Thrombolytic Science (TSI) has announced initiation of a phase 2 clinical trial to confirm the efficacy and safety of its sequential dual-treatment regimen of low-dose tissue plasminogen activator (tPA) and HisproUK (TSI’s mutant prourokinase [proUK]) in patients who have experienced ischaemic stroke. The study follows a recently completed phase 1 study that confirmed the safety and tolerability of TSI’s regimen in healthy volunteers (n=26).
The phase 2 study will be led by Diederik Dippel, co-director of the Erasmus MC Stroke Center in Rotterdam, The Netherlands, and will compare the TSI regimen against high-dose tPA monotherapy—the current standard of care—following an ischaemic stroke in patients with distal blood clots (i.e., those not retrievable with a surgical device). TSI also plans to initiate a phase 2 study of a pre-hospital dual-treatment regimen in heart attack patients, in 2019, for which the company is currently fund raising.
“Initiation of our phase 2 trial in ischaemic stroke is an important milestone for TSI, the medical community, and patients, as we take a step closer to possibly treating ischaemic stroke faster, safely, and with greater confidence,” said Alexis Wallace, TSI co-founder and CEO. “Having been greatly encouraged by the favourable results from our phase 1 trial of low-dose tPA and HisproUK, we are confident that the phase 2 study will further characterise the clinical utility of this next-generation clot-dissolving regimen. We look forward to exploring potential partnerships with pharmaceutical companies as we continue to advance the clinical development program for this promising dual-therapy.”
TSI’s flagship product, HisproUK, is a more stable and safer version of proUK. Created by recombinant technology, HisproUK is designed to modulate the high intrinsic activity of proUK, which led to bleeding in previous studies. TSI’s sequential dual-therapy regimen starts with low-dose tPA, which initiates the natural process of thrombolysis. Low dose tPA activates 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 natural and synergistic mechanisms enable the process of clot dissolution at low doses.
“Timely and rapid clot dissolution is key to treating ischaemic stroke, especially when the clots are distal, a situation that asks for medical treatment with a next generation thrombolytic drug to minimise complications and maximise chances of good outcome,” explained Dippel. “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.”