patients were followed up to assess the safety and efficacy of tocilizumab injection in lowering the incidence of newly diagnosis ischemic stroke and improving prognosis.

Conditions

Brain Diseases; Ischemic Stroke; Ischemia; Stroke; Cerebral Infarction; Atherosclerosis of Artery; Atheroscleroses, Intracranial

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Tocilizumab group

Intravenously for more than 1 hour.

Group Type: EXPERIMENTAL

Tocilizumab

Intervention Type: DRUG

Single dose intravenous application

Control group

Intravenously for more than 1 hour.

Group Type: PLACEBO_COMPARATOR

NaCl 0.9% 100ml

Intervention Type: DRUG

Single dose intravenous application

Interventions

Tocilizumab

Single dose intravenous application

Intervention Type: DRUG

NaCl 0.9% 100ml

Single dose intravenous application

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male or non-pregnant women with acute stroke symptoms aged over 18 years.
• Patients having an ischemic stroke or a TIA prior to randomization (Patients having an acute ischemic stroke within 72 hours with NIHSS score≤5 at baseline, or patients having a TIA within 72 hours with Oxfordshire Community Stroke Project on the basis of age, blood pressure, clinical features, and duration of TIA symptoms (ABCD2) score≥4 at baseline).
• The entry event is attributed to symptomatic atherosclerosis (50-99%) in an intracranial qualifying artery (intracranial carotid artery (C4-7), middle cerebral artery (M1), intracranial vertebral artery or basilar artery) confirmed by CT, MR angiography, or digital subtraction angiography.
• Informed consent obtained from patients or their legal representatives.
• Willing to be followed up as required by the clinical study protocol.

Exclusion Criteria

• Thrombolytic therapy or thrombectomy within 24 hours prior to enrollment.
• Pre-stroke mRS score ≥ 2.
• Combined or previous intracranial hemorrhage: hemorrhagic stroke, epidural hematoma, subdural hematoma, intraventricular hemorrhage, subarachnoid hemorrhage, etc.
• Any of the following unequivocal cardiac source of embolism: chronic or paroxysmal atrial fibrillation, sinus node dysfunction, mitral stenosis, prosthetic heart valves, endocarditis, left ventricular mural thrombus or valvular vegetation, myocardial infarction within three months, dilated cardiomyopathy, spontaneous echogenic defects in the left atrium or an ejection fraction of less than 30%.
• Intracranial arterial stenosis due to arterial dissection, Moya Moya disease; herpes zoster, varicella zoster or other viral vasculopathy; neurosyphilis; radiation induced vasculopathy; fibromuscular dysplasia; sickle cell disease; neurofibromatosis; post-partum angiopathy; suspected vasospastic process, suspected recanalized embolus; any known vasculitic disease.
• Extracranial stenosis ≥50%, subclavian arterial stenosis≥50% or subclavian steal syndrome.
• Previous interventions for intracranial arterial stenosis.
• Concurrent intracranial tumors, intracranial aneurysms or arteriovenous malformations
• Neutrophil < 2×10 9/L.
• Platelet < 100×10 9/L.
• Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels greater than 1.5 times the upper limit of normal.
• Active infections including localized.
• Evidence of HIV or hepatitis B positivity.
• Positive tuberculosis-related tests.
• Concurrent peptic ulcer, diverticulitis or inflammatory bowel disease.
• Concurrent malignant tumors, recent bone marrow transplant or recent organ transplant.
• Systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg despite blood pressure control.
• Known allergy to tocilizumab or excipients.
• Use of immunosuppressive drugs or systemic use of antibiotics.
• Received any live or live attenuated vaccine within 4 weeks prior to enrollment or plan to receive a live or live attenuated vaccine during the study.
• History of demyelination or presence of neurological symptoms suggestive of demyelination.
• Previously existing neurological or psychiatric disorders that could potentially confuse neurological function assessment.
• An expected survival less than 90 days.
• Participation in another interventional clinical study.
• Patients unsuitable for enrollment in the clinical trial according to investigators decision making.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shenzhen Second People's Hospital

OTHER

Sponsor Role: collaborator

Central People's Hospital of Zhanjiang

OTHER

Sponsor Role: collaborator

Shantou Central Hospital

OTHER

Sponsor Role: collaborator

Eighth Affiliated Hospital, Sun Yat-sen University

OTHER

Sponsor Role: collaborator

Guangzhou First People's Hospital

OTHER

Sponsor Role: collaborator

Peking University Shenzhen Hospital

OTHER

Sponsor Role: collaborator

Guangdong Provincial People's Hospital

OTHER

Sponsor Role: collaborator

Zhujiang Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Other Identifiers

LC2024ZD025

Identifier Type: -

Identifier Source: org_study_id