Background Laquinimod is an oral immunomodulator in clinical development to
treat relapsing-remitting multiple sclerosis (RRMS). Laquinimod is in clinical
development for the treatment of multiple sclerosis and Huntington Disease
(HD). The objective of this study is to assess the safety, tolerability,
pharmacokinetics (PK) and cytoimmunologic effects following escalating doses
of laquinimod in patients with RRMS. Methods One hundred twelve patients were
randomly assigned to laquinimod/placebo in a series of separate dose-
escalating cohorts starting from a daily oral dose of 0.9 mg/1.2 mg escalating
to 2.7 mg, in 0.3 mg increments. Results Twenty-eight patients received
placebo and 84 received laquinimod ranging from 0.9 to 2.7 mg. No deaths
occurred. One serious adverse event (SAE) of perichondritis was reported,
which was unrelated to laquinimod (0.9 mg). There was no increased incidence
of adverse events (AEs) with escalating doses. Laquinimod-treated patients
showed more abnormal laboratory levels in liver enzymes, P-amylase, C-reactive
protein (CRP), and fibrinogen, but most shifts were clinically non-
significant. The exposure of laquinimod was dose proportional and linear in
the tested dose range. An immunological substudy showed significant dose-
dependent decreases in 6-sulpho LacNAc + dendritic cell (slanDC) frequency
following laquinimod compared to placebo. Conclusion Laquinimod doses up to
2.7 mg were safely administered to patients with RRMS. An in vivo effect of
laquinimod on the innate immune system was demonstrated. Trial registration
EudraCT Number: 2009-011234-99. Registered 23 June 2009
