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Ischemic StrokePhase 2SISTERNCT05948566

Strategy for Improving Stroke Treatment Response

A Phase 2 study testing TS23 in people with Ischemic Stroke, run by Translational Sciences, Inc. at 52 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Ischemic Stroke
What is being tested?
TS23
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
300 participants
Where
52 sitesUnited States
Study dates
18 Mar 2024to Dec 2028
Phase
Phase 2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age 18 years and older
  • Suspected anterior circulation acute ischemic stroke
  • NIH Stroke Scale score ≥4 prior to randomization
  • 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)
Show all 12Show fewer
  • Favorable perfusion imaging on CT perfusion (CTP)/MR-perfusion weighted imaging (PWI) consisting of all of the following:
  • Mismatch ratio of penumbra: core >1.2 ii. Mismatch volume >10 cc iii. Core <70 cc
  • 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.
  • Anticipate being 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.

Who cannot join

  • 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.
Show all 30Show fewer
  • 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.
  • Serious systemic hemorrhage in the past 30 days.
  • Known hereditary or acquired hemorrhagic diathesis, coagulation factor deficiency, or oral anticoagulant therapy with International Normalized Ratio (INR) >1.7.
  • Platelets <100,000/mm3.
  • Hematocrit <25 %.
  • Elevated aPTT above laboratory upper limit of normal.
  • Creatinine > 4 mg/dl, or patients receiving renal dialysis, regardless of creatinine.
  • Received the following within the previous 24 hours:
  • If patient received unfractionated heparin within the last 24 hours, the patient must have an aPTT within normal range prior to enrollment.
  • Low molecular weight heparins such as Dalteparin, enoxaparin, tinzaparin in full dose within the previous 24 hours.
  • Received Factor Xa inhibitors (such as Fondaparinux, apixaban or rivaroxaban) within the past 48 hours.
  • Received direct thrombin inhibitors (e.g., argatroban, dabigatran, bivalirudin, desirudin, lepirudin) within 48 hours.
  • Received glycoprotein IIb/IIIa inhibitors within the past 14 days.
  • Known pre-existing neurological or psychiatric disease which would confound the neurological/functional evaluations.
  • Current participation in another research drug treatment protocol (i.e., participants could not start another experimental agent until after 90 days).
  • Concurrent acute myocardial infarction, pulmonary embolism, deep venous thrombosis or other thrombotic event that requires anticoagulation or anti-platelet treatment.

Trial locations and contacts

52 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Rebeca Aragon Garcia, BS, CCRC contact

