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

Phase 3

Active, not recruiting

• Conditions: Subarachnoid Hemorrhage
• Interventions: Drug: IL-1Ra Placebo; Drug: IL-1Ra

• Registration Number: NCT03249207
• Lead Sponsor: University of Manchester

Brief Summary

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 Patients who are found to be non-aneurysmal following randomisation will be withdrawn from the study treatment.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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-08-09
• Study First Submitted QC: 2017-08-09
• Study First Posted: 2017-08-15
• Study Start: 2018-10-11
• Status Verified: 2023-10
• Last Update Submitted: 2023-11-17
• Last Update Posted: 2023-11-21
• Primary Completion: 2024-04
• Study Completion: 2024-09

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 612

Inclusion Criteria

1. 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.
2. 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.
3. 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.
4. Male or female aged 18 years or above.

Exclusion Criteria

1. Unconfirmed or uncertain diagnosis of spontaneous SAH.
2. Known active tuberculosis or active hepatitis.
3. Known active malignancy.
4. Known Still's Disease
5. Neutropenia (ANC <1.5 x 109/L ).
6. Abnormal renal function (creatinine clearance or estimated Glomerular Filtration Rate (eGFR) < 30 ml/minute) documented in the last 3 months prior to this SAH.
7. Live vaccinations within the last 10 days of this SAH.
8. Previous or concurrent treatment with IL-1Ra known at the time of trial entry or previous participation in this trial.
9. Current treatment with TNF antagonists.
10. Known to have participated in a clinical trial of an investigational agent or device in the 30 days prior to ictus.
11. 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.
12. Known to be pregnant or breast feeding or inability to reliably confirm that the patient is not pregnant
13. 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.
14. Known allergy to IL-1Ra or any of the excipients listed in the drug SmPC
15. Known allergy to other products that are produced by DNA technology using the micro-organism E. coli (e.g. E.coli derived protein).
16. Current treatment with IL-6 or IL-1 inhibitors or drugs affecting the IL-1 axis.
17. History of DRESS syndrome.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo twice daily	IL-1Ra Placebo	-
IL-1Ra twice daily	IL-1Ra	-

Primary Outcome Measures

Name	Time	Method
Ordinal shift in modified Rankin Score (mRS)	6 months post randomisation

Secondary Outcome Measures

Name	Time	Method
Measurement of quality of life using EQ-5D-5L score	6 months post randomisation
Measurement of fatigue using Fatigue score	6 months post randomisation
Measurement of mood using HADS	6 months post randomisation

Trial Locations

Locations (17)

Derriford Hospital; 🇬🇧 Plymouth, Devon, United Kingdom

Royal Sussex County Hospital; 🇬🇧 Brighton, United Kingdom

University Hospital of Wales; 🇬🇧 Cardiff, Wales, United Kingdom

Royal Hallamshire Hospital; 🇬🇧 Sheffield, South Yorkshire, United Kingdom

Leeds General Infirmary; 🇬🇧 Leeds, Yorkshire, United Kingdom

Royal London Hospital; 🇬🇧 London, United Kingdom

Addenbrookes Hospital; 🇬🇧 Cambridge, United Kingdom

Southmead Hospital; 🇬🇧 Bristol, United Kingdom

The Walton Centre; 🇬🇧 Liverpool, United Kingdom

St George's Hospital; 🇬🇧 London, United Kingdom

National Hospital for Neurology and Neurosurgery, Queen Square; 🇬🇧 London, United Kingdom

Queens Medical Centre; 🇬🇧 Nottingham, United Kingdom

Northern Care Alliance NHS Foundation Trust; 🇬🇧 Manchester, United Kingdom

Royal Preston Hospital; 🇬🇧 Preston, United Kingdom

Southampton General Hospital; 🇬🇧 Southampton, United Kingdom

Royal Stoke University Hospital; 🇬🇧 Stoke-on-Trent, United Kingdom

Charing Cross Hospital; 🇬🇧 London, United Kingdom