PARADIGMS: a randomised double-blind study of fingolimod versus interferon β-1a in paediatric multiple sclerosis
ECTRIMS Online Library. Chitnis T. Oct 28, 2017; 202640; 276
Tanuja Chitnis
Tanuja Chitnis

Abstract: 276

Type: Oral

Background: Approximately 3‒5% of all patients with multiple sclerosis (MS) have disease onset before 18 years of age. These paediatric patients have a 2‒3 times higher relapse rate than patients with adult-onset MS. The PARADIGMS trial is the first global, controlled trial investigating the efficacy and safety of fingolimod in paediatric patients with MS.
Objective: To investigate the efficacy and safety of fingolimod up to 0.5 mg daily versus interferon (IFN) β-1a 30 µg intramuscular (IM) in paediatric patients with relapsing-remitting MS (RRMS).
Methods: PARADIGMS is an up to 2-year, double-blind, double-dummy, active-controlled, parallel-group, multicentre study, followed by a 5-year fingolimod open-label extension phase in paediatric patients with MS aged 10 to less than 18 years at randomisation. Patients were randomised (1:1) to receive either oral fingolimod once daily (dose adjusted for body weight) or IFN β-1a 30 µg IM once weekly. The study included patients who have experienced at least one relapse in the past year or two relapses in the previous 2 years or have evidence of one or more gadolinium-enhancing (Gd+) lesions on magnetic resonance imaging (MRI) within 6 months prior to randomisation. The primary objective was to evaluate the efficacy of fingolimod versus IFN β-1a IM in reducing the annualised relapse rate. Other assessments included other relapse and MRI related outcomes, Expanded Disability Status Scale (EDSS), safety and tolerability.
Results: Baseline characteristics of the first 190 randomised patients who were representative of a paediatric population with RRMS are reported here. The mean age of these patients at the time of randomisation was 15.3 years (median=16; range 10-18); the majority were white non-Hispanic (88%, n=168) females (63%, n=120). Their mean disease duration was 1.2 years, the mean number of relapses in the 12 months before screening was 1.5 and number of Gd+ T1 lesions 3.1; median EDSS score was 1.5. Baseline characteristics of all patients (N=215; database lock August, 2017), patient disposition, and the primary efficacy and safety results will be presented at the time of the congress.
Conclusion: PARADIGMS is the first randomised clinical trial in paediatric MS. The results of the study will determine if fingolimod is beneficial in a paediatric population with short disease duration and high clinical and MRI disease activity.
Disclosure: Funding source: This study is supported by Novartis Pharma AG, Basel, Switzerland. The following authors have received compensation for serving as consultants or speakers, or they or the institutions they work for have received research support from the companies indicated:
Tanuja Chitnis has received personal compensation for advisory boards/consulting for F. Hoffman-La Roche, Biogen and Novartis Pharmaceuticals and financial support for research activities from Biogen, Merck Serono, Verily and Novartis Pharmaceuticals.
Douglas L. Arnold has received honoraria from Acorda, Biogen Idec, Genentech, Genzyme, Novartis, F. Hoffmann-La Roche and Sanofi-Aventis, has received research support from Novartis and Biogen, and has an equity interest in NeuroRx Research, which performed the MRI analysis for the trial.
Brenda Banwell has served as an unpaid consultant to Biogen-Idec, Novartis, Teva Neuroscience, Merck-Serono, Canadian MS society scientific research foundation (CMSRF), Canadian Multiple Sclerosis Society (CMSS), National Multiple Sclerosis Society (NMSS) and Canadian Institutes of Health Research (CIHR); as a remunerated central MRI reviewer for the present trial.
Wolfgang Brück has received honoraria for lectures by Bayer Vital, Biogen, Merck Serono Teva Pharma, Genzyme, Sanofi-Aventis and Novartis and is a member of scientific advisory boards for Teva Pharma, Biogen, Medday, Novartis and Genzyme. He received funding for research projects by Teva Pharma, Biogen, Novartis and Genzyme. He serves on the editorial boards of Neuropathology and Applied Neurobiology, Multiple Sclerosis International and Therapeutic Advances in Neurological Disorders.
Angelo Ghezzi has received speaker honoraria from Almirall, Biogen Idec, Merck Serono, Novartis, Genzyme and Sanofi-Aventis; and for consultancy from Merck Serono, Biogen Idec, Teva, F. Hoffmann-La Roche and Novartis Pharmaceuticals.
Gavin Giovannoni has received fees for participation in advisory board for AbbVie, Almirall, Atara Bio, Biogen, Canbex, Ironwood, Novartis, Merck, Merck Serono, F. Hoffmann-La Roche, Sanofi Genzyme, Synthon, Teva, and Vertex; speaker fees from AbbVie Biotherapeutics Inc., Biogen, Bayer HealthCare, Genzyme, Merck Serono, SanofiAventis, and Teva; coeditor in chief of Multiple Sclerosis and Related Disorders; research support unrelated to study from Biogen, Genzyme, Ironwood, Merck Serono, and Novartis.
Benjamin Greenberg has received compensation for consulting services from EMD Serono and Novartis. He has received grant support from Chugai, Biogen, Acorda, Medimmune, PCORI, NIH, Genentech, and Guthy Jackson Charitable Foundation.
Lauren Krupp has received personal compensation for activities as a speaker, consultant and/or participant on an advisory board from Biogen Idec, Novartis Pharmaceuticals, Teva Neurosciences, and Multicell; royalty or license fees from ER Squibb & Sons, Avenir, Johnson & Johnson, and Osmotica; grant support from the National Multiple Sclerosis Society, National Institutes of Health, and the Department of Defense; and research support from Novartis, Biogen Idec, Celgene Corporation, and Genentech. She has also received support from the Lourie Foundation, Slomo and Cindy Silvian Foundation, and the Multiple Sclerosis Foundation.
Kevin Rostasy has served as a consultant for PARADIGMS study.
Marc Tardieu is a member of scientific boards for Novartis, Sanofi and Uniqure.
Emmanuelle Waubant is funded by the NIH, NMSS, PCORI and Race to Erase MS. She volunteers on an advisory board for a Novartis trial. She is a site PI for clinical trials with Roche and Novartis.
Jerry Wolinsky in the last 3 years has received compensation for service on steering committees or data monitoring boards for F. Hoffmann-La Roche, Medday Pharmaceuticals, Novartis, Sanofi Genzyme and Teva Pharmaceuticals; consultant fees from AbbVie, Actelion, Alkermes, EMD Serono, Forward Pharma, Genentech, Inc., F. Hoffmann-La Roche, Novartis, Sanofi Genzyme, Takeda, Teva, and XenoPort; research support from, Sanofi Genzyme, the NIH and the NMSS through the University of Texas Health Science Center at Houston (UTHSCH) and royalties for monoclonal antibodies out-licensed to Chemicon International through UTHSCH.
Amit Bar-Or has participated as a speaker at meetings sponsored by, received consulting fees and/or received grant support from: Biogen Idec, F. Hoffmann-La Roche/Genentech, GlaxoSmithKline, Merck/EMD Serono, Medimmune, Novartis, Celgene/Receptos and Sanofi-Genzyme.
Jutta Gärtner in the last three years has received honoraria for lectures and consultancy fees from Bayer Vital, Biogen, Teva and Novartis.
Tracy Stites, Yu Chen and Martin Merschhemke are employees of Novartis.

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