Phase 2 Trial Evaluates Thrombolytic Science's HisproUK With Low-Dose tPA to Treat Ischemic Stroke
September 5, 2018—Thrombolytic Science, LLC (TSI) announced the initiation of a phase 2 clinical trial to confirm the safety and efficacy of its sequential dual-treatment regimen of low-dose tissue plasminogen activator (tPA) and HisproUK in patients who have experienced ischemic stroke. HisproUK is the company's mutant prourokinase (proUK).
The phase 2 study will be led by Professor Diederik Dippel, MD. Prof. Dippel is Co-Director of the Erasmus MC Stroke Center in Rotterdam, The Netherlands. The study follows a recently completed phase 1 study that confirmed the safety and tolerability of TSI’s regimen in healthy volunteers (n = 26).
In the phase 2 study, the TSI regimen will be compared to high-dose tPA monotherapy—the current standard of care—after an ischemic stroke in patients with distal blood clots (ie, those not retrievable with a surgical device). TSI also plans to initiate a phase 2 study in 2019 to evaluate prehospital dual-treatment regimen in heart attack patients.
According to TSI, HisproUK is a more stable and safer version of proUK. HisproUK is created by recombinant technology and designed to modulate the high intrinsic activity of proUK, which has led to bleeding in previous studies.
The company explained that its sequential dual-therapy regimen starts with low-dose tPA, which initiates the natural process of thrombolysis, activating plasminogen into plasmin, which degrades the surface of the clot. HisproUK then activates two additional plasminogen binding sites on the degraded clot surface, a step that accelerates thrombolysis. Together, these mechanisms enable the process of clot dissolution at low doses.
Prof. Dippel stated in TSI's announcement, “Timely and rapid clot dissolution is key to treating ischemic stroke, especially when the clots are distal, a situation that asks for medical treatment with a next-generation thrombolytic drug to minimize complications and maximize chances of good outcome. That makes this phase 2 trial particularly important, as we hope to show that sequential dual-therapy with low-dose tPA and HisproUK can initiate thrombolysis safely and effectively.”