A randomized, open-label, single-dose parallel-group trial to determine the pharmacokinetics and safety of GP2017 following a single subcutaneous injection by an autoinjector or by a pre-filled syringe in healthy male subjects

GP2017 is a new investigational compound that is being developed as a copy of
Humira®, a drug already approved for the treatment of certain autoimmune
diseases, including rheumatoid arthritis and psoriasis. The aim for GP2017 is
to be approved for the treatment of the same autoimmune diseases as Humira®.
Autoimmune diseases arise from an abnormal immune response of the body against
substances and tissues normally present in the body. GP2017 inhibits
inflammatory reactions by binding to certain proteins in the body, which
decreases the immune response. Specifically, it interferes with the working of
a cytokine involved in inflammation, called TNF-* (a cytokine is a small
protein involved in the communication between many different kinds of cells in
the human body).The active substance of GP2017 (and Humira®) is called
*adalimumab*, and consists of several parts (building blocks) that are
naturally present in the human body. Therefore, the drug is called *a
biological*. Since the active substance of both GP2017 and Humira® is
adalimumab, it is expected that the treatment effect of GP2017 will be similar
in comparison to Humira®. GP2017 is not registered as a drug, but has been
given to humans before in other clinical studies.

The purpose of the study is to investigate how quickly and to what extent
GP2017 is absorbed and eliminated from the body (this is called
pharmacokinetics) after a single injection under the skin of the abdomen. This
injection is administered by either an autoinjector (a medical device for
injecting a drug) or a pre-filled syringe, to see whether the pharmacokinetics
is comparable for both administration methods. It will also be investigated to
what extent GP2017 is safe and tolerated. Finally, the formation of antibodies
against adalimumab will be investigated.

The study will consist of 1 period during which you will receive one single
subcutaneous injection of 40 mg GP2017 diluted in 0.8 ml solution. GP2017 will
be given either by an autoinjector or by a pre-filled syringe. The
administration method by which you will receive GP2017 is chosen by chance.
At Day 1 the volunteer will receive GP2017 within 1-2 hours after breakfast.
The volunteer will stay in the clinical research center in Zuidlaren for 11
days (10 nights; from Day -1 to Day 10), followed by a period of 62 days during
which he will visit the clinical research center in Zuidlaren for 6 short
visits on Days 16, 23, 30, 44, 58 and 72 (the post-study screening will be on
Day 72).
During the first 4 hours after administration of study medication he will be
required to lie down in bed, because another position may influence the uptake
of the drug.

The study will consist of 1 period during which the volunteer will receive one
single subcutaneous injection of 40 mg GP2017 diluted in 0.8 ml solution on Day
1.

The overall risks of GP2017 administration are considered to be minimal,
although some are unforeseeable as this is still an early stage in the testing
of this drug in man.
The first trial with GP2017 in healthy volunteers was conducted recently. In
total, 73 volunteers received GP2017 injections. The study revealed that the
adverse effects of 40 mg of GP2017 did not differ from Humira®. Adverse effects
of GP2017 were similar to the adverse effects of volunteers who received
marketed product Humira®. Adverse effects which were observed in this study in
more than 10% of volunteers were headache, common cold, muscle ache, and
abdominal pain. The majority of adverse effects were mild. With the dose used
in this study no serious adverse effects are expected, but as all drugs may
potentially cause adverse events to some extent the occurrence of known or
other effects cannot be excluded.

Humira® is now marketed in the European Union and in USA for at least 10 years.
The following list represents most of the side effects known for adalimumab,
reported by patients with pre-existing inflammatory diseases like rheumatoid
arthritis and psoriasis who were treated with multiple doses of Humira® and
over longer time periods. Because this study includes only healthy volunteers
who will receive a single dose, the probability of any of the following events
to happen is considered low in this study.
- Adalimumab is a medicine that affects the immune system and can lower the
ability of the immune system to fight infections or make any infection worse
(including serious infections).
- Allergic reactions can happen with symptoms like hives, swelling of your
face, eyes, lips or mouth, trouble with breathing.
- Nervous system problems with signs and symptoms that include: numbness or
tingling of legs, arms and/or fingers, problems with your vision, weakness in
your arms or legs, and dizziness, can occur.
- Blood dyscrasias (an imbalance of components of the blood) may occur in case
the body does not make enough of the blood cells that help fight infections or
help to stop bleeding. Symptoms can include fever that does not go away,
bruising or bleeding very easily, or looking very pale.
- New heart failure or worsening of a pre-existing heart failure may occur with
symptoms like shortness of breath, swelling of ankles or feet, sudden weight
gain.
- Immune reactions have been reported and symptoms may include chest discomfort
or pain that does not go away, shortness of breath, joint pain, or a rash on
the cheeks or arms that gets worse in the sun.
- Liver problems can happen in people who use adalimumab. Possible symptoms
are: feel very tired, skin or eyes look yellow, poor appetite or vomiting, pain
on the right side of the stomach (abdomen).
- Some people using adalimumab had new onset of psoriasis. Tell the principal
investigator if you develop red scaly patches or raised bumps that are filled
with pus.
- In patients taking adalimumab on a long term basis, occurrence of cancer has
been reported, e.g. skin cancer (generally not life-threatening if treated) or
blood cancer and solid tumors (with a frequency of less than 1% of all
patients).
However, the most common side effects for adalimumab are:
- Injection site reactions (redness, rash, swelling, itching, or bruising;
these symptoms usually will go away within a few days), infections (such as
upper respiratory tract infections and sinus infections), headaches, nausea
(feeling unwell) and vomiting, rash and musculoskeletal pain (pain in the
muscles and bones).

GP2017 is a so-called *biological*; with respect to the properties of these
drugs there is a chance that the volunteers body will develop antibodies
against adalimumab or that a hypersensitivity reaction will be induced. Based
on experience with Humira® and an earlier study with GP2017, the chance that he
will develop antibodies against adalimumab is likely. Should he develop
antibodies, this is not expected to have consequences for his health. However,
in case he would develop a condition that could be treated with adalimumab in
the future, it cannot be predicted whether and how these antibodies may
influence the effect of treatment. Currently, the following conditions could be
treated with adalimumab: rheumatoid arthritis, ankylosing spondylitis, axial
spondyloarthritis, psoriatic arthritis, psoriasis, Crohn*s disease, and
ulcerative colitis. In that case, his doctor will suggest the best possible
treatment. As of today several medications are available for the treatment of
the conditions mentioned above with a mode of action, efficacy and safety
profile which is similar to adalimumab.