Efficacy and Safety of Trans Sodium Crocetinate (TSC) for Treatment of Suspected Stroke (PHAST-TSC)

• ClinicalTrials.gov Identifier: NCT03763929
• Recruitment Status: Terminated
• First Posted: December 4, 2018
• Results First Posted: June 18, 2021
• Last Update Posted: June 18, 2021
• Sponsor: Diffusion Pharmaceuticals Inc
• Collaborators: University of California, Los Angeles; University of Virginia
• Information provided by (Responsible Party): Diffusion Pharmaceuticals Inc

Tracking Information

• First Submitted Date: December 3, 2018
• First Posted Date: December 4, 2018
• Results First Submitted Date: May 24, 2021
• Results First Posted Date: June 18, 2021
• Last Update Posted Date: June 18, 2021
• Actual Study Start Date: August 22, 2019
• Actual Primary Completion Date: October 19, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 24, 2021)

Global Disability Level on the Modified Rankin Score (mRS) [ Time Frame: 90 days ]

Modified Rankin Scale (mRS) is a measure of global disability. Total scale range is 0-6, with lower values indicating better outcomes. 0 = No symptoms at all

1. = No significant disability despite symptoms; able to carry out all usual duties and activities
2. = Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance
3. = Moderate disability; requiring some help, but able to walk without assistance
4. = Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance
5. = Severe disability; bedridden, incontinent and requiring constant nursing care and attention
6. = Dead

Original Primary Outcome Measures (submitted: December 3, 2018)

Modified Rankin Scale (UW - mRS) [ Time Frame: 90 days ]

The primary efficacy objective is to test the hypothesis that treatment with TSC reduces the level of long-term disability of hyperacute stroke subjects. The study endpoint analysis to evaluate this hypothesis will be the difference in distribution of scores between TSC and placebo groups on the utility-weighted modified Rankin Scale (UW-mRS) measure of global disability, assessed 90-days post-stroke

• Current Secondary Outcome Measures: Not Provided

Original Secondary Outcome Measures (submitted: December 3, 2018)

• Functional Independence (mRS 0-2) and improved quality of life [ Time Frame: 90 days ]
  Test the hypothesis that treatment with TSC improves the long-term outcome of hyperacute stroke subjects in achieving functional independence (mRS 0-2) at 90 days.
• Freedom from Disability (mRS 0-1) [ Time Frame: 90 days ]
  Evaluate for signals of benefit of treatment with TSC upon freedom from disability (mRS 0-1) at 90 days.
• Activities of Daily Living (Barthel Index [BI]) [ Time Frame: 90 days ]
  Evaluate for signals of benefit of treatment with TSC upon activities of daily living (Barthel Index [BI]) at 90 days
• Neturologic Deficit (National Institutes of Health Stroke Score [NIHSS]) [ Time Frame: 90 days ]
  Evaluate for signals of benefit of treatment with TSC upon neurologic deficit (National Institutes of Health Stroke Score [NIHSS]) at 90 days.
• Qualify of Life (Stroke Impact Scale [SIS-16]) [ Time Frame: 90 days ]
  Evaluate for signals of benefit of treatment with TSC upon quality of life (Stroke Impact Scale [SIS-16] at 90 days.
• Quality of Life (AMC - Linear Disability Scale) [ Time Frame: 90 days ]
  Evaluate for signals of benefit of treatment with TSC upon quality of life (Stroke (AMC-Linear Disability Scale) at 90 days.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy and Safety of Trans Sodium Crocetinate (TSC) for Treatment of Suspected Stroke
• Official Title: Double-Blind, Randomized, Placebo-Controlled, Phase 2 Study of Efficacy and Safety of Trans Sodium Crocetinate (TSC) Administered Onboard Emergency Vehicles for Treatment of Suspected Stroke: PHAST-TSC
• Brief Summary: This study will assess the potential efficacy and safety of TSC as early treatment for both ischemic and hemorrhagic stroke when administered while subject is in ambulance being transported to hospital.

Detailed Description

This is a multicenter, randomized, placebo-controlled, double-blind, parallel group trial of intravenous trans sodium crocetinate (TSC) initiated by emergency medical service (EMS) responders in the field within 2 hours of symptom onset in 160 subjects with acute stroke. The primary objectives of the study are to evaluate the efficacy and safety of field-initiated TSC in improving the long-term functional outcome of subjects with acute stroke.

