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STRATÉGIE POUR AMÉLIORER LA RÉPONSE AU TRAITEMENT DE L'AVC (SISTER)

13 octobre 2026 mis à jour par: Translational Sciences, Inc.

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.

Aperçu de l'étude

Statut

Recrutement

Les conditions

Intervention / Traitement

Description détaillée

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.

Type d'étude

Interventionnel

Inscription (Estimé)

300

Phase

  • Phase 2

Contacts et emplacements

Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.

Coordonnées de l'étude

Sauvegarde des contacts de l'étude

Lieux d'étude

  • États-Unis
    • Alabama
      • Birmingham, Alabama, États-Unis, 35233
        • Recrutement
        • University of Alabama Hospital
        • Contact:
        • Chercheur principal:
          • Felix Guerra Castanon, MD
    • Arizona
      • Phoenix, Arizona, États-Unis, 85006
        • Recrutement
        • Banner University Medical Center
        • Chercheur principal:
          • Savdeep Singh, MD
        • Contact:
      • Phoenix, Arizona, États-Unis, 85054
        • Retiré
        • Mayo Clinic Phoenix
      • Tucson, Arizona, États-Unis, 85719
        • Recrutement
        • Banner University Medical Center - Tucson
        • Contact:
        • Chercheur principal:
          • Firas Kaddouh, MD, MHS
    • California
      • La Jolla, California, États-Unis, 92093
      • Los Angeles, California, États-Unis, 90027
        • Recrutement
        • Kaiser Permanente Los Angeles
        • Contact:
        • Chercheur principal:
          • Navdeep Sangha, MD
      • Sacramento, California, États-Unis, 95816
        • Retiré
        • Sutter Medical Center
      • San Diego, California, États-Unis, 92103
        • Recrutement
        • UCSD Medical Center- Hillcrest Hospital
        • Contact:
        • Chercheur principal:
          • Royya Modir, MD
        • Contact:
    • Connecticut
      • Hartford, Connecticut, États-Unis, 06102
      • New Haven, Connecticut, États-Unis, 06511
        • Recrutement
        • Yale New Haven Hospital
        • Contact:
        • Chercheur principal:
          • James Giles, MD, PhD
    • Delaware
      • Newark, Delaware, États-Unis, 19718
        • Retiré
        • Christiana Hospital
    • Florida
      • Gainesville, Florida, États-Unis, 32608
        • Résilié
        • UF Health Shands Hospital
      • Miami, Florida, États-Unis, 33136
    • Georgia
      • Atlanta, Georgia, États-Unis, 30303
        • Recrutement
        • Grady Memorial Hospital
        • Contact:
        • Chercheur principal:
          • Nicolas Bianchi, MD
    • Illinois
      • Chicago, Illinois, États-Unis, 60637
        • Actif, ne recrute pas
        • University of Chicago Medical Center
    • Iowa
      • Iowa City, Iowa, États-Unis, 52242
        • Retiré
        • University of Iowa Hospitals & Clinics
    • Kentucky
      • Lexington, Kentucky, États-Unis, 40503
      • Louisville, Kentucky, États-Unis, 40202
        • Recrutement
        • University of Louisville Hospital
        • Chercheur principal:
          • Isaac Abecassis, MD
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, États-Unis, 02115
        • Recrutement
        • Brigham and Women's Hospital
        • Chercheur principal:
          • Rahul Mahajan, MD, PhD
        • Contact:
      • Boston, Massachusetts, États-Unis, 02171
        • Recrutement
        • Massachusetts General Hospital
        • Chercheur principal:
          • Aneesh Singhal, MD, MBBS
        • Contact:
    • Minnesota
      • Burnsville, Minnesota, États-Unis, 55337
        • Recrutement
        • M Health Fairview Ridges Hospital
        • Contact:
        • Contact:
        • Chercheur principal:
          • Muhammad Affan, MD, MBBS
      • Edina, Minnesota, États-Unis, 55435
        • Recrutement
        • M Health Fairview Southdale Hospital
        • Contact:
        • Chercheur principal:
          • Muhammad Affan, MD, MBBS
        • Contact:
      • Minneapolis, Minnesota, États-Unis, 55455
        • Recrutement
        • M Health Fairview University of Minnesota Medical Center
        • Contact:
        • Contact:
        • Chercheur principal:
          • Muhammad Affan, MD,MBBS
      • Saint Paul, Minnesota, États-Unis, 55102
        • Retiré
