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

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 Overview

• Status: Recruiting
• Conditions: Ischemic Stroke; Tandem Occlusion
• Intervention / Treatment: Drug: TBO-309: 60 mg; Drug: TBO-309: 120 mg; Drug: TBO-309: 30 mg

Detailed 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:

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.

• Study Type: Interventional
• Enrollment (Estimated): 78
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ferdinand Miteff - Interventional Neurologist, RACP, CCINR; Phone Number: 612 4921 3490; Email: ferdi.miteff@health.nsw.gov.au
• Study Contact Backup: Name: Candice Delcourt, MD, PhD and FRACP; Phone Number: 61 2 8052 4601; Email: cdelcourt@georgeinstitute.org.au

Study Locations

• Australia
  • New South Wales
    • Newcastle, New South Wales, Australia, 2305
      • Recruiting
      • John Hunter Hospital
      • Contact: Ferdinand Miteff; Email: ferdi.miteff@health.nsw.gov.au
      • Principal Investigator: Ferdinand Miteff
    • St Leonards, New South Wales, Australia, 2065
      • Not yet recruiting
      • Royal North Shore Hospital
      • Contact: Alice Ma, MBBS; Phone Number: +61299267111; Email: Alice.Ma@health.nsw.gov.au
      • Principal Investigator: Alice Ma, MBBS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / 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; TBO-309 is a potent, selective and ATP competitive PI3Kβ inhibitor which blocks platelet activation adhesion/aggregation and promotes platelet disaggregation. By targeting PI3Kβ, TBO-309 specifically inhibits thrombosis whilst minimizing the impact on normal haemostasis.
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; TBO-309 is a potent, selective and ATP competitive PI3Kβ inhibitor which blocks platelet activation adhesion/aggregation and promotes platelet disaggregation. By targeting PI3Kβ, TBO-309 specifically inhibits thrombosis whilst minimizing the impact on normal haemostasis.
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; TBO-309 is a potent, selective and ATP competitive PI3Kβ inhibitor which blocks platelet activation adhesion/aggregation and promotes platelet disaggregation. By targeting PI3Kβ, TBO-309 specifically inhibits thrombosis whilst minimizing the impact on normal haemostasis.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients achieving a composite outcome of efficacy and safety	The 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 Measures

Outcome Measure	Measure Description	Time 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 commencement		24-36 hours
Proportion of all patients with any ICH within 24-36 hours post study drug commencement	All 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 Discharge	The 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 days	The 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.		90 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients with sICH	The safety outcome is symptomatic intra-cranial haemorrhage (sICH) within 24-36 hours of study drug commencement. sICH is defined as parenchymal haemorrhage type 2 (PH2) on imaging within 24-36 hours after treatment, associated with a ≥ four-point deterioration on the National Institutes of Health Stroke Scale (NIHSS) from baseline or from the lowest score to 24-36 hours or leading to death.	24-36 hours

Collaborators and Investigators

• Sponsor: ThromBio Pty. Ltd.
• Investigators: Principal Investigator: Ferdinand Miteff - Interventional Neurologist, RACP, CCINR, John Hunter Hospital, Newcastle, NSW Australia

