Randomized, single-dose, parallel-arm, open-label Phase I trial to compare the pharmacokinetics, safety and tolerability of BI 695501 administered subcutaneously via prefilled syringe or autoinjector

BI 695501 is being developed as an alternative to Humira®, a compound which is
already approved as a drug for the treatment of several autoimmune diseases
including rheumatoid arthritis, Crohn*s disease, ulcerative colitis, psoriasis,
hidradenitis suppurativa (acne inversa), and non-infectious uveitis. Autoimmune
diseases arise from an abnormal immune response of the body against substances
and tissues normally present in the body. BI 695501 inhibits inflammatory
reactions by binding to a certain protein in the body, which decreases the
immune response. Specifically, BI 695501 interferes with the working of a
cytokine involved in inflammation, called TNF-alpha. The active substance of
Humira® is called *adalimumab*. The Sponsor has manufactured BI 695501 to be
biologically similar to adalimumab (biosimilar). BI 695501 has already been
studied in the laboratory and given to animals and humans.

The main purpose of this study is to compare the pharmacokinetic
characteristics of BI 695501 after subcutaneous (under the skin) injection in
the thigh using either a prefilled syringe or autoinjector (a medical device
for injecting a drug). The pharmacokinetics of a compound looks at how the
compound gets into the bloodstream, how it is distributed throughout the body,
as well as the chemical changes the drug undergoes as it is broken down by the
body. It also examines the effects of the break down products and how they are
passed out of the body.

A second purpose of this study is to test how safe BI 695501 is and what (if
any) side effects are observed when it is administered has been taken.

Finally, the formation of antibodies against BI 695501 will be investigated.

The study will consist of 1 period during which the volunteer will stay in the
clinical research center for 9 days (8 nights). The volunteer will stay from
the afternoon of Day -1 (1 day before administration of the study compound;
also called admission) to the morning of Day 8. This will be followed by 6 days
during which the volunteer will visit the clinical research center for a short
ambulatory visit: Days 10, 15, 22, 29, 36 and 43.

At admission on Day -1, the volunteer is expected at the clinical research
center at 14:00 h in the afternoon. The volunteer will be required not to have
consumed any food or drinks during the 4 hours prior to admission (with the
exception of water).

For each short ambulatory visit, the volunteer is expected at the clinical
research center at 8:00 h in the morning. For the short ambulatory visit on Day
22, the volunteer 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). There are no food or fluid restrictions prior to arrival
for the short ambulatory visits on Days 10, 15, 29, 36 and 43.

The participation to the entire study, from pre-study screening until the
telephonic follow-up, will be approximately 100 days.

On Day 1 the volunteer will receive a single subcutaneous injection in the
thigh of 40 mg BI 695501 in a 0.8 mL solution, either by a pre-filled syringe
or by an autoinjector.

The volunteer will receive one single subcutaneous injection in the thigh of 40
mg BI 695501 in a 0.8 milliliter (mL) solution. BI 695501 will be given either
by a pre-filled syringe or by an autoinjector. With a pre-filled syringe the
drug is delivered through a needle which is inserted manually into the skin. An
autoinjector contains a pre-filled syringe with a needle which is automatically
inserted by pressing the autoinjector against the skin.

Based on the laboratory results, testing in animals and humans, and the fact
that BI 695501 is biologically similar to adalimumab, the side effects of BI
695501 are expected to be similar to those observed for adalimumab. BI 695501
acts by decreasing the activity of the immune system (part of the body which
helps to protect against disease or other damaging foreign bodies). The
expected side effects are related to the suppression of the immune system. To
date, a total of 246 male healthy subjects received subcutaneous doses of 40 mg
BI 695501 via a prefilled glass syringe in 2 trials. The dose of 40 mg BI
695501 was generally well tolerated. The most frequently reported AEs were
headache and upper respiratory tract infections and mild injection site
reactions.

Additionally, 614 patients with moderate to severe rheumatoid arthritis have
been included and treated with BI 695501 or adalimumab in an ongoing clinical
study. There have been no unexpected safety findings or clinically relevant
safety concerns. The side effects observed so far are in line with the known
safety profile of adalimumab.

Adalimumab is now marketed in the European Union and in USA for at least 10
years. The side effects documented for adalimumab and which are described below
have been reported by patients with pre existing inflammatory diseases like
rheumatoid arthritis and psoriasis who were treated with multiple doses of
adalimumab and over longer time periods.

Because this study includes only healthy volunteers who will receive a single
dose, the probability is considered low that any of the events described below
will happen in this study.

The most common side effects (may affect more than 1 in 10 people) reported for
adalimumab are:
* Injection site reactions (including pain, swelling, redness or itching)
* Respiratory tract infections (including cold, runny nose, sinus infection,
pneumonia)
* Headache
* Abdominal pain
* Nausea and vomiting
* Rash
* Musculoskeletal pain.

Common side effects (may affect up to 1 in 10 people) for adalimumab reported
in patients are:
* 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 responsible
doctor 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).
Serious side effects that occurred less frequently with adalimumab are:
* Formulation of nodules on the organs (sarcoidosis)
* Stroke (cerebrovascular accident)
* Heart attack (myocardial infarction), irregular heartbeat (arrhythmia) or
missing heartbeat(s) by inhibiting the impulse for the heartbeat (sinus
arrest), swelling of the aorta - the main blood vessel that leads away from the
heart, down through the abdomen to the rest of the body * (aortic aneurysm),
blockage of the arteries (arterial occlusion)
* Blood clot in the lung (lung embolism), interstitial lung disease, scarring
of the lungs (pulmonary fibrosis)
* Inflammation of the pancreas (pancreatitis), hole in the bowel (intestinal
perforation).
* Kidney failure (renal impairment)
* Impotence (erectile dysfunction)

BI 695501 is a so-called *biological*; with respect to the properties of these
drugs there is a chance that the body will develop antibodies against BI 695501
or that a hypersensitivity reaction will be induced. Based on experience with
adalimumab, the chance that the volunteer will develop antibodies against BI
695501 is likely. Should the volunteer develop antibodies, this is not expected
to have consequences for his or her health. However, in case the volunteer
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, your doctor will suggest the best possible
treatment for the volunteer. 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.

Overall the safety data of adalimumab show that it is considered a safe drug
provided certain precautions are taken. It is expected that the same will be
the case for BI 695501.

The needle cap on the prefilled syringe and autoinjector contains dry, natural
rubber. In rare cases this may cause severe allergic reactions. However, since
the injection will be performed by experienced study staff, the risk that this
will happen is minimal. Also, volunteers with a known history of allergic
reactions will not be included into the trial.

Procedures: possibility for pain, minor bleeding, bruising, possible infection.