A phase 1, single center, randomized, double-blind, placebo-controlled, single (Part 1) and multiple (Part 2) ascending dose study to evaluate the safety,tolerability, pharmacokinetics and pharmacodynamics of M281 administered to healthy volunteers.

M281 is a new investigational compound that may eventually be used for the
treatment of autoimmune and inflammatory diseases mediated by a specific kind
of antibody, called IgG antibodies. M281 is an antibody that binds to a protein
that is called the neonatal Fc receptor. This Fc receptor can be found on many
cell types of the human body, such as white blood cells and cells in the kidney
and the liver. The neonatal Fc receptor is involved in transport of IgG
antibodies and inhibition of breakdown of these IgG antibodies. In autoimmune
diseases there are *wrong* IgG antibodies that are involved in the disease
process. The new investigational compound M281 is able to bind the neonatal Fc
receptor. It is hoped that this binding will ultimately lead to less IgG
antibodies, including the *wrong* IgG antibodies that are involved in
autoimmune or inflammatory diseases. This is the first time that this study
compound is being given to humans.

The study will be performed in 2 parts, Parts 1 and 2. The purpose of the study
is to investigate whether M281 is safe and to what extent M281 is tolerated.
It will also be investigated how quickly and to what extent M281 is absorbed
and eliminated from the body (this is called pharmacokinetics). In addition,
the effect of M281 on the antibodies and inflammatory markers in the blood will
be studied (this is called pharmacodynamics).

In Part 1 the effect of one single dose on safety, pharmacokinetics and
pharmacodynamics will be investigated, whereas in Part 2, the effect of
multiple doses on safety, pharmacokinetics and pharmacodynamics will be
investigated.

Part 1:
The actual study will consist of 1 period during which the volunteers will stay
in the clinical research center in Groningen for 9 days (8 nights) followed by
8 days (over a period of 7 weeks) during which they will visit the clinical
research center in Groningen for a short visit. The follow-up period may be
extended if deemed necessary by the responsible doctor.

Day 1 is the day of administration of the study compound. The volunteers are
expected at the clinical research center at 14:00 h in the afternoon prior to
the day of administration of the study compound. They will be required not to
have consumed any food or drinks during the 4 hours prior to arrival in the
clinical research center (with the exception of water).

They will leave the clinical research center on Day 8. However, if the
concentrations of IgG antibodies in the blood are too low on Day 8, they will
need to remain in the clinical research center until the concentrations of IgG
have increased again to a predetermined level.

The post-study screening will take place 7 weeks after the end of the
participation in this study. The appointment for the post-study screening will
be made with the volunteer during the study.

The participation to the entire study, from the pre-study screening until the
post study screening, will be a maximum of 12 weeks.

Part 2:

The actual study will consist of 4 periods during which the volunteers will
stay in the clinical research center in Groningen for 4 days (3 nights) each
period. Between these 4 periods they will go home. The inclinic period will be
followed by 15 days (over a period of approximately 11 weeks) during which they
will visit the clinical research center in Groningen for a short visit. The
follow-up period may be extended if deemed necessary by the responsible doctor.

Day 1 is the day of first administration of the study compound. For the first
period, the volunteers are expected at the clinical research center at 14:00 h
in the afternoon prior to the day of first administration of the study
compound. They will be required not to have consumed any food or
drinks during the 4 hours prior to arrival in the clinical research center
(with the exception of water).

They will leave the clinical research center on Day 3. For the periods
thereafter they are expected at the clinical research center at 14:00 h in the
afternoon on Days 7, 14 and 21, which are the days prior to the remaining dose
administrations. They will leave the clinical research center 3 days
thereafter, thus on Days 10, 17 and 24. However, if the concentrations of IgG
antibodies in your blood are too low on the day they will leave, they will
need to remain in the clinical research center until the concentrations of IgG
have increased again to a predetermined level.

the volunteers will be asked to return to the clinical research center for a
short visit on Days 29, 31, 36, 39, 43, 47, 50, 53, 57 and then once weekly in
the 6 weeks thereafter. The post-study screening will take place 11 weeks after
they have left the clinical research center on Day 24. The appointment for the
post-study screening will be made with the volunteers during the study. The
participation to the entire study, from the pre-study screening until the
post-study screening, will be a maximum of 18 weeks.

Part 1:
Group 1: 1 x 0.3 mg per kg bodyweight M281 or placebo
Group 2: 1 x 3 mg per kg bodyweight M281 or placebo
Group 3: 1 x 10 mg per kg bodyweight M281 or placebo
Group 4: 1 x 30 mg per kg bodyweight M281 or placebo
Group 5: 1x 100 mg per kg bodyweight M281 or placebo

Part 2:

Group 1: 4 x 30 mg per kg bodyweight M281 or placebo
Group 2: To be determined
Group 3: To be determined

Pain, minor bleeding, bruising, possibly an infection due too blood sampling.