TS23 for Stroke

(SISTER Trial)

Recruiting at 50 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called TS23 for individuals who have experienced an acute ischemic stroke, where a blood clot blocks blood flow to the brain. The researchers aim to determine if TS23 is safe and can improve recovery by targeting a protein involved in blood clot breakdown. Participants will receive either a placebo or one of four different doses of TS23 to identify the optimal dose. The trial seeks individuals who have recently had a stroke with noticeable symptoms and specific brain scan results. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that TS23 is likely to be safe for humans?

Research shows that TS23, a monoclonal antibody, has shown promise in safety studies by targeting a protein involved in blood clotting. Earlier research tested TS23 in people with acute pulmonary embolism, a condition involving blood clots in the lungs. The study examined the safety of different doses and found it was generally well-tolerated. Although some side effects occurred, they were not serious enough to halt the research.

This trial tests TS23 for ischemic stroke, which occurs when blood flow to the brain is blocked. The trial is in Phase 2, indicating that TS23 has already passed initial safety tests in humans, suggesting it is generally safe. However, this phase will provide more detailed information about TS23's safety at different doses. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for stroke?

Researchers are excited about TS23 for stroke because it might offer a new way to help the brain recover after an attack. Unlike current treatments that focus on breaking down clots or controlling risk factors, TS23 is designed to potentially enhance brain repair through a novel mechanism that hasn't been fully explored before. This treatment comes in varying doses, which might allow for personalized therapy tailored to a patient's specific needs, optimizing effectiveness and safety. The potential for TS23 to improve recovery outcomes makes it a promising candidate in the fight against stroke.

What evidence suggests that TS23 might be an effective treatment for stroke?

Research shows that TS23, a monoclonal antibody, may help treat sudden strokes by targeting a protein called alpha-2 antiplasmin. Studies suggest that blocking this protein can improve blood flow by reducing clots. Early results indicate it might be safe and effective for patients treated within 4.5 to 24 hours after a stroke. This treatment could offer a new way to enhance stroke recovery. The current trial focuses on determining the optimal dose of TS23 to ensure safety and effectiveness, with participants receiving varying doses of TS23 or a placebo. ^{1 2 3 6}

Who Is on the Research Team?

Eva Mistry, MBBS

Principal Investigator

University of Cincinnati

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

Citations

1. reporter.nih.gov reporter.nih.gov/search/14E9CE024F8FC5D27598B8961CAA4A01A2FFCEB861BF/project-details/11083854

Strategy for Improving Stroke Treatment ... - NIH RePORTER Following a successful Phase I trial of an a2AP-I called TS23, this Phase II NIH StrokeNet trial will investigate whether a particular dose is safe and ...

2. reporter.nih.gov reporter.nih.gov/project-details/11376143

RePORT RePORTER - National Institutes of Health (NIH) | Taken together, these data suggest that an a2AP-I alone has extraordinary potential for safe treatment of human ischemic stroke, particularly in an extended ...

3. nihstrokenet.org nihstrokenet.org/trials/sister/home

SISTER TRIAL - StrokeNet To identify a dose of TS23 that is safe and more efficacious than placebo for the treatment of patients from 4.5 – 24 hours of ischemic stroke onset, or last ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05948566

Strategy for Improving Stroke Treatment Response (SISTER) 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 ...

5. reporter.nih.gov reporter.nih.gov/project-details/10443870

Novel α2-Antiplasmin Inactivation for Lysis of Intravascular ... On the basis of pre-clinical data, we project that by comparison to current therapy, treatment with TS23 could significantly reduce right heart failure, improve ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05408546

Study Details | NCT05408546 | Novel α2-Antiplasmin ... Evaluation of safety and thrombolytic effect of ascending doses of TS23 in subjects with intermediate-risk (sub-massive) acute pulmonary embolism (PE).