- Poster presentation
- Open Access
Safety and tolerability of an ovine-derived polyclonal anti-TNFα Fab fragment (AZD9773) in patients with severe sepsis
© Morris et al. 2011
- Published: 1 March 2011
- Severe Sepsis
- Placebo Administration
- Laboratory Safety
- Underlying Illness
- Significant Medical Problem
Sepsis remains a significant medical problem. TNFα is a central cytokine in sepsis pathophysiology. We conducted a phase IIa trial in patients with severe sepsis to assess the safety and tolerability of an intravenously infused ovine-derived polyclonal anti-TNFα Fab fragment (AZD9773).
This was a double-blind, placebo-controlled, dose-escalation trial (NCT00615017) with 2:1 randomisation (active:placebo). Two single-dose cohorts (50 units/kg and 250 units/kg) and three multiple-dose cohorts (250 units/kg followed by nine doses of 50 units/kg every 12 hours, 500 units/kg followed by nine doses of 100 units/kg, 750 units/kg followed by nine doses of 250 units/kg) were studied. Safety was assessed by monitoring adverse events (AEs), mortality, and laboratory safety measures, including formation of human anti-sheep antibodies (HASA) and their association with AEs.
Safety outcomes with AZD9773 administration
Single-dose cohorts combined (n= 17)
Multiple-dose cohorts combined (n= 30)
Placebo (n= 23)
Mortality, n (%)
Any treatment-emergent AEs
Treatment-emergent AEs related to study drug
Patients with any serious AEs
Administration of AZD9773 in patients with severe sepsis reduced circulating TNFα levels and had a safety profile similar to placebo administration. A larger randomised phase IIb clinical trial (NCT01145560) is ongoing to further characterise the safety and efficacy of AZD9773 in patients with severe sepsis.
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.