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
Condition: Severe Sepsis; Septic Shock
MeSH terms: Sepsis; Toxemia; Shock, Septic; Shock
Intervention: AZD9773; Placebo
Intervention description: A single loading dose following by up to 9 maintenance doses; doses to be given every 12 hours over a period of 5 days; Placebo
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 300.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: severe sepsis; TNF neutralisation; septic shock patients

Summary:

      The primary purpose of this study to evaluate the effect of two different doses of AZD9773
      (CytoFab™) versus placebo on ventilator free days (VFDs) over the first 28 days after the
      start of dosing with AZD9773 in patients with severe sepsis and/or septic shock, who are
      already receiving appropriate standard of care treatment for sepsis.
    

Eligibility criteria:

        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:

               1. Advanced human immunodeficiency virus (HIV) infection (CD4 ≤50/mm3).

               2. Stage III or IV cancer.

               3. Haemopoietic or lymphoreticular malignancies not in remission.

               4. Receiving radiation therapy or chemotherapy.

               5. Stem cell, organ or bone marrow transplant in the past 6 months.

               6. Absolute neutrophil count <500 per μL.

               7. High dose steroids or other immunocompromising drugs.

          -  Concomitant diseases:

               1. Deep seated fungal infection or active tuberculosis.

               2. Cirrhosis with portal hypertension or Childs-Pugh Class C.

               3. History of chronic hypercarbia, respiratory failure in past 6 months or use of
                  home oxygen in the setting of severe chronic respiratory disease.

               4. Neuromuscular disorders that impact breathing/spontaneous ventilation.

               5. Quadriplegia.

               6. Cardiac arrest in the past 30 days.

               7. New York Heart Association functional Class IV due to heart failure or any
                  disorder.

               8. Burns over > 30% of body surface area.

          -  Medication and allergy disqualifications.

               1. Treatment with anti-TNF agents within the last 8 weeks.

               2. Previously received ovine derived products (CroFab™, DigiFab™).

               3. Sheep product allergy or allergy to latex, papain, chymopapain.