SFX-01 After Subarachnoid Haemorrhage

Phase 2

Completed

• Conditions: Subarachnoid Hemorrhage, Spontaneous
• Interventions: Drug: Placebo; Drug: SFX-01

• Registration Number: NCT02614742
• Lead Sponsor: Evgen Pharma

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.

Study Timeline

• Study First Submitted: 2015-11-16
• Study First Submitted QC: 2015-11-23
• Study First Posted: 2015-11-25
• Study Start: 2016-04
• Status Verified: 2019-07
• Primary Completion: 2019-09
• Study Completion: 2019-11
• Last Update Submitted: 2020-01-14
• Last Update Posted: 2020-01-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 90

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	300mg placebo bid for up to 28 days
SFX-01	SFX-01	300mg bid for up to 28 days.

Primary Outcome Measures

Name	Time	Method
Maximum CSF Concentration [Cmax],	up to 28 days	To detect the presence of SFN in Cerebrospinal Fluid (CSF)
Number of participants with treatment-related adverse events as assessed by Common Toxicity Criteria	up to 28 days	To evaluate the safety of up to 28 days of SFX-01 dosed at up to 96 mg Sulforaphane (SFN) per day
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	up to 28 days	To determine if a minimum of 7 days treatment with SFX-01 reduces Middle Cerebral Artery (MCA) peak flow velocity following Subarachnoid Haemorrhage (SAH).

Secondary Outcome Measures

Name	Time	Method
Delayed Cerebral Ischaemia	Up to 28 days	To determine if up to 28 days treatment with SFX-01 can reduce the incidence of Delayed Cerebral Ischaemia (DCI) following SAH.
modified Rankin Scale	up to 180 days post ictus	To determine if a minimum of 7 days treatment with SFX-01 improves clinical outcome following SAH as measured using the modified Rankin Scale assessed at 7 , 28, 90 and 180 days post ictus.
CSF drug levels	up to 14 days	To determine CSF drug levels following treatment with SFX-01 (300mg bid).
Serum Haptoglobin levels	Up to 28 days	To determine if up to 28 days treatment with SFX-01 increases serum haptoglobin (HP) levels following SAH
Plasma PK	up to 28 days	To determine plasma SFN levels (and its metabolites) with treatment with SFX-01 (300mg bid).

Trial Locations

Locations (3)

Western General Hospital; 🇬🇧 Edinburgh, United Kingdom

Southampton General Hospital; 🇬🇧 Southampton, Hampshire, United Kingdom

The Royal London Hospital; 🇬🇧 London, United Kingdom