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Strategy for Improving Stroke Treatment Response (SISTER)

Primary Purpose

Ischemic Stroke

Status
Not yet recruiting
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
TS23
Sponsored by
Translational Sciences, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ischemic Stroke

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age 18 years and older Suspected anterior circulation acute ischemic stroke Presenting NIH Stroke Scale score >/= 6 Favorable baseline neuroimaging CT scan with ASPECTS of >/=6, or MRI with ASPECTS of >/=7 and CT or MR Perfusion with a mismatch ratio >1.2 between the volume of hypoperfusion and the volume of the ischemic core, an absolute difference in volume > 10 ml, and an ischemic-core volume of less than 70 ml. and Able to receive assigned study drug within 4.5 to 24 hours of stroke onset or last known well Informed consent for the study participation obtained from participant or their legally authorized representatives. Exclusion Criteria: Patients planned to receive endovascular treatment. Patients that received or planned to receive intravenous thrombolysis. Pre-stroke modified Rankin score >2. Known previous allergy to antibody therapy. Known pregnancy or positive urine or serum pregnancy test for women of child bearing potential. Known previous stroke in the past 90 days. Known previous intracranial hemorrhage, neoplasm, subarachnoid hemorrhage, or arterial venous malformation. 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 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 INR >1.7. Platelets <100,000/mm3. Hematocrit <25 %. Elevated PTT above laboratory upper limit of normal. Creatinine > 4 mg/dl, or patients receiving renal dialysis, regardless of creatinine. Received heparin or 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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm Type

    Placebo Comparator

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    Placebo

    Dose 1 TS23

    Dose 2 TS23

    Dose 3 TS23

    Dose 4 TS23

    Arm Description

    Placebo

    low dose

    next higher dose

    next higher dose

    highest dose

    Outcomes

    Primary Outcome Measures

    Safety - intracranial hemorrhage
    any intracranial hemorrhage
    Efficacy - neurological disability
    NIH Stroke Scale

    Secondary Outcome Measures

    Full Information

    First Posted
    July 8, 2023
    Last Updated
    July 14, 2023
    Sponsor
    Translational Sciences, Inc.
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05948566
    Brief Title
    Strategy for Improving Stroke Treatment Response
    Acronym
    SISTER
    Official Title
    Strategy for Improving Stroke Treatment Response
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    March 2024 (Anticipated)
    Primary Completion Date
    July 2027 (Anticipated)
    Study Completion Date
    December 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Translational Sciences, Inc.

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    SISTER is a Phase-2, 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
    The primary objective is 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 ischemic stroke onset (or last known well), who have evidence of core-penumbra mismatch on perfusion imaging and are not a candidate for standard of care reperfusion therapies.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Ischemic Stroke

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    300 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Placebo
    Arm Title
    Dose 1 TS23
    Arm Type
    Experimental
    Arm Description
    low dose
    Arm Title
    Dose 2 TS23
    Arm Type
    Experimental
    Arm Description
    next higher dose
    Arm Title
    Dose 3 TS23
    Arm Type
    Experimental
    Arm Description
    next higher dose
    Arm Title
    Dose 4 TS23
    Arm Type
    Experimental
    Arm Description
    highest dose
    Intervention Type
    Biological
    Intervention Name(s)
    TS23
    Intervention Description
    Monoclonal antibody
    Primary Outcome Measure Information:
    Title
    Safety - intracranial hemorrhage
    Description
    any intracranial hemorrhage
    Time Frame
    At 30 (+/- 4) hours after study drug
    Title
    Efficacy - neurological disability
    Description
    NIH Stroke Scale
    Time Frame
    At 30 (+/- 4) hours after study drug

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Age 18 years and older Suspected anterior circulation acute ischemic stroke Presenting NIH Stroke Scale score >/= 6 Favorable baseline neuroimaging CT scan with ASPECTS of >/=6, or MRI with ASPECTS of >/=7 and CT or MR Perfusion with a mismatch ratio >1.2 between the volume of hypoperfusion and the volume of the ischemic core, an absolute difference in volume > 10 ml, and an ischemic-core volume of less than 70 ml. and Able to receive assigned study drug within 4.5 to 24 hours of stroke onset or last known well Informed consent for the study participation obtained from participant or their legally authorized representatives. Exclusion Criteria: Patients planned to receive endovascular treatment. Patients that received or planned to receive intravenous thrombolysis. Pre-stroke modified Rankin score >2. Known previous allergy to antibody therapy. Known pregnancy or positive urine or serum pregnancy test for women of child bearing potential. Known previous stroke in the past 90 days. Known previous intracranial hemorrhage, neoplasm, subarachnoid hemorrhage, or arterial venous malformation. 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 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 INR >1.7. Platelets <100,000/mm3. Hematocrit <25 %. Elevated PTT above laboratory upper limit of normal. Creatinine > 4 mg/dl, or patients receiving renal dialysis, regardless of creatinine. Received heparin or 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.

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    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."

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    Strategy for Improving Stroke Treatment Response

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