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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2017

Open Access 01-12-2017 | Research

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

Authors: Tjalf Ziemssen, Hayrettin Tumani, Tony Sehr, Katja Thomas, Friedemann Paul, Nils Richter, Emil Samara, Ofer Spiegelstein, Ella Sorani, Oren Bar-Ilan, Dorit Mimrod, Liat Hayardeny

Published in: Journal of Neuroinflammation | Issue 1/2017

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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.
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Metadata
Title
Safety and in vivo immune assessment of escalating doses of oral laquinimod in patients with RRMS
Authors
Tjalf Ziemssen
Hayrettin Tumani
Tony Sehr
Katja Thomas
Friedemann Paul
Nils Richter
Emil Samara
Ofer Spiegelstein
Ella Sorani
Oren Bar-Ilan
Dorit Mimrod
Liat Hayardeny
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2017
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-017-0945-z

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