9736688644

aragonra@ucmail.uc.edu

Pam Plummer, MSN,RN, CCRC contact

5138852437

plummepa@ucmail.uc.edu

52 sites in 1 country

United States52 sites, 38 recruiting

  • Grady Memorial Hospital

    Atlanta, Georgia, 30303

    Nicolas Bianchi, MD, nicolas.a.bianchi@emory.edu

    Nicolas Bianchi, MD

    Recruiting

  • Saint Luke's Hospital of Bethlehem Pennsylvania

    Bethlehem, Pennsylvania, 18015

    Daniel Ackerman, MD, Daniel.Ackerman@sluhn.org

    Daniel Ackerman, MD

    Recruiting

  • University of Alabama Hospital

    Birmingham, Alabama, 35233

    Felix Guerra Castanon, MD, fguerracastanon@uabmc.edu

    Felix Guerra Castanon, MD

    Recruiting

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

    Rahul Mahajan, MD, PhD, rmahajan@bwh.harvard.edu

    Rahul Mahajan, MD, PhD

    Recruiting

  • Massachusetts General Hospital

    Boston, Massachusetts, 02171

    Aneesh Singhal, MD, MBBS, ASINGHAL@mgh.harvard.edu

    Aneesh Singhal, MD, MBBS

    Recruiting

  • NYU Langone Health

    Brooklyn, New York, 11220

    Maria Cotrina-Vidal, maria.cotrina@nyulangone.org

    Aaron Lord, MD, MSc, aaron.lord@nyulangone.org

    Recruiting

  • Buffalo General Medical Center

    Buffalo, New York, 14203

    Withdrawn

  • M Health Fairview Ridges Hospital

    Burnsville, Minnesota, 55337

    Jessica Staloch, staloch@umn.edu

    Muhammad Affan, MD, MBBS, affan004@umn.edu

    Recruiting

  • Medical University of South Carolina University Hospital

    Charleston, South Carolina, 32608

    Caitlan LeMatty, lemattyc@musc.edu

    Christine Holmstedt, DO, holmsted@musc.edu

    Recruiting

  • UVA Medical Center

    Charlottesville, Virginia, 22901

    Amna Sohail, MBBS, MD, ZRX5FU@uvahealth.org

    Amna Sohail, MBBS, MD

    Recruiting

  • University of Chicago Medical Center

    Chicago, Illinois, 60637

    Active, not recruiting

  • University of Cincinnati Medical Center

    Cincinnati, Ohio, 45267

    Yasmin Aziz, MD, azizyn@ucmail.uc.edu

    Yasmin Aziz, MD

    Recruiting

  • OSU Wexner Medical Center

    Columbus, Ohio, 43210

    Jan Bittar, MD, jan.bittar@osumc.edu

    Jan Bittar, MD

    Recruiting

  • Duke University Hospital

    Durham, North Carolina, 27710

    Rosanna Escobar-Spadina, rosanna.escobar@duke.edu

    Alexander Limkakeng, MD, MHSc, alexander.limkakeng@duke.edu

    Recruiting

  • M Health Fairview Southdale Hospital

    Edina, Minnesota, 55435

    Jessica Staloch, staloch@umn.edu

    Muhammad Affan, MD,MBBS, affan004@umn.edu

    Recruiting

  • JFK Medical Center

    Edison, New Jersey, 08837

    Nancy Gadallah, DO, nancy.gadallah@hmhn.org

    Nancy Gadallah, DO

    Recruiting

  • UF Health Shands Hospital

    Gainesville, Florida, 32608

    Terminated

  • Prisma Health Greenville Memorial

    Greenville, South Carolina, 29605

    Sanjeev Sivakumar, MD, Sanjeev.Sivakumar@prismahealth.org

    Sanjeev Sivakumar, MD

    Recruiting

  • Hartford Hospital

    Hartford, Connecticut, 06102

    Ajay Tunguturi, MD, ajay.tunguturi@hhchealth.org

    Ajay Tunguturi, MD

    Recruiting

  • Memorial Hermann Texas Medical Center

    Houston, Texas, 77030

    Prasen Marella, prasen.r.marella@uth.tmc.edu

    Andrew Barreto, MD, MS, andrew.d.barreto@uth.tmc.edu

    Recruiting

  • University of Iowa Hospitals & Clinics

    Iowa City, Iowa, 52242

    Withdrawn

  • UCSD Health La Jolla

    La Jolla, California, 92093

    Maryo Jajo, mjajo@health.ucsd.edu

    Royya Modir, MD, rmodir@ucsd.edu

    Recruiting

  • Baptist Healthcare System, Inc.

