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

• Published in: Journal of neuroinflammation Vol. 14; no. 1; p. 172
• Main Authors: Ziemssen, Tjalf, Tumani, Hayrettin, Sehr, Tony, Thomas, Katja, Paul, Friedemann, Richter, Nils, Samara, Emil, Spiegelstein, Ofer, Sorani, Ella, Bar-Ilan, Oren, Mimrod, Dorit, Hayardeny, Liat
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 31-08-2017; BioMed Central; BMC
• Subjects: Administration, Oral; Adolescent; Adult; Cohort Studies; Complications and side effects; Dosage and administration; Dose-Response Relationship, Drug; Double-Blind Method; Drug therapy; Female; Follow-Up Studies; Humans; Immunity; Immunity, Innate - drug effects; Immunity, Innate - immunology; Immunologic Factors - administration & dosage; Immunology; Laquinimod; Male; Middle Aged; Multiple sclerosis; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Multiple Sclerosis, Relapsing-Remitting - immunology; Pharmacokinetics; Quinolones - administration & dosage; Safety; slanDC; Young Adult; Germany; slanDC; Laquinimod; Multiple sclerosis; Immunology; Safety
• ISSN: 1742-2094; 1742-2094
• DOI: 10.1186/s12974-017-0945-z

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.
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.
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.
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.
EudraCT Number: 2009-011234-99 . Registered 23 June 2009.