A Study to Compare the Efficacy and Safety of 2 Dosing Regimens of IV Infusions of AZD9773 (CytoFab™) With Placebo in Adult Patients With Severe Sepsis and/or Septic Shock

Inclusion criteria

• 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).
• Stage III or IV cancer.
• Haemopoietic or lymphoreticular malignancies not in remission.
• Receiving radiation therapy or chemotherapy.
• Stem cell, organ or bone marrow transplant in the past 6 months.
• Absolute neutrophil count <500 per μL.
• High dose steroids or other immunocompromising drugs.
• Concomitant diseases:

• Deep seated fungal infection or active tuberculosis.
• Cirrhosis with portal hypertension or Childs-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 IV due to heart failure or any disorder.
• Burns over > 30% of body surface area.
• 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 latex, papain, chymopapain.