An open-label, single-dose, parallel-arm study to evaluate the pharmacokinetics and absolute bioavailability of GBR 830 following single dose administration by the subcutaneous (SC) route

GBR 830 is a new investigational compound that may eventually be used for the
treatment of several autoimmune diseases. An autoimmune disease is an illness
that occurs when the body tissues are attacked by its own immune system. GBR
830 is being developed for autoimmune diseases like rheumatoid arthritis,
ankylosing spondylitis, axial spondyloarthritis, psoriatic arthritis,
psoriasis, Crohn*s disease, and ulcerative colitis.

Antibodies are produced by our own body for host defense against for example
bacteria and viruses. However, antibodies can also be prepared in a custom made
way by pharmaceutical companies, so that they can be used for medical research
and various therapeutic applications. GBR 830 is an antibody designed to
specifically recognize, bind and block the function of the OX40 receptor on T
cells. A receptor is a protein on the cell surface that can initiate a cell
response when a signal molecule binds to the receptor. T cells are a specific
type of white blood cells that play an important role in immune responses.

GBR 830 is not registered as a drug, but has been given to humans before.

The purpose of the study is to investigate how quickly and to what extent GBR
830 is absorbed into, distributed in, and eliminated from the body (this is
called pharmacokinetics). Furthermore, the pharmacokinetics of GBR 830
administered as subcutaneous injection compared to GBR 830 administered as
intravenous (iv; in the vein) infusion will be investigated (this is called
absolute bioavailability). It will also be investigated how safe GBR 830 is and
how well GBR 830 is tolerated. In addition, it will be investigated to what
extent the body produces antibodies against GBR 830.

The actual study will consist of 1 period during which the volunteer will stay
in the clinical research center for 11 days (10 nights): from the afternoon (at
14:00 h) of Day -1 (1 day before administration of the study compound) to the
morning of Day 10. The in-clinic stay will be followed by 6 days (Days 12, 15,
29, 43, 57 and 71) during which the volunteer will visit the clinical research
center for a short visit; he/she will be informed at what time the volunteer is
expected at the clinical research center for these short visits.

The volunteer will receive a single dose of GBR 830 on Day 1 as an iv infusion
of 1 hour or as a subcutaneous injection in the abdomen.

Day Treatment How often Number of volunteers
1 A 600 milligrams GBR 830 as an iv infusion Once 10
1 B 600 milligrams GBR 830 as a subcutaneous injection Once 15
1 C 75 milligrams GBR 830 as a subcutaneous injection Once 15

Healthy male and female volunteers between the age of 18-55 years, inclusive,
with a BMI between 18.5 and 32.0 kg / m2, inclusive.

All potential drugs cause adverse effects; the extent to which this occurs
differs. GBR 830 has been studied in animals. In animals no abnormalities were
observed and the study medication was well tolerated. GBR 830 has already been
studied at PRA in humans with dose levels of 10 mg/kg intravenously; this dose
level is approximately the same as those of the current study. In this previous
study GBR 830 was well tolerated without clear adverse effects. Development of
a hypersensitivity reaction to GBR 830 may occur and you may become more
susceptible to infections.

GBR 830 is a so-called *biological*; with respect to the properties of these
drugs there is a chance that your body will develop antibodies against GBR 830
or that a hypersensitivity reaction will be induced. Based on experience with
GBR 830, the chance that the volunteer will develop antibodies against the
study compound is likely. If antibodies against the new investigational
compound are found in your blood, we expect that with the current knowledge
this will have no consequences for the volunteers health. Should the volunteer
develop antibodies, this is not expected to have consequences for their health.
However, in case the volunteer would develop a condition that could be treated
with GBR 830 in the future, it cannot be predicted whether and how these
antibodies may influence the effect of treatment. GBR 830 is being developed
for autoimmune diseases like rheumatoid arthritis, ankylosing spondylitis,
axial spondyloarthritis, psoriatic arthritis, psoriasis, Crohn*s disease, and
ulcerative colitis. If the volunteer would need treatment for one of these
diseases, their doctor will suggest the best possible treatment for them. As of
today several medications are available or being developed for the treatment of
the conditions mentioned.