An adaptive Phase I/II study to assess safety, efficacy, pharmacokinetics and pharmacodynamics of RO7112689 in healthy volunteers and patients with paroxysmal nocturnal hemoglobinuria (PNH)

RO7112689 is a new investigational compound that may eventually be used for the
treatment of paroxysmal nocturnal hemoglobinuria (PNH). PNH is a rare,
acquired, chronic disease of the blood characterized by destruction of red
blood cells by the complement system, a part of the body's immune system.
RO7112689 is a monoclonal antibody, a type of protein that is normally made by
the immune system to help defend the body from infection and cancer. RO7112689
binds to the complement protein C5 and is expected to stop complement mediated
destruction of red blood cells in the blood vessels of patients with PNH.

RO7112689 is not registered as a drug and has not been given to humans before.

The purpose of Part 1A is to investigate how safe RO7112689 is and how well
RO7112689 is tolerated. Part 1A will also investigate how quickly and to what
extent RO7112689 is absorbed into, distributed in, and eliminated from the body
(this is called pharmacokinetics). In addition, the effect of RO7112689 on
certain blood markers will be investigated (this is called pharmacodynamics).

The actual study will consist of 1 period during which the volunteer will stay
in the clinical research center for a minimum of 8 days (7 nights): from the
afternoon of Day -1 (1 day before administration of the study compound) to the
morning of Day 7. Depending on the results for safety and blood markers the
volunteer may be asked to stay longer than the planned 8 days. The in-clinic
stay will be followed by 7 days (Days 14, 21, 28, 35, 42, 56 and 84) during
which the volunteer will visit the clinical research center for a short visit
during which blood will be collected; the volunteer will be informed at what
time he is expected at the clinical research center for these short visits.

The volunteer will receive a single dose of RO7112689 or placebo as an
intravenous (iv) infusion of 1 hour or as a subcutaneous injection on Day 1.
The placebo dose is an iv infusion or a subcutaneous injection without the
active ingredient RO7112689.

All potential drugs cause adverse effects; the extent to which this occurs
differs. As RO7112689 will be administered to man for the first time in this
study, adverse effects of RO7112689 in man have not been reported to date.

In patients who were treated with eculizumab, a registered drug with the same
mechanism of action as RO7112689, serious to fatal cases of meningitis were
seen. These were, however, patients who were treated with this compound for a
long time. Also, infections with other bacteria were reported. Because
RO7112689 (and also eculizumab) are biologicals, there is a chance that your
body will develop antibodies against RO7112689, especially with prolonged use.
In animal studies there were sporadic cases in which immune complexes of these
antibodies with RO7112689 were formed. These immune complexes caused an
inflammation process in the vessels of arteries, which however did not lead to
permanent damage.

Procedures: pain, minor bleeding, bruising, possible infection