A randomized, adaptive, investigator/subject blind, single ascending dose, placebo-controlled phase I study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of subcutaneously administered RO7049665 in healthy volunteers.

RO7049665 is a new investigational compound that may eventually be used for the
treatment of chronic autoimmune diseases like type 1 diabetes (T1D), rheumatoid
arthritis (RA), psoriasis, multiple sclerosis (MS) and inflammatory bowel
disease (IBD) like ulcerative colitis and Crohn*s disease (CD). In these
diseases, the immune system reacts in an abnormal way to a normal body part.
RO7049665 is designed to boost the parts of the immune system which are
believed to combat auto-immune disease (regulatory T-cells or Treg), without
stimulating or damaging those parts of
the immune system which are not involved. It is designed to have fewer side
effects than similar, currently available products.
This is the first time that this study compound will be given to humans.

The purpose of the study is to investigate to what extent RO7049665 is
tolerated. It will also be investigated how quickly and to what extent
RO7049665 is absorbed and eliminated from the body (this is called
pharmacokinetics). In addition, the effect of RO7049665 on specific white blood
cells (regulatory T cells, also called Treg) will be investigated (this is
called pharmacodynamics).

This study will be performed in approximately 70 (but no more than 100) healthy
male volunteers, divided over approximately 10 groups.

This study is not intended to improve the health, but is necessary for the
further development of RO7049665.

The actual study will consist of 1 period during which the volunteers will stay
in the clinical research center in Groningen (location UMCG) for 7 days (6
nights) followed by 7 days during which they will visit the clinical research
center in Groningen (location UMCG) for a short visit.

They are expected at the clinical research center at 14:00 h in the afternoon
prior to the day of administration of the study compound. They 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).

They will leave the clinical research center on Day 6 (Day 1 is the day of
administration of the study compound). They will have to return for short
visits in the morning on Day 8, 12, 15, 21, 29, 43 and 57. The follow-up visit
will take place on Day 57.

Your participation to the entire study, from the pre-study screening until the
follow-up visit, will be a maximum of 90 days (approximately 13 weeks).

Group - Treatment
1 RO7049665 1.5 µg* or placebo
2 RO7049665 5 µg or placebo
3 RO7049665 16 µg or placebo
4 RO7049665 55 µg or placebo
5 RO7049665 190 µg or placebo
6 RO7049665 650 µg or placebo
7 RO7049665 2200 µg or placebo
8 RO7049665 7500 µg or placebo
9 RO7049665 XXXX µg or placebo
10 RO7049665 XXXX µg or placebo

Pain, minor bleedings, bruises, possibly an infection.
Update per protocol version 2: In previous groups (group 1 to 7), skin rash was
reported.