Satralizumab in Aneurysmal Subarachnoid Hemorrhage

Study Overview
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Brief Summary
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In this study, satralizumab will be administered to see whether satralizumab is safe in patients with a burst brain aneurysm and if it may prevent strokes in patients with a burst brain aneurysm.

Detailed Description
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SASH is a prospective single-arm, single-center, open-label Phase 1 trial of satralizumab 120mg subcutaneous Day 0 and Day 14 in subjects with Hunt Hess grade 1-3, Fisher score 3 aneurysmal subarachnoid hemorrhage and an external ventricular drain or lumbar drain. The trial is designed to demonstrate safety and to detect a signal that satralizumab prevents delayed cerebral ischemia in these patients.

Official Title
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A Phase 1 Clinical Trial of Satralizumab as a Treatment for Aneurysmal Subarachnoid Hemorrhage

Conditions
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Aneurysmal Subarachnoid Hemorrhage, Delayed Cerebral Ischemia

Intervention / Treatment
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* Drug: Satralizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients (aged ≥18 years) with Hunt Hess Grade 1-3, Fisher score 3 aneurysmal subarachnoid hemorrhage within 72 hours of symptom onset (ruptured aneurysm confirmed by CTA, MRA or DSA) Must have surgical or endovascular adequate occlusion of the ruptured aneurysm Must have external ventricular drain or lumbar drain. Female subjects of child-bearing potential must have negative pregnancy test Signed informed consent from subject or legally authorized representative Able and willing to comply with followup visits Women and males of childbearing potential must agree to appropriate methods of contraception during study participation Exclusion Criteria: Evidence for vasospasm or DCI prior to study enrollment Hemodynamically unstable pre-enrollment Severe or unstable concomitant condition or disease (e.g., known significant neurological deficit, cancer, hematologic or coronary disease), or chronic condition (e.g., liver disease, kidney disease, or psychiatric disorder), that may increase the risk associated with study participation, or may interfere with the interpretation of study results Subjects who have received an investigational product or participated in another interventional clinical study within 30 days prior to enrollment. Known hypersensitivity to satralizumab Active or untreated latent tuberculosis Serious infection defined as pneumonia, sepsis/septic shock, and neutropenic fever prior to enrollment Any previous treatment with IL-6 inhibitory therapy (e.g. tocilizumab), alemtuzumab, total body irradiation or bone marrow transplantation within 6 months prior to baseline. Any previous treatment with anti-CD20, anti-CD19, eculizumab, belimumab, interferon, natalizumab, glatiramer acetate, fingolimod, teriflunomide or dimethyl fumarate within 6 months prior to baseline. Any previous treatment with anti-CD4, cladribine or mitoxantrone within 2 years prior to baseline Treatment with any investigational agent within 3 months prior to baseline. Pregnant or breastfeeding, or intending to become pregnant during the study or within 2 months after the final dose of satralizumab Women of childbearing potential must have a negative serum pregnancy test result prior to initiation of study drug. Any surgical procedure (except for minor surgeries) within 4 weeks prior to baseline. Evidence of other demyelinating disease or progressive multifocal leukoencephalopathy (PML). Evidence of serious uncontrolled concomitant diseases that may preclude patient participation, such as: other nervous system disease, cardiovascular disease, hematologic/hematopoiesis disease, respiratory disease, muscular disease, endocrine disease, renal/urologic disease, digestive system disease, congenital or acquired severe immunodeficiency. Known active infection (excluding fungal infections of nail beds or caries dentium) within 4 weeks prior to baseline. Evidence of chronic active hepatitis B or C. History of drug or alcohol abuse within 1 year prior to baseline. History of diverticulitis that, in the Investigator's opinion, may lead to increased risk of complications such as lower gastrointestinal perforation. Evidence of active tuberculosis (TB; excluding patients receiving chemoprophylaxis for latent TB infection). Evidence of active interstitial lung disease Receipt of any live or live attenuated vaccine within 6 weeks prior to baseline and throughout the duration of the study. History of malignancy within the last 5 years, including solid tumors, hematologic malignancies and in situ carcinoma (except basal cell and squamous cell carcinomas of the skin, or in situ carcinoma of the cervix uteri that have been completely excised and cured). History of severe allergic reaction to a biologic agent (e.g. shock, anaphylactic reactions). Active suicidal ideation within 6 months prior to screening, or history of suicide attempt within 3 years prior to screening. Laboratory exclusion criteria (at screening): White blood cells (WBC) <3.0 x103/μL Absolute neutrophil count (ANC) <2.0 x103/μL Absolute lymphocyte count <0.5 x103/μL Platelet count <10 x 104/μL Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >1.5 times the upper limit of normal (ULN). Positive for hepatitis C virus (HCV) antibody at screening Positive for hepatitis B surface antigen (HBsAg) at screening Known HIV infection Illicit drug or alcohol abuse within 12 months prior to screening, in the investigator's judgment Poor peripheral venous access Serious infection requiring oral or IV antibiotics prior to screening Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study History or presence of an abnormal ECG that is clinically significant in the investigator's opinion, including complete left bundle branch block, second- or third degree atrioventricular heart block, or evidence of prior myocardial infarction QT-related criteria: QT interval corrected through use of Fridericia's formula (QTcF) 440 ms demonstrated by at least two ECGs 30 minutes apart History of ventricular dysrhythmias or risk factors for ventricular dysrhythmias such as structural heart disease (e.g., severe left ventricular systolic dysfunction, left ventricular hypertrophy), coronary heart disease (symptomatic or with ischemia demonstrated by diagnostic testing), clinically significant electrolyte abnormalities (e.g., hypokalemia, hypomagnesemia, hypocalcemia), or family history of sudden unexplained death or long QT syndrome Current treatment with medications that are well known to prolong the QT interval

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Satralizumab<br>Subjects will receive satralizumab 120mg subcutaneous Day 0 and Day 14 after enrollment. | Drug: Satralizumab<br>* 120mg subcutaneous Day 0 and Day 14<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with elevation of liver transaminases | Elevation of liver transaminase (ALT, AST) is defined as >5x upper limit of normal. | baseline up to 21 days | 
| Number of participants with neutropenia | Neutropenia is defined as neutrophil count below 1 x 10^9/L. | baseline up to 21 days | 
| Number of participants with decreased platelet count | Decreased platelet count is defined as a platelet count below the lower institutional limit of normal. | baseline up to 21 days | 
| Frequency of observed and reported adverse events | An adverse event will be defined as any unfavorable and unintended sign, symptom, or disease temporally associated with the use of an investigational medicinal product (IMP) or other protocol-imposed intervention, regardless of attribution. | baseline up to 90 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier | 
| Frequency of death | All deaths that occur during the protocol-specified AE reporting period, regardless of attribution, will be recorded. | baseline up to 90 days following the last administration of study treatment or study discontinuation/termination, whichever is earlier |