        • United Hospital
    • Missouri
      • St Louis, Missouri, États-Unis, 63110
        • Recrutement
        • Barnes Jewish Hospital
        • Chercheur principal:
          • Charles Kircher, MD
        • Contact:
    • New Jersey
      • Edison, New Jersey, États-Unis, 08837
        • Recrutement
        • JFK Medical Center
        • Chercheur principal:
          • Nancy Gadallah, DO
        • Contact:
    • New York
      • Brooklyn, New York, États-Unis, 11220
      • Buffalo, New York, États-Unis, 14203
        • Retiré
        • Buffalo General Medical Center
      • Manhasset, New York, États-Unis, 11030
      • New York, New York, États-Unis, 10029
        • Recrutement
        • The Mount Sinai Hospital
        • Contact:
        • Chercheur principal:
          • Laura Stein, MD, MPH
      • New York, New York, États-Unis, 10032
      • New York, New York, États-Unis, 10029
        • Retiré
        • Mount Sinai West
      • Syracuse, New York, États-Unis, 13202
        • Recrutement
        • SUNY Upstate Medical University
        • Contact:
        • Chercheur principal:
          • Julius-Gene LaTorre, MD, MPH
        • Contact:
      • Valhalla, New York, États-Unis, 10595
        • Retiré
        • Westchester Medical Center
    • North Carolina
      • Durham, North Carolina, États-Unis, 27710
      • Winston-Salem, North Carolina, États-Unis, 27157
        • Résilié
        • Wake Forest Baptist Medical Center
    • Ohio
      • Cincinnati, Ohio, États-Unis, 45267
        • Recrutement
        • University of Cincinnati Medical Center
        • Chercheur principal:
          • Yasmin Aziz, MD
        • Contact:
      • Columbus, Ohio, États-Unis, 43210
        • Recrutement
        • OSU Wexner Medical Center
        • Chercheur principal:
          • Jan Bittar, MD
        • Contact:
    • Oklahoma
      • Tulsa, Oklahoma, États-Unis, 74104
    • Oregon
      • Portland, Oregon, États-Unis, 97225
        • Recrutement
        • Providence St. Vincent Medical Center
        • Chercheur principal:
          • Kishan Patel, MD
        • Contact:
    • Pennsylvania
      • Bethlehem, Pennsylvania, États-Unis, 18015
        • Recrutement
        • Saint Luke's Hospital of Bethlehem Pennsylvania
        • Chercheur principal:
          • Daniel Ackerman, MD
        • Contact:
      • Philadelphia, Pennsylvania, États-Unis, 19140
        • Recrutement
        • Temple University Hospital
        • Contact:
        • Chercheur principal:
          • Nina Gentile, MD
    • Rhode Island
      • Providence, Rhode Island, États-Unis, 02903
        • Recrutement
        • Rhode Island Hospital
        • Chercheur principal:
          • Farhan Khan, MD
        • Contact:
    • South Carolina
      • Charleston, South Carolina, États-Unis, 32608
        • Recrutement
        • Medical University of South Carolina University Hospital
        • Contact:
        • Contact:
        • Chercheur principal:
          • Christine Holmstedt, DO
      • Greenville, South Carolina, États-Unis, 29605
    • Tennessee
      • Memphis, Tennessee, États-Unis, 38104
        • Recrutement
        • Methodist University Hospital
        • Contact:
        • Chercheur principal:
          • Balaji Krishnaiah, MD
        • Contact:
    • Texas
    • Utah
      • Salt Lake City, Utah, États-Unis, 84132
        • Retiré
        • University of Utah Healthcare
    • Virginia
      • Charlottesville, Virginia, États-Unis, 22901
        • Recrutement
        • UVA Medical Center
        • Chercheur principal:
          • Amna Sohail, MBBS, MD
        • Contact:
      • Richmond, Virginia, États-Unis, 23298
        • Retiré
        • VCU Medical Center
    • Washington
      • Seattle, Washington, États-Unis, 98104
        • Retiré
        • Harborview Medical Center
    • Wisconsin

Critères de participation

Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.

Critère d'éligibilité

Âges éligibles pour étudier

18 ans et plus (Adulte, Adulte plus âgé)

Accepte les volontaires sains

Non

Sexes éligibles pour l'étude

Tout

La description

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. Anticipate being 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.

Plan d'étude

Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.

Comment l'étude est-elle conçue ?

