NCT06813651

Brief Summary

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
78

participants targeted

Target at P50-P75 for phase_2

Timeline
8mo left

Started Oct 2025

Shorter than P25 for phase_2

Geographic Reach
1 country

2 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress48%
Oct 2025Dec 2026

First Submitted

Initial submission to the registry

January 21, 2025

Completed
17 days until next milestone

First Posted

Study publicly available on registry

February 7, 2025

Completed
8 months until next milestone

Study Start

First participant enrolled

October 4, 2025

Completed
1.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 30, 2026

Expected
1 day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2026

Last Updated

November 25, 2025

Status Verified

November 1, 2025

Enrollment Period

1.2 years

First QC Date

January 21, 2025

Last Update Submit

November 19, 2025

Conditions

Ischemic StrokeTandem Occlusion

Keywords

Ischaemic strokeStentingEndovascular thrombectomytandem occlusion

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (7)

  • Proportion of patients achieving reperfusion.

    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

    24-36 hours

  • Proportion of patients experiencing any bleeding within 24-36 hours of study drug commencement.

    24-36 hours

  • National Institutes of Health Stroke Scale (NIHSS) at 24 hours, and 7 days/at hospital Discharge

    24 hours and 7 days

  • +2 more secondary outcomes

Other Outcomes (1)

  • Proportion of patients with sICH

    24-36 hours

Study Arms (3)

TBO-309 - 60 mg

EXPERIMENTAL

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 - 120 mg

EXPERIMENTAL

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 - 30 mg

EXPERIMENTAL

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

Interventions

TBO-309: 60 mgDRUG

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.

TBO-309 - 60 mg
TBO-309: 120 mgDRUG

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.

TBO-309 - 120 mg
TBO-309: 30 mgDRUG

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.

TBO-309 - 30 mg

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • Patient is considered unlikely to benefit from study intervention defined by one of the following:
  • Advanced dementia
  • Severe pre-stroke disability (mRS score 4-5)
  • Glasgow Coma Score (GCS) 3 to 5
  • 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
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

John Hunter Hospital

Newcastle, New South Wales, 2305, Australia

RECRUITING

Royal North Shore Hospital

St Leonards, New South Wales, 2065, Australia

NOT YET RECRUITING

Related Publications (9)

  • 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.

    PMID: 34320814BACKGROUND

  • 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.

    PMID: 7459811BACKGROUND

  • 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.

    PMID: 19109560BACKGROUND

  • 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.

    PMID: 26330447BACKGROUND

  • 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.

    PMID: 17258667BACKGROUND

  • 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.

    PMID: 22943292BACKGROUND

  • 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.

    PMID: 26096765BACKGROUND

  • 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.

    PMID: 22906130BACKGROUND

  • 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.

    PMID: 15834429BACKGROUND

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

StrokeCerebrovascular DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesVascular DiseasesCardiovascular Diseases

Study Officials

  • Ferdinand Miteff - Interventional Neurologist, RACP, CCINR

    John Hunter Hospital, Newcastle, NSW Australia

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Ferdinand Miteff - Interventional Neurologist, RACP, CCINR

CONTACT

612 4921 3490ferdi.miteff@health.nsw.gov.au

Candice Delcourt, MD, PhD and FRACP

CONTACT

61 2 8052 4601cdelcourt@georgeinstitute.org.au

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NON RANDOMIZED
Masking
SINGLE
Who Masked
OUTCOMES ASSESSOR
Masking Details
Masking Description: Independent imaging assessors will review and adjudicate blinded study data to ensure the primary endpoint meets consistent pre-determined diagnostic criteria. Imaging assessors will be qualified physicians who are independent of the study and not involved in study management.
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: Multicenter, prospective, open-label, Bayesian Optimal Phase 2 (BOP2) trial. Two intervention doses will be tested sequentially for TBO-309, with 60mg tested first. Then either a higher (120mg) or lower (30mg) dose will be tested, based on results of the 60 mg dose. The maximum number of subjects is estimated to be 78 in this two-dose BOP2 design study.
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 21, 2025

First Posted

February 7, 2025

Study Start

October 4, 2025

Primary Completion (Estimated)

December 30, 2026

Study Completion (Estimated)

December 31, 2026

Last Updated

November 25, 2025

Record last verified: 2025-11

Locations

AU(2)