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

NCT ID: NCT05363397

Last Updated: 2025-12-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-09-27

Study Completion Date

2026-05-01

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

STARS is a prospective, multicentre, open-label, dose escalation, Phase IIa study to assess the safety and tolerability of TBO-309, an adjuvant antiplatelet therapy, in patients with AIS.

Acute ischaemic stroke (AIS) is caused by a severe blockage of an artery leading to immediate reduced blood flow to part of the brain. Standard therapies target the blocked artery by either dissolving the blockage or removing the blockage. However, even after successful treatment, re-blockage of arteries can occur. The use of an antiplatelet therapy, TBO-309, in addition to standard therapies offers the possibility of improved restoration of blood flow and reduced rates of artery re-blockage.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Stroke is a leading cause of disability worldwide, with most strokes in Australia being Acute ischaemic stroke (AIS). AIS is caused by a severe blockage of an artery leading to immediate reduced blood flow to part of the brain. Timely restoration of blood flow is critical to preserve brain function. Standard therapies target the blocked artery by either dissolving the blockage (intravenous thrombolysis (IVT)) or removing the blockage (endovascular thrombectomy (EVT)). However, even after successful treatment, re-blockage of arteries can occur. The use of an antiplatelet therapy in addition to IVT/EVT offers the possibility of improved restoration of blood flow and reduced rates of artery re-blockage.

STARS is a prospective, multicentre, open-label, dose escalation, Phase IIa study to assess the safety and tolerability of TBO-309, an adjuvant antiplatelet therapy, in patients with AIS. The study will test the hypothesis that AIS patients who are treated with TBO-309 in conjunction with standard therapy (IVT alone or IVT + EVT) will not experience higher rates of ICH compared to the expected rates of ICH in patients treated with only standard therapy (IVT alone or IVT + EVT).

TBO-309 is a potent, selective and ATP competitive PI3Kβ inhibitor which blocks platelet activation adhesion/aggregation and promotes platelet disaggregation, thereby specifically inhibiting thrombosis without interfering with normal haemostasis. In order to evaluate safety at lower doses, four dose levels in total will be administered using a serial dose-escalation design. Doses will be assigned based on a dose escalation methodology commencing with lower doses assigned early in the study. As safety criteria are satisfied (based on ICH rates) doses will be increased. The dosage strength of TBO-309 to be administered (30mg, 60mg, 120mg or 180mg) will be assigned by the study database.

Patients presenting to hospital with an AIS will be assessed according to the trial inclusion and exclusion criteria by the Principal Investigator, or nominated delegate, on admission to the Emergency Department. Consent will be sought from either the patient or their Person Responsible/Medical Treatment Decision Maker prior to enrolment into the study. Standard therapy, either IVT alone or IVT + EVT, will commence and the TBO-309 will be administered at the same time as standard therapy. Following administration of study drug and treatment with standard therapies, patients will receive usual supportive care either in the Intensive Care Unit or in the hospital ward. Any significant neurological deterioration will require an emergency non-contrast CT head to assess for the presence of ICH. All patients will receive a 24-36 hour MRI or a multimodal CT to assess asymptomatic bleeding, recanalisation and infarct volume.

During the patients hospital stay clinical outcome data will be collected during the study period to document response to treatment and to monitor safety. Study patients will be followed-up for 90 days post-enrolment, or to death, whichever is the earlier.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Acute Ischemic Stroke

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Continual Reassessment Method
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
Independent imaging assessors will review and adjudicate blinded study data to ensure the primary endpoint meets consistent pre-determined diagnostic criteria. This will include centralised review of de-identified CT and MRI/MRA images. Members will be qualified physicians who are independent of the study and not involved in study management.

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

TBO-309 30mg (25% of target dose)

Following randomisation, 30mg TBO-309 will be administered at the same time as the rt-PA infusion or tenecteplase bolus (as part of intravenous thrombolysis) or as soon as practical.

The allocated dose of TBO-309 will be given intravenously as follows:

* 20% of the dose will be administered as a bolus over approximately one minute; then
* the remainder of the dose (80%) will be administered over 3 hours as an infusion

Only one dose will be administered to the patient.

Group Type EXPERIMENTAL

TBO-309

Intervention Type DRUG

TBO-309 is a potent, selective and ATP competitive PI3Kβ inhibitor which blocks platelet activation adhesion/aggregation and promotes platelet disaggregation, thereby specifically inhibiting thrombosis without interfering with normal haemostasis.

