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NCT05948566PHASE2Recruiting

Strategy for Improving Stroke Treatment Response

Translational Sciences, Inc.

Start Date

3/18/2024

Completion Date

12/1/2027

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.

Detailed 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 \>/=4 (with the patient having a clearly disabling deficit if the NIHSS is 4 or 5) 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 up to 300 subjects at up to 60 participating US sites and up to 17 Canadian 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 (+/-4) hours and 2) primary efficacy outcome: NIH Stroke Scale score at 30 (+/-4) 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.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: 1. Age 18 years and older 2. Suspected anterior circulation acute ischemic stroke 3. NIH Stroke Scale score ≥4 prior to randomization a. The participant must have a clearly disabling deficit if NIHSS is 4-5. 4. Favorable baseline neuroimaging consisting of all of the following: 1. ASPECTS of 6 or more on CT (or ASPECTS of ≥7 on MRI) 2. Favorable perfusion imaging on CT perfusion (CTP)/MR-perfusion weighted imaging (PWI) consisting of all of the following: i. Mismatch ratio of penumbra: core \>1.2 ii. Mismatch volume \>10 cc iii. Core \<70 cc c. If CT hypodensity is present, then in the investigator's visual assessment, the total acute infarct volume combined area of (a) the CT hypodensity and (b) the perfusion-based core volume (CBF\<30%) should be smaller than perfusion-based volume (area of Tmax\>6s minus CBF\<30%). 5. Able to receive assigned study drug within 4.5 to 24 hours of stroke onset or last known well. 6. Able to receive assigned study drug within 120 minutes of qualifying perfusion imaging. \* 7. Informed consent for the study participation obtained from participant or their legally authorized representatives. * Study drug administration is encouraged within 90 minutes after qualifying perfusion image but is allowed up to 120 minutes. After 120 minutes, another perfusion image to ensure that inclusion criteria are met is required. Exclusion Criteria: 1. Received endovascular treatment with clot engagement. 1. Patients who undergo groin puncture but clot engagement is not attempted due to spontaneous distal migration are permitted to be enrolled in the trial if all other eligibility criteria are met. 2. Patients who undergo groin puncture but clot is not engaged due to reasons other than spontaneous distal migration are NOT permitted. 2. Received or planned to receive intravenous thrombolysis. 3. Pre-stroke modified Rankin score \>2. 4. Previous treatment with TS23 or known previous allergy to antibody therapy. 5. Known pregnancy, women who are breastfeeding or plan to breastfeed within 3 months of receiving TS23 or have a positive urine or serum pregnancy test for women of childbearing potential. 6. Known previous stroke in the past 90 days. 7. Known previous intracranial hemorrhage, intracranial neoplasm, subarachnoid hemorrhage, or arterial venous malformation. 8. Known active diagnosis of intracranial neoplasm. 9. Clinical presentation suggestive of a subarachnoid hemorrhage, even if initial CT scan was normal. 10. Surgery or biopsy of parenchymal organ in the past 30 days. 11. Known trauma with internal injuries or persistent ulcerative wounds in the past 30 days. 12. Severe head trauma in the past 90 days. 13. Persistent systolic blood pressure \>180mmHg or diastolic blood pressure \>105mmHg despite best medical management. 14. Serious systemic hemorrhage in the past 30 days. 15. Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with International Normalized Ratio (INR) \>1.7. 16. Platelets \<100,000/mm3. 17. Hematocrit \<25 %. 18. Elevated aPTT above laboratory upper limit of normal. 19. Creatinine \> 4 mg/dl, or patients receiving renal dialysis, regardless of creatinine. 20. Received the following within the previous 24 hours: 1. If patient received unfractionated heparin within the last 24 hours, the patient must have an aPTT within normal range prior to enrollment. 2. Low molecular weight heparins such as Dalteparin, enoxaparin, tinzaparin in full dose within the previous 24 hours. 21. Received Factor Xa inhibitors (such as Fondaparinux, apixaban or rivaroxaban) within the past 48 hours. 22. Received direct thrombin inhibitors (e.g., argatroban, dabigatran, bivalirudin, desirudin, lepirudin) within 48 hours. 23. Received glycoprotein IIb/IIIa inhibitors within the past 14 days. 24. Known pre-existing neurological or psychiatric disease which would confound the neurological/functional evaluations. 25. Current participation in another research drug treatment protocol (i.e., participants could not start another experimental agent until after 90 days). 26. Concurrent acute myocardial infarction, pulmonary embolism, deep venous thrombosis or other thrombotic event that requires anticoagulation or anti-platelet treatment.

