TS23 for Stroke

(SISTER Trial)

Recruiting at 45 trial locations

Overseen By Navdeep Sangha, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Translational Sciences, Inc.

Must not be taking: Thrombolytics, Anticoagulants, Antiplatelets, others

Disqualifiers: Pregnancy, Recent stroke, Hypertension, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 30

Duration: 30 hours

300 Participants Needed

Trial Summary

What is the purpose of this 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.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain blood thinners and anticoagulants (medications that prevent blood clots) before participating. Specifically, you must not have taken heparin or low molecular weight heparins in the past 24 hours, Factor Xa inhibitors in the past 48 hours, direct thrombin inhibitors in the past 48 hours, or glycoprotein IIb/IIIa inhibitors in the past 14 days.

What data supports the effectiveness of the drug TS23 for stroke?

The research highlights the effectiveness of recombinant tissue plasminogen activator (rt-PA), a similar drug, in improving outcomes for stroke patients when administered within a specific time window. This suggests that antithrombotic agents like TS23 could potentially offer benefits in stroke treatment by reducing injury size and improving recovery. ^{1 2 3 4 5}

Research Team

Eva Mistry, MBBS

Principal Investigator

University of Cincinnati

Eligibility Criteria

This trial is for adults 18+ who've had a stroke affecting the brain's anterior circulation, with specific imaging results showing a moderate to severe impact. They must be able to start treatment within 4.5 to 24 hours after the stroke or when they were last known well.

Inclusion Criteria

Presenting NIH Stroke Scale score >/= 6

I can take the study medication within 4.5 to 24 hours after my stroke started.

Informed consent for the study participation obtained from participant or their legally authorized representatives.

Exclusion Criteria

My blood pressure remains high despite taking medication.

Known previous allergy to antibody therapy

Current participation in another research drug treatment protocol (i.e., participants could not start another experimental agent until after 90 days)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive randomized doses of TS23 or placebo for acute ischemic stroke

30 hours

In-patient treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days

Multiple visits including 30 days and 90 days follow-up

Extension

Long-term monitoring of safety and efficacy outcomes

Additional 90 days

Treatment Details

Interventions

• TS23

Trial Overview The SISTER trial is testing TS23, an antibody targeting a clotting factor in blood, as a new treatment for acute ischemic strokes. Participants are randomly chosen to receive either TS23 or a placebo without knowing which one they get.

Participant Groups

Group I: Dose 4 TS23 Experimental Treatment 1 Intervention

highest dose

Group II: Dose 3 TS23 Experimental Treatment 1 Intervention

next higher dose

Group III: Dose 2 TS23 Experimental Treatment 1 Intervention

next higher dose

Group IV: Dose 1 TS23 Experimental Treatment 1 Intervention

low dose

Group V: Placebo Placebo Group 1 Intervention

Placebo

Who Is Running the Clinical Trial?

Translational Sciences, Inc.

Lead Sponsor

Trials

3

Recruited

360+

Medical University of South Carolina

Collaborator

Trials

994

Recruited

7,408,000+

National Institutes for Neurologic Disorders and Stroke (NINDS)

Collaborator

Trials

1

Recruited

300+

University of Arizona

Collaborator

Trials

545

Recruited

161,000+

National Institute of Neurological Disorders and Stroke (NINDS)

Collaborator

Trials

1,403

Recruited

655,000+

University of Cincinnati

Collaborator

Trials

442

Recruited

639,000+

Findings from Research

Intravenous rt-PA is the only proven pharmacological treatment for ischemic stroke, and its effectiveness is highly time-dependent, requiring administration within three hours of stroke onset in specialized stroke units to minimize hemorrhage risks.

Secondary prevention strategies, including antiplatelet therapy, controlling risk factors like hypertension and diabetes, and using statins to lower LDL cholesterol, are crucial for reducing the risk of recurrent strokes and improving long-term outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Acute management and secondary prevention of ischemic stroke]. Mahagne, MH.[2016]

The acute use of recombinant tissue plasminogen activator (rt-PA) significantly increases the chances of patients with ischemic stroke experiencing little to no residual disability, highlighting its efficacy as an antithrombotic treatment.

Despite the benefits of rt-PA, there has been limited progress in increasing the number of patients who benefit from acute interventions, indicating a need for improved clinical trial designs and exploration of other antithrombotic agents to enhance stroke outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thrombolysis: from the experimental findings to the clinical practice. del Zoppo, GJ.[2007]

Intravenous recombinant tissue plasminogen activator (rt-PA) has been established as a standard treatment for acute stroke, significantly improving patient outcomes when administered within 3 hours of symptom onset, as demonstrated by the 1995 NINDS study.

Recent studies, including the European Cooperative Acute Stroke Study III, have shown that extending the treatment window for rt-PA to 4.5 hours can further enhance clinical outcomes, leading to updated treatment guidelines in multiple regions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Intravenous rt-PA therapy for acute ischemic stroke: efficacy and limitations]. Toyoda, K.[2019]

Intravenous tissue plasminogen activator (IV tPA) is effective for treating acute ischemic stroke patients up to 4.5 hours from symptom onset, showing benefits in favorable outcomes without increasing mortality, based on the ECASS III trial.

The study highlights the importance of strict patient selection criteria for IV tPA treatment, as not all stroke patients benefit from thrombolysis, and the need for careful evaluation increases with longer time intervals from symptom onset.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous tissue plasminogen activator for stroke: a review of the ECASS III results in relation to prior clinical trials. Cronin, CA.[2010]

The implementation of a 24-hour stroke thrombolysis emergency treatment in 2013 significantly reduced the door-to-needle time for administering IV rt-PA thrombolysis from 81 minutes in 2012 to 42 minutes in 2014, indicating improved efficiency in acute stroke care.

Despite the faster treatment times, the study found that this change did not lead to improved functional outcomes for patients with acute ischemic stroke, suggesting that while timely intervention is critical, it may not always translate to better recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the implementation of a 24-hr stroke thrombolysis emergency treatment for patients with acute ischaemic stroke. Zhao, J., Li, X., Liang, Y., et al.[2019]

References

1. France pubmed.ncbi.nlm.nih.gov

[Acute management and secondary prevention of ischemic stroke]. [2016]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Thrombolysis: from the experimental findings to the clinical practice. [2007]

3. Japan pubmed.ncbi.nlm.nih.gov

[Intravenous rt-PA therapy for acute ischemic stroke: efficacy and limitations]. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Intravenous tissue plasminogen activator for stroke: a review of the ECASS III results in relation to prior clinical trials. [2010]

5. England pubmed.ncbi.nlm.nih.gov

Evaluation of the implementation of a 24-hr stroke thrombolysis emergency treatment for patients with acute ischaemic stroke. [2019]