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ANTIBODY
SAATELLITE Testing a new approach: antibodies against hospital-associated pneumonia
SAATELLITE is adding Phase II testing to the ongoing development of a monoclonal antibody against pulmonary Staphylococcus aureus infections. Immunological approaches towards the prevention of ventilator-associated pneumonia may circumvent current and future problems of antibiotic resistance.
T
he SAATELLITE project is dedicated to address the challenge by carrying out clinical trials of MEDI4893, a promising monoclonal antibody against S. aureus ‘alpha toxin’ (AT). Alpha toxin is a key toxin that is secreted by S. aureus bacteria during infection. The toxin kills a patient’s cells and damages tissues and organs, which helps microbes to spread and cause serious infections and disease. MEDI4893 is being developed by MedImmune, the global biologics research and development arm of AstraZeneca. Its first goal would be the prevention of hospital-associated pneumonia caused by S. aureus in patients who are at high risk of infection.
Antibodies Patients in intensive-care units who need mechanical ventilation will be tested for the presence of S. aureus in their lower airways before they have developed a full-fledged infection and pneumonia. If they are positive for the bug, they
would receive one intravenous dose of MEDI4893 antibody to help protect them from developing pneumonia. It is anticipated that no antibiotics would have to be used for preventing pneumonia, and prevention with the antibody would work against S. aureus, regardless of whether this bug is resistant to antibiotics. What’s more, this antibody approach itself is not expected to lead to new antibiotic resistance.
Next step After laboratory and animal studies, an earlier Phase I study in healthy volunteers found that MEDI4893 was generally safe to use. The SAATELLITE project will now take the next step: a randomised, double-blind, placebo-controlled Phase II study in actual patients who are at high risk of developing ventilator-associated pneumonia in an intensive-care unit. The study will test the safety, the pharmacokinetic and pharmacodynamic characteristics and
the efficacy of MEDI4893 in approximately 450 adult patients. The patients will be enrolled in approximately 60 to 80 ICUs, most of them in Europe.
Over 50 sites activated Since the study planning was launched in March 2014, more than 50 clinical sites have already been fully activated. The early birds were located in 8 countries: Belgium, Czech Republic, France, Germany, Greece, Hungary, Spain, and Switzerland. A small number of sites remains to be put online. As of February 4, 2016, 65 patients have been enrolled and randomized in the study and have received either one intravenous dose of MEDI4893 or a placebo.
BACKGROUND
ND4BB Topic #1B - Clinical development of compounds against Gram-positive
Staphylococcus aureus is a com-
estimates, an infection adds about
beforehand, prophylactically, at
mon cause of hospital-associated
$100,000 on average to one pa-
a lower dose. An alternative and
infections. Patients who undergo
tient’s treatment costs.
potentially more durable strategy
Project
would be to harness the body’s
COMBACTE-NET WP6B
surgery, for example, can develop
bacteria
infections around the site of their
Fewer options left
immune system to keep small,
surgical wounds. Patients in inten-
S. aureus infections are treated
environmental quantities of S. au-
sive-care units (ICUs) also are at a
with antibiotics. Ever more often,
reus from growing into full-blown
double-blind, placebo-controlled,
high risk for developing serious S.
however, the infection-causing
infections. To date, however, no
single-dose, dose-ranging study
aureus infections. Infections can
strain is resistant to one or more
active immunization therapies (i.e.
of the efficacy and safety of
invade their lungs, blood, bones,
antibiotics. Methicillin-resistant
vaccines) or passive immuniza-
MEDI4893, a human monoclonal
joints, heart, or meninges, the pro-
Staphylococcus aureus (MRSA)
tion therapies (i.e. antibodies) are
antibody against Staphylococcus
tective layer around the brain.
is a prominent example, as are
available.
glycopeptides-resistant strains.
Description A Phase II randomized,
aureus alpha toxin in mechanically ventilated adult subjects.
Mechanical ventilation
As a result, doctors today are left
Objective
The most common hospital-asso-
with significantly fewer treatment
Test safety, pharmacokinetic and
ciated infection is pneumonia. It
options than some years ago.
particularly strikes intensive-care
"Doctors today are left with significantly fewer treatment options than some years ago"
pharmacodynamic characteristics and efficacy of MEDI489 in high-risk patients.
unit patients who receive mechani-
The challenge
cal ventilation to help them breath.
Despite the ongoing emergence
Hospital-associated pneumonia
and spread of resistance, antibi-
is a serious and costly condition,
otics still form our main line of
For more information please contact
with high levels of mortality. It is
defense against post-surgical S.
the Academic WP Lead Bruno Francois at
most often caused by S. aureus.
aureus infections and ventilator-
bruno.francois@chu-limoges.fr or
According to a recent study, almost
associated pneumonias. They are
one in four mechanically ventilated
either given when an infection has
Hasan Jafri
ICU patients develop pneumonia
been established or, in the case
MedImmune, AstraZeneca
from S. aureus. According to some
of surgery, by administering them
EFPIA WP Lead Hasan Jafri at jafrih@medimmune.com.
Status Ongoing; recruiting patients in up to 80 centers. WP Leads Bruno Francois Limoges University Hospital