Severe sepsis and/or septic shock MedDRA version: 12.1 Level: LLT Classification code 10040047 Term: Sepsis
Conditions
Interventions
Product Name: CytoFab
Product Code: AZD9773
Pharmaceutical Form: Powder for solution for infusion
Current Sponsor code: AZD9773
Other descriptive name: Recombinant human TNFa immune Fab (ovine)
Concen
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Adults with a first episode of sepsis during this hospitalisation. 2. Objective evidence of infection that requires parenteral antibiotics. 3. At least 2 of 4 SIRS criteria in the 24 hours before organ dysfunction (must include either fever OR elevated white blood cells [WBC]). 4. Cardiovascular or respiratory dysfunction. Note: complete details are listed in Section 5.1 of the protocol. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Moribund (not likely to survive 24 hours) or significant comorbidities making survival for 3 months unlikely. 2. 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 30% of body surface area. 4. 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. 5. Pregnancy or plans to breast feed upon resolution of sepsis. Note: complete details are listed in Section 5.2 of the protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: The secondary objectives are to evaluate the effect of two different doses of AZD9773 versus placebo in patients with severe sepsis and/or septic shock on 7 day and 28 day mortality, the safety profile, morbidity, mortality at Day 90, health related Quality of Life (QoL) and the biological effect on plasma tumour necrosis factor alfa (TNFa) levels and relevant cytokines. There will also be an attempt to determine the population pharmacokinetics (PK) of AZD9773 and to assess the relationship between PK and measures of pharmacodynamic (PD) response, efficacy and adverse events (AEs) in patients with severe sepsis and/or septic shock. ;Main Objective: The primary objective is to evaluate the effect of two different doses of AZD9773 (CytoFab™) versus placebo on ventilator free days (VFDs) over 28 days in patients with severe sepsis and/or septic shock, who are receiving appropriate standard of care. ;Primary end point(s): Ventilator free days over the 28 day study period | — |
Countries
Belgium, Czech Republic, Finland, France, Spain
Outcome results
None listed