A Phase 1, Randomized, Double-Blind, Placebo-Controlled, Single and Multiple-Ascending Dose Study of FPA008 in Healthy Volunteers and Subjects with Rheumatoid Arthritis

FPA008 is a new investigational compound that may eventually be used for the
treatment of rheumatoid arthritis and possibly for other immune mediated
disorders. The study is performed to gain insight in the side effects of the
drug administered at different dose levels.

The purpose of the study is to investigate to what extent FPA008 is safe and
tolerated, specifically what side effects the drug (FPA008) may have at
different dose levels, when given intravenously over approximately 30 minutes.
The study will also investigate how quickly FPA008 circulates and eliminated
from the body. In addition, the effect of FPA008 on immune response and bone
turnover will be investigated by assessing the extent of change in certain
protein levels in blood and urine. In this study the possible development of
antibodies against FPA008 in your blood will be investigated.

Part 1: Randomized, placebo-controlled, single-dose, sequential ascending
FPA008 dose cohorts in healthy volunteer subjects.
a) Planned dose cohorts are 0.2 mg/kg, 1 mg/kg, 3 mg/kg, 10 mg/kg (or
alternative dose), and possibly higher (up to 20 mg/kg) based on safety, PK,
and PD data.
b) Each dose cohort will start with 2 sentinel subjects (1 active and 1
placebo), who will be observed for 24 hours prior to enrolling the remainder of
the cohort.

Part 2: Randomized, placebo-controlled, dual-dose (q 14 days), sequential
ascending FPA008 dose cohorts in healthy volunteer subjects.
a) Planned dose cohorts are 1 mg/kg, 3 mg/kg, 10 mg/kg, and possibly higher (up
to 20 mg/kg) based on safety, PK, and PD data.
b) The first dose cohort will initiate once safety has been cleared in Part 1.

During part 1 the volunteers will receive a single ascending dose of FPA008,
during part 2 a multiple ascending dose. Each group of volunteers will be
divided into 2 subgroups. The first 2 volunteers will be dosed on the same day
(one with FPA008 and one with placebo [inactive formulation]). After dosing,
the safety and tolerability of FPA008 in these volunteers will be closely
monitored for at least 24 hours. If there are no concerns about the safety and
tolerability, the next day the remaining 6 volunteers will be dosed (5 with
FPA008 and one with placebo).

- possible side-effects as described under E9
- venapunctures and canula
- screening and follow-up visit
- admission to the clinic
- study activities: physical examinations, vital signs, ECG, local
tolerability
- eye test and eye foto