A Study to Assess Safety,and Tolerability of 2 Doses of AZD9773 (CytoFab™) in Japanese With Severe Sepsis/Septic Shock

Inclusion criteria

• Japanese adults with a first episode of sepsis during this hospitalisation and objective evidence of infection that requires parenteral antibiotics.
• At least 2 of 4 SIRS criteria in the 24 hours before organ dysfunction (must include either fever OR elevated white blood cells [WBC])
• Cardiovascular or respiratory dysfunction.

Exclusion criteria

• Immunocompromising comorbidities or concomitant medications:

• Advanced human immunodeficiency virus (HIV) infection (CD4 ≤50/mm3).
• Haemopoietic or lymphoreticular malignancies not in remission.
• Receiving radiation therapy or chemotherapy.
• Any organ or bone marrow transplant within the past 24 weeks.
• Absolute neutrophil count <500 per μL.
• High dose steroids or other immunocompromising drugs.
• Concomitant diseases:

• Deep-seated fungal infection or active tuberculosis.
• Severe chronic liver disease associated with portal hypertension, cirrhosis, chronic ascites or Child-Pugh class C.
• History of chronic hypercarbia, respiratory failure in past 6 months or use of home oxygen in the setting of severe chronic respiratory disease.
• Neuromuscular disorders that impact breathing/spontaneous ventilation.
• Quadriplegia.
• Cardiac arrest in the past 30 days.
• New York Heart Association functional Class III or IV due to heart failure or any disorder.
• Burns over > 30% of body surface area in the past 5 days.
• Medication and allergy disqualifications.

• Treatment with anti-TNF agents within the last 8 weeks.
• Previously received ovine derived products (CroFab™, DigiFab™).
• Sheep product allergy or allergy to papain, chymopapain.