Date: 2014-11-04
Type of information: Interim results
phase: 2
Announcement: interim results
Company: D-Pharm (Israel)
Product: THR-18
Action
mechanism: THR-18 is a synthetic therapeutic peptide derived from plasminogen activator inhibitor-1 (PAI-1). 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 hemorrhage and brain edema.
Disease: acute ischemic stroke
Therapeutic area: Cerebrovascular diseases
Country:
Trial details:
Latest
news: * On November 4, 2014, D-Pharm reported top-line safety results following completion of its Phase 2 clinical study of THR-18 in acute ischemic stroke (AIS) patients treated with tissue plasminogen activator (tPA). The study has successfully defined the maximal tolerated and safe dose of THR-18 in AIS patients. Compared to placebo, THR-18 significantly decreased the number of AIS patients with brain edema and intracranial hemorrhage. This Phase 2 clinical study of THR-18 was the first double-blind, placebo-controlled, escalating single-dose, study to assess the safety, pharmacokinetics, and pharmacodynamics of THR-18 (0.18 or 0.54 mg/kg) in thirty AIS patients treated with tPA. The main pre-specified endpoints in the study include the numbers of patients with ICH and brain edema, and clinical stroke outcome assessed by the modified Rankin scale (mRS) and the NIH stroke scale (NIHSS) up to 30 days following stroke. The data indicate that in contrast to the placebo group, no patients treated with THR-18 had an intracranial hemorrhage, (p=0.02). Similarly, THR-18 reduced by more than twice the occurrence of brain edema (p<0.05). These results correlate well with the interim analysis performed on the first treatment groups that completed the 30 day follow-up period. The interim data show that THR-18 markedly reduces the degree of disability and enhances neurological recovery of stroke patients compared to placebo. * On March 4, 2014, D-Pharm has announced the successful interim analysis of the first group of stroke patients that completed follow-up in the Phase 2 clinical study of THR-18. 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 ischemic 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 neutralize the life-threatening adverse effects of tPA, such as intracranial hemorrhage (ICH) and brain edema. The current study is the first double-blind, placebo-controlled, escalating single-dose, Phase 2a study to assess the safety, pharmacokinetics, and pharmacodynamics of THR-18 in acute ischemic stroke patients treated with tPA.
