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Updated: Dec 15, 2025
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
A randomized, placebo-controlled, phase 2 trial of laquinimod in primary progressive multiple sclerosis
Gavin Giovannoni1, Volker Knappertz2, Joshua R Steinerman2
1From Barts and The London School of Medicine and Dentistry (G.G.), Blizard Institute, Queen Mary University of London, UK; Teva Pharmaceuticals R&D (V.K.), Teva Pharmaceutical Industries (T.L.), Great Valley, PA; Department of Neurology, Medical Faculty (V.K., H.-P.H.), Heinrich-Heine Universität Düsseldorf, Germany; Teva Pharmaceutical Industries (J.R.S., A.P.T.), Malvern, PA; Corinne Goldsmith Dickinson Center for Multiple Sclerosis (S.K.) and Neurology (F.L.), Icahn School of Medicine at Mount Sinai, New York, NY; Departments of Neuroscience, Rehabilitation, Ophthalmology, Genetics, and Maternal and Child Health and Center of Excellence for Biomedical Research (A.U.) and Department of Health Sciences (M.P.S.), University of Genoa; Ospedale Policlinico San Martino-IRCCS (A.U.), Genoa, Italy; Department of Neurology (B.M.J.U.), MS Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, the Netherlands; Division of Neurology (X.M.), University of Toronto/MS Centre St Michael's Hospital, Canada; Neurology-Neuroimmunology Department and Neurorehabilitation Unit (X.M.), Multiple Sclerosis Centre of Catalonia; Department of Neurology (X.M.), Hospital Universitari de la Vall d'Hebron, Barcelona, Spain; Weill Institute for Neurosciences (B.A.C.C.), Department of Neurology, University of California San Francisco; Radiology & Nuclear Medicine (F.L.), VU University Medical Center, Amsterdam, the Netherlands; and UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK. g.giovannoni@qmul.ac.uk.
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.
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