Subjects with acute stroke will be identified and screened in the ambulance by (EMS) responders who have received training in basic and advanced cardiac life support, stroke recognition, and specific procedures relevant to the proposed study. The EMS responders will contact a Study Neurologist, who will enroll eligible stroke patients into the study. Effort will be made to obtain prospective informed consent in the ambulance when deemed to be feasible. If not feasible, subjects will be enrolled under regulations for exception from explicit informed consent (EFIC) in emergency research circumstances, after public disclosure and community consultation. Written informed consent to continue in the study is obtained from subjects or their legally authorized representatives as soon as possible after hospital arrival.

EMS responders will deliver the single, field, bolus dose of study agent, TSC at 0.25 mg/kg or matched placebo, followed after hospital arrival by standard of care (SOC). No additional study drug will be administered in the hospital. Follow-up assessments will be performed at Emergency Department (ED) arrival, 24 hours, 48 hours, Day 4, Day 30, and Day 90. The study will be performed at up to 30 receiving hospital sites in Los Angeles County, CA, and central Virginia.

• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Multicenter, randomized, placebo-controlled, double-blind, parallel group

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

TSC injections will be prepared and injected by unblinded personnel on each ambulance. All other study personnel will be blinded

Primary Purpose: Treatment

• Condition: Stroke, Acute

Intervention

• Drug: Trans-Sodium Crocetinate
  In the study drug kit containing the experimental drug (TSC), TSC will be reconstituted with the Sterile Water for Injection (USP) supplied in the same kit. There will be an unblinded paramedic who will reconstitute and inject the TSC on the ambulance.
  Other Name: TSC
• Other: Placebo
  The study drug kit containing placebo (sterile saline for Injection) will be prepared and injected by the unblinded paramedic on the ambulance.

Study Arms

• Experimental: Trans Sodium Crocetinate
  Trans sodium crocetinate (TSC) will be administered intravenously as a bolus to subjects randomized to experimental drug. The bolus dose will consist of 0.25 mg/kg of TSC based on the estimated subject weight.
  Intervention: Drug: Trans-Sodium Crocetinate
• Placebo Comparator: Placebo
  The placebo consists of commercially available sterile saline. Placebo will be administered intravenously as a bolus to subjects randomized to placebo. The volume of sterile saline will be based on the estimated subject weight.
  Intervention: Other: Placebo

• Publications *: Zachrison KS, Amati V, Schwamm LH, Yan Z, Nielsen V, Christie A, Reeves MJ, Sauser JP, Lomi A, Onnela JP. Influence of Hospital Characteristics on Hospital Transfer Destinations for Patients With Stroke. Circ Cardiovasc Qual Outcomes. 2022 May;15(5):e008269. doi: 10.1161/CIRCOUTCOMES.121.008269. Epub 2022 Apr 4.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: December 14, 2020): 6
• Original Estimated Enrollment (submitted: December 3, 2018): 160
• Actual Study Completion Date: October 19, 2020
• Actual Primary Completion Date: October 19, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Age 40-85, inclusive
2. Last known well time 15-120 minutes before anticipated study drug injection
3. Suspected stroke identified by the LAPSS
4. Moderate to severe motor deficit, with Los Angeles Motor Scale (LAMS) 2 or higher
5. No seizure

Exclusion Criteria:

1. Coma
2. Rapidly improving neurologic deficit
3. History of seizures or epilepsy
4. Pre-existing neurologic, psychiatric, or advanced systemic disease that would confound the neurological or functional outcome evaluations
5. SBP < 90 or > 220
6. Major head trauma in the last 24 hours
7. Recent stroke within 30 days
8. Known to be pregnant or lactating

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years to 85 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03763929
• Other Study ID Numbers: 100-501
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

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

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Diffusion Pharmaceuticals Inc
• Original Responsible Party: Same as current
• Current Study Sponsor: Diffusion Pharmaceuticals Inc
• Original Study Sponsor: Same as current

Collaborators

• University of California, Los Angeles
• University of Virginia

Investigators

• Principal Investigator: Andrew Southerland, MD; University of Virginia
• Principal Investigator: Nerses Sanossian, MD; University of Southern California
• Study Chair: Karen Johnston, MD; University of Virginia
• Study Chair: Jeffrey Saver, MD; University of California, Los Angeles

• PRS Account: Diffusion Pharmaceuticals Inc
• Verification Date: December 2020