Clinical trial NCT02614742: SFX-01 After Subarachnoid Haemorrhage
Official title: SFX-01 After Subarachnoid Haemorrhage
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Subarachnoid Hemorrhage, Spontaneous
Lead sponsor: Evgen Pharma
Sponsor class: INDUSTRY
First posted: 2015-11-25
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Study of SFX-01 in Subarachnoid Haemorrhage, with exploratory evaluations of efficacy.

Detailed description: The study is a randomised, double-blind, parallel-group design comparing SFX-01 (300 mg) taken orally as capsules or as a suspension via a nasogastric tube (NG) twice-daily for up to 28 days versus placebo in 90 patients who have had SAH and present within 48 hours of ictus.

Subjects will receive SFX-01/Placebo in order to review potential outcomes investigating the long-term complications of SAH such as Delayed Cerebral Ischaemia, as reflected by Trans-Cranial Doppler (TCD) readings. The objective is to demonstrate safety and search for signals of efficacy in patients that have had SAH.

A sub-study will be conducted in up to 12 patients where an External Ventricular Drain (EVD) fitted; serial CSF samples will be taken pre- \& post-dose on two occasions to determine pharmacokinetics of Sulforaphane in CSF in comparison with plasma pharmacokinetics. Sub-study patients will undergo all other procedures (with the exception of lumbar puncture).

Treatment duration is up to 28 days; follow up duration is 28 days, three and six months. The planned trial period is 24 months.

Eligibility criteria: Inclusion Criteria:

1. Patients with radiological evidence of spontaneous SAH
2. Fisher grade 3 or 4 on CT
3. Definitive treatment of aneurysm has not been ruled out
4. Previously living independently
5. In the opinion of the investigator, the delay from ictus to randomisation and initiation of trial medication will not exceed 48 hours
6. Aged 18 to 80 years
7. In the opinion of the investigator it will be possible to obtain Informed Consent from the Patient, Personal Legal Representative or Professional Legal representative within 24 hours of first dose

Exclusion Criteria:

1. Traumatic SAH
2. Fisher grade 1 or 2
3. SAH diagnosed on lumbar puncture with no evidence of blood on CT
4. Decision not to treat aneurysm has been made
5. Plan to withdraw treatment
6. Significant kidney disease as defined as plasma creatinine ≥2.5mg/dL (221 µmol/l)
7. Liver disease as defined as total bilirubin ≥2-fold the upper limit of normal; (ULN) as measured by the local laboratory
8. Females who are pregnant or lactating.
9. Participants enrolled in another interventional research trial in the last 30 days
10. Patients for whom it is known, at the time of screening, that clinical follow-up will not be feasible Patients unwilling to use two forms of contraception (one of which being a barrier method) 30 days for men and 90 days for women after last IMP dose

Primary outcomes:
measure: Number of participants with treatment-related adverse events as assessed by Common Toxicity Criteria
timeFrame: up to 28 days
measure: Maximum CSF Concentration [Cmax],
timeFrame: up to 28 days
measure: Number of participants with treatment related reduction in middle cerebral artery (MCA) peak flow velocity following Subarachnoid Haemorrhage (SAH) measured by trans cranial doppler ultrasound
timeFrame: up to 28 days
Secondary outcomes:
measure: modified Rankin Scale
timeFrame: up to 180 days post ictus
measure: Plasma PK
timeFrame: up to 28 days
measure: CSF drug levels
timeFrame: up to 14 days
measure: Serum Haptoglobin levels
timeFrame: Up to 28 days
measure: Delayed Cerebral Ischaemia
timeFrame: Up to 28 days
Other outcomes:
Locations:
city: Southampton
country: United Kingdom
facility: Southampton General Hospital
state: Hampshire
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: London
country: United Kingdom
facility: The Royal London Hospital
Study officials:
affiliation: University Hospital Southampton NHS Foundation Trust
name: Diederik Bulters, MBChB, BSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zolnourian AH, Franklin S, Galea I, Bulters DO. Study protocol for SFX-01 after subarachnoid haemorrhage (SAS): a multicentre randomised double-blinded, placebo controlled trial. BMJ Open. 2020 Mar 25;10(3):e028514. doi: 10.1136/bmjopen-2018-028514.