Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis

New England Journal of Medicine

Volumn 367, Issue 12, 2012, Pages 1098-1107

  Gold, Ralf ^a   Kappos, Ludwig ^b   Arnold, Douglas L ^c,d   Bar Or, Amit ^d   Giovannoni, Gavin ^e   Selmaj, Krzysztof ^f   Tornatore, Carlo ^g   Sweetser, Marianne T ^h   Yang, Minhua ^h   Sheikh, Sarah I ^h   Dawson, Katherine T ^h  

^a ST JOSEF HOSPITAL   (Germany)

^b UNIVERSITY HOSPITAL BASEL   (Switzerland)

^c NEURORX RESEARCH   (Canada)

^d MCGILL UNIVERSITY   (Canada)

^e QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

^f MEDICAL UNIVERSITY OF LODZ   (Poland)

^g GEORGETOWN UNIVERSITY HOSPITAL   (United States)

^h BIOGEN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

FUMARIC ACID DIMETHYL ESTER; GADOLINIUM; PLACEBO;

ABDOMINAL PAIN; ADULT; ARTICLE; CONTROLLED STUDY; DIARRHEA; DISEASE ASSOCIATION; DISEASE COURSE; DISEASE SEVERITY; DOSAGE SCHEDULE COMPARISON; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG FATALITY; DRUG INDUCED HEADACHE; DRUG RESPONSE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; FEMALE; FLUSHING; GASTROENTERITIS; GASTROINTESTINAL SYMPTOM; HUMAN; HYPERTRANSAMINASEMIA; INCIDENCE; INFECTION; INTENTION TO TREAT ANALYSIS; KIDNEY FAILURE; LYMPHOCYTE COUNT; MAJOR CLINICAL STUDY; MALE; MALIGNANT NEOPLASTIC DISEASE; MULTIPLE SCLEROSIS; NAUSEA; NUCLEAR MAGNETIC RESONANCE IMAGING; OUTCOME ASSESSMENT; OVARY CYST; PHASE 3 CLINICAL TRIAL; PNEUMONIA; PRIORITY JOURNAL; PROTEINURIA; PRURITUS; RANDOMIZED CONTROLLED TRIAL; RISK REDUCTION; SIDE EFFECT; VOMITING;

EID: 84866423965     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJMoa1114287     Document Type: Article

References (21)

1. Linker RA, Lee DH, Ryan S, et al. Fumaric acid esters exert neuroprotective effects in neuroinflammation via activation of the Nrf2 antioxidant pathway. Brain 2011;134:678-92.
2. Gilgun-Sherki Y, Melamed E, Offen D. The role of oxidative stress in the pathogenesis of multiple sclerosis: the need for effective antioxidant therapy. J Neurol 2004;251:261-8.
3. Johnson DA, Amirahmadi S, Ward C, Fabry Z, Johnson JA. The absence of the pro-antioxidant transcription factor Nrf2 exacerbated experimental autoimmune encephalomyelitis. Toxicol Sci 2010;114:237-46.
4. Scannevin RH, Chollate S, Jung MY, et al. Fumarates promote cytoprotection of central nervous system cells against oxidative stress via the Nrf2 pathway. J Pharmacol Exp Ther 2012;341:274-84.
5. Ghoreschi K, Bruck J, Kellerer C, et al. Fumarates improve psoriasis and multiple sclerosis by inducing type II dendritic cells. J Exp Med 2011;208:2291-303.
6. Loewe R, Holnthoner W, Groger M, et al. Dimethylfumarate inhibits TNFinduced nuclear entry of NF-kappa B/p65 in human endothelial cells. J Immunol 2002;168:4781-7.
7. Kappos L, Gold R, Miller DH, et al. Efficacy and safety of oral fumarate in patients with relapsing-remitting multiple sclerosis: a multicentre, randomised, double-blind, placebo-controlled phase IIb study. Lancet 2008;372:1463-72. [Erratum, Lancet 2009;373:1340.]
8. Polman CH, Reingold SC, Edan G, et al. Diagnostic criteria for multiple sclerosis: 2005 revisions to the "McDonald Criteria." Ann Neurol 2005;58:840-6.
9. Lublin FD, Reingold SC. Defining the clinical course of multiple sclerosis: results of an international survey. Neurology 1996;46:907-11.
10. Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an Expanded Disability Status Scale (EDSS). Neurology 1983;33:1444-52.
11. International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). ICH harmonized tripartite guideline - guideline for good clinical practice: E6(R1). Geneva: ICH, June 10, 1996 (http://www.ich.org/fileadmin/Public-Web-Site/ICH-Products/Guidelines/ Efficacy/E6-R1/Step4/E6-R1--Guideline.pdf).
12. Declaration of Helsinki - ethical principles for medical research involving human subjects. Ferney-Voltaire, France: World Medical Association (http://www.wma.net/en/30publications/10policies/b3/index.html).
13. Polman CH, O'Connor PW, Havrdova E, et al. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med 2006;354:899-910.
14. Fox RJ, Miller DH, Phillips JT, et al. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med 2012;367:1087-97.
15. Biogen Idec announces positive topline results from second phase 3 trial investigating oral BG-12 (dimethyl fumarate) in multiple sclerosis. Press release of Biogen Idec, Weston, MA, October 26, 2011 (http://www.biogenidec.com/ PRESS-RELEASE-DETAILS.aspx?ID=5981&ReqId=1621631).
16. PRISMS Study Group. PRISMS-4: long-term efficacy of interferon-beta-1a in relapsing MS. Neurology 2001;56:1628-36. [Erratum, Neurology 2001;57:1146.]
17. Jacobs LD, Cookfair DL, Rudick RA, et al. Intramuscular interferon beta-1a for disease progression in relapsing multiple sclerosis. Ann Neurol 1996;39:285-94. [Erratum, Ann Neurol 1996;40:480.]
18. Johnson KP, Brooks BR, Cohen JA, et al. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind placebo-controlled trial. Neurology 1995;45:1268-76.
19. Vollmer TL, Soelberg Sørensen P, Arnold DL, et al. A placebo-controlled and active comparator phase III trial (BRAVO) for relapsing-remitting multiple sclerosis. Mult Scler 2011;17:Suppl:S507. abstract.
20. Cohen JA, Barkhof F, Comi G, et al. Oral fingolimod or intramuscular interferon for relapsing multiple sclerosis. N Engl J Med 2010;362:402-15.
21. Kappos L, Radue EW, O'Connor P, et al. A placebo-controlled trial of oral fingolimod in relapsing multiple sclerosis. N Engl J Med 2010;362:387-401.