Publications and helpful links

General Publications

• von Kummer R, Broderick JP, Campbell BC, Demchuk A, Goyal M, Hill MD, Treurniet KM, Majoie CB, Marquering HA, Mazya MV, San Roman L, Saver JL, Strbian D, Whiteley W, Hacke W. The Heidelberg Bleeding Classification: Classification of Bleeding Events After Ischemic Stroke and Reperfusion Therapy. Stroke. 2015 Oct;46(10):2981-6. doi: 10.1161/STROKEAHA.115.010049. Epub 2015 Sep 1. No abstract available.
• Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer. 1981 Jan 1;47(1):207-14. doi: 10.1002/1097-0142(19810101)47:13.0.co;2-6.
• Saver JL, Chaisinanunkul N, Campbell BCV, Grotta JC, Hill MD, Khatri P, Landen J, Lansberg MG, Venkatasubramanian C, Albers GW; XIth Stroke Treatment Academic Industry Roundtable. Standardized Nomenclature for Modified Rankin Scale Global Disability Outcomes: Consensus Recommendations From Stroke Therapy Academic Industry Roundtable XI. Stroke. 2021 Aug;52(9):3054-3062. doi: 10.1161/STROKEAHA.121.034480. Epub 2021 Jul 29.
• Heddle NM, Cook RJ, Tinmouth A, Kouroukis CT, Hervig T, Klapper E, Brandwein JM, Szczepiorkowski ZM, AuBuchon JP, Barty RL, Lee KA; SToP Study Investigators of the BEST Collaborative. A randomized controlled trial comparing standard- and low-dose strategies for transfusion of platelets (SToP) to patients with thrombocytopenia. Blood. 2009 Feb 12;113(7):1564-73. doi: 10.1182/blood-2008-09-178236. Epub 2008 Dec 24.
• Jackson SP, Schoenwaelder SM. Antithrombotic phosphoinositide 3-kinase beta inhibitors in humans: a 'shear' delight! J Thromb Haemost. 2012 Oct;10(10):2123-6. doi: 10.1111/j.1538-7836.2012.04912.x. No abstract available.
• Nylander S, Wagberg F, Andersson M, Skarby T, Gustafsson D. Exploration of efficacy and bleeding with combined phosphoinositide 3-kinase beta inhibition and aspirin in man. J Thromb Haemost. 2015 Aug;13(8):1494-502. doi: 10.1111/jth.13027. Epub 2015 Jul 23.
• Nylander S, Kull B, Bjorkman JA, Ulvinge JC, Oakes N, Emanuelsson BM, Andersson M, Skarby T, Inghardt T, Fjellstrom O, Gustafsson D. Human target validation of phosphoinositide 3-kinase (PI3K)beta: effects on platelets and insulin sensitivity, using AZD6482 a novel PI3Kbeta inhibitor. J Thromb Haemost. 2012 Oct;10(10):2127-36. doi: 10.1111/j.1538-7836.2012.04898.x.
• Jackson SP, Schoenwaelder SM, Goncalves I, Nesbitt WS, Yap CL, Wright CE, Kenche V, Anderson KE, Dopheide SM, Yuan Y, Sturgeon SA, Prabaharan H, Thompson PE, Smith GD, Shepherd PR, Daniele N, Kulkarni S, Abbott B, Saylik D, Jones C, Lu L, Giuliano S, Hughan SC, Angus JA, Robertson AD, Salem HH. PI 3-kinase p110beta: a new target for antithrombotic therapy. Nat Med. 2005 May;11(5):507-14. doi: 10.1038/nm1232. Epub 2005 Apr 17.
• Wahlgren N, Ahmed N, Davalos A, Ford GA, Grond M, Hacke W, Hennerici MG, Kaste M, Kuelkens S, Larrue V, Lees KR, Roine RO, Soinne L, Toni D, Vanhooren G; SITS-MOST investigators. Thrombolysis with alteplase for acute ischaemic stroke in the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST): an observational study. Lancet. 2007 Jan 27;369(9558):275-82. doi: 10.1016/S0140-6736(07)60149-4.

Study record dates

Study Major Dates

• Study Start (Actual): October 4, 2025
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: January 21, 2025
• First Submitted That Met QC Criteria: February 3, 2025
• First Posted (Actual): February 7, 2025

Study Record Updates

• Last Update Posted (Actual): November 25, 2025
• Last Update Submitted That Met QC Criteria: November 19, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: Stenting; Endovascular thrombectomy; tandem occlusion; Ischaemic stroke
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Ischemic Stroke
• Other Study ID Numbers: Co-STARS; Application No. 00039 (Other Grant/Funding Number: NSW Biosciences Fund 2023 [2023 NSW BioSF])

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No