Clinical trial NCT00451451: Efficacy and Safety Study of Oral BG00012 With Active Reference in Relapsing-Remitting Multiple Sclerosis
Official title: A Randomized, Multicenter, Placebo-Controlled and Active Reference (Glatiramer Acetate) Comparison Study to Evaluate the Efficacy and Safety of BG00012 in Subjects With Relapsing-Remitting Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Relapsing-Remitting Multiple Sclerosis
Keywords: relapsing
multiple sclerosis
oral
remitting
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2007-03-23
Enrollment: 1417
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To determine if treatment with BG00012 can decrease the number of MS relapses during a certain time period. Other goals of the study are to determine if, over time, BG00012 treatment can decrease the number of certain types of brain lesions commonly seen in MS patients and slow down the time it takes for MS to get worse.

Other objectives of the study are to determine the safety and tolerability of BG00012, as well as the effect it may have on tests and evaluations used to assess MS. Additionally, glatiramer acetate is being used to compare its benefits and risks with placebo and BG00012.

Detailed description: Multiple sclerosis (MS) is a chronic disease of the central nervous system that affects approximately 400,000 persons in North America and 365,000 persons in Europe. It is predominantly a disease of young adults, primarily women, with disease onset typically occurring between the ages of 20 and 40.

Eligibility criteria: Unless otherwise specified, to be eligible to participate in this study, candidates must meet the following eligibility criteria at the time of the randomization:

Key Inclusion Criteria:

* Must have confirmed diagnosis of RRMS according to McDonald criteria #1-4
* Must have a baseline EDSS between 0.0 and 5.0, inclusive.
* Must have relapsing-remitting disease course.

Key Exclusion Criteria:

* Other chronic disease of immune system, malignancies, urologic, pulmonary, gastrointestinal disease
* Pregnant or nursing women

Note: Other protocol-defined inclusion/exclusion criteria may apply.

