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

作者：Gavin Giovannoni, Volker Knappertz, Joshua R. Steinerman, Aaron Tansy, Thomas M. Li, Stephen Krieger, Antonio Uccelli, Bernard M.J. Uitdehaag, Xavier Montalbán, Hans‐Peter Hartung, Maria Pia Sormani, Bruce Cree, Fred Lublin, Frederik Barkhof · 发表于：Neurology · 年份：2020 · DOI：10.1212/wnl.0000000000010284 · 被引用次数：42 · 研究领域：Pediatric health and respiratory diseases、Vector-borne infectious diseases、Herpesvirus Infections and Treatments

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 La...