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

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 PPMS patients 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: 374 patients were randomized to laquinimod 0.6 mg (n = 139) or 1.5 mg (n = 95) or placebo (n = 140)....