OverviewStudy detailsEligibilityThings to knowResearchStudy plan
info
Simplify with AI

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

PHASE2RECRUITING

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.

Study details:

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:. 1.

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. 2. 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.

Eligibility criteria

Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.

Inclusion criteria

  1. Patient aged 18 years or more
  2. 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
  3. CT perfusion indicates 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 (NIHSS >4)
  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:
  2. Advanced dementia
  3. Severe pre-stroke disability (mRS score 4-5)
  4. Glasgow Coma Score (GCS) 3 to 5
  5. Evidence of a large well-defined ischaemic lesion measuring more than one third of the middle cerebral artery (MCA) territory
  6. Uncontrolled hypertension (SBP >180 or DBP >110, refractory to medical therapy)
  7. Intracranial haemorrhage within the last 90 days
  8. Myocardial infarction or stroke within the last 30 days
  9. Patient has an underlying disease process with a life expectancy of <90 days
  10. Known treatment with anticoagulants
  11. Known severe liver disease
  12. Known bleeding disorder
  13. Cardiopulmonary resuscitation or arterial puncture at non-compressible site or lumbar puncture within 7 days
  14. Another medical illness or social circumstance that may interfere with outcome assessments and follow-up
  15. Known or suspected pregnancy
  16. Patients currently participating in another interventional clinical trial
  17. Informed consent unable to be obtained from the patient or their Person Responsible/Medical Treatment Decision Maker prior to study interventions

Eligibility

Age eligible for study : NA

Healthy volunteers accepted : No

Gender eligible for study: ALL

Things to know

Study dates

Study start:

Primary completion:

Study completion finish:

study type

Study type

TREATMENT

phase

Phase

    PHASE2

trial

Study ID

NCT06813651

Intervention or treatment

DRUG: TBO-309: 60 mg

DRUG: TBO-309: 120 mg

DRUG: TBO-309: 30 mg

Conditions

  • Ischemic Stroke
  • Tandem Occlusion

  • Condition: Ischemic Stroke, Tandem Occlusion

  • DRUG: TBO-309: 60 mg and other drugs

  • Newcastle, New South Wales, Australia and more

  • Sponsor: ThromBio Pty. Ltd.

Save

Share

You may be eligible to participate in this trial based on your search. Check eligibility by answering some questions.

Are you running this trial?

If you're a clinic or sponsor, you can claim this study

Research sites nearby

Closest Location:

John Hunter Hospital

Select from list below to view details:

  • John Hunter Hospital

    Newcastle, New South Wales, Australia

  • Royal North Shore Hospital

    St Leonards, New South Wales, Australia

Loading map...

Who is running the clinical trial?

TPL

ThromBio Pty. Ltd.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Participant Group/ArmIntervention/Treatment
EXPERIMENTAL: TBO-309 - 60 mg
  • 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.
Drug: TBO-309: 60 mg
    EXPERIMENTAL: TBO-309 - 120 mg
    • 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.
    Drug: TBO-309: 120 mg
      EXPERIMENTAL: TBO-309 - 30 mg
      • 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.
      Drug: TBO-309: 30 mg

        What is the study measuring?

        Primary Outcome

        MeasureDescriptionTime Frame
        Proportion of patients achieving a composite outcome of efficacy and safetyThe primary endpoint is a composite outcome of efficacy and safety, defined by the proportion of patients who 1) avoid 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 2) have no sICH. sICH is defined as parenchymal haemorrhage type 2 (PH2) on imaging.24-36 hours

        Secondary Outcome

        MeasureDescriptionTime Frame
        Proportion of patients achieving reperfusion.The proportion of patients achieving reperfusion, where reperfusion is defined by the expanded Thrombolysis in Cerebral Infarction scale (eTICI) 2b50 or better (i.e. 50% to 100%)24 hours
        Infarct volume 24-36 hours post study drug commencementNot Specified24-36 hours
        Proportion of all patients with any ICH within 24-36 hours post study drug commencementAll ICH as demonstrated on brain imaging at 24-36 hours, where ICH will be classified according to The Heidelberg Bleeding Classification.24-36 hours
        Proportion of patients experiencing any bleeding within 24-36 hours of study drug commencement.The proportion of patients experiencing any bleeding within 24-36 hours of study drug commencement. Bleeding will be determined using a modified WHO scale with grades 1 and 2 classified as minor bleeding, and grades 3 and 4 as major bleeding.24-36 hours
        National Institutes of Health Stroke Scale (NIHSS) at 24 hours, and 7 days/at hospital DischargeThe National Institutes of Health Stroke Scale (NIHSS) is a 15-item neurological examination stroke scale. Scores range from 0 to 42, with higher scores indicating greater severity.24 hours and 7 days
        Modified Rankin Scale (mRS) score at discharge and 90 daysThe Modified Rankin Scale (mRS) is a scale from 0 to 6, with higher scores indicating greater disability (5), and death (6).90 days
        Proportion of patients with all-cause mortality at 90 days.Not Specified90 days
        Are you running this trial?If you're a clinic or sponsor, you can claim this study.
        Claim this trial

        References

        Clinical Trials Gov: Safety, Tolerability and Efficacy of Adjunctive TBO-309 in Reperfusion for Stroke With Tandem Occlusion

        Other trials to consider

        Loading suggested trials...

        Top searched conditions

        Breast CancerLung CancerType 2 DiabetesDermatitisAlzheimersParkinsonsLupusCrohn’s DiseaseAsthmaHypertensionCOPDMultiple SclerosisOsteoarthritisHIV/AIDSPsoriasisStrokeObesityProstate CancerDepressionCardiovascular