NCT05948566

Brief 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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
300

participants targeted

Target at P75+ for phase_2

Timeline
18mo left

Started Mar 2024

Typical duration for phase_2

Geographic Reach
1 country

52 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress61%
Mar 2024Dec 2027

First Submitted

Initial submission to the registry

July 8, 2023

Completed
9 days until next milestone

First Posted

Study publicly available on registry

July 17, 2023

Completed
8 months until next milestone

Study Start

First participant enrolled

March 18, 2024

Completed
3.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2027

Expected
5 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2027

Last Updated

June 2, 2026

Status Verified

June 1, 2026

Enrollment Period

3.3 years

First QC Date

July 8, 2023

Last Update Submit

June 1, 2026

Conditions

Outcome Measures

Primary Outcomes (2)

  • 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

  • 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 Outcomes (13)

  • Improvement in level of global disability measured by modified Rankin Score (mRS distribution)

    90 (±7) days

  • Frequency of Modified Rankin (mRS) score of 0-1 or returning to pre-stroke mRS.

    Proportion of patients with modified Rankin scale score 0-1 or return to pre-stroke mRS at 90 (+/-7) days.

  • NIHSS

    72 (±12) hours (or at discharge if sooner) after study drug administration.

  • α2-antiplasmin (a2AP) level in plasma

    at 3 (±1) h after completion of study drug administration

  • Matrix metalloproteinase-9 level in plasma

    3 (±1) h after completion of study drug

  • +8 more secondary outcomes

Study Arms (5)

Placebo

PLACEBO COMPARATOR

Placebo

Biological: TS23

Dose 1 TS23

EXPERIMENTAL

low dose

Biological: TS23

Dose 2 TS23

EXPERIMENTAL

next higher dose

Biological: TS23

Dose 3 TS23

EXPERIMENTAL

next higher dose

Biological: TS23

Dose 4 TS23

EXPERIMENTAL

highest dose

Biological: TS23

Interventions

TS23BIOLOGICAL

Monoclonal antibody

Dose 1 TS23Dose 2 TS23Dose 3 TS23Dose 4 TS23Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age 18 years and older
  • Suspected anterior circulation acute ischemic stroke
  • NIH Stroke Scale score ≥4 prior to randomization
  • a. The participant must have a clearly disabling deficit if NIHSS is 4-5.
  • Favorable baseline neuroimaging consisting of all of the following:
  • ASPECTS of 6 or more on CT (or ASPECTS of ≥7 on MRI)
  • 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%).
  • Able to receive assigned study drug within 4.5 to 24 hours of stroke onset or last known well.
  • Able to receive assigned study drug within 120 minutes of qualifying perfusion imaging. \*
  • Informed consent for the study participation obtained from participant or their legally authorized representatives.

You may not qualify if:

  • Received endovascular treatment with clot engagement.
  • 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.
  • Patients who undergo groin puncture but clot is not engaged due to reasons other than spontaneous distal migration are NOT permitted.
  • Received or planned to receive intravenous thrombolysis.
  • Pre-stroke modified Rankin score \>2.
  • Previous treatment with TS23 or known previous allergy to antibody therapy.
  • 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.
  • Known previous stroke in the past 90 days.
  • Known previous intracranial hemorrhage, intracranial neoplasm, subarachnoid hemorrhage, or arterial venous malformation.
  • Known active diagnosis of intracranial neoplasm.
  • Clinical presentation suggestive of a subarachnoid hemorrhage, even if initial CT scan was normal.
  • Surgery or biopsy of parenchymal organ in the past 30 days.
  • Known trauma with internal injuries or persistent ulcerative wounds in the past 30 days.
  • Severe head trauma in the past 90 days.
  • Persistent systolic blood pressure \>180mmHg or diastolic blood pressure \>105mmHg despite best medical management.
  • +15 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (52)

University of Alabama Hospital

Birmingham, Alabama, 35233, United States

RECRUITING

Banner University Medical Center

Phoenix, Arizona, 85006, United States

RECRUITING

Mayo Clinic Phoenix

Phoenix, Arizona, 85054, United States

WITHDRAWN

Banner University Medical Center - Tucson

Tucson, Arizona, 85719, United States

NOT YET RECRUITING

UCSD Health La Jolla

La Jolla, California, 92093, United States

RECRUITING

Kaiser Permanente Los Angeles

Los Angeles, California, 90027, United States

RECRUITING

Sutter Medical Center

Sacramento, California, 95816, United States

WITHDRAWN

UCSD Medical Center- Hillcrest Hospital

San Diego, California, 92103, United States

RECRUITING

Hartford Hospital

Hartford, Connecticut, 06102, United States

RECRUITING

Yale New Haven Hospital

New Haven, Connecticut, 06511, United States

RECRUITING

Christiana Hospital

Newark, Delaware, 19718, United States

RECRUITING

UF Health Shands Hospital

Gainesville, Florida, 32608, United States

TERMINATED

Jackson Memorial Hospital

Miami, Florida, 33136, United States

RECRUITING

Grady Memorial Hospital

Atlanta, Georgia, 30303, United States

RECRUITING

University of Chicago Medical Center

Chicago, Illinois, 60637, United States

RECRUITING

University of Iowa Hospitals & Clinics

Iowa City, Iowa, 52242, United States

WITHDRAWN

Baptist Healthcare System, Inc.

