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Safety and in vivo immune assessment of escalating doses of oral laquinimod in patients with RRMS

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Item Type:Article
Title:Safety and in vivo immune assessment of escalating doses of oral laquinimod in patients with RRMS
Creators Name:Ziemssen, T. and Tumani, H. and Sehr, T. and Thomas, K. and Paul, F. and Richter, N. and Samara, E. and Spiegelstein, O. and Sorani, E. and Bar-Ilan, O. and Mimrod, D. and Hayardeny, L.
Abstract: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.
Keywords:Laquinimod, Multiple Sclerosis, Safety, Immunology, slanDC
Source:Journal of Neuroinflammation
Publisher:BioMed Central
Page Range:172
Date:31 August 2017
Official Publication:https://doi.org/10.1186/s12974-017-0945-z
PubMed:View item in PubMed

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