Mast Therapeutics has initiated a phase II, clinical proof-of-concept study of MST-188 in combination with recombinant tissue plasminogen activator (rt-PA) in patients with acute lower limb ischemia.

Acute limb ischemia (ALI), an acute complication of peripheral arterial disease, describes a sudden decrease in perfusion of a limb, typically in the legs, that often threatens viability of the limb. Patients presenting with ALI have a poor short-term outlook, with 30-day amputation rates as high as 30% and a mortality rate around 15%. MST-188 for the treatment of ALI has been granted Orphan Drug Designation by the FDA.

Martin Emanuele, Ph.D., senior vice president, development, said, "Numerous experimental models, as well as clinical studies, demonstrate that MST-188 facilitates thrombolysis, repairs damaged cell membranes and improves microvascular blood flow. When combined with rt-PA, we believe these activities will translate into faster thrombolysis in patients with ALI and in other acute thrombotic events such as stroke, while at the same time reducing vessel re-occlusion, reperfusion injury and tissue necrosis."

Brian M. Culley, CEO, said, "Initiating the ALI study represents further execution of our long-term strategy to maximize the value of MST-188 through its development in multiple areas of significant unmet medical need.  I congratulate our clinical operations team for initiating this study consistent with our guidance, while at the same time opening 40 clinical sites in the U.S., as well as clinical sites in multiple countries outside the U.S., in our pivotal phase III EPIC study in sickle cell disease."

The phase II study will enroll approximately 60 patients from approximately 15 sites within and outside the U.S. with Rutherford Category IIa and IIb acute lower limb ischemia receiving catheter-directed rt-PA and compare a high and low dose of MST-188 against rt-PA alone. The primary objectives are to evaluate the safety and efficacy of MST-188 in combination with rt-PA and whether MST-188 results in more rapid thrombolysis and tissue perfusion. Secondary objectives are to assess the clinically-meaningful benefit of MST-188 in combination with rt-PA by measures such as duration of thrombolytic therapy, amputation-free survival, target limb re-interventions, and the need for endovascular or open surgical re-interventions. These objectives will be measured through up to 90 days of follow-up. The study is expected to take approximately 18 months to enroll.