D-Pharm Ltd., a clinical stage, technology-driven biopharmaceutical company, has received the approval from the regulatory authorities in the Ukraine to commence a phase IIa clinical study of THR-18, to be given with the clot buster drug tissue plasminogen activator (tPA), in patients with acute ischemic stroke. THR-18 is a synthetic therapeutic peptide derived from plasminogen activator inhibitor-1 (PAI-1).
This clinical study is a double-blind, placebo-controlled, escalating single-dose, phase IIa study to assess, for the first time, the safety, pharmacokinetics and pharmacodynamics of THR-18 given with tPA to patients with acute ischemic stroke.
The study will enroll 30 patients divided into three escalating dose groups, each group with an active and placebo arm, which will be conducted at a single site in Kharkov, Ukraine. The site initiation is scheduled for October 22, 2013. THR-18 has successfully completed a phase I clinical study in healthy volunteers.
Tissue plasminogen activator is approved for treatment of myocardial infarction, pulmonary embolism and it is the only drug approved by the FDA and EMA for treatment of acute ischemic stroke. However, in stroke, tPA is used, on average, in less than five per cent of patients and within a narrow time window, due to the risk of life-threatening adverse effects, in particular, intra-cerebral hemorrhage (ICH).
D-Pharm’s VP for clinical development, Dr Gilad Rosenberg commented, “We are excited to continue the clinical testing of THR-18. THR-18 is designed to neutralize the harmful effects of tPA and thus significantly increase the patient population eligible for thrombolytic therapy. We’ve ensured that precious minutes to treatment will not be lost, by developing a new THR-18 formulation suitable for easy preparation and co-administration with tPA. This study, in thirty patients, will provide crucial information regarding safe doses of THR-18 that may be administered in this critically ill population.”
THR-18 corresponds to a fragment of plasminogen activator inhibitor-1 (PAI-1), a natural inhibitor of tPA. THR-18 binds at one of the PAI-1 docking sites on tPA that leaves tPA’s catalytic activity intact. This binding uncouples the clot-dissolving properties of tPA from its deleterious non-fibrinolytic effects, including ICH and brain edema.
Results from a survey of neurologists and payors suggest that, if approved, up to 90 per cent of patients treated with tPA would also receive treatment with THR-18. THR-18, therefore, has enormous potential in acute ischemic stroke (AIS), as well as in the other tPA markets of myocardial infarction and pulmonary embolism.
D-Pharm assumed responsibility for THR-18 development in 2012 when D-Pharm wholly acquired the clinical stage company Thrombotech Ltd. D-Pharm is committed to the development of THR-18, and will continue to leverage its clinical development experience to advance this product to market.
D-Pharm is a clinical stage, technology-driven biopharmaceutical company developing proprietary products for treatment of CNS disorders.