US-based biopharmaceutical firm Mast Therapeutics has started a proof-of-concept Phase II clinical trial of its lead product candidate MST-188 in combination with recombinant tissue plasminogen activator (rt-PA) for treatment of patients with acute lower limb ischemia (ALI).
Around 60 patients are expected to be enrolled in the trial from about 15 sites within and outside the US with Rutherford Category IIa and IIb acute lower limb ischemia receiving catheter-directed rt-PA and the study will compare a high and low dose with MST-188 against rt-PA alone.
Mast chief executive officer Brian Culley said starting the ALI trial represents further execution of our long-term strategy to maximise 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 US, as well as clinical sites in multiple countries outside the US, in our pivotal phase 3 EPIC study in sickle cell disease," Culley said.
The trial's primary objectives are to assess the safety and efficacy of MST-188 in combination with rt-PA and whether MST-188 results in more rapid thrombolysis and tissue perfusion.
Its secondary objectives include evaluation of 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.
The objectives will be measured through up to 90 days of follow-up, while the trial is expected to take about 18 months to complete patient enrolment.
Mast Therapeutics senior vice-president of development Martin Emanuele said numerous experimental models, as well as clinical studies, show 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," Emanuele said.
The US Food and Drug Administration (FDA) has already granted orphan drug designation to MST-188 for treatment of ALI, an acute complication of peripheral arterial disease that describes a sudden decrease in perfusion of a limb, typically in the legs, that often threatens viability of the limb.
The company said that MST-188 is a cytoprotective, haemorheologic, anti-inflammatory and anti-thrombotic agent that has potential utility in diseases or conditions characterised by microcirculatory insufficiency.