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

Subarachnoid Hemorrhage Clinical Trial

— SCIL  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03249207
• Other study ID #: R121178
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 11, 2018
• Est. completion date: September 2024

Study information

• Verified date: October 2023
• Source: University of Manchester
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

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 Patients who are found to be non-aneurysmal following randomisation will be withdrawn from the study treatment.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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 612
• Est. completion date: September 2024
• Est. primary completion date: April 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hemorrhage
• Subarachnoid Hemorrhage

Intervention

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).
• 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).

Locations

Country	Name	City	State
United Kingdom	Royal Sussex County Hospital	Brighton
United Kingdom	Southmead Hospital	Bristol
United Kingdom	Addenbrookes Hospital	Cambridge
United Kingdom	University Hospital of Wales	Cardiff	Wales
United Kingdom	Leeds General Infirmary	Leeds	Yorkshire
United Kingdom	The Walton Centre	Liverpool
United Kingdom	Charing Cross Hospital	London
United Kingdom	National Hospital for Neurology and Neurosurgery, Queen Square	London
United Kingdom	Royal London Hospital	London
United Kingdom	St George's Hospital	London
United Kingdom	Northern Care Alliance NHS Foundation Trust	Manchester
United Kingdom	Queens Medical Centre	Nottingham
United Kingdom	Derriford Hospital	Plymouth	Devon
United Kingdom	Royal Preston Hospital	Preston
United Kingdom	Royal Hallamshire Hospital	Sheffield	South Yorkshire
United Kingdom	Southampton General Hospital	Southampton
United Kingdom	Royal Stoke University Hospital	Stoke-on-Trent

Sponsors (4)

Lead Sponsor	Collaborator
University of Manchester	Clinical Trials Unit, Manchester, National Institute for Health Research, United Kingdom, Northern Care Alliance NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ordinal shift in modified Rankin Score (mRS)		6 months post randomisation
Secondary	Measurement of mood using HADS		6 months post randomisation
Secondary	Measurement of fatigue using Fatigue score		6 months post randomisation
Secondary	Measurement of quality of life using EQ-5D-5L score		6 months post randomisation