SC IL-1Ra in SAH - Phase III Trial (SCIL)

Study Overview
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Brief Summary
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This phase III trial will establish whether IL-1Ra, with sub-cutaneous (SC) administration twice daily for up to 21 days post aneurysmal subarachnoid haemorrhage (aSAH), improves clinical outcome as measured by ordinal shift in mRS at 6 months. Patients with SAH transferred to a neurosurgical centre will be identified and approached for study participation. Following consent, patients will be randomised to receive either IL-1Ra or placebo for a maximum of 21 days from onset of symptoms. Patients who are found to be non-aneurysmal following randomisation will be withdrawn from the study treatment. Blood samples for plasma IL-6 will be obtained prior to randomisation and at day 3-5 post randomisation for IL-6 & IL-1 measurement. Safety will be measured at 30 days post randomisation and outcome assessed at 6 months post randomisation.

Official Title
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Does Interleukin-1 Receptor Antagonist Improve Outcome Following Aneurysmal Subarachnoid Haemorrhage (aSAH)? A Phase III Trial

Conditions
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Subarachnoid Hemorrhage

Intervention / Treatment
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* Drug: IL-1Ra
* Drug: IL-1Ra Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with CT positive spontaneous SAH admitted to a participating neurosurgical centre where written informed consent can be obtained and study drug can be administered within 72 hours of ictus. No concomitant health problems that, in the opinion of the PI or designee, would interfere with participation, administration of study drug or assessment of outcomes including safety. Willing and able to give informed consent or consent available from a patient representative for trial inclusion including agreement in principle to receive study drug and undergo all study assessments. Male or female aged 18 years or above. Exclusion Criteria: Unconfirmed or uncertain diagnosis of spontaneous SAH. Known active tuberculosis or active hepatitis. Known active malignancy. Known Still's Disease Neutropenia (ANC <1.5 x 109/L ). Abnormal renal function (creatinine clearance or estimated Glomerular Filtration Rate (eGFR) < 30 ml/minute) documented in the last 3 months prior to this SAH. Live vaccinations within the last 10 days of this SAH. Previous or concurrent treatment with IL-1Ra known at the time of trial entry or previous participation in this trial. Current treatment with TNF antagonists. Known to have participated in a clinical trial of an investigational agent or device in the 30 days prior to ictus. Known to have participated in a clinical trial of an investigational agent or device within 5 half-lives (of the previous agent or device) prior to ictus. Known to be pregnant or breast feeding or inability to reliably confirm that the patient is not pregnant Clinically significant serious concurrent medical condition, pre morbid illnesses, or concurrent serious infection, at the PI's (or designee's) discretion, which could affect the safety or tolerability of the intervention. Known allergy to IL-1Ra or any of the excipients listed in the drug SmPC Known allergy to other products that are produced by DNA technology using the micro-organism E. coli (e.g. E.coli derived protein). Current treatment with IL-6 or IL-1 inhibitors or drugs affecting the IL-1 axis. History of DRESS syndrome.

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: IL-1Ra twice daily<br> | Drug: IL-1Ra<br>* Doses to be administered subcutaneously (SC) twice daily (12 hourly) starting within 72 hours of ictus (onset of symptoms) for a maximum of 21 days from ictus (or sooner if discharged from neurosurgical centre).<br>|
| Placebo Comparator: Placebo twice daily<br> | Drug: IL-1Ra Placebo<br>* Doses to be administered subcutaneously (SC) twice daily (12 hourly) starting within 72 hours of ictus (onset of symptoms) for a maximum of 21 days from ictus (or sooner if discharged from neurosurgical centre).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ordinal shift in modified Rankin Score (mRS) |  | 6 months post randomisation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of mood using HADS |  | 6 months post randomisation | 
| Measurement of fatigue using Fatigue score |  | 6 months post randomisation | 
| Measurement of quality of life using EQ-5D-5L score |  | 6 months post randomisation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aneurysmal