Primary outcomes:
measure: Annualized Relapse Rate
timeFrame: 2 years
Secondary outcomes:
measure: Number of New or Newly Enlarging T2 Hyperintense Lesions
timeFrame: 2 years
measure: Number of New T1 Hypointense Lesions
timeFrame: 2 years
measure: Proportion of Subjects Relapsed
timeFrame: 2 years
measure: Proportion of Subjects Experiencing Progression of Disability Assessed Using the Expanded Disability Status Scale (EDSS)
timeFrame: 2 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Research Site
state: Alabama
city: Cullman
country: United States
facility: Research Site
state: Alabama
city: Huntsville
country: United States
facility: Research Site
state: Alabama
city: Phoenix
country: United States
facility: Research Site
state: Arizona
city: La Jolla
country: United States
facility: Research Site
state: California
city: Loma Linda
country: United States
facility: Research Site
state: California
city: Pasadena
country: United States
facility: Research Site
state: California
city: Sacramento
country: United States
facility: Research Site
state: California
city: Walnut Creek
country: United States
facility: Research Site
state: California
city: Boulder
country: United States
facility: Research Site
state: Colorado
city: Colorado Springs
country: United States
facility: Research Site
state: Colorado
city: Fort Collins
country: United States
facility: Research Site
state: Colorado
city: Maitland
country: United States
facility: Research Site
state: Florida
city: Miami
country: United States
facility: Research Site
state: Florida
city: Naples
country: United States
facility: Research Site
state: Florida
city: Pompano Beach
country: United States
facility: Research Site
state: Florida
city: Sarasota
country: United States
facility: Research Site
state: Florida
city: St. Petersburg
country: United States
facility: Research Site
state: Florida
city: Tallahassee
country: United States
facility: Research Site
state: Florida
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Augusta
country: United States
facility: Research Site
state: Georgia
city: Columbus
country: United States
facility: Research Site
state: Georgia
city: Meridan
country: United States
facility: Research Site
state: Idaho
city: Indianapolis
country: United States
facility: Research Site
state: Indiana
city: Kansas City
country: United States
facility: Research Site
state: Kansas
city: Louisville
country: United States
facility: Research Site
state: Kentucky
city: Shreveport
country: United States
facility: Research Site
state: Louisiana
city: Baltimore
country: United States
facility: Research Site
state: Maryland
city: Boston
country: United States
facility: Research Site
state: Massachusetts
city: Clinton Township
country: United States
facility: Research Site
state: Michigan
city: Grand Rapids
country: United States
facility: Research Site
state: Michigan
city: Dover
country: United States
facility: Research Site
state: New Hampshire
city: Lebanon
country: United States
facility: Research Site
state: New Hampshire
city: Freehold
country: United States
facility: Research Site
state: New Jersey
city: Teaneck
country: United States
facility: Research Site
state: New Jersey
city: Amherst
country: United States
facility: Research Site
state: New York
city: Buffalo
country: United States
facility: Research Site
state: New York
city: Cedarhurst
country: United States
facility: Research Site
state: New York
city: Mineola
country: United States
facility: Research Site
state: New York
city: Patchogue
country: United States
facility: Research Site
state: New York
city: Plainview
country: United States
facility: Research Site
state: New York
city: Staten Island
country: United States
facility: Research Site
state: New York
city: Stony Brook
country: United States
facility: Research Site
state: New York
city: Charlotte
country: United States
facility: Research Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Research Site
state: North Carolina
city: Bellevue
country: United States
facility: Research Site
state: Ohio
city: Cleveland
country: United States
facility: Research Site
state: Ohio
city: Columbus
country: United States
facility: Research Site
state: Ohio
city: Edmond
country: United States
facility: Research Site
state: Oklahoma
city: Eugene
country: United States
facility: Research Site
state: Oregon
city: Medford
country: United States
facility: Research Site
state: Oregon
city: Portland
country: United States
facility: Research Site
state: Oregon
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Research Site
state: Pennsylvania
city: Souderton
country: United States
facility: Research Site
state: Pennsylvania
city: Cordova
country: United States
facility: Research Site
state: Tennessee
city: Franklin
country: United States
facility: Research Site
state: Tennessee
city: Knoxville
country: United States
facility: Research Site
state: Tennessee
city: Memphis
country: United States
facility: Research Site
state: Tennessee
city: Nashville
country: United States
facility: Research Site
state: Tennessee
city: Dallas
country: United States
facility: Research Site
state: Texas
city: Galveston
country: United States
facility: Research Site
state: Texas
city: Houston
country: United States
facility: Research Site
state: Texas
city: Round Rock
country: United States
facility: Research Site
state: Texas
city: San Antonio
