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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05363397
Other study ID # CCD78277
Secondary ID U1111-1270-5195
Status Recruiting
Phase Phase 2
First received
Last updated
Start date September 27, 2023
Est. completion date May 1, 2025

Study information

Verified date November 2023
Source The George Institute
Contact Candice Delcourt, Dr
Phone +61 2 8052 4601
Email cdelcourt@georgeinstitute.org.au
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

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.


Description:

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.


Recruitment information / eligibility

Status Recruiting
Enrollment 80
Est. completion date May 1, 2025
Est. primary completion date February 1, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria 1. Patient aged 18 years or more 2. Patient has an acute ischaemic stroke (AIS) 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 LVO in the internal carotid artery, proximal middle cerebral artery (M1 segment), proximal M2 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 (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 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

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
TBO-309
TBO-309 is a potent, selective and ATP competitive PI3Kß inhibitor which blocks platelet activation adhesion/aggregation and promotes platelet disaggregation, thereby specifically inhibiting thrombosis without interfering with normal haemostasis.

Locations

Country Name City State
Australia Royal Adelaide Hospital Adelaide South Australia
Australia Timothy Ang Camperdown New South Wales
Australia Liverpool Hospital Liverpool New South Wales
Australia John Hunter Hospital New Lambton Heights New South Wales
Australia Royal Melbourne Hospital Parkville Victoria
Australia Prince of Wales Hospital Randwick New South Wales

Sponsors (2)

Lead Sponsor Collaborator
The George Institute Heart Research Institute

Country where clinical trial is conducted

Australia, 

Outcome

Type Measure Description Time frame Safety issue
Other Recanalisation rate CT Angiogram (CTA) or MR angiogram (MRA) assessment to measure recanalisation rate by the Thrombolysis in Myocardial Infarction (TIMI) scale Within 24-36 hours of study drug administration
Other Reperfusion rates Reperfusion rates by expanded thrombolysis in Cerebral Infarction scale (eTICI) 2b (50 or better = 50% to 100%) Within 24-36 hours of study drug administration
Other Infarct volume Infarct volume measured with diffusion weighted imaging (DWI) MRI and fluid attenuated inversion recovery (FLAIR) MRI Within 24-36 hours of study drug administration
Other NIHSS score Quantifies stroke severity At 24 hours, 72 hours and 7 days post study drug administration or hospital discharge (whichever is sooner)
Other Modified Rankin Scale (mRS) score Measures the degree of disability or dependence in the daily activities of people who have suffered a stroke. At hospital discharge and 90 days post study drug administration
Other Mortality All-cause mortality At 90 days post study drug administration
Other Plasma levels of TBO-309 Plasma levels of TBO-309 will be measured to generate a population pharmacokinetic model At the end of infusion, and 1 and 3 hours post end of infusion
Other AKT phosphorylation relative to total AKT AKT phosphorylation relative to total AKT (pAKT/AKT) from platelets at the end of infusion At the end of infusion and 24 hours post end of infusion
Other Genomic markers Genomic markers of delayed TBO-309 clearance when individuals with delayed clearance are identified 24 hours post end of infusion
Other Genetic markers for stroke outcome Putative genetic markers for stroke outcome, including bleeding and reperfusion, following TBO-309 administration 24 hours post end of infusion
Primary Proportion of patients with intracerebral hemorrhage (ICH) Proportion of patients with ICH within 24-36 hours of study drug (TBO-309) commencement. This includes parenchymal haemorrhage type II based on the Heidelberg Bleeding Classification and any intracranial haemorrhage leading to an increase in NIHSS of 4 points or more. Within 24-36 hours of initiation of study drug
Secondary All bleeding All bleeding within 72 hours of study drug (TBO-309) administration according to a modified WHO scale Within 72 hours of study drug administration
Secondary All intracerebral hemorrhage (ICH) All ICH as demonstrated on CT/MRI up to 90 days Up to 90 days post study drug administration
Secondary All bleeding All bleeding reported up to 90 days according to a modified WHO scale Up to 90 days post study drug administration
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