A Single-Center, Phase I, Randomized, Double-Blind, Placebo-Controlled Trial to Assess the Safety, Tolerability, Immunogenicity, Pharmacokinetics, and Pharmacodynamics of Multiple Ascending Doses of Subcutaneous MSB0010841 (Anti-IL-17A/F Nanobody) in Healthy Male Subjects

MSB0010841 is an experimental drug that may eventually be used for the
treatment of inflammatory responses in several autoimmune diseases. An
autoimmune disease is an illness that occurs when the body tissues are attacked
by its own immune system. This occurs for example in rheumatoid arthritis and
psoriasis patients.

MSB0010841 is a drug made of 3 so-called nanobodies. A nanobody is a very small
fragment of an antibody. Antibodies are produced by our own body for host
defense against for example bacteria and viruses. However, antibodies can also
be prepared in a custom made way by pharmaceutical companies, so that they can
be used for medical research and various therapeutical applications.
Interleukin (IL) 17A and IL-17F are important mediators of inflammation in
autoimmune diseases, including rheumatoid arthritis and psoriasis. MSB0010841
is designed to specifically recognize, bind and block the function of IL 17A
and IL-17F.
Because MSB0010841 is a protein, the body may recognize the drug as foreign. As
a result an immune response can occur, for example by making antibodies. The
ability of a compound to elicit an immune response is called immunogenicity.
The production of antibodies towards the drug may only cause adverse events
upon repeated administration. In monkeys only minor allergic reactions were
observed upon repeated administrations with MSB0010841. The production of
antibodies towards the medication leads to reduced efficacy of the medical
product. Therefore it will be investigated whether antibodies are produced
after administration of multiple doses of MSB0010841.

MSB0010841 is an experimental drug, which means that it is not yet approved by
the Health Authorities to use as a prescribed drug in clinical practice.
However, MSB0010841 has been given to humans before in a study at PRA which is
performed simultaneously with this study, i.e., the first dose you receive has
already been investigated in this first study.

The purpose of this research is to investigate the safety and tolerability of
MSB0010841. This study will also investigate how quickly and to what extent the
study medication is absorbed and eliminated from the body (this is called
pharmacokinetics [PK]). In addition, the effect of MSB0010841 on the body will
be investigated by the evaluation of different markers in the blood, IL-17A and
IL-17F in particular (this is called pharmacodynamics). This study will also
investigate to what extent the body produces antibodies towards MSB0010841
(immunogenicity).

A Single-Center, Phase I, Randomized, Double-Blind, Placebo-Controlled Trial to
Assess the Safety, Tolerability, Immunogenicity, Pharmacokinetics, and
Pharmacodynamics of Multiple Ascending Doses of Subcutaneous MSB0010841
(Anti-IL-17A/F Nanobody) in Healthy Male Subjects.

Depending on the dose you will receive at least 1 injection and maximally 4
injections per dosing, with a maximum volume of 1 mL per injection.
* Group 1 (18 mg) 1 injection (0.3 mL), 3 injections in total
* Group 2 (60 mg) 1 injection (1 mL), 3 injections in total
* Group 3 (120 mg) 2 injections with 1mL per injection (total of 2mL), 6
injections in total
* Group 4 (240 mg) 4 injections with 1mL per injection (total of 4mL), 12
injections in total

- possible side-effect as described under E9
- venapunctures
- subcutaneous injections
- screening and follow-up visit
- admission to the clinic
- study activities: physical examinations, spirometry, vital signs, ECG,
holter, telemetry, local tolerability assessment