A randomized, open label, two-way cross-over study to determine the pharmacokinetics and safety of GP2015 following a single subcutaneous injection by an autoinjector and by a pre-filled syringe in healthy male subjects

GP2015 is a new investigational compound that is being developed as a copy of
Enbrel®, a drug already approved for the treatment of certain autoimmune
diseases, including Rheumatoid Arthritis and Psoriasis. The aim for GP2015 is
to be approved for the treatment of the same autoimmune diseases as Enbrel®.
Autoimmune diseases arise from an abnormal immune response of the body against
substances and tissues normally present in the body. GP2015 inhibits
inflammatory reactions by binding to certain proteins in the body, which
decreases the immune response. Specifically, it interferes with the working of
a cytokine involved in inflammation, called TNF-alpha (a cytokine is a small
protein involved in the communication between many different kinds of cells in
the human body).The active substance of GP2015 (and Enbrel®) is called
etanercept, and consists of several parts (building blocks) that are naturally
present in the human body. Therefore, the drug is called *a biological*. GP2015
is not registered as a drug, but has been given to humans before in other
clinical studies.

Primary objective:
To demonstrate bioequivalence of GP2015 applied by an autoinjector
(delta-GP2015_50) and a pre-filled syringe (PFS) as single subcutaneous
injection of 50 mg to healthy adult male subjects

Secondary objectives
- To study and compare delta-GP2015_50 and pre-filled syringe (PFS) for the PK
parameters by weight catagory
- To evaluate the overall safety, tolerability and local tolerance

The study will be conducted in maximally 51 healthy male volunteers, divided
into two periods. After each period, the volunteers will come back for five
ambulant visits.

During the study, blood samples are regularly taken for PK and ADA (please
refer to the protocol). Also physical examinations, ECGs and clinical chemical
laboratory will be performed on several pre-defined timepoints..

On day 1 of each period, a single dose of 50mg GP2015 subcutaneous injection
via an auto-injector or an syringe is administered.

All potential drugs cause adverse events; the extent to which this occurs
differs. GP2015 is a drug that affects the immune system, and may lower the
ability of the immune system to fight infections or make any infection that a
person may have worse (including serious infections). Allergic reactions may
happen, with symptoms like hives, swelling of the face, eyes, lips or mouth, or
trouble with breathing.

GP2015 has been given to healthy volunteers before, in clinical studies that
compared it to Enbrel®. In those studies, the most frequent adverse events were
infections of the nose and throat, headache, injection site reaction, and
throat pain. There were also cases of reduction of the number of neutrophils (a
kind of white blood cell involved in fighting infections). All these adverse
events occurred with similar frequency after administration of GP2015 or
Enbrel®.

Enbrel® is approved in many countries for the treatment of several autoimmune
diseases, and therefore a significant amount of safety information has been
collected about its use with patients. The most frequently reported adverse
reactions with Enbrel® are: injection site reactions (such as pain, swelling,
itching, reddening and bleeding at the puncture site), infections (such as ear
nose and throat infections, bronchitis, bladder infections and skin
infections), allergic reactions, development of auto antibodies (antibodies
against substances and tissues of the body), rash with or without itching,
and/or fever.

More serious adverse reactions have been reported with Enbrel®. These include
the occurrence of cancer (skin cancer, blood cancer and solid tumors), serious
infections including tuberculosis and reactivation of viral hepatitis, and
serious allergic reactions. Nervous system problems have been reported leading
to symptoms including numbness and weakness of the body, vision problems and
dizziness. Blood problems may occur and your body may not make enough of the
blood cells that help fight infections or help to stop bleeding. Symptoms may
include persistent fever, bruising or bleeding very easily, or looking very
pale. New heart failure or worsening of a pre-existing heart failure may occur
with symptoms like shortness of breath, swelling of the ankles or feet, or
sudden weight gain.

Most of the adverse events reported for Enbrel® occurred in patients being
treated for pre-existing inflammatory diseases like arthritis and psoriasis. In
this study with healthy volunteers, only two doses of GP2015 will be
administered. Therefore, it is thought that the probability of these events to
happen is lower, and no serious adverse effects are expected.