Lexington, Kentucky, 40503, United States

RECRUITING

University of Louisville Hospital

Louisville, Kentucky, 40202, United States

RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02171, United States

RECRUITING

M Health Fairview Ridges Hospital

Burnsville, Minnesota, 55337, United States

RECRUITING

M Health Fairview Southdale Hospital

Edina, Minnesota, 55435, United States

RECRUITING

M Health Fairview University of Minnesota Medical Center

Minneapolis, Minnesota, 55455, United States

RECRUITING

United Hospital

Saint Paul, Minnesota, 55102, United States

WITHDRAWN

Barnes Jewish Hospital

St Louis, Missouri, 63110, United States

RECRUITING

JFK Medical Center

Edison, New Jersey, 08837, United States

RECRUITING

NYU Langone Health

Brooklyn, New York, 11220, United States

RECRUITING

Buffalo General Medical Center

Buffalo, New York, 14203, United States

WITHDRAWN

North Shore University Hospital

Manhasset, New York, 11030, United States

RECRUITING

Mount Sinai West

New York, New York, 10029, United States

RECRUITING

The Mount Sinai Hospital

New York, New York, 10029, United States

RECRUITING

NYP Columbia University Medical Center

New York, New York, 10032, United States

RECRUITING

SUNY Upstate Medical University

Syracuse, New York, 13202, United States

RECRUITING

Westchester Medical Center

Valhalla, New York, 10595, United States

NOT YET RECRUITING

Duke University Hospital

Durham, North Carolina, 27710, United States

RECRUITING

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, 27157, United States

TERMINATED

University of Cincinnati Medical Center

Cincinnati, Ohio, 45267, United States

RECRUITING

OSU Wexner Medical Center

Columbus, Ohio, 43210, United States

RECRUITING

Ascension St. John

Tulsa, Oklahoma, 74104, United States

RECRUITING

Providence St. Vincent Medical Center

Portland, Oregon, 97225, United States

RECRUITING

Saint Luke's Hospital of Bethlehem Pennsylvania

Bethlehem, Pennsylvania, 18015, United States

RECRUITING

Temple University Hospital

Philadelphia, Pennsylvania, 19140, United States

RECRUITING

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

RECRUITING

Medical University of South Carolina University Hospital

Charleston, South Carolina, 32608, United States

RECRUITING

Prisma Health Greenville Memorial

Greenville, South Carolina, 29605, United States

RECRUITING

Methodist University Hospital

Memphis, Tennessee, 38104, United States

RECRUITING

Memorial Hermann Texas Medical Center

Houston, Texas, 77030, United States

RECRUITING

University of Utah Healthcare

Salt Lake City, Utah, 84132, United States

WITHDRAWN

UVA Medical Center

Charlottesville, Virginia, 22901, United States

RECRUITING

VCU Medical Center

Richmond, Virginia, 23298, United States

WITHDRAWN

Harborview Medical Center

Seattle, Washington, 98104, United States

RECRUITING

Ascension Columbia St. Mary's Hospital

Milwaukee, Wisconsin, 53211, United States

RECRUITING

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

StrokeCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular Diseases

Study Officials

  • Eva Mistry, MBBS

    University of Cincinnati

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Rebeca Aragon Garcia, BS, CCRC

CONTACT

Pam Plummer, MSN,RN, CCRC

CONTACT

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: 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.
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 8, 2023

First Posted

July 17, 2023

Study Start

March 18, 2024

Primary Completion (Estimated)

July 1, 2027

Study Completion (Estimated)

December 1, 2027

Last Updated

June 2, 2026

Record last verified: 2026-06

Data Sharing

IPD Sharing
Will share

The SISTER trial will comply with the NIH Public Access Policy, which ensures that the public has access to the published results of NIH funded research, and the StrokeNet SOP (ADM 03) regarding results publication. Manuscripts and abstracts that use data from SISTER require approval from the Publication Committee of an original proposal before the concept may proceed. All publications will include this acknowledgement: "Research reported in this publication was supported by the National Institute of Neurological Disorders and Stroke of the National Institutes of Health under Award Number \[to be determined\]. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health."

Locations