A randomized, open-label, two-period, two-sequence, single-dose, cross-over study to compare the pharmacokinetics, safety, and tolerability of the auto injector and pre-filled syringe of SB4 in healthy male subjects.

SB4 is a compound which is already approved as a drug in the European Union
(EU), the Republic of Korea, Canada and Australia for the treatment of several
autoimmune diseases including rheumatoid arthritis and psoriasis. In the EU,
the trade name for SB4 is Benepali® and in the Republic of Korea, Canada and
Australia the trade name for SB4 is Brenzys®. The active substance of SB4 is
called *etanercept*. Etanercept is a fusion protein which is produced by
joining 2 small pieces of DNA that code for 2 separate human proteins.
Etanercept is a compound that is composed of natural proteins and therefore is
also called a *biological*.

Autoimmune diseases arise from an abnormal immune response of the body against
substances and tissues normally present in the body. The most important
characteristic of an autoimmune disease is an inflammation reaction, which can
cause redness, heat, pain, and swelling. SB4 inhibits inflammatory reactions by
binding to a certain protein in the body, which decreases the immune response.
Specifically, SB4 interferes with the working of a cytokine involved in
inflammation, called TNF-* (a cytokine is a small protein involved in the
communication between different kinds of cells in the human body).

Benepali® and Brenzys® are approved as drugs that are administered as a
subcutaneous (under the skin) injection using a pre-filled syringe. With a
pre-filled syringe the drug is delivered through a needle which is inserted
manually into the skin. The Sponsor has now developed a method to administer
SB4 as a subcutaneous injection using an autoinjector. An autoinjector contains
a pre filled syringe with a needle which is automatically inserted by pressing
the autoinjector against the skin. In this study, SB4 will be administered
using both the autoinjector and the pre filled syringe. As such, it can be
investigated if the volume of SB4 administered to a volunteer is the same for
the two methods of administration.

The main purpose of this study is to compare the pharmacokinetic
characteristics of SB4 after subcutaneous injection in the abdomen using an
autoinjector and a prefilled syringe. The pharmacokinetics of a compound looks
at how the compound gets into the bloodstream, how it is distributed throughout
the body, as well as the chemical changes the drug undergoes as it is broken
down by the body. It also examines the effects of the breakdown products and
how they are passed out of the body.

A second purpose of this study is to test how safe SB4 is and what (if any)
side effects are observed when it has been taken.

Finally, the formation of antibodies against SB4 will be investigated.

This study will be conducted in a maximum of 46 healthy male volunteers.

The actual study will consist of 2 periods (Periods 1 and 2) during each of
which the volunteers will stay in the clinical research center for 6 days (5
nights): from the afternoon of Day -1 (1 day before administration of the study
compound [Day 1]; also called admission) to the morning of Day 5.

The time interval between dosing in Periods 1 and 2 is 35 days.

Each period they are expected at the clinical research center on Day -1 at
14:00 h in the afternoon. They will be required not to have consumed any food
or drinks during the 8 hours prior to arrival in the clinical research center
(with the exception of water).

They will leave the clinical research center on Day 5 of both periods.

After the volunteers have left the clinical research center on Day 5 in each
period, they will visit the clinical research center for short ambulatory
visits on Days 6, 7, 8, 10, 14 and 21. For the short ambulatory visit on Day 8
and Day 21, they will be required not to have consumed any food or drinks (with
the exception of water) during the 8 hours prior to arrival in the clinical
research center. There are no food or fluid restrictions prior to arrival for
the short ambulatory visits on Days 6, 7, 10 and 14 of both periods. The short
ambulatory visit on Day 21 of Period 2 is the follow-up visit for this study;
as stated before, prior to the follow-up visit they will be required not to
have consumed any food or drinks during the 8 hours prior to arrival in the
clinical research center (with the exception of water).

The participation to the entire study, from pre-study screening until the
follow-up visit on Day 21 of Period 2, will be a maximum of 84 days.

Not applicable.

Infections, pain, minor bleedings, bruises and possibly an infection.