ImaRx Therapeutics, Inc. would suspend further enrolment in its TUCSON (Transcranial Ultrasound in Clinical SONolysis) clinical trial in patients with acute ischemic stroke.
The TUCSON trial is a phase I/II randomised, placebo controlled clinical trial. This trial is designed to evaluate the safety, tolerability and activity of four escalating doses of MRX-801 microbubbles and ultrasound as an adjunctive therapy to tissue plasminogen activator (tPA) treatment in subjects with acute ischemic stroke. The trial design includes four dose cohorts of 18 subjects each randomised to receive either treatment (MRX-801, ultrasound and tPA) or control (tPA alone). Safety is assessed by the incidence of symptomatic intracranial haemorrhage (sICH) within 36 hours following the initiation of treatment.
Activity of the component is assessed by recanalisation, defined as increased blood flow in the occluded artery, which is viewed by clinicians as a key factor in improving the probability of complete clinical recovery. Improvements in functional and neurological outcomes are measured by improvement in NIHSS and Modified Rankin scores, widely accepted instruments used to assess clinical outcomes for stroke. To date, the company has completed enrolment of all 18 subjects in Cohort 1 (12 treated and 6 control) and 17 subjects in Cohort 2 (11 treated and 6 control).
Cohort 1 evaluated one vial of MRX-801. There were no unexpected safety events and there were signs of improved recanalisation in treated patients compared to controls. In clinical recovery endpoints, the number and proportion of patients who experienced dramatic or early clinical recovery were higher in the treatment group compared to controls. Clinical recovery at 24-36 hours was roughly equivalent in both groups as was neurological improvement at 24-36 hours. Clinical evaluations at 90 days post-treatment favoured the treatment group.
Cohort 2: The second dose cohort evaluated two vials of MRX-801. Activity data from subjects in this cohort is currently being collected and will be available in the second quarter of 2008. From a preliminary evaluation of the safety data that have been collected to date, there were a greater number of intracranial haemorrhage events observed in subjects receiving treatment relative to controls.
Upon a review of these data, consultation with the Data and Safety Monitoring Board and review by the TUCSON Steering Committee, the company has elected to suspend further enrolment in the study and intends to conclude the study at this stage.
According to Garen Manvelian, MD, chief medical officer, ImaRx, "We are very encouraged by the data from Cohort 1 and are pleased to have observed activity with the lowest dose of MRX-801. We have learned what we set out to accomplish through this clinical trial." Dr Manvelian further stated, "It is well known that tPA has an associated risk of bleeding. We believe that the intracranial haemorrhage events, such as those observed in Cohort 2, may be reduced by eliminating tPA in our future SonoLysis clinical studies in stroke."
Paul Sierzenski, MD, North American Principal Investigator for the TUCSON study, stated, "As an Emergency Physician, I diagnose and treat a significant number of patients who are victims of stroke. Physicians of all specialties recognize the devastating impact this disease has on our patient's lives. ImaRx's SonoLysis therapy employs a fundamentally unique approach to the treatment of ischemic stroke. I am excited about the opportunity to participate in future clinical trials to advance the development of this important stroke therapy."
The company intends to initiate its next SonoLysis clinical study in the second half of 2008. To avoid the inherent bleeding risk associated with tPA, the company plans to conduct its future clinical trials under its SEDONA program, MRX-801 microbubbles and ultrasound, without tPA. Prior to commencing the trials, the company also aims to conduct its previously announced pre- clinical studies designed to further optimise the ultrasound delivery parameters.
"Concluding the TUCSON study ahead of schedule allows us early access to data and helps us to reduce our expenses," said Bradford A. Zakes, president and CEO, ImaRx Therapeutics. "We look forward to the continued advancement of our SonoLysis technology for stroke under our SEDONA program."
ImaRx Therapeutics is a biopharmaceutical company developing and commercialising therapies for vascular disorders. The company's research and development efforts are focused on therapies for stroke and other vascular disorders using its proprietary microbubble technology.