SFX-01 After Subarachnoid Haemorrhage (SAS)

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

Study Overview

• Status: Completed
• Conditions: Subarachnoid Hemorrhage, Spontaneous
• Intervention / Treatment: Drug: SFX-01; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 90
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • Edinburgh, United Kingdom, EH4 4XU
    • Western General Hospital
  • London, United Kingdom, E1 1BB
    • The Royal London Hospital
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • Southampton General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: SFX-01; 300mg bid for up to 28 days.	Drug: SFX-01; An intervention releasing sulforaphane.; Other Names: Sulforadex
Placebo Comparator: Placebo; 300mg placebo bid for up to 28 days	Drug: Placebo; Placebo otherwise identical to Active product; Other Names: Cyclodextrin

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
modified Rankin Scale	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.	up to 180 days post ictus
Plasma PK	To determine plasma SFN levels (and its metabolites) with treatment with SFX-01 (300mg bid).	up to 28 days
CSF drug levels	To determine CSF drug levels following treatment with SFX-01 (300mg bid).	up to 14 days
Serum Haptoglobin levels	To determine if up to 28 days treatment with SFX-01 increases serum haptoglobin (HP) levels following SAH	Up to 28 days
Delayed Cerebral Ischaemia	To determine if up to 28 days treatment with SFX-01 can reduce the incidence of Delayed Cerebral Ischaemia (DCI) following SAH.	Up to 28 days

Collaborators and Investigators

• Sponsor: Evgen Pharma
• Investigators: Principal Investigator: Diederik Bulters, MBChB, BSc, University Hospital Southampton NHS Foundation Trust

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Actual): September 1, 2019
• Study Completion (Actual): November 1, 2019

Study Registration Dates

• First Submitted: November 16, 2015
• First Submitted That Met QC Criteria: November 23, 2015
• First Posted (Estimate): November 25, 2015

Study Record Updates

• Last Update Posted (Actual): January 18, 2020
• Last Update Submitted That Met QC Criteria: January 14, 2020
• Last Verified: July 1, 2019

More Information

Terms related to this study

• 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
• Other Study ID Numbers: EVG001SAH; 2014-003284-38 (EudraCT Number)

Drug and device information, study documents

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