TBO-309 60mg (50% of target dose)

Following randomisation, 60mg TBO-309 will be administered at the same time as the rt-PA infusion or tenecteplase bolus (as part of intravenous thrombolysis) or as soon as practical.

The allocated dose of TBO-309 will be given intravenously as follows:

* 20% of the dose will be administered as a bolus over approximately one minute; then
* the remainder of the dose (80%) will be administered over 3 hours as an infusion

Only one dose will be administered to the patient.

Group Type EXPERIMENTAL

TBO-309

Intervention Type DRUG

TBO-309 is a potent, selective and ATP competitive PI3Kβ inhibitor which blocks platelet activation adhesion/aggregation and promotes platelet disaggregation, thereby specifically inhibiting thrombosis without interfering with normal haemostasis.

TBO-309 120mg (100% of target dose)

Following randomisation, 120mg TBO-309 will be administered at the same time as the rt-PA infusion or tenecteplase bolus (as part of intravenous thrombolysis) or as soon as practical.

The allocated dose of TBO-309 will be given intravenously as follows:

* 20% of the dose will be administered as a bolus over approximately one minute; then
* the remainder of the dose (80%) will be administered over 3 hours as an infusion

Only one dose will be administered to the patient.

Group Type EXPERIMENTAL

TBO-309

Intervention Type DRUG

TBO-309 is a potent, selective and ATP competitive PI3Kβ inhibitor which blocks platelet activation adhesion/aggregation and promotes platelet disaggregation, thereby specifically inhibiting thrombosis without interfering with normal haemostasis.

TBO-309 180mg (150% of target dose)

Following randomisation, 180mg TBO-309 will be administered at the same time as the rt-PA infusion or tenecteplase bolus (as part of intravenous thrombolysis) or as soon as practical.

The allocated dose of TBO-309 will be given intravenously as follows:

* 20% of the dose will be administered as a bolus over approximately one minute; then
* the remainder of the dose (80%) will be administered over 3 hours as an infusion

Only one dose will be administered to the patient.

Group Type EXPERIMENTAL

TBO-309

Intervention Type DRUG

TBO-309 is a potent, selective and ATP competitive PI3Kβ inhibitor which blocks platelet activation adhesion/aggregation and promotes platelet disaggregation, thereby specifically inhibiting thrombosis without interfering with normal haemostasis.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

TBO-309

TBO-309 is a potent, selective and ATP competitive PI3Kβ inhibitor which blocks platelet activation adhesion/aggregation and promotes platelet disaggregation, thereby specifically inhibiting thrombosis without interfering with normal haemostasis.

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Neuroscience Trials Australia

OTHER

Sponsor Role collaborator

The Florey Institute of Neuroscience and Mental Health

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Candice Delcourt, Dr

Role: STUDY_CHAIR

The George Institute

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Royal Prince Alfred Hospital

Camperdown, New South Wales, Australia

Site Status RECRUITING

Liverpool Hospital

Liverpool, New South Wales, Australia

Site Status RECRUITING

John Hunter Hospital

New Lambton Heights, New South Wales, Australia

Site Status RECRUITING

Prince of Wales Hospital

Randwick, New South Wales, Australia

Site Status RECRUITING

Royal Adelaide Hospital

Adelaide, South Australia, Australia

Site Status RECRUITING

Eastern Health- Box Hill Hospital

Box Hill, Victoria, Australia

Site Status RECRUITING

Royal Melbourne Hospital

Parkville, Victoria, Australia

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

Australia

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Candice Delcourt, Dr

Role: CONTACT

+61 2 8052 4601

Michele Sallaberger

Role: CONTACT

+61 438471423

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Timothy Ang, Professor

Role: primary

Christopher Blair, Dr

Role: primary

Chris Levi, Professor

Role: primary

Ken Butcher, Professor

Role: primary

Tim Kleinig, Professor

Role: primary

Philip Choi

Role: primary

Bruce Campbell, Professor

Role: primary

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

CCD78277

Identifier Type: -

Identifier Source: org_study_id

U1111-1270-5195

Identifier Type: OTHER

Identifier Source: secondary_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

DLBS1033 for Acute Ischemic Stroke Patients
NCT02133521 TERMINATED PHASE2/PHASE3