ARPEGGIO: a placebo-controlled trial of oral laquinimod in primary progressive multiple sclerosis

Objective: To evaluate oral laquinimod (LAQ) treatment in patients with primary progressive multiple sclerosis (PPMS). Background: LAQ is a novel agent that modulates innate immune cell lineages in both the periphery (dendritic cells and monocytes) and within the CNS (microglia and astrocytes). Based on its distinctive mechanism of action in relapsing-remitting MS (RRMS), laquinimod is a promising candidate for the treatment of PPMS. Design/Methods: ARPEGGIO is an ongoing phase 2 randomized, double-blind, placebo-controlled study to assess the efficacy, safety, and tolerability of oral, once-daily laquinimod in patients with PPMS. Eligible patients were originally randomly assigned 1:1:1 to receive laquinimod 0.6 or 1.5 mg or placebo. Following discontinuation of the 1.5-mg dose due to safety concerns, entering patients were randomly assigned 1:1 to 0.6-mg laquinimod or placebo. Key inclusion criteria included diagnosis of PPMS (2010 revised McDonald criteria); age 25–55 years; Expanded Disability Status Scale (EDSS) score 3–6.5, inclusive; presence of lesions consistent with PPMS; and evidence of disability progression in the 2 years prior to screening. The primary endpoint is percent brain volume change (PBVC) on MRI from baseline to Week 48. Key secondary endpoints include new T2 lesions on MRI and CDP documented by either EDSS, Timed 25-Foot Walk, 9-Hole Peg Test, or Symbol Digit Modalities Test. Results: Three-hundred seventy-four patients from 10 countries in North America and Europe were randomly assigned to treatment. The primary efficacy analysis, as well as other efficacy and safety data will be presented. The anticipated date of database lock is November 8, 2017. Conclusions: Results from this study will inform understanding of laquinimod as a potential treatment for patients with PPMS. Study Supported by: Teva Pharmaceutical Industries Disclosure: Dr. Giovannoni has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Received compensation for participating on Advisory Boards in relation to clinical trial design, trial steering committees and data and safety monitoring committees from: Abbvie, Almirall, Atara Bio, Biogen, Sanofi-Genzyme, Genentech, GSK, Merck, Novartis. Dr. Giovannoni has received personal compensation in an editorial capacity for Elsevier as Editor of MSARDs. Dr. Giovannoni has received research support from Takeda. Dr. Barkhof has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Has received personal compensation for activities with Apitope Ltd., GeNeuro, Biogen Idec, Sanofi-Genzyme, Janssen Research, Merck-Serono, Novartis, IXICO Ltd, Roche and TEVA as a consultant. He also received compensation from IXICO Ltd. for development o. Dr. Barkhof has received research support from Grants from AMYPAD (IMI), EuroPOND (H2020), UK MS Society, Dutch MS Society, PICTURE (IMDI-NWO), NIHR UCLH Biomedical Research Centre (BRC) and ECTRIMS-MAGNIMS. Dr. Hartung has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen Idec, GeNeuro, Sanofi Genzyme, Merck, Novartis Pharmaceuticals, Octapharma, Opexa Therapeutics, Teva Pharmaceuticals, MedImmune, Bayer HealthCare, Forward Pharma, and Roche. Dr. Cree has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Abbvie, Biogen, EMD Serono, GeNEuro, Novartis, Sanofi Genzyme. Dr. Cree has received research support from Acorda, Hoffman La Roche, MedImmune, Novartis, Receptos and Teva. Dr. Krieger has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with acorda, bayer, biogen, emd serono, genentech, genzyme, mallinckrodt, medday, novartis, teva, and tg therapeutics . Dr. Montalban has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Actelion, Bayer, Biogen, Celgene, Genzyme, Merck, Novartis, Oryzon, Roche, Sanofi and Teva Pharmaceutical. Dr. Sormani has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Received compensation for serving on Scientific Advisory Boards from TEVA, Genzyme, Novartis, Roche, and Vertex; funding for travel or speaker honoraria from Merck Serono, TEVA, Genzyme, Novartis, Biogen, and Roche; consultancy from Merck Serono, Biogen,. Dr. Uccelli has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Novartis, Merck Serono, Teva, Genzyme, Roche. Dr. Uccelli has received research support from Merck-Serono, Biogen, Novartis. Dr. Uitdehaag has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Genzyme, Biogen Idec, TEVA, Merck Serono, Roche. Dr. Vollmer has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Academic CME, Alcimed, Anthem Blue Cross, Genentech/Roche, Biogen IDEC, Novartis, CellGene, Epigene, Rocky Mountain MS Center, GLG Consulting, Ohio Health, TG Therapeutics, Topaz Therapeutics, Dleara Lawyers, Teva. Dr. Vollmer has received research support from Teva, NIH/NINDS, Rocky Mountain MS Center, Actelion, Roche/Genentech, UT Southwestern, TG Therapeutics. Dr. Reshef has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Teva. Dr. Li has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Teva. Dr. Feldman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Teva. Dr. Tansy has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Teva. Dr. Steinerman has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Employee of Teva.