A randomized, placebo-controlled, phase 2 trial of laquinimod in primary progressive multiple sclerosis. (25th August 2020)

• Record Type: Journal Article
• Authors: Giovannoni, Gavin; Knappertz, Volker; Steinerman, Joshua R.; Tansy, Aaron P.; Li, Thomas; Krieger, Stephen; Uccelli, Antonio; Uitdehaag, Bernard M.J.; Montalban, Xavier; Hartung, Hans-Peter; Pia Sormani, Maria; Cree, Bruce A.C.; Lublin, Fred; Barkhof, Frederik
• Is Part Of: Neurology. Volume 95:Number 8(2020)
• Publication Date: 2020-08-25
• Subjects: Neurology -- Periodicals; Neurology -- Periodicals; Neurologie -- Périodiques; 616.8
• DOI: 10.1212/WNL.0000000000010284
• Languages: English
• ISSNs: 0028-3878

Abstract

Abstract : 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. Clinicaltrials.gov 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.