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

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

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 Patients who are found to be non-aneurysmal following randomisation will be withdrawn from the study treatment.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

Study Overview

• Status: Active, not recruiting
• Conditions: Subarachnoid Hemorrhage
• Intervention / Treatment: Drug: IL-1Ra; Drug: IL-1Ra Placebo

• Study Type: Interventional
• Enrollment (Actual): 612
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Kayle-Anne Sands, BSc, MSc; Phone Number: 0161 306 3196; Email: scil@manchester.ac.uk
• Study Contact Backup: Name: Andrew King; Email: andrew.king@manchester.ac.uk

Study Locations

• United Kingdom
  • Brighton, United Kingdom, BN2 5BE
    • Royal Sussex County Hospital
  • Bristol, United Kingdom, BS10 5NB
    • Southmead Hospital
  • Cambridge, United Kingdom, CB2 0QQ
    • Addenbrookes Hospital
  • Liverpool, United Kingdom, L9 7LJ
    • The Walton Centre
  • London, United Kingdom, E1 1FR
    • Royal London Hospital
  • London, United Kingdom, SW17 0QT
    • St George's Hospital
  • London, United Kingdom, W6 8RF
    • Charing Cross Hospital
  • London, United Kingdom, WC1N 3BG
    • National Hospital for Neurology and Neurosurgery, Queen Square
  • Manchester, United Kingdom
    • Northern Care Alliance NHS Foundation Trust
  • Nottingham, United Kingdom, NG7 2UH
    • Queens Medical Centre
  • Preston, United Kingdom, PR2 9HT
    • Royal Preston Hospital
  • Southampton, United Kingdom, SO16 6YD
    • Southampton General Hospital
  • Stoke-on-Trent, United Kingdom, ST4 6QG
    • Royal Stoke University Hospital
  • Devon
    • Plymouth, Devon, United Kingdom, PL6 8DH
      • Derriford Hospital
  • South Yorkshire
    • Sheffield, South Yorkshire, United Kingdom, S10 2JF
      • Royal Hallamshire Hospital
  • Wales
    • Cardiff, Wales, United Kingdom, CF14 4XW
      • University Hospital of Wales
  • Yorkshire
    • Leeds, Yorkshire, United Kingdom, LS1 3EX
      • Leeds General Infirmary

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo twice daily	Drug: IL-1Ra Placebo; 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).
Active Comparator: IL-1Ra twice daily	Drug: IL-1Ra; 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).

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: University of Manchester
• Collaborators: Northern Care Alliance NHS Foundation Trust; National Institute for Health Research, United Kingdom; Clinical Trials Unit, Manchester
• Investigators: Principal Investigator: Andrew King, University of Manchester

Study record dates

Study Major Dates

• Study Start (Actual): October 11, 2018
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: August 9, 2017
• First Submitted That Met QC Criteria: August 9, 2017
• First Posted (Actual): August 15, 2017

Study Record Updates

• Last Update Posted (Estimated): November 21, 2023
• Last Update Submitted That Met QC Criteria: November 17, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Aneurysmal
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Intracranial Hemorrhages; Hemorrhage; Subarachnoid Hemorrhage; Antirheumatic Agents; Interleukin 1 Receptor Antagonist Protein
• Other Study ID Numbers: R121178

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No