Strategy for Improving Stroke Treatment Response

Ischemic Stroke Clinical Trial

— SISTER  

Official title:

Strategy for Improving Stroke Treatment Response (SISTER) Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05948566
• Other study ID #: TS23-U202
• Status: Recruiting
• Phase: Phase 2
• Start date: March 18, 2024
• Est. completion date: December 2027

Study information

• Verified date: May 2024
• Source: Translational Sciences, Inc.
• Contact: Pam Plummer, MSN,RN, CCRC
• Phone: 5138852437
• Email: plummepa[@]ucmail.uc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

SISTER is a Phase-II, prospective, randomized, placebo-controlled, blinded, dose finding trial that aims to determine the safety and preliminary efficacy of TS23, a monoclonal antibody against the alpha-2 antiplasmin (a2-AP), in acute ischemic stroke.

Description:

SISTER is a Phase II, Bayesian, adaptive, randomized, dose-finding trial of TS23 in patients with acute ischemic stroke. Patients with an anterior cerebral circulation acute ischemic stroke and present between 4.5 to 24 hours of their last known well with a presenting NIH Stroke Scale Score >/=6 and an imaging evidence of salvageable brain tissue will be eligible and will be approached for an informed consent for study participation. After informed consent is provided, the study will randomize to 4 doses of TS23 and placebo. The trial will enroll 300 subjects at up to 50 participating sites.

The effects of TS23 will be evaluated on two following primary outcomes using a utility function: 1) primary safety outcome: any intracerebral hemorrhage at 30 (+/-6) hours and 2) primary efficacy outcome: NIH Stroke Scale score at 30 (+/-6) hours after drug administration. The study will follow participants for 90 (+/-7) days.

Primary Objective: To identify a dose of TS23 that is safe and more efficacious than placebo for the treatment of patients from 4.5 to 24 hours of last known well, who have evidence of core-penumbra mismatch on perfusion imaging and are not a candidate for standard of care reperfusion therapies.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 2027
• Est. primary completion date: July 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Age 18 years and older

2. Suspected anterior circulation acute ischemic stroke

3. Presenting NIH Stroke Scale score >/= 6

4. Favorable baseline neuroimaging

1. CT scan with ASPECTS of >/=6, or MRI with ASPECTS of >/=7 and

2. CT or MR Perfusion with a mismatch ratio >1.2 between the volume of hypoperfusion and the volume of the ischemic core, an absolute difference in volume > 10 ml, and an ischemic-core volume of less than 70 ml. and

3. Able to receive assigned study drug within 4.5 to 24 hours of stroke onset or last known well

5. Informed consent for the study participation obtained from participant or their legally authorized representatives.

Exclusion Criteria:

1. Patients planned to receive endovascular treatment.

2. Patients that received or planned to receive intravenous thrombolysis.

3. Pre-stroke modified Rankin score >2.

4. Known previous allergy to antibody therapy.

5. Known pregnancy or positive urine or serum pregnancy test for women of child bearing potential.

6. Known previous stroke in the past 90 days.

7. Known previous intracranial hemorrhage, neoplasm, subarachnoid hemorrhage, or arterial venous malformation.

8. Clinical presentation suggestive of a subarachnoid hemorrhage, even if initial CT scan was normal.

9. Surgery or biopsy of parenchymal organ in the past 30 days.

10. Known trauma with internal injuries or ulcerative wounds in the past 30 days.

11. Severe head trauma in the past 90 days.

12. Persistent systolic blood pressure >180mmHg or diastolic blood pressure >105mmHg despite best medical management.

13. Serious systemic hemorrhage in the past 30 days.

14. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with INR >1.7.

15. Platelets <100,000/mm3.

16. Hematocrit <25 %.

17. Elevated PTT above laboratory upper limit of normal.

18. Creatinine > 4 mg/dl, or patients receiving renal dialysis, regardless of creatinine.

19. Received heparin or low molecular weight heparins (such as dalteparin, enoxaparin, tinzaparin) in full dose within the previous 24 hours.

20. Received Factor Xa inhibitors (such as fondaparinux, apixaban or rivaroxaban) within the past 48 hours.

21. Received direct thrombin inhibitors (e.g., argatroban, dabigatran, bivalirudin, desirudin, lepirudin) within 48 hours.

22. Received glycoprotein IIb/IIIa inhibitors within the past 14 days.

23. Known pre-existing neurological or psychiatric disease which would confound the neurological/functional evaluations.

24. Current participation in another research drug treatment protocol (i.e., participants could not start another experimental agent until after 90 days).

25. Concurrent acute myocardial infarction, pulmonary embolism, deep venous thrombosis or other thrombotic event that requires anticoagulation or anti-platelet treatment.

