AstraZeneca announced that it has commenced dosing patients in a global Phase IIb study to compare the efficacy and safety of AZD9773 (CytoFab) with placebo in adult patients with severe sepsis and/or septic shock receiving best supportive care.
Sepsis occurs when the body’s immune system sets off a chain reaction and “overreacts” to an infection. Rather than being localized to the site of infection, the severe immune response develops throughout the body. A person suffering from sepsis can rapidly deteriorate, with the systemic response to an infection distorting the body’s natural balance and damaging one or more vital organs. A patient can continue to deteriorate into septic shock, where blood pressure falls dangerously low and many organs malfunction because of inadequate blood flow. Sepsis remains a significant problem in medical management, with an annual worldwide incidence of about 3 million and a 30 percent mortality rate. Current treatment options for patients are extremely limited and there are few products in late stage development.
The Phase IIb study is a multicentre, randomized, double-blind, placebo controlled trial in 300 patients which will evaluate the efficacy of two intravenous dosing regimens of AZD9773. The primary outcome measure will be the number of ventilator-free days over 28 days following first dose. Secondary outcome measures include 7 and 28 day patient mortality and characterization of the safety and tolerability of AZD9773.
AZD9773 is a first in class anti-TNF-alpha polyclonal antibody fragment (Fab) product. This Phase IIb study follows successful completion of a 74-patient Phase IIa study by AstraZeneca in 2009. In a previous Phase II clinical study in 81 patients with severe sepsis, D-CytoFab, a closely related product to AZD9773, was well tolerated and significantly reduced the number of days patients spent on a ventilator and in the intensive care unit compared with patients on placebo.
AstraZeneca has also initiated a separate Phase II study of AZD9773 in Japan. This is a dose escalation study to assess the safety, tolerability and pharmacokinetics of intravenous infusions of AZD9773 in Japanese patients with severe sepsis and/or septic shock.
Under the terms of the global development and commercialization agreement for AZD9773, BTG is responsible for bulk drug manufacturing, including the supply of clinical trial materials, and AstraZeneca is responsible for development and commercialization of AZD9773.