A Phase 2 Study of VLX-1005 Versus Placebo in Suspected Heparin Induced Thrombocytopenia

Over 12 million patients are treated with heparin each year in the United States. Heparin

induced thrombocytopenia (HIT) is a recognized complication of heparin therapy and is

characterized by the formation of antibodies to heparin and platelet factor 4 (PF4). The

scale of the clinical problem is illustrated by cardiopulmonary bypass patients, half of

whom develop antibodies to PF4/heparin complexes. In a significant proportion of such

seropositive HIT patients, these antibodies will bind to and activate platelets,

resulting in a drop in the number of platelets (thrombocytopenia) and activation of the

coagulation (clotting) system. Formation of clots in this manner can lead to stroke,

heart attacks, damage to internal organs or to limbs, and even death.

The current standard of care with anticoagulants such as argatroban or bivalirudin have

not proven effective in reducing poor outcomes in HIT: major morbidity and death rates

remain high (> 20%). In addition, these anticoagulants increase the risk of major

bleeding (~20%) which can prove to be a fatal complication of such therapy.

VLX-1005 has been developed to address the major unmet clinical need for safer, more

effective therapy for HIT. VLX-1005 is a drug that blocks the 12-lipoxygenase (12-LOX)

pathway that is believed to be responsible for platelet activation in HIT. In animal

models of HIT, VLX-1005 can prevent or treat HIT and halt the development of both

thrombocytopenia and abnormal blood clots. The drug has not been associated with

increased bleeding in either animals or healthy human volunteers.

The current study will enroll patients suspected of having HIT by clinical measures (4T

score) and by laboratory testing (heparin-PF4 immunoassay). Patients will be randomly

assigned in a double-blind fashion to either VLX-1005 intravenously or placebo. All

patients will receive current guideline mandated therapy for HIT that will include the

standard of care anticoagulation: either argatroban or bivalirudin. Patients will be

treated for 7 to 14 days until the platelet count has recovered into the normal range.

The study will measure important outcomes including platelet count recovery time, stroke,

pulmonary embolus, deep vein thrombosis, myocardial infarction, limb and organ injury,

and major bleeding.