Phase 3 Safety and Efficacy Study of ART-123 in Subjects With Severe Sepsis and Coagulopathy

Study is to evaluate if ART-123 given to patients who have severe sepsis complicated by at least one organ dysfunction and coagulopathy can decrease mortality.

Inclusion criteria

• Subject must be receiving treatment in an ICU, or in an acute care setting (e.g., ER, RR)
• Clinical objective evidence of bacterial infection and a known site of infection.
• Cardiovascular dysfunction or Respiratory Failure due to sepsis.
• Coagulopathy characterized by an INR >1.40 without other known causes.

Exclusion criteria

• Subject or Authorized Representative is unable to provide informed consent.
• Subject is pregnant or breastfeeding or intends to get pregnant within 28 days of enrolling into the study.
• Subject is of childbearing potential and does not have a negative pregnancy test.
• Subject is < 18 years of age.
• Subject has a known allergy to ART-123 or any components of the drug product.
• Subject is unwilling to allow transfusion of blood or blood products.
• Subject has an advance directive to withhold life-sustaining treatment.
• Subject has had previous treatment with ART-123.
• Body weight ≥ 175 kg.
• Platelets < 30,000/ mm3 for any reason, PT prolongation or thrombocytopenia that is not due to sepsis.
• Any surgery that is potentially hemorrhagic (e.g. intra-thoracic, intra-abdominal or non-traumatic orthopedic surgery of the femur or pelvis) that is completed within 12 hours prior to first dose of study drug, or ongoing impairment of hemostasis as a result of one of these procedures
• History of head trauma, spinal trauma, or other acute trauma with an increased risk of bleeding within 3 months prior to consent.
• Cerebral Vascular Accident (CVA) within 3 months prior to consent.
• Any history of intracerebral arteriovenous malformation (AVM), cerebral aneurysm, or mass lesions of the central nervous system.
• History of congenital bleeding diathesesor anatomical anomaly that predisposes to hemorrhage (e.g. hemophilia, hereditary hemorrhagic telangiectasia).
• Significant gastrointestinal bleeding within 6 weeks prior to consent.
• Subject is diagnosed with a known medical condition associated with a hypercoagulable state.
• Child-Pugh score of 10-15 (Class C)
• Portosystemic hypertension or known history of bleeding esophageal varices.
• History of solid organ, allogeneic bone marrow, or stem cell transplantation within the 6 months prior to consent.
• Acute pancreatitis where infection has not been documented by a positive blood or abdominal fluid culture or gram stain consistent with bacterial infection.
• Subjects with renal dysfunction defined as (a) Chronic renal failure requiring renal replacement therapy (RRT), or (b) Acute renal failure with onset of oliguria (urine output < 0.3 ml/kg/hr) > 48 hours prior to first dose of study drug whether receiving RRT or not
• Use of anticoagulants, antiplatelet agents, antithrombotics and thrombolytics within the 72 hours prior to first does of study drug.
• Life expectancy < 90 days.
• Current use of any chemotherapy agent likely to cause myeloablation (severe or complete depletion of bone marrow).
• Participation in another research study involving an investigational agent within 30 days prior to consent or projected study participation during the 28 days post study randomization.
• Confirmed or suspected endocarditis