Clinical Accelerator is pleased to announce the timely completion of an interesting trial it has been conducting for D-Pharm in patients with ischaemic stroke at the State Medical Preventive Institution “Central Clinical Hospital of Ukrzaliznytsia”, Kharkov, Ukraine (1).
This study tested D-Pharm’s experimental drug “THR-18” given together with thrombolytic (‘clot-busting’) tissue plasminogen activator (tPA) therapy for the treatment of stroke with the aim of limiting unwanted effects associated with the tPA and increasing confidence and safety of this underused treatment.
Ischaemic strokes result from blockage of blood supply by blood clots forming within vessels supplying the brain. Treatment, which should be instigated as soon as possible after onset of the event, can be aimed at breaking up the blood clot(s) and renewing the blood flow with intravenous thrombolytic agents such as tPA (the only current FDA-approved agent for acute stroke). However, tPA can cause adverse effects such as intracranial haemorrhage as well as some other ‘non-haemorrhagic’ effects, which has limited confidence in its use. THR-18 is a synthetic (‘18 mer’) peptide derived from the sequence of human plasminogen activator inhibitor 1 (PAI-1). It has the ability to bind to tPA such that the beneficial clot-dissolving properties of tPA are preserved while its deleterious and unwanted non-fibrinolytic effects are reduced.
This Phase IIa trial is primarily a safety, pharmacokinetics and pharmacodynamics study of THR-18 in at different doses compared with placebo – both in conjunction with tPA. Blood markers of brain damage (S100B and matrix metalloproteinase-9), blood chemistry and haematology were assessed along with vital signs, ECG and brain CT scans, up to 30 days after treatment in 30 patients. Endpoints included the numbers of patients with intra-cerebral haemorrhage (ICH) and brain oedema, and clinical stroke outcome (modified Rankin scale and the NIH stroke scale)
The initial data indicate that, in contrast to the placebo group, no patients treated with THR-18 had an intracranial haemorrhage. Similarly, THR-18 reduced by more than twice the occurrence of brain oedema. 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.
The study has also successfully defined the maximal tolerated and safe dose of THR-18 in patients with acute ischaemic stroke (2).
Playing an important part in the successful completion of this trial of 30 patients within tight timelines – it commenced only in October last year – was Clinical Accelerator’s dedicated patient enrolment support managers, who work alongside our clinical operations department. A single site was selected to help increase the proficiency of the team in this complex trial as well as the homogeneity of the data. The site in question was carefully chosen for their expertise and their realistic potential for patient enrolment, which was augmented by the implementation of our locally-tailored and study-specific patient enrolment strategies. These included working closely with the investigators and ambulance physicians, who we’d like to thank for their co-operation, and which all helped accelerate patient enrolment for this challenging stroke study at this site.
D-Pharm is a drug-development company focused on innovative drug-candidates for the treatment of central nervous system (CNS) conditions, in particular those for degenerative and age-related disorders. THR-18 is one of three novel agents in development (DP-VPA for the treatment of epilepsy, migraine and manic depression and DP-b99 for protection of cells under stress in acute pancreatitis are the other two).
Clinical Accelerator has been delighted to work with such an inspirational team and wish them well with the further development of their products.
- Double-blind, Placebo-controlled, Escalating Single-dose, Phase 2a Study to Assess the Safety, Pharmacokinetics, and Pharmacodynamics of THR-18 in Subjects With Acute Ischemic Stroke and Treated With tPA : http://www.clinicaltrials.gov/ct2/show/NCT01957774?term=d-pharm+ukraine&rank=1