    Lexington, Kentucky, 40503

    Murali Kolikonda, MD, murali.kolikonda@bhsi.com

    Franklin Echevarria, Franklin.echevarriagonzalez@bhsi.com

    Recruiting

  • Kaiser Permanente Los Angeles

    Los Angeles, California, 90027

    Navdeep Sangha, MD, navdeep.x.sangha@kp.org

    Navdeep Sangha, MD

    Recruiting

  • University of Louisville Hospital

    Louisville, Kentucky, 40202

    Isaac Abecassis, MD, Isaac.Abecassis@uoflhealth.org

    Isaac Abecassis, MD

    Recruiting

  • North Shore University Hospital

    Manhasset, New York, 11030

    Rohan Arora, neuroscienceresearch@northwell.edu

    Rohan Arora, MD

    Recruiting

  • Methodist University Hospital

    Memphis, Tennessee, 38104

    Quentin Thacker, qthacker@uthsc.edu

    Balaji Krishnaiah, MD, bkrishn4@uthsc.edu

    Recruiting

  • Jackson Memorial Hospital

    Miami, Florida, 33136

    Andrea Escobar, a.escobar1@med.miami.edu

    Gillian Gordon Perue, MD, MBBS, DM, ggordonperue@miami.edu

    Recruiting

  • Ascension Columbia St. Mary's Hospital

    Milwaukee, Wisconsin, 53211

    Lakiesha Coleman, lakiesha.coleman@ascension.org

    William Taylor, DO, william.taylor3@ascension.org

    Recruiting

  • M Health Fairview University of Minnesota Medical Center

    Minneapolis, Minnesota, 55455

    Jessica Staloch, staloch@umn.edu

    Muhammad Affan, MD,MBBS, affan004@umn.edu

    Recruiting

  • Yale New Haven Hospital

    New Haven, Connecticut, 06511

    James Giles, MD, PhD, james.giles@yale.edu

    James Giles, MD, PhD

    Recruiting

  • Mount Sinai West

    New York, New York, 10029

    Withdrawn

  • The Mount Sinai Hospital

    New York, New York, 10029

    Laura Stein, MD, MPH, laura.stein@mountsinai.org

    Laura Stein, MD, MPH

    Recruiting

  • NYP Columbia University Medical Center

    New York, New York, 10032

    Angela Velazquez, Agv2113@cumc.columbia.edu

    Shivani Ghoshal, MD, sg3450@cumc.columbia.edu;

    Recruiting

  • Christiana Hospital

    Newark, Delaware, 19718

    Withdrawn

  • Temple University Hospital

    Philadelphia, Pennsylvania, 19140

    Nina Gentile, MD, ngentile@temple.edu

    Nina Gentile, MD

    Recruiting

  • Banner University Medical Center

    Phoenix, Arizona, 85006

    Savdeep Singh, MD, savdeepsingh@arizona.edu

    Savdeep Singh, MD

    Recruiting

  • Mayo Clinic Phoenix

    Phoenix, Arizona, 85054

    Withdrawn

  • Providence St. Vincent Medical Center

    Portland, Oregon, 97225

    Kishan Patel, MD, kishan.patel@providence.org

    Kishan Patel, MD

    Recruiting

  • Rhode Island Hospital

    Providence, Rhode Island, 02903

    Farhan Khan, MD, fkhan@brownhealth.org

    Farhan Khan, MD

    Recruiting

  • VCU Medical Center

    Richmond, Virginia, 23298

    Withdrawn

  • Sutter Medical Center

    Sacramento, California, 95816

    Withdrawn

  • United Hospital

    Saint Paul, Minnesota, 55102

    Withdrawn

  • University of Utah Healthcare

    Salt Lake City, Utah, 84132

    Withdrawn

  • UCSD Medical Center- Hillcrest Hospital

    San Diego, California, 92103

    Maryo Jajo, mjajo@health.ucsd.edu

    Royya' Modir, MD, rmodir@ucsd.edu

    Recruiting

  • Harborview Medical Center

    Seattle, Washington, 98104

    Withdrawn

  • Barnes Jewish Hospital

    St Louis, Missouri, 63110

    Charles Kircher, MD, charles.kircher@wustl.edu

    Charles Kircher, MD

    Recruiting

  • SUNY Upstate Medical University

    Syracuse, New York, 13202

    Deb Lena, debl@upstate.edu

    Julius-Gene LaTorre, MD, MPH, latorrej@upstate.edu

    Recruiting

  • Banner University Medical Center - Tucson

    Tucson, Arizona, 85719

    Firas Kaddouh, MD, MHS, firaskaddouh@arizona.edu

    Firas Kaddouh, MD, MHS

    Recruiting

  • Ascension St. John

    Tulsa, Oklahoma, 74104

    Rahul Rahangdale, MD, rahul.rahangdale@ascension.org

    Rahul Rahangdale, MD

    Recruiting

  • Westchester Medical Center

    Valhalla, New York, 10595

    Withdrawn

  • Wake Forest Baptist Medical Center

    Winston-Salem, North Carolina, 27157

    Terminated

Other trials in United States

About this study

Official title: Strategy for Improving Stroke Treatment Response (SISTER) Trial

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.