Interventions

BIOLOGICAL

TS23

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Conditions

Ischemic Stroke

Locations

University of Alabama Hospital

Birmingham, Alabama 35233

United States

Banner University Medical Center

Phoenix, Arizona 85006

United States

Mayo Clinic Phoenix

Phoenix, Arizona 85054

United States

Banner University Medical Center - Tucson

Tucson, Arizona 85719

United States

UCSD Health La Jolla

La Jolla, California 92093

United States

Kaiser Permanente Los Angeles

Los Angeles, California 90027

United States

Sutter Medical Center

Sacramento, California 95816

United States

UCSD Medical Center- Hillcrest Hospital

San Diego, California 92103

United States

Hartford Hospital

Hartford, Connecticut 06102

United States

Yale New Haven Hospital

New Haven, Connecticut 06511

United States

Christiana Hospital

Newark, Delaware 19718

United States

UF Health Shands Hospital

Gainesville, Florida 32608

United States

Jackson Memorial Hospital

Miami, Florida 33136

United States

Grady Memorial Hospital

Atlanta, Georgia 30303

United States

University of Chicago Medical Center

Chicago, Illinois 60637

United States

University of Iowa Hospitals & Clinics

Iowa City, Iowa 52242

United States

Baptist Healthcare System, Inc.

Lexington, Kentucky 40503

United States

University of Louisville Hospital

Louisville, Kentucky 40202

United States

Brigham and Women's Hospital

Boston, Massachusetts 02115

United States

Massachusetts General Hospital

Boston, Massachusetts 02171

United States

M Health Fairview Ridges Hospital

Burnsville, Minnesota 55337

United States

M Health Fairview Southdale Hospital

Edina, Minnesota 55435

United States

M Health Fairview University of Minnesota Medical Center

Minneapolis, Minnesota 55455

United States

United Hospital

Saint Paul, Minnesota 55102

United States

Barnes Jewish Hospital

St Louis, Missouri 63110

United States

JFK Medical Center

Edison, New Jersey 08837

United States

NYU Langone Health

Brooklyn, New York 11220

United States

Buffalo General Medical Center

Buffalo, New York 14203

United States

North Shore University Hospital

Manhasset, New York 11030

United States

Mount Sinai West

New York, New York 10029

United States

The Mount Sinai Hospital

New York, New York 10029

United States

NYP Columbia University Medical Center

New York, New York 10032

United States

SUNY Upstate Medical University

Syracuse, New York 13202

United States

Westchester Medical Center

Valhalla, New York 10595

United States

Duke University Hospital

Durham, North Carolina 27710

United States

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina 27157

United States

University of Cincinnati Medical Center

Cincinnati, Ohio 45267

United States

OSU Wexner Medical Center

Columbus, Ohio 43210

United States

Ascension St. John

Tulsa, Oklahoma 74104

United States

Providence St. Vincent Medical Center

Portland, Oregon 97225

United States

Saint Luke's Hospital of Bethlehem Pennsylvania

Bethlehem, Pennsylvania 18015

United States

Temple University Hospital

Philadelphia, Pennsylvania 19140

United States

Rhode Island Hospital

Providence, Rhode Island 02903

United States

Medical University of South Carolina University Hospital

Charleston, South Carolina 32608

United States

Prisma Health Greenville Memorial

Greenville, South Carolina 29605

United States

Methodist University Hospital

Memphis, Tennessee 38104

United States

Memorial Hermann Texas Medical Center

Houston, Texas 77030

United States

University of Utah Healthcare

Salt Lake City, Utah 84132

United States

UVA Medical Center

Charlottesville, Virginia 22901

United States

VCU Medical Center

Richmond, Virginia 23298

United States

Harborview Medical Center

Seattle, Washington 98104

United States

Ascension Columbia St. Mary's Hospital

Milwaukee, Wisconsin 53211

United States