CLINICAL TRIAL / NCT05948566
Strategy for Improving Stroke Treatment Response
- Interventional
- Active
- NCT05948566
Contact Information
- Elida Romo
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.
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 300 subjects at up to 50 participating 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.
Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers
No
Inclusion Criteria:
1. Age 18 years and older
2. Suspected anterior circulation acute ischemic stroke
3. Presenting NIH Stroke Scale score ≥4
a. The participant must have a clearly disabling deficit if NIHSS is 4-5.
4. Favorable baseline neuroimaging consisting of all of the following:
a. ASPECTS of 6 or more on CT (or ASPECTS of ≥7 on MRI) b. 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
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.
- Study drug administration is encouraged within 90 minutes after qualifying
perfusion image but is allowed up to 120 minutes. After 120 minutes, another
perfusion image to ensure that inclusion criteria are met is required.
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 heparin or 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.