Read the 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. Patients with an NIHSS of 4-5 must have a new, disabling neuro-logic deficit to be eligible for the study. After informed consent is provided, the study will randomize to 4 doses of TS23 and placebo. The trial will enroll up to 150 subjects at up to 70 participating US 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
Ischemic Stroke
Being tested
TS23
Medical subject headings
Ischemic Stroke

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TS23Biological

    Monoclonal antibody

Study groups in NCT05948566
Study groupRoleWhat they receive
PlaceboPlacebo comparatorPlacebo
Receives: Biological: TS23
Dose 1 TS23Experimentallow dose
Receives: Biological: TS23
Dose 2 TS23Experimentalnext higher dose
Receives: Biological: TS23
Dose 3 TS23Experimentalnext higher dose
Receives: Biological: TS23
Dose 4 TS23Experimentalhighest dose
Receives: Biological: TS23

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. The proportion of patients with ANY intracerebral hemorrhage (ICH)

    Any ICH visualized on the follow-up CT scan

    Measured: At 30 (+/- 4) hours after study drug

  2. 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.

    Measured: At 30 (+/- 4) hours after study drug

Secondary outcomes (13)

  1. 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.

    Measured: 90 (±7) days

  2. 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.

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

  3. 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.

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

  4. α2-antiplasmin (a2AP) level in plasma

    A serine protease inhibitor responsible for inactivating plasmin.

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

  5. Matrix metalloproteinase-9 level in plasma

    An enzyme that regulates the pathological remodeling process that involve inflammation and fibrosis associated with cardiovascular disease.

    Measured: 3 (±1) h after completion of study drug

  6. % 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

    Measured: 30 (±4) h after study drug administration

  7. Pharmacokinetic analyses

    Measure of plasma concentrations of TS23

    Measured: 3 (±1) h, 30 (±4) h, 30 (±5) days & 90 (±7) days after study drug administration. At 90 (±7) days for approximately 50 mITT participants. After approximately 50 mITT participants, it will be obtained at 72h(+12 hrs)/discharge visit, whichever comes 1st.

  8. Evaluation of anti-drug antibodies

    commonly used for characterization of therapeutic antibodies

    Measured: will be measured at baseline and 90 (±7) days follow-up visit for approximately 50 mITT participants.

  9. Proportion of patients with symptomatic intracerebral hemorrhage

    a blood clot large enough to cause significant neurological deterioration.

    Measured: 30 (±4) h of study drug administration

  10. 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

    Measured: 30 days of study drug administration.

  11. Plasma fibrinogen level

    Clotting factor

    Measured: 3 (±1) h after completion of study drug

  12. Proportion of patients with non-bleeding severe adverse events

    Assessment of untoward events

    Measured: 90 (±7) days

  13. Proportion of patients with stroke-related and all-cause deaths

    measure of important patient outcomes

    Measured: 90 (±7) days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Jul 2023
  2. Study start18 Mar 2024
  3. Primary completionJul 2028 (estimated)
  4. Study completionDec 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
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.
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
300 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05948566
Sponsor's protocol ID
TS23-U202
Other IDs
UH3NS125023
Acronym
SISTER
Status last verified
Oct 2026
First submitted
8 Jul 2023
Last updated
19 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: 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."

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing TS23 in people with Ischemic Stroke, run by Translational Sciences, Inc. at 52 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 19 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 52 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Rebeca Aragon Garcia, BS, CCRC (9736688644, aragonra@ucmail.uc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The proportion of patients with ANY intracerebral hemorrhage (ICH) (time frame: At 30 (+/- 4) hours after study drug). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05948566.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2026.

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Strategy for Improving Stroke Treatment Response | AzTrials