country: United States
facility: Research Site
state: Texas
city: Salt Lake City
country: United States
facility: Research Site
state: Utah
city: Burlington
country: United States
facility: Research Site
state: Vermont
city: Richmond
country: United States
facility: Research Site
state: Virginia
city: Seattle
country: United States
facility: Research Site
state: Washington
city: Tacoma
country: United States
facility: Research Site
state: Washington
city: Madison
country: United States
facility: Research Site
state: Wisconsin
city: Milwaukee
country: United States
facility: Research Site
state: Wisconsin
city: Gomel
country: Belarus
facility: Research Site
city: Minsk
country: Belarus
facility: Research Site
city: Vitebsk
country: Belarus
facility: Research Site
city: Lommel
country: Belgium
facility: Research Site
city: Sijsele-Damme
country: Belgium
facility: Research Site
city: Woluwe
country: Belgium
facility: Research Site
city: Tuzla
country: Bosnia and Herzegovina
facility: Research Site
state: B&H Federation
city: Banja Luka
country: Bosnia and Herzegovina
facility: Research Site
state: Republic Srpska
city: Sarajevo B&H Federation
country: Bosnia and Herzegovina
facility: Research Site
city: Plovdiv
country: Bulgaria
facility: Research Site
city: Rousse
country: Bulgaria
facility: Research Site
city: Sofia
country: Bulgaria
facility: Research Site
city: Stara Zagora
country: Bulgaria
facility: Research Site
city: Varna
country: Bulgaria
facility: Research Site
city: Edmonton
country: Canada
facility: Research Site
city: London
country: Canada
facility: Research Site
city: Montreal
country: Canada
facility: Research Site
city: Osijek
country: Canada
facility: Research Site
city: San Jose
country: Costa Rica
facility: Research Site
city: Rijeka
country: Croatia
facility: Research Site
city: Zagreb
country: Croatia
facility: Research Site
city: Ostrava-Moravska
country: Czech Republic
facility: Research Site
city: Ostrava
country: Czech Republic
facility: Research Site
city: Praha
country: Czech Republic
facility: Research Site
city: Kuressaare
country: Estonia
facility: Research Site
city: Parnu
country: Estonia
facility: Research Site
city: Tallinn
country: Estonia
facility: Research Site
city: Tartu
country: Estonia
facility: Research Site
city: Caen
country: France
facility: Research Site
city: Dijon
country: France
facility: Research Site
city: Marseille
country: France
facility: Research Site
city: Montpellier
country: France
facility: Research Site
city: Nancy
country: France
facility: Research Site
city: Nimes
country: France
facility: Research Site
city: Strasbourg
country: France
facility: Research Site
city: Bamberg
country: Germany
facility: Research Site
city: Bayreuth
country: Germany
facility: Research Site
city: Berg Starnberger
country: Germany
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Dusseldorf
country: Germany
facility: Research Site
city: Erbach
country: Germany
facility: Research Site
city: Erlangen
country: Germany
facility: Research Site
city: Giessen
country: Germany
facility: Research Site
city: Halle (Saale)
country: Germany
facility: Research Site
city: Hanburg
country: Germany
facility: Research Site
city: Heidelberg
country: Germany
facility: Research Site
city: Koln
country: Germany
facility: Research Site
city: Magdeburg
country: Germany
facility: Research Site
city: Marburg
country: Germany
facility: Research Site
city: Munchen
country: Germany
facility: Research Site
city: Regensburg
country: Germany
facility: Research Site
city: Schwerin
country: Germany
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Larisa
country: Greece
facility: Research Site
city: Patra
country: Greece
facility: Research Site
city: Thessaloniki
country: Greece
facility: Research Site
city: Ahmedabad
country: India
facility: Research Site
city: Bangalore
country: India
facility: Research Site
city: Calicut
country: India
facility: Research Site
city: Chandigarh
country: India
facility: Research Site
city: Chennai
country: India
facility: Research Site
city: Cochin
country: India
facility: Research Site
city: Coimbatore
country: India
facility: Research Site
city: Kochi
country: India
facility: Research Site
city: Kolkata
country: India
facility: Research Site
city: Lucknow
country: India
facility: Research Site
city: Ludhiana
country: India
facility: Research Site
city: Mangalore
country: India
facility: Research Site
city: Mumbai
country: India
facility: Research Site
city: New Delhi
country: India
facility: Research Site
city: Pune
country: India
facility: Research Site
city: Cork
country: Ireland
facility: Research Site
city: Dublin
country: Ireland
facility: Research Site
city: Galway
country: Ireland
facility: Research Site
city: Holon
country: Israel
facility: Research Site
city: Safed
country: Israel
facility: Research Site
city: Riga
country: Latvia
facility: Research Site
city: Skopje
country: Macedonia, The Former Yugoslav Republic of
facility: Research Site
city: Guadalajara
country: Mexico
facility: Research Site
state: Jal
city: Morelia
country: Mexico
facility: Research Site
state: Michoacan
city: Monterrey
country: Mexico
facility: Research Site
state: Nuevo Leon
city: Aguascalientes
country: Mexico
facility: Research Site
city: Guadalajara
country: Mexico
facility: Research Site
city: Mexico DF
country: Mexico
facility: Research Site
city: Mexico DF
country: Mexico
