Adding TBO-309 to reperfusion treatment for acute ischemic stroke.

Safety and Tolerability of Adjunctive TBO-309 in Reperfusion for Stroke

This trial will test whether giving the antiplatelet drug TBO-309 together with clot-dissolving or clot-removal treatment is safe for adults who have just had an acute ischemic stroke.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: The Florey Institute of Neuroscience and Mental Health (Academic / other)
• Locations: 7 sites (Camperdown, New South Wales and 6 other locations)
• Trial ID: NCT05363397 on ClinicalTrials.gov

What this trial studies

STARS is a prospective, multicentre, open-label, dose-escalation Phase IIa trial enrolling adults with acute ischemic stroke who receive intravenous thrombolysis with or without endovascular thrombectomy. Participants will receive one of several escalating doses of TBO-309 in addition to standard reperfusion therapy, with close monitoring for safety events, especially intracranial hemorrhage. TBO-309 is a selective, ATP-competitive PI3Kβ inhibitor designed to block platelet activation and aggregation while sparing normal haemostasis. The primary focus is tolerability and safety compared to expected hemorrhage rates after standard reperfusion care.

Who should consider this trial

Good fit: Adults (≥18 years) with acute ischemic stroke who are treated with IV thrombolysis (alteplase or tenecteplase) with or without endovascular thrombectomy, have NIHSS ≥5, and present within the reperfusion time windows (≤6 hours or 6–24 hours with favorable perfusion imaging) are the intended candidates.

Not a fit: Patients with hemorrhagic stroke, those not eligible for IV thrombolysis or EVT, people with very mild deficits (NIHSS <5), or those with contraindications to antiplatelet/anticoagulant therapy are unlikely to benefit from this adjunctive treatment.

Why it matters

Potential benefit: If successful, adding TBO-309 could lower the risk of artery re-blockage after reperfusion and improve restoration of blood flow, potentially reducing disability from stroke.

How similar studies have performed: Previous attempts to add antiplatelet agents around reperfusion have shown mixed results because of bleeding risk, so while adjunctive antiplatelet therapy has precedent, TBO-309's selective PI3Kβ mechanism is novel and largely untested in this setting.

Eligibility criteria

Inclusion Criteria

1. Patient aged 18 years or more
2. Patient has an acute ischaemic stroke
3. Patient will be treated with either:

   1. Intravenous thrombolysis (IVT) with alteplase or tenecteplase for a diagnosis of AIS that is confirmed by CT imaging;

      alone/OR WITH
   2. Endovascular Thrombectomy (EVT) for large vessel occlusion (LVO) in the internal carotid artery, middle cerebral artery (M1 segment), middle cerebral artery (M2 segment) or with tandem occlusion of both the cervical carotid and intracranial large arteries who either:

   i. presented within 6 hours of stroke onset

   OR

   ii. presented between 6-24 hours after they were last known to be well and clinical observations and either CT perfusion or MRI features indicate the presence of salvageable brain tissue, defined as ischaemic core \<70mL with a mismatch ratio \>1.8 and absolute mismatch \>15mL.
4. Patient has at least a mild grade of neurological impairment i.e. NIHSS of 5 or more
5. Patient has an estimated pre-stroke mRS of less than 4

Exclusion Criteria

1. Patient is considered unlikely to benefit from study intervention defined by one of the following:

   1. Advanced dementia
   2. Severe pre-stroke disability (mRS score 4-5)
   3. Glasgow Coma Score (GCS) 3 to 5
   4. Evidence of a large well-defined ischaemic lesion measuring more than one third of the MCA territory
2. High likelihood of undergoing stent insertion and requiring additional antithrombotic(s)
3. Uncontrolled hypertension (SBP \>180 or DBP \>110, refractory to medical therapy)
4. ICH within the last 90 days
5. Myocardial infarction or stroke within the last 30 days
6. Patient has an underlying disease process with a life expectancy of \<90 days
7. Contraindication to thrombolysis i.e. increased bleeding risk
8. Contraindication to intravenous contrast agents including renal impairment or allergy
9. Known treatment with dual antiplatelet therapy or anticoagulant medication
10. Known severe liver disease
11. Known bleeding disorder
12. Cardiopulmonary resuscitation or arterial puncture at non-compressible site or lumbar puncture within 7 days
13. Another medical illness or social circumstance that may interfere with outcome assessments and follow-up
14. Known or suspected pregnancy
15. Patients currently participating in another interventional clinical trial
16. Informed consent unable to be obtained from the patient or their Person Responsible/Medical Treatment Decision Maker prior to study interventions
17. Study drug cannot be given within one hour of thrombolytic drug bolus

Where this trial is running

Camperdown, New South Wales and 6 other locations

• Royal Prince Alfred Hospital — Camperdown, New South Wales, Australia (Recruiting)
• Liverpool Hospital — Liverpool, New South Wales, Australia (Recruiting)
• John Hunter Hospital — New Lambton Heights, New South Wales, Australia (Recruiting)
• Prince of Wales Hospital — Randwick, New South Wales, Australia (Recruiting)
• Royal Adelaide Hospital — Adelaide, South Australia, Australia (Recruiting)
• Eastern Health- Box Hill Hospital — Box Hill, Victoria, Australia (Recruiting)
• Royal Melbourne Hospital — Parkville, Victoria, Australia (Recruiting)

Study contacts

• Study coordinator: Candice Delcourt, Dr

Conditions Acute Ischemic Stroke; Antiplatelet therapy; Stroke; Blood clot; Intravenous thrombolysis; Endovascular Thrombectomy; TBO-309