A randomized, placebo-controlled, phase 2 trial of laquinimod in primary progressive multiple sclerosis

Gavin Giovannoni, Volker Knappertz, Joshua R. Steinerman, Aaron P. Tansy, Thomas Li, Stephen Krieger, Antonio Uccelli, Bernard M. J. Uitdehaag, Xavier Montalban, Hans-Peter Hartung, Maria Pia Sormani, Bruce A. C. Cree, Fred Lublin, Frederik Barkhof

Research output: Contribution to journalArticleAcademicpeer-review


OBJECTIVE: To evaluate efficacy, safety, and tolerability of laquinimod in patients with primary progressive multiple sclerosis (PPMS). METHODS: In the randomized, double-blind, placebo-controlled, phase 2 study, ARPEGGIO (A Randomized Placebo-controlled Trial Evaluating Laquinimod in PPMS, Gauging Gradations in MRI and Clinical Outcomes), eligible patients with PPMS were randomized 1:1:1 to receive once-daily oral laquinimod 0.6 mg or 1.5 mg or matching placebo. Percentage brain volume change (PBVC; primary endpoint) from baseline to week 48 was assessed by MRI. Secondary and exploratory endpoints included clinical and MRI measures. Efficacy endpoints were evaluated using a predefined, hierarchical statistical testing procedure. Safety was monitored throughout the study. The laquinimod 1.5 mg dose arm was discontinued on January 1, 2016, due to findings of cardiovascular events. RESULTS: A total of 374 patients were randomized to laquinimod 0.6 mg (n = 139) or 1.5 mg (n = 95) or placebo (n = 140). ARPEGGIO did not meet the primary endpoint of significant treatment effect with laquinimod 0.6 mg vs placebo on PBVC from baseline to week 48 (adjusted mean difference = 0.016%, p = 0.903). Laquinimod 0.6 mg reduced the number of new T2 brain lesions at week 48 (risk ratio 0.4; 95% confidence interval, 0.26-0.69; p = 0.001). Incidence of adverse events was higher among patients treated with laquinimod 0.6 mg (83%) vs laquinimod 1.5 mg (66%) and placebo (78%). CONCLUSIONS: Laquinimod 0.6 mg did not demonstrate a statistically significant effect on brain volume loss in PPMS at week 48. CLINICALTRIALSGOV IDENTIFIER: NCT02284568. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that, although well tolerated, laquinimod 0.6 mg did not demonstrate a significant treatment effect on PBVC in patients with PPMS.
Original languageEnglish
Pages (from-to)e1027-e1040
Issue number8
Early online date10 Jul 2020
Publication statusPublished - 25 Aug 2020

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