facility: Research Site
city: Mexico
country: Mexico
facility: Research Site
city: Monterray
country: Mexico
facility: Research Site
city: Chisinau
country: Moldova, Republic of
facility: Research Site
city: Kishinev
country: Moldova, Republic of
facility: Research Site
city: Hamilton
country: New Zealand
facility: Research Site
city: Bialystok
country: Poland
facility: Research Site
city: Gdansk
country: Poland
facility: Research Site
city: Katowice
country: Poland
facility: Research Site
city: Lodz
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Poznan
country: Poland
facility: Research Site
city: Szczecin
country: Poland
facility: Research Site
city: Warsaw
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Wroclaw
country: Poland
facility: Research Site
city: Guaynabo
country: Puerto Rico
facility: Research Site
city: Bucuresti
country: Romania
facility: Research Site
city: Iasi
country: Romania
facility: Research Site
city: Oradea
country: Romania
facility: Research Site
city: Tirgu Mures
country: Romania
facility: Research Site
city: Tirgu-Mures
country: Romania
facility: Research Site
city: Belgrade
country: Serbia
facility: Research Site
city: Kragujevac
country: Serbia
facility: Research Site
city: Nis
country: Serbia
facility: Research Site
city: Novi Sad
country: Serbia
facility: Research Site
city: Kosice
country: Slovakia
facility: Research Site
city: Martin
country: Slovakia
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Bilbao
country: Spain
facility: Research Site
city: Cordoba
country: Spain
facility: Research Site
city: Gandia
country: Spain
facility: Research Site
city: Madrid
country: Spain
facility: Research Site
city: Malaga
country: Spain
facility: Research Site
city: Santiago de Compostela
country: Spain
facility: Research Site
city: Sevilla
country: Spain
facility: Research Site
city: Kharkiv
country: Ukraine
facility: Research Site
city: Kyiv
country: Ukraine
facility: Research Site
city: Lviv
country: Ukraine
facility: Research Site
city: Odessa
country: Ukraine
facility: Research Site
city: Poltava
country: Ukraine
facility: Research Site
city: Simferopol
country: Ukraine
facility: Research Site
city: Zaporozhye
country: Ukraine
facility: Research Site
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Gold R, Arnold DL, Bar-Or A, Fox RJ, Kappos L, Chen C, Parks B, Miller C. Safety and efficacy of delayed-release dimethyl fumarate in patients with relapsing-remitting multiple sclerosis: 9 years' follow-up of DEFINE, CONFIRM, and ENDORSE. Ther Adv Neurol Disord. 2020 May 12;13:1756286420915005. doi: 10.1177/1756286420915005. eCollection 2020.
citation: Mehta D, Miller C, Arnold DL, Bame E, Bar-Or A, Gold R, Hanna J, Kappos L, Liu S, Matta A, Phillips JT, Robertson D, von Hehn CA, Campbell J, Spach K, Yang L, Fox RJ. Effect of dimethyl fumarate on lymphocytes in RRMS: Implications for clinical practice. Neurology. 2019 Apr 9;92(15):e1724-e1738. doi: 10.1212/WNL.0000000000007262. Epub 2019 Mar 27.
citation: Fox RJ, Gold R, Phillips JT, Okwuokenye M, Zhang A, Marantz JL. Efficacy and Tolerability of Delayed-release Dimethyl Fumarate in Black, Hispanic, and Asian Patients with Relapsing-Remitting Multiple Sclerosis: Post Hoc Integrated Analysis of DEFINE and CONFIRM. Neurol Ther. 2017 Dec;6(2):175-187. doi: 10.1007/s40120-017-0077-5. Epub 2017 Aug 2.
citation: Fernandez O, Giovannoni G, Fox RJ, Gold R, Phillips JT, Potts J, Okwuokenye M, Marantz JL. Efficacy and Safety of Delayed-release Dimethyl Fumarate for Relapsing-remitting Multiple Sclerosis in Prior Interferon Users: An Integrated Analysis of DEFINE and CONFIRM. Clin Ther. 2017 Aug;39(8):1671-1679. doi: 10.1016/j.clinthera.2017.06.012. Epub 2017 Jul 25.
citation: Fox RJ, Chan A, Zhang A, Xiao J, Levison D, Lewin JB, Edwards MR, Marantz JL. Comparative effectiveness using a matching-adjusted indirect comparison between delayed-release dimethyl fumarate and fingolimod for the treatment of multiple sclerosis. Curr Med Res Opin. 2017 Feb;33(2):175-183. doi: 10.1080/03007995.2016.1248380. Epub 2016 Nov 10.
citation: Gold R, Giovannoni G, Phillips JT, Fox RJ, Zhang A, Marantz JL. Sustained Effect of Delayed-Release Dimethyl Fumarate in Newly Diagnosed Patients with Relapsing-Remitting Multiple Sclerosis: 6-Year Interim Results From an Extension of the DEFINE and CONFIRM Studies. Neurol Ther. 2016 Jun;5(1):45-57. doi: 10.1007/s40120-016-0042-8. Epub 2016 Mar 1.
citation: Giovannoni G, Gold R, Fox RJ, Kappos L, Kita M, Yang M, Sarda SP, Zhang R, Viglietta V, Havrdova E. Relapses Requiring Intravenous Steroid Use and Multiple-Sclerosis-related Hospitalizations: Integrated Analysis of the Delayed-release Dimethyl Fumarate Phase III Studies. Clin Ther. 2015 Nov 1;37(11):2543-51. doi: 10.1016/j.clinthera.2015.09.011. Epub 2015 Oct 31.
citation: Fox RJ, Kita M, Cohan SL, Henson LJ, Zambrano J, Scannevin RH, O'Gorman J, Novas M, Dawson KT, Phillips JT. BG-12 (dimethyl fumarate): a review of mechanism of action, efficacy, and safety. Curr Med Res Opin. 2014 Feb;30(2):251-62. doi: 10.1185/03007995.2013.849236. Epub 2013 Oct 22.
citation: Fox RJ, Miller DH, Phillips JT, Hutchinson M, Havrdova E, Kita M, Yang M, Raghupathi K, Novas M, Sweetser MT, Viglietta V, Dawson KT; CONFIRM Study Investigators. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med. 2012 Sep 20;367(12):1087-97. doi: 10.1056/NEJMoa1206328.