A phase 1, randomized, open-label, parallel group trial to investigate the pharmacodynamics, pharmacokinetics, safety, and tolerability of different single subcutaneous dose levels of Efgartigimod co administered with rHuPH20 in healthy adult male subjects

Efgartigimod is a new compound that may eventually be used for the treatment of
autoimmune diseases such as myasthenia gravis and immune thrombocytopenia.
Autoimmune diseases are diseases where antibodies produced by the body*s immune
system, attack cells of their own body.

In the autoimmune diseases myasthenia gravis, pemphigus and immune
thrombocytopenia the immune system specifically produces so called IgG
antibodies. In myasthenia gravis these IgG antibodies affect muscle cells so
that these cannot contract anymore. This causes muscle weakness in the arms and
legs, or in extreme cases it may affect. the muscles involved in breathing. In
immune thrombocytopenia these antibodies attack blood platelets, which results
in an increased tendency to bleed, bruise or cause a rash.
Efgartigimod promotes the break-down of these IgG antibodies so they cannot
attack the body*s own cells, and is expected to improve the symptoms of these
autoimmune diseases.

The purpose of this study is to investigate the effects of the new compound
efgartigimod on IgG antibodies. It will also be investigated how quickly and to
what extent efgartigimod given together with rHuPH20, is absorbed and
eliminated from the body and how fast it can be injected. In addition, the
effect of efgartigimod on the body will be investigated.

It will also be investigated how safe efgartigimod in combination with rHuPH20
is, and how well it is tolerated when it is administered to healthy volunteers.

rHuPH20 is an enzyme that is used to temporarily improve the spreading of
fluids that are injected under the skin, so it causes less swelling. It is
thought to improve absorption of the study drug into the body. rHuPH20 has been
co-administered with other approved drugs for this purpose.

Efgartigimod has been administered to humans before. It also has been
previously tested in the laboratory and on animals. Efgartigimod will be tested
at various dose levels in this study.

The study will consist of 1 period during which you will stay in the research
center for 8 days (7 nights). This will be followed by 7 days during which the
volunteer will visit the research center for a short visit. These short visits
will take place on Day 9, 11, 15, 22, 29, 43 and 57 (the follow-up).

Efgartigimod (1 of 4 doses) together with rHuPH20 will be given as a single
injection under the skin in a total volume of approximately 4.7 mL to 10.8 mL.
It is anticipated that the dose can be administered in approximately 5 minutes
or less.

The planned dose levels and volumes for the study are as follows:

Group Efgartigimod (+ rHuPH20*) Administered volume
1 750 mg 4.7 mL
2 1250 mg 7.7 mL
3 1750 mg 10.8 mL
4 10 mg/kg# XX mL

* The concentration of rHuPH20 (0.018 mg/ml for the administered volume) will
be the same for all doses of efgartigimod.
# This means that 10 mg of efgartigimod will be administered per 1 kg of body
weight, so the actual dose and volume will depend on the body weight.

Efgartigimod (1 of 4 doses) together with rHuPH20 will be given as a single
injection under the skin in a total volume of approximately 4.7 mL to 10.8 mL.
It is anticipated that the dose can be administered in approximately 5 minutes
or less.

The planned dose levels and volumes for the study are as follows:

Group Efgartigimod (+ rHuPH20*) Administered volume
1 750 mg 4.7 mL
2 1250 mg 7.7 mL
3 1750 mg 10.8 mL
4 10 mg/kg# XX mL

* The concentration of rHuPH20 (0.018 mg/ml for the administered volume) will
be the same for all doses of efgartigimod.
# This means that 10 mg of efgartigimod will be administered per 1 kg of body
weight, so the actual dose and volume will depend on the body weight.

Efgartigimod has been investigated in 4 clinical trials up to date, and was
found to be well-tolerated. Efgartigimod has been administered to healthy
volunteers intravenously in doses up to 50 mg/kg. A few subjects treated with
doses of 25 mg/kg or 50 mg/kg showed abnormalities in white blood cell counts,
but all subjects recovered within 2 to 4 days after stopping with the
treatment. Also, some subjects showed increased C-reactive protein levels, but
these levels went back to normal within 3 to 6 days after stopping with the
treatment, and there were no signs of possible infections.

Patients with myasthenia gravis who received 10 mg/kg efgartigimod
intravenously for 4 weeks, showed a decrease in IgG antibodies and improvement
of symptoms, and treatment with efgartigimod was well tolerated. The most
common side effect was headache, reported in some patients treated with
efgartigimod but also common in patients who received placebo.

In patients with immune thrombocytopenia, treatment with 5 or 10 mg/kg
intravenous efgartigimod for 4 weeks resulted in a decrease in IgG antibodies
and an increase in blood platelets (the blood cells that are destroyed by the
disease). Treatment with efgartigimod was well tolerated. The few observed side
effects were petechiae (tiny red patches on the skin or inside the mouth or
eyelids), high blood pressure, and vomiting.

The study compound may also have side effects that are still unknown. If during
the study more information becomes available regarding adverse events that may
be related to the study compound, the responsible doctor will inform the
volunteer about this.

rHuPH20 is a permeation (diffusion) enhancer with a well-characterized
nonclinical and clinical safety profile that allows the rapid delivery of large
volumes of fluid and/or co-administered drugs under the skin (subcutaneously).
In clinical studies, the subcutaneous administration of rHuPH20 in combination
with other substances was well-tolerated. Adverse effects may include mild and
short-lived injection site reactions, such as redness, swelling, pain and
itching. Adverse events in these trials were related to the co-administered
drug or have been associated with the rapid introduction of a relatively large
volume of fluid in the subcutaneous space. rHuPH20 is co-formulated or
co-administered with several products in the US and EU (e.g., Herceptin® SC,
MabThera® SC, HyQvia®).

Possible discomforts due to procedures

Drawing blood and/or insertion of the indwelling cannula may be painful or
cause some bruising.

A subcutaneous injection may be painful and may cause mild swelling

In total, we will take up to 180 milliliters of blood from the volunteer. This
amount does not cause any problems in adults.

To make a heart tracing, electrodes will be pasted at specific locations on
your arms, chest and legs. Prolonged use of these electrodes can cause skin
irritation.