Efficacy of Intravenous Tocilizumab on Infarct Growth in Acute Ischemic Stroke Patients Undergoing Endovascular Thrombectomy: A Phase II Randomized Controlled Trial

The primary objective is to evaluate the efficacy of tocilizumab administration before or during endovascular thrombectomy (EVT) on infarct growth at 72 hours following the procedure in patients with acute ischemic stroke. This assessment is performed using diffusion weighted imaging on MRI. 5

Secondary objectives include:

• Evaluation of mean infarct volume and lesion growth at 72 hours post-EVT.
• Assessment of neurological outcomes using the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS) at discharge, 30, and 90 days.
• Measurement of quality of life via the EQ-5D-5L scale after 90 days.
• Analysis of mortality rates, including all-cause death and stroke-related death.
• Monitoring of intracranial haemorrhage, including symptomatic presentations, and the incidence of infections such as stroke-associated pneumonia.
• Evaluation of safety through the incidence of adverse events and serious adverse events.
• Quantification of biomarkers, specifically brain derived (BD)-Tau, high-sensitivity C-reactive protein (hsCRP), neurofilament light chain (NfL), APP, and S100b.
• Investigation of cerebral hyperperfusion via transcranial doppler ultrasound as a risk factor for intracranial hemorrhage.
• Exploration of long-term outcomes at 5 years and sex-based differences in treatment effects.

The sponsor did not provide information regarding the total number of participants. The study population consists of patients diagnosed with acute ischemic stroke. Eligible participants include both male and female individuals. The age range for inclusion is not specifically defined beyond the requirement of being adults. Selected participants must present with a large vessel occlusion in the anterior circulation, involving the terminal internal carotid artery, M1, or M2 segments of the middle cerebral artery. A critical requirement is that the time from symptom onset to randomization must be within 12 hours. Individuals must be candidates for emergency endovascular treatment according to established clinical guidelines. Women of childbearing potential are eligible only if utilizing highly effective contraception. All participants must be capable of providing informed consent or have consent provided by a legal representative.

This Phase II, randomized, placebo-controlled, double-blind, two-arm study is designed to investigate the efficacy of tocilizumab in patients presenting with acute ischemic stroke undergoing endovascular thrombectomy. Participants are assigned to receive either an intravenous infusion of tocilizumab or a sodium chloride placebo. The primary objective is to evaluate infarct growth at 72 hours post-treatment, as assessed via diffusion weighted imaging on MRI. The study sequence involves a screening process to ensure eligibility based on criteria such as age, large vessel occlusion, and symptom onset within 12 hours. Following administration before or during the procedure, the assessment of the primary endpoint, ΔDWI lesion volume, occurs at the 72-hour mark. Secondary endpoints include neurological assessments using the NIHSS and mRS score, as well as monitoring for symptomatic intracranial haemorrhage and other safety parameters. The total duration of the study period is estimated to conclude by December 31, 2030.

The experimental treatment consists of tocilizumab, provided as a solution for infusion. The dosage is administered at 8 mg/kg via intravenous infusion.

The control group receives a placebo consisting of sodium chloride. This is administered as a 40 ml solution for infusion through infusion.

The primary efficacy endpoint is the change in diffusion weighted imaging (DWI) lesion volume. Secondary efficacy assessments include FLAIR lesion volume and the change in lesion volume for both modalities. Neurological outcomes are evaluated using the National Institutes of Health Stroke Scale (NIHSS) and the modified Rankin Scale (mRS) score. Patient-reported outcomes are measured through EQ-5D-5L domains and the Visual Analogue Scale (VAS).

Biomarker analysis involves measuring changes in brain derived (BD)-Tau levels and high-sensitivity C-reactive protein (hsCRP) levels. Additional assessments include blood levels of circulating surrogate markers, immune activation and inflammatory markers, and serum concentrations of tocilizumab. Immune cell transcriptomics and genomic alterations are also analyzed in relation to clinical endpoints. Structural brain changes, such as atrophy and infarct volume, are assessed via magnetic resonance imaging (MRI).

Safety and clinical progression endpoints include:

• Occurrence of all-cause mortality and stroke-related mortality.
• Incidence of symptomatic intracranial haemorrhage and any intracranial haemorrhage.
• Occurrence of infection, pneumonia, adverse events, and serious adverse events.
• Rate of major adverse cardiovascular events (MACE).
• Worsening of the index stroke, defined by infarct core progression, haemorrhagic transformation, or significant increases in disability.
• Mean MCA peak systolic velocity ratio.