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

Study Overview
=================
Brief 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.

Official Title
-----------------
A MultiCentre, Randomized, Double-blind, Placebo-controlled Phase IIb Study to Compare the Efficacy and Safety of Two Dosing Regimens of Intravenous Infusions of AZD9773 (CytoFab™) in Adult Patients With Severe Sepsis and/or Septic Shock

Conditions
-----------------
Severe Sepsis, Septic Shock

Intervention / Treatment
-----------------
* Drug: AZD9773
* Drug: Placebo


Participation Criteria
=================
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: 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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>AZD9773 250/50 units/kg | Drug: AZD9773<br>* A single loading dose following by up to 9 maintenance doses; doses to be given every 12 hours over a period of 5 days<br>* Other names: CytoFab™;|
| Experimental: 2<br>AZD9773 500/100 units/kg | Drug: AZD9773<br>* A single loading dose following by up to 9 maintenance doses; doses to be given every 12 hours over a period of 5 days<br>* Other names: CytoFab™;|
| Placebo Comparator: 3<br> | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ventilator-free Days (VFDs) Over 28 Days | Number of ventilator-free days (VFDs) | Over 28 days following first dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 7-day Mortality | Number of patients who died over 7 days | Over 7 days following first dose | 
| 28-day Mortality | Number of patients who died over 28 days | Over 28 days following first dose | 
| Safety and Tolerability | Number of patients with treatment-emergent adverse events | All study visits (over 90 days following first dose) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
severe sepsis, TNF neutralisation, septic shock patients