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

University of Manchester

Status and phase: Active, not recruiting; Phase 3

Conditions: Subarachnoid Hemorrhage

Treatments: Drug: IL-1Ra Placebo; Drug: IL-1Ra

Study type: Interventional

Funder types: Other

Identifiers

NCT03249207

R121178

Details and patient eligibility

About

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 Patients who are found to be non-aneurysmal following randomisation will be withdrawn from the study treatment.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

Enrollment: 612 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

612 participants in 2 patient groups, including a placebo group

IL-1Ra twice daily

Active Comparator group

Treatment:

Drug: IL-1Ra

Placebo twice daily

Placebo Comparator group

Treatment:

Drug: IL-1Ra Placebo