SFX-01 After Subarachnoid Haemorrhage (SAS)

• ClinicalTrials.gov Identifier: NCT02614742
• Recruitment Status: Completed
• First Posted: November 25, 2015
• Last Update Posted: January 18, 2020
• Sponsor: Evgen Pharma
• Information provided by (Responsible Party): Evgen Pharma

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Subarachnoid Hemorrhage, Spontaneous	Drug: SFX-01; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: SFX-01 After Subarachnoid Haemorrhage
• Actual Study Start Date: April 2016
• Actual Primary Completion Date: September 2019
• Actual Study Completion Date: November 2019

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Number of participants with treatment-related adverse events as assessed by Common Toxicity Criteria [ Time Frame: 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
2. Maximum CSF Concentration [Cmax], [ Time Frame: up to 28 days ]
   To detect the presence of SFN in Cerebrospinal Fluid (CSF)
3. 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 [ Time Frame: 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 :

1. modified Rankin Scale [ Time Frame: 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.
2. Plasma PK [ Time Frame: up to 28 days ]
   To determine plasma SFN levels (and its metabolites) with treatment with SFX-01 (300mg bid).
3. CSF drug levels [ Time Frame: up to 14 days ]
   To determine CSF drug levels following treatment with SFX-01 (300mg bid).
4. Serum Haptoglobin levels [ Time Frame: Up to 28 days ]
   To determine if up to 28 days treatment with SFX-01 increases serum haptoglobin (HP) levels following SAH
5. Delayed Cerebral Ischaemia [ Time Frame: 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.

Eligibility Criteria

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

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

Contacts and Locations

Locations

United Kingdom

Southampton General Hospital

Southampton, Hampshire, United Kingdom, SO16 6YD

Western General Hospital

Edinburgh, United Kingdom, EH4 4XU

The Royal London Hospital

London, United Kingdom, E1 1BB

Sponsors and Collaborators

Evgen Pharma

Investigators

• Principal Investigator: Diederik Bulters, MBChB, BSc; University Hospital Southampton NHS Foundation Trust

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Evgen Pharma
• ClinicalTrials.gov Identifier: NCT02614742
• Other Study ID Numbers: EVG001SAH; 2014-003284-38 ( EudraCT Number )
• First Posted: November 25, 2015
• Last Update Posted: January 18, 2020
• Last Verified: July 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Subarachnoid Hemorrhage; Hemorrhage; Pathologic Processes; Intracranial Hemorrhages; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases