Safety and Tolerability of Adjunctive TBO-309 in Reperfusion for Stroke
- Registration Number
- NCT05363397
- Lead Sponsor
- The George Institute
- Brief 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.
- Detailed 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 & Eligibility
- Status
- SUSPENDED
- Sex
- All
- Target Recruitment
- 80
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description TBO-309 30mg (25% of target dose) TBO-309 Following randomisation, 30mg TBO-309 will be administered at the same time as the rt-PA infusion or tenecteplase bolus (as part of intravenous thrombolysis) or as soon as practical. The allocated dose of TBO-309 will be given intravenously 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 Only one dose will be administered to the patient. TBO-309 120mg (100% of target dose) TBO-309 Following randomisation, 120mg TBO-309 will be administered at the same time as the rt-PA infusion or tenecteplase bolus (as part of intravenous thrombolysis) or as soon as practical. The allocated dose of TBO-309 will be given intravenously 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 Only one dose will be administered to the patient. TBO-309 180mg (150% of target dose) TBO-309 Following randomisation, 180mg TBO-309 will be administered at the same time as the rt-PA infusion or tenecteplase bolus (as part of intravenous thrombolysis) or as soon as practical. The allocated dose of TBO-309 will be given intravenously 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 Only one dose will be administered to the patient. TBO-309 60mg (50% of target dose) TBO-309 Following randomisation, 60mg TBO-309 will be administered at the same time as the rt-PA infusion or tenecteplase bolus (as part of intravenous thrombolysis) or as soon as practical. The allocated dose of TBO-309 will be given intravenously 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 Only one dose will be administered to the patient.
- Primary Outcome Measures
Name Time Method Proportion of patients with intracerebral hemorrhage (ICH) Within 24-36 hours of initiation of study drug 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.
- Secondary Outcome Measures
Name Time Method All intracerebral hemorrhage (ICH) Up to 90 days post study drug administration All ICH as demonstrated on CT/MRI up to 90 days
All bleeding Up to 90 days post study drug administration All bleeding reported up to 90 days according to a modified WHO scale
Trial Locations
- Locations (6)
Timothy Ang
🇦🇺Camperdown, New South Wales, Australia
Royal Adelaide Hospital
🇦🇺Adelaide, South Australia, Australia
Royal Melbourne Hospital
🇦🇺Parkville, Victoria, Australia
Liverpool Hospital
🇦🇺Liverpool, New South Wales, Australia
John Hunter Hospital
🇦🇺New Lambton Heights, New South Wales, Australia
Prince of Wales Hospital
🇦🇺Randwick, New South Wales, Australia