Related Conditions & MeSH terms

• Ischemic Stroke
• Stroke

Intervention

Biological:
• TS23
Monoclonal antibody

Locations

Country	Name	City	State
United States	Grady Memorial Hospital	Atlanta	Georgia
United States	University of Alabama Hospital	Birmingham	Alabama
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	NYU Langone Health	Brooklyn	New York
United States	Buffalo General Medical Center	Buffalo	New York
United States	M Health Fairview Ridges Hospital	Burnsville	Minnesota
United States	Medical University of South Carolina University Hospital	Charleston	South Carolina
United States	UVA Medical Center	Charlottesville	Virginia
United States	University of Chicago Medical Center	Chicago	Illinois
United States	University of Cincinnati Medical Center	Cincinnati	Ohio
United States	OSU Wexner Medical Center	Columbus	Ohio
United States	Duke University Hospital	Durham	North Carolina
United States	M Health Fairview Southdale Hospital	Edina	Minnesota
United States	JFK Medical Center	Edison	New Jersey
United States	UF Health Shands Hospital	Gainesville	Florida
United States	Prisma Health Greenville Memorial	Greenville	South Carolina
United States	Houston Methodist Hospital	Houston	Texas
United States	Memorial Hermann Texas Medical Center	Houston	Texas
United States	University of Iowa Hospitals & Clinics	Iowa City	Iowa
United States	UCSD Health La Jolla	La Jolla	California
United States	Kaiser Permanente Los Angeles	Los Angeles	California
United States	North Shore University Hospital	Manhasset	New York
United States	Methodist University Hospital	Memphis	Tennessee
United States	Jackson Memorial Hospital	Miami	Florida
United States	M Health Fairview University of Minnesota Medical Center	Minneapolis	Minnesota
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	Mount Sinai West	New York	New York
United States	NYP Columbia University Medical Center	New York	New York
United States	The Mount Sinai Hospital	New York	New York
United States	Christiana Hospital	Newark	Delaware
United States	Temple University Hospital	Philadelphia	Pennsylvania
United States	Banner University Medical Center	Phoenix	Arizona
United States	Mayo Clinic Phoenix	Phoenix	Arizona
United States	Rhode Island Hospital	Providence	Rhode Island
United States	Sutter Medical Center	Sacramento	California
United States	Barnes Jewish Hospital	Saint Louis	Missouri
United States	United Hospital	Saint Paul	Minnesota
United States	University of Utah Healthcare	Salt Lake City	Utah
United States	UCSD Medical Center- Hillcrest Hospital	San Diego	California
United States	Harborview Medical Center	Seattle	Washington
United States	SUNY Upstate Medical University	Syracuse	New York
United States	Ascension St. John	Tulsa	Oklahoma
United States	Wake Forest Baptist Medical Center	Winston-Salem	North Carolina

Sponsors (5)

Lead Sponsor	Collaborator
Translational Sciences, Inc.	Medical University of South Carolina, National Institute of Neurological Disorders and Stroke (NINDS), University of Arizona, University of Cincinnati

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The proportion of patients with ANY intracerebral hemorrhage (ICH)	Any ICH visualized on the follow-up CT scan	At 30 (+/- 4) hours after study drug
Primary	Stroke severity as measured by the National Institutes of Health Stroke Scale (NIHSS)	NIHSS is a stroke severity score that ranges from 0 to 42, with higher numbers indicating a more severe stroke. The NIHSS will be adjusted for the baseline value in analysis.	At 30 (+/- 4) hours after study drug
Secondary	Improvement in level of global disability measured by modified Rankin Score (mRS distribution)	The modified Rankin Score assessment is a 7-level disability scale that measures the degree of disability or dependence in daily activities of people who have suffered a stroke. Range 0= no disability and 6=dead.	90 (±7) days
Secondary	Frequency of excellent functional outcome	Proportion of patients with modified Rankin scale score 0-1, denoting a symptom free outcome	Proportion of patients with modified Rankin scale score 0-1, denoting a symptom free outcome
Secondary	NIHSS	NIHSS is a stroke severity score that ranges from 0 to 42, with higher numbers indicating a more severe stroke. The NIHSS will be adjusted for the baseline value in analysis.	72 (±12) hours (or at discharge if sooner) after study drug administration.
Secondary	a2-antiplasmin (a2AP) level in plasma	A serine protease inhibitor responsible for inactivating plasmin.	at 3 (±1) h after completion of study drug administration
Secondary	Matrix metalloproteinase-9 level in plasma	An enzyme that regulates the pathological remodeling process that involve inflammation and fibrosis associated with cardiovascular disease.	3 (±1) h after completion of study drug
Secondary	% brain tissue reperfusion	Proportion of brain tissue that is reperfused on the follow-up perfusion scan compared to the baseline, calculated as: ([baseline minus follow up perfusion imaging area of hypoperfusion]/ baseline area of hypoperfusion); hypoperfusion=T max>6 seconds	30 (±4) h after study drug administration
Secondary	Pharmacokinetic analyses	Measure of plasma concentrations of TS23	at 3 (±1) h, and 30 (±4) h, 30 (±5) days, and 90 (±7) days, after completion of study drug administration.
Secondary	Evaluation of anti-drug antibodies	commonly used for characterization of therapeutic antibodies	baseline and 90 (±7) days follow-up visit
Secondary	Proportion of patients with symptomatic intracerebral hemorrhage	a blood clot large enough to cause significant neurological deterioration.	30 (±6) h of study drug administration
Secondary	Proportion of patients with non-intracerebral hemorrhage major or clinically relevant non-major bleeding	major and non-major events of bleeding that is not in the brain	30 days of study drug administration.
Secondary	Plasma fibrinogen level	Clotting factor	3 (±1) h after completion of study drug
Secondary	Proportion of patients with non-bleeding severe adverse events	Assessment of untoward events	90 (±7) days
Secondary	Proportion of patients with stroke-related and all-cause deaths	measure of important patient outcomes	90 (±7) days