Détails de conception

  • Objectif principal: Traitement
  • Répartition: Randomisé
  • Modèle interventionnel: Affectation parallèle
  • Masquage: Quadruple

Armes et Interventions

Groupe de participants / Bras
Intervention / Traitement
Comparateur placebo: Placebo

Placebo
Biologique: TS23

Monoclonal antibody
Expérimental: Dose 1 TS23

low dose
Biologique: TS23

Monoclonal antibody
Expérimental: Dose 2 TS23

next higher dose
Biologique: TS23

Monoclonal antibody
Expérimental: Dose 3 TS23

next higher dose
Biologique: TS23

Monoclonal antibody
Expérimental: Dose 4 TS23

highest dose
Biologique: TS23

Monoclonal antibody

Que mesure l'étude ?

Principaux critères de jugement

Mesure des résultats
Description de la mesure
Délai
The proportion of patients with ANY intracerebral hemorrhage (ICH)
Délai: At 30 (+/- 4) hours after study drug

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

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

Mesures de résultats secondaires

Mesure des résultats
Description de la mesure
Délai
Improvement in level of global disability measured by modified Rankin Score (mRS distribution)
Délai: 90 (±7) days

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

Proportion of patients with modified Rankin scale score 0-1 or return 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
Délai: 72 (±12) hours (or at discharge if sooner) after study drug administration.

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.
α2-antiplasmin (a2AP) level in plasma
Délai: at 3 (±1) h after completion of study drug administration

A serine protease inhibitor responsible for inactivating plasmin.
at 3 (±1) h after completion of study drug administration
Matrix metalloproteinase-9 level in plasma
Délai: 3 (±1) h after completion of study drug

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
% brain tissue reperfusion
Délai: 30 (±4) h after study drug administration

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
Pharmacokinetic analyses
Délai: 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.

Measure of plasma concentrations of TS23
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.
Evaluation of anti-drug antibodies
Délai: will be measured at baseline and 90 (±7) days follow-up visit for approximately 50 mITT participants.

commonly used for characterization of therapeutic antibodies
will be measured at baseline and 90 (±7) days follow-up visit for approximately 50 mITT participants.
Proportion of patients with symptomatic intracerebral hemorrhage
Délai: 30 (±4) h of study drug administration

a blood clot large enough to cause significant neurological deterioration.
30 (±4) h of study drug administration
Proportion of patients with non-intracerebral hemorrhage major or clinically relevant non-major bleeding
Délai: 30 days of study drug administration.

major and non-major events of bleeding that is not in the brain
30 days of study drug administration.
Plasma fibrinogen level
Délai: 3 (±1) h after completion of study drug

Clotting factor
3 (±1) h after completion of study drug
Proportion of patients with non-bleeding severe adverse events
Délai: 90 (±7) days

Assessment of untoward events
90 (±7) days
Proportion of patients with stroke-related and all-cause deaths
Délai: 90 (±7) days

measure of important patient outcomes
90 (±7) days

Collaborateurs et enquêteurs

C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.

Parrainer

Translational Sciences, Inc.

Collaborateurs

Medical University of South Carolina
National Institute of Neurological Disorders and Stroke (NINDS)
University of Cincinnati
University of Arizona

Les enquêteurs

  • Chercheur principal: Eva Mistry, MBBS, University of Cincinnati

Dates d'enregistrement des études

Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.

Dates principales de l'étude

Début de l'étude (Réel)

18 mars 2024

Achèvement primaire (Estimé)

1 juillet 2028

Achèvement de l'étude (Estimé)

1 décembre 2028

Dates d'inscription aux études

Première soumission

8 juillet 2023

Première soumission répondant aux critères de contrôle qualité

8 juillet 2023

Première publication (Réel)

17 juillet 2023

Mises à jour des dossiers d'étude

Dernière mise à jour publiée (Réel)

19 octobre 2026

Dernière mise à jour soumise répondant aux critères de contrôle qualité

13 octobre 2026

Dernière vérification

1 octobre 2026

Plus d'information

Termes liés à cette étude

Termes MeSH pertinents supplémentaires

Autres numéros d'identification d'étude

  • TS23-U202
  • UH3NS125023 (Subvention/contrat des NIH des États-Unis)

Plan pour les données individuelles des participants (IPD)

Prévoyez-vous de partager les données individuelles des participants (DPI) ?

OUI

Description du régime IPD

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."

Informations sur les médicaments et les dispositifs, documents d'étude

Étudie un produit pharmaceutique réglementé par la FDA américaine

Oui

Étudie un produit d'appareil réglementé par la FDA américaine

Non

Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .

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