A Phase 1 Double-Blind, Placebo-Controlled, Single- and Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneous Nipocalimab in Healthy Male and Female Participants.

Nipocalimab is a compound that may potentially be used for the treatment of
autoimmune and inflammatory diseases caused by a specific kind of antibody,
called IgG antibodies. Nipocalimab 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
compound nipocalimab is able to bind the neonatal Fc receptor leading to an
increased degradation of all IgG antibodies. It is hoped that this will
ultimately lead to the treatment of autoimmune diseases with *wrong* IgG
antibodies.

In this study we will investigate how safe the new compound nipocalimab is and
how well it is tolerated when it is used by healthy participants.

We also investigate how quickly and to what extent nipocalimab is absorbed,
transported, and eliminated from the body. The effect of the route of
administration is also investigated. In addition, we look at the effect of
nipocalimab on IgG, IgA, IgM, and IgE levels, albumin levels, and possibly the
amount of binding of nipocalimab to proteins in the serum.

We compare the effects of nipocalimab with the effects of a placebo.

Nipocalimab has been used by humans before. In addition, it has been
extensively tested in the laboratory and on animals. Nipocalimab will be tested
at various dose levels.

Part 1:
For the study it is necessary that the volunteer stays in the research center
for 1 period of 9 days (8 nights). This will be followed by 5 short visits to
the research center.
In Groups 1 to 4, the volunteer will be given nipocalimab or placebo once
subcutaneous. Up to 4 separate injections may be given for the subcutaneous
administration, each given at a different injection site.
In Groups 5 and 6, the volunteer will be given nipocalimab or placebo once as
an intravenous infusion.
In optional Groups 7 and 8, the volunteer will be given nipocalimab or placebo
once via a subcutaneous administration via a syringe pump.
Per group, 6 participants receive nipocalimab and 2 participants receive
placebo.

Part 2 Group 9a and 9b:
For the study it is necessary that the volunteer stays in the research center 2
periods of 9 days (8 nights). Period 1 will be followed by 3 short visits to
the research center. Period 2 will be followed by 4 short visits to the
research center.
The volunteer will be given nipocalimab or placebo four times as an injection
under the skin (subcutaneous).
Per group, 5 participants will receive nipocalimab and 1 participant will
receive placebo.

Part 2 Group 10a and 10b: (Groups 10a and 10b are optional)
For the study it is necessary that you stay in the research center 2 periods of
9 days (8 nights). Period 1 will be followed by 5 short visits to the research
center. Period 2 will be followed by 4 short visits to the research center.
The volunteer will be given nipocalimab or placebo four times as an injection
under the skin (subcutaneous).
Per group, 5 participants will receive nipocalimab and 1 participant will
receive placebo.

N/A

Possible Side effects:

The study compound may also have (serious) side effects that are still unknown.
In addition to unknown side effects, there is a (small) chance that an allergic
reaction will occur. This can be caused by the study compound or other
ingredients that are used to prepare the formulation.

Possible discomforts:
Blood draw
Drawing blood may be painful or cause some bruising. The use of the indwelling
cannula (a tube in a vein in the arm) can sometimes lead to inflammation,
swelling, hardening of the vein, blood clotting, and bleeding in the
environment (bruising) of the puncture site. In some individuals, a blood draw
can sometimes cause pallor, nausea, sweating, low heart rate, or drop in blood
pressure with dizziness or fainting.

In total, we will take about 510 milliliters (mL) (Group 9a and 9b) or 550 mL
(Group 10a and 10b) of blood from the volunteer. This amount does not cause any
problems in adults. To compare: a blood donation involves 500 mL of blood being
taken each time. If the investigator thinks it is necessary for the safety of a
participant, extra samples might be taken for possible additional testing. If
this happens, the total amount of blood drawn will be more than the amount
indicated above.

Heart tracing
To make a heart tracing, electrodes (small, plastic patches) will be placed at
specific locations on your arms, chest and legs. Prolonged use of these
electrodes can cause skin irritation (rash and itching).

Coronavirus test
Samples for the coronavirus test will be taken from the back of the volunteers
nose and throat using swabs. Taking the samples only takes a few seconds, but
can cause discomfort and can give an unpleasant feeling. Taking a sample from
the back of the volunteers throat may cause him to gag. When the sample is
taken from the back of his nose, he may experience a stinging sensation and his
eyes may become watery.