Strategy for Improving Stroke Treatment Response

NCT ID: NCT05948566

Last Updated: 2025-11-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

300 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-03-18

Study Completion Date

2027-12-31

Brief Summary

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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

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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.

Conditions

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Ischemic Stroke

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Model Description: The first 50 subjects will be randomized equally to the five arms. Response Adaptive Randomization updates will occur every 50 subjects, thereafter, (favoring doses with maximum utility). For each block of 50 subjects, 13 will be allocated to control.
Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo

Placebo

Group Type PLACEBO_COMPARATOR

TS23

Intervention Type BIOLOGICAL

Monoclonal antibody

Dose 1 TS23

low dose

Group Type EXPERIMENTAL

TS23

Intervention Type BIOLOGICAL

Monoclonal antibody

Dose 2 TS23

next higher dose

Group Type EXPERIMENTAL

TS23

Intervention Type BIOLOGICAL

Monoclonal antibody

Dose 3 TS23

next higher dose

Group Type EXPERIMENTAL

TS23

Intervention Type BIOLOGICAL

Monoclonal antibody

Dose 4 TS23

highest dose

Group Type EXPERIMENTAL

TS23

Intervention Type BIOLOGICAL

Monoclonal antibody

Interventions

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TS23

Monoclonal antibody

Intervention Type BIOLOGICAL

Eligibility Criteria

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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.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Cincinnati

OTHER

Sponsor Role collaborator

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role collaborator

Medical University of South Carolina

OTHER

Sponsor Role collaborator

University of Arizona

OTHER

Sponsor Role collaborator

Translational Sciences, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Eva Mistry, MBBS

Role: PRINCIPAL_INVESTIGATOR

University of Cincinnati

Locations

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University of Alabama Hospital

Birmingham, Alabama, United States

Site Status RECRUITING

Banner University Medical Center

Phoenix, Arizona, United States

Site Status RECRUITING

Mayo Clinic Phoenix

Phoenix, Arizona, United States

Site Status WITHDRAWN

Banner University Medical Center - Tucson

Tucson, Arizona, United States

Site Status NOT_YET_RECRUITING

UCSD Health La Jolla

La Jolla, California, United States

Site Status RECRUITING

Kaiser Permanente Los Angeles

Los Angeles, California, United States

Site Status RECRUITING

Sutter Medical Center

Sacramento, California, United States

Site Status WITHDRAWN

UCSD Medical Center- Hillcrest Hospital

San Diego, California, United States

Site Status RECRUITING

Hartford Hospital

Hartford, Connecticut, United States

Site Status RECRUITING

Yale New Haven Hospital

New Haven, Connecticut, United States

Site Status RECRUITING

Christiana Hospital

Newark, Delaware, United States

Site Status RECRUITING

UF Health Shands Hospital

Gainesville, Florida, United States

Site Status RECRUITING

Jackson Memorial Hospital

Miami, Florida, United States

Site Status RECRUITING

Grady Memorial Hospital

Atlanta, Georgia, United States

Site Status RECRUITING

University of Chicago Medical Center

Chicago, Illinois, United States

Site Status RECRUITING

University of Iowa Hospitals & Clinics

Iowa City, Iowa, United States

Site Status RECRUITING

Baptist Healthcare System, Inc.

