Safety, Tolerability and Efficacy of Adjunctive TBO-309 in Reperfusion for Stroke With Tandem Occlusion (Co-STARS)

ThromBio Pty. Ltd.

Status and phase

Not yet enrolling

Phase 2

Conditions

Ischemic Stroke

Tandem Occlusion

Treatments

Drug: TBO-309: 120 mg

Drug: TBO-309: 60 mg

Drug: TBO-309: 30 mg

Study type

Interventional

Funder types

Industry

Identifiers

NCT06813651

Application No. 00039 (Other Grant/Funding Number)

Co-STARS

Details and patient eligibility

About

Co-STAR is a multicenter, prospective, open-label, Bayesian Optimal Phase 2 (BOP2) trial that aims to assess the safety and efficacy of adjunctive intravenous TBO-309 in Acute Ischaemic Stroke (AIS) patients with tandem occlusion receiving intra-cranial endovascular thrombectomy (EVT) and acute extracranial carotid artery stenting.

Co-STARS study will test the hypothesis that patients with tandem occlusion treated with EVT and acute stenting in conjunction with TBO-309 will:

have persistent stent patency without requiring rescue therapy with GPIIb/IIIa inhibitors and
not experience high rates of symptomatic intra-cranial haemorrhage (sICH).

Patients with tandem occlusion undergoing EVT and acute stenting will receive intravenous TBO-309 bolus and infusion. TBO-309 is a potent, selective and ATP competitive PI3K[beta] inhibitor which reduces platelet activation adhesion/aggregation particularly under conditions of disturbed blood flow and promotes platelet disaggregation. By targeting PI3K[beta], TBO-309 specifically inhibits thrombosis whilst minimizing the impact on normal hemostasis.

Full description

Stroke due to large vessel occlusion (LVO) typically causes large infarcts and results in severe disability and a high case fatality rate. Treating LVO by thrombectomy poses technical challenges, especially when the lesion involves not only the extracranial (cervical) part of the internal carotid artery but also its concomitant intracranial distal segment or the ipsilateral middle cerebral artery (tandem occlusion). For patients with tandem occlusion, stenting of the internal carotid is considered acceptable, but it requires the use of antiplatelet therapy to avoid stent thrombosis, often necessitating rescue therapy with GPIIb/IIIa inhibitors. This can lead to an increased risk of hemorrhage especially when potent antiplatelet agents such as GPIIb/IIIa inhibitors are used.

The novel investigational agent TBO-309 is a potent, selective and ATP competitive PI3K[beta] inhibitor which reduces platelet activation adhesion/aggregation particularly under conditions of disturbed blood flow and promotes platelet disaggregation. By targeting PI3K[beta], TBO-309 specifically inhibits thrombosis whilst minimizing the impact on normal hemostasis. This study aims to assess the safety and efficacy of adjunctive TBO-309 in acute ischaemic stroke with tandem occlusion eligible to undergo intra-cranial EVT and acute extracranial carotid artery stenting.

The primary endpoint of this trial is a composite outcome of efficacy and safety, defined by:

Avoidance of intra-procedural GPIIb/IIIa inhibitor rescue therapy due to stent thrombosis, combined with persistent stent patency seen on angiographic imaging at 24-36 hours, and
no sICH.

This trial will use Bayesian Optimal Phase 2 (BOP2) trial design, and two intervention doses will be tested sequentially for TBO-309. TBO-309 at the dose of 60 mg will be tested first. Then either a higher dose of 120 mg or a lower dose of 30 mg will be tested based on the results of the 60 mg dose.

Enrollment

78 estimated patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patient aged 18 years or more
Patient has an AIS due to tandem occlusion, including large vessel occlusion (LVO) within the intra-cranial anterior circulation and presumed atherosclerotic occlusion of the cervical internal carotid artery origin
CT perfusion indicates the presence of salvageable brain tissue, defined as ischaemic core <70mL with a mismatch ratio >1.8 and absolute mismatch >15mL.
Patient has at least a mild grade of neurological impairment (NIHSS >4)
Patient has an estimated pre-stroke mRS of less than 4

Exclusion criteria

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 middle cerebral artery (MCA) territory
Uncontrolled hypertension (SBP >180 or DBP >110, refractory to medical therapy)
Intracranial haemorrhage within the last 90 days
Myocardial infarction or stroke within the last 30 days
Patient has an underlying disease process with a life expectancy of <90 days
Known treatment with anticoagulants
Known severe liver disease
Known bleeding disorder
Cardiopulmonary resuscitation or arterial puncture at non-compressible site or lumbar puncture within 7 days
Another medical illness or social circumstance that may interfere with outcome assessments and follow-up
Known or suspected pregnancy
Patients currently participating in another interventional clinical trial
Informed consent unable to be obtained from the patient or their Person Responsible/Medical Treatment Decision Maker prior to study interventions

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Sequential Assignment

Masking

Single Blind

78 participants in 3 patient groups

TBO-309 - 60 mg

Experimental group

Description:

An intravenous (IV) bolus of TBO-309 will be administered before the acute stent procedure. The allocated dose of TBO-309 will be given IV 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.

Treatment:

Drug: TBO-309: 60 mg

TBO-309 - 120 mg

Experimental group

Description:

Treatment:

Drug: TBO-309: 120 mg

TBO-309 - 30 mg

Experimental group

Description:

Treatment:

Drug: TBO-309: 30 mg