A multi-center, prospective, blinded validation study to assess the accuracy of a host-response based diagnostics for distinguishing between bacterIal and viral etiology in pediatric patients with lower respiratory tract infections and fever without source

In the past 70 years antibiotics have served as the first line of defense
against infectious diseases. However, antibiotics are only effective against
bacterial infections and are not the solution for infections caused by viruses
such as common colds or flu. Despite their contribution to healthcare,
antibiotics are currently recognized as the most misused drugs in the world
with global overuse estimated at 40%-70%, mostly due to the ineffectiveness of
current diagnostic solutions to distinguish between bacterial and viral
infections. Antibiotics misuse often causes preventable adverse events that
impact patient care and lead to the emergence of antibiotic-resistant bacteria,
one of the major threats to global health today. To address these challenges,
MeMed has been developing the ImmunoDx*, a novel technology that relies on the
best available detection system for differentiating between viruses and
bacteria - the body*s own immune system. The ImmunoDx* technology employs a
simple blood test that provides the physician, within two-hours, the
information he needs to decide whether to treat the patient with antibiotics or
not. This technology has been tested on over 1000 patients of different ages
and diseases and was found to be highly accurate and safe.
The current study is a non-interventional study and the participants do not
receive any investigational drug nor any experimental examination or procedure.
Therefore, the collected data in this study will not affect the diagnosis,
prognosis, or treatment of the participants. Participation includes the
collection of a teaspoon of blood and collection of a specimen using a nasal
swab. These procedures are common in the clinical practice and are widely
performed and possess no significant risk. By participating in the study, the
subjects impact the development of the ImmunoDx* technology, which is expected
to enable a future faster and more accurate diagnosis of infectious diseases as
well as more appropriate prescription of antibiotics. This will open the way to
improve treatment decisions in millions of patients around the world.

To externally validate the accuracy of a host-response based diagnostics for
differentiating between bacterial and viral etiology in pediatric patients aged
2 to 60 months with LRTI or FWS.

This is a prospective clinical validation study of a novel in-vitro diagnostic
(IVD) assay that will enroll 830 pediatric patients. The study will be
conducted in two stages: In stage A 50 patients will be enrolled with the aim
of verifying proper protocol execution including proper collection of patient
samples, accurate data retrieval and precise etiology determination. In stage B
780 patients will be enrolled with the aim of blinded validation of the
host-response based diagnostics using a fresh independent cohort of patients.
Patients enrolling into the study will be managed according to the current
standard of care (GCP) and per standard institutional procedures. Participation
in this study requires the collection of an additional blood sample and a nasal
swab sampling.
The investigated assay will classify each patient into one of three
categories: (i) bacterial immune response (i.e., pure bacterial infections and
mixed bacterial and viral co-infection), (ii) viral immune response, and (iii)
marginal immune response (inconclusive or non-infectious). It is estimated that
10-20% of the infected patients will have a marginal immune response. A
composite reference standard will be used in order to determine the diagnosis
of each patient. Specifically, all the clinical, radiological, microbiological
and laboratory data of each patient, will be recorded in a dedicated eCRF.
Based on this data, the diagnosis of each patient will be determined by a panel
of three independent pediatricians. Each pediatrician will be blinded to the
diagnosis of his peers and to the assay results. In the current study,
unanimous agreement between the experts (*consensus agreement*) will be
considered as the true diagnosis for the purpose of computing the assay
performance.

This study is designed to clinically validate a novel IVD. Patients
participating in the study do not receive any investigational drug nor any
experimental examination or procedure. The participants are exposed to the
minimal risk associated with the collection of a venous blood sample
(Phlebotomy) and with an additional, non-invasive nasal swab sampling.
The risk of standard phlebotomy may include infection, discomfort, pain or
subcutaneous bleeding which may be caused by venous rupture. The risk in nasal
swab sampling may include mainly discomfort or limited pain. The described
procedures are very common in the clinical practice and are widely performed.
In addition, the medical staff that will perform these procedures is highly
qualified and experienced in performing these tests.
The participants in the study are not expected to have any direct benefit
following their enrollment to the study. Study results will not affect the
diagnosis, prognosis, or treatment of the participants. Still, by participating
in the study, the subjects contribute to the validation of the host-response
based assay, which is aimed at differentiating between viral and bacterial
infections, and is expected to enable a faster and more accurate diagnosis of
infectious etiology as well as a more appropriate prescription of antibiotics.