Lexington, Kentucky, United States

Site Status RECRUITING

University of Louisville Hospital

Louisville, Kentucky, United States

Site Status RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

M Health Fairview Ridges Hospital

Burnsville, Minnesota, United States

Site Status RECRUITING

M Health Fairview Southdale Hospital

Edina, Minnesota, United States

Site Status RECRUITING

M Health Fairview University of Minnesota Medical Center

Minneapolis, Minnesota, United States

Site Status RECRUITING

United Hospital

Saint Paul, Minnesota, United States

Site Status RECRUITING

Barnes Jewish Hospital

St Louis, Missouri, United States

Site Status RECRUITING

JFK Medical Center

Edison, New Jersey, United States

Site Status RECRUITING

NYU Langone Health

Brooklyn, New York, United States

Site Status RECRUITING

Buffalo General Medical Center

Buffalo, New York, United States

Site Status WITHDRAWN

North Shore University Hospital

Manhasset, New York, United States

Site Status RECRUITING

Mount Sinai West

New York, New York, United States

Site Status RECRUITING

The Mount Sinai Hospital

New York, New York, United States

Site Status RECRUITING

NYP Columbia University Medical Center

New York, New York, United States

Site Status RECRUITING

SUNY Upstate Medical University

Syracuse, New York, United States

Site Status RECRUITING

Westchester Medical Center

Valhalla, New York, United States

Site Status NOT_YET_RECRUITING

Duke University Hospital

Durham, North Carolina, United States

Site Status RECRUITING

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, United States

Site Status TERMINATED

University of Cincinnati Medical Center

Cincinnati, Ohio, United States

Site Status RECRUITING

OSU Wexner Medical Center

Columbus, Ohio, United States

Site Status RECRUITING

Ascension St. John

Tulsa, Oklahoma, United States

Site Status RECRUITING

Providence St. Vincent Medical Center

Portland, Oregon, United States

Site Status NOT_YET_RECRUITING

Saint Luke's Hospital of Bethlehem Pennsylvania

Bethlehem, Pennsylvania, United States

Site Status RECRUITING

Temple University Hospital

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Rhode Island Hospital

Providence, Rhode Island, United States

Site Status RECRUITING

Medical University of South Carolina University Hospital

Charleston, South Carolina, United States

Site Status RECRUITING

Prisma Health Greenville Memorial

Greenville, South Carolina, United States

Site Status RECRUITING

Methodist University Hospital

Memphis, Tennessee, United States

Site Status RECRUITING

Memorial Hermann Texas Medical Center

Houston, Texas, United States

Site Status RECRUITING

University of Utah Healthcare

Salt Lake City, Utah, United States

Site Status RECRUITING

UVA Medical Center

Charlottesville, Virginia, United States

Site Status RECRUITING

VCU Medical Center

Richmond, Virginia, United States

Site Status NOT_YET_RECRUITING

Harborview Medical Center

Seattle, Washington, United States

Site Status RECRUITING

Ascension Columbia St. Mary's Hospital

Milwaukee, Wisconsin, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Rebeca Aragon Garcia, BS, CCRC

Role: CONTACT

Phone: 9736688644

Email: [email protected]

Pam Plummer, MSN,RN, CCRC

Role: CONTACT

Phone: 5138852437

Email: [email protected]

Facility Contacts

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Felix Guerra Castanon, MD

Role: primary

Savdeep Singh, MD

Role: primary

Firas Kaddouh, MD, MHS

Role: primary

Maryo Jajo

Role: primary

Royya Modir, MD

Role: backup

Navdeep Sangha, MD

Role: primary

Maryo Jajo

Role: primary

Royya' Modir, MD

Role: backup

Ajay Tunguturi, MD

Role: primary

James Giles, MD, PhD

Role: primary

Jason Nomura, MD

Role: primary

Amita Singh, MD, MS

Role: primary

Andrea Escobar

Role: primary

Gillian Gordon Perue, MD, MBBS, DM

Role: backup

Nicolas Bianchi, MD

Role: primary

James Siegler, MD, FAHA

Role: primary

Heena Olalde

Role: primary

Enrique Leira, MD

Role: backup

Murali Kolikonda, MD

Role: primary

Franklin Echevarria

Role: backup

Isaac Abecassis, MD

Role: primary

Rahul Mahajan, MD, PhD

Role: primary

Aneesh Singhal, MD, MBBS

Role: primary

Jessica Staloch

Role: primary

Muhammad Affan, MD, MBBS

Role: backup

Jessica Staloch

Role: primary

Muhammad Affan, MD,MBBS

Role: backup

Jessica Staloch

Role: primary

Muhammad Affan, MD,MBBS

Role: backup

Ganesh Asaithambi, MD

Role: primary

Charles Kircher, MD

Role: primary

Nancy Gadallah, DO

Role: primary

Maria Cotrina-Vidal

Role: primary

Aaron Lord, MD, MSc

Role: backup

Rohan Arora

Role: primary

Laura Stein, MD, MPH

Role: primary

Laura Stein, MD, MPH

Role: primary

Angela Velazquez

Role: primary

Shivani Ghoshal, MD

Role: backup

Deb Lena

Role: primary

Julius-Gene LaTorre, MD, MPH

Role: backup

Gurmeen Kaur, MD

Role: primary

Rosanna Escobar-Spadina

Role: primary

Alexander Limkakeng, MD, MHSc

Role: backup

Yasmin Aziz, MD

Role: primary

Jan Bittar, MD

Role: primary

Rahul Rahangdale, MD

Role: primary

Kishan Patel, MD

Role: primary

Daniel Ackerman, MD

Role: primary

Nina Gentile, MD

Role: primary

Farhan Khan, MD

Role: primary

Caitlan LeMatty

Role: primary

Christine Holmstedt, DO

Role: backup

Sanjeev Sivakumar, MD

Role: primary

Quentin Thacker

Role: primary

Balaji Krishnaiah, MD

Role: backup

Prasen Marella

Role: primary

Andrew Barreto, MD, MS

Role: backup

Vivek Reddy, MD, MMM

Role: primary

Amna Sohail, MBBS, MD

Role: primary

Shraddha Mainali, MD

Role: primary

David Tirschwell, MD, MSc.

Role: primary

Lakiesha Coleman

Role: primary

William Taylor, DO

Role: backup

Other Identifiers

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UH3NS125023

Identifier Type: NIH

Identifier Source: secondary_id

View Link

TS23-U202

Identifier Type: -

Identifier Source: org_study_id