D-Pharm has announced the successful interim analysis of the first group of stroke patients that completed follow-up in the phase II clinical study of THR-18. According to a company release, the interim report confirms the safety and tolerability of THR-18 at a dose of 0.18mg/kg, administered together with tissue plasminogen activator (tPA) in acute ischaemic stroke patients. The interim report gives a green light to proceed to recruit the second group of patients for treatment with THR-18 at a higher dose level.
THR-18 is novel drug-candidate designed to reduce or neutralise the life-threatening adverse effects of tPA, such as intracranial haemorrhage and brain oedema. The current study is the first double-blind, placebo-controlled, escalating single-dose, phase IIa study to assess the safety, pharmacokinetics, and pharmacodynamics of THR-18 in acute ischaemic stroke patients treated with tPA.
Gilad Rosenberg, D-Pharm’s vice president for Clinical Development comments: “It is reassuring to see that safety and tolerability of the first dose of THR-18 has been confirmed. It enables us to move forward and test the higher dose of 0.54mg/kg in stroke patients treated with tPA.”
THR-18 corresponds to a fragment of plasminogen activator inhibitor-1 (PAI-1), a natural inhibitor of tPA activity. THR-18 binds at one of the PAI-1 docking sites on tPA that leaves tPA’s catalytic activity intact. THR-18 binding uncouples the clot-dissolving properties of tPA from its deleterious non-fibrinolytic effects on the blood vessel wall, including intracranial haemorrhage and brain oedema.