Clinical trial NCT00168701: Efficacy and Safety of BG00012 in MS
Official title: Double-Blind, Placebo-Controlled, Dose-Ranging Study to Determine the Efficacy and Safety of BG00012 in Subjects With Relapsing-Remitting Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Multiple Sclerosis
Keywords: Multiple Sclerosis
MRI
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2005-09-15
Enrollment: 260
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: Determine the efficacy, safety, and tolerability of BG00012 in MS patients.

Detailed description: The study will be divided into two parts: Part 1 will be a 24-week, blinded, placebo-controlled treatment phase followed by Part 2, a 24-week blinded, safety extension phase in which all subjects will receive BG00012.

Eligibility criteria: Inclusion Criteria:

1. Must be 18 to 55 years old, inclusive, at the time of informed consent.
2. Must have a confirmed diagnosis of relapsing-remitting MS according to McDonald criteria #1-4 (McDonald et al, 2001; Appendix 2).
3. Must have a baseline EDSS between 0.0 and 5.0, inclusive.
4. Must have experienced at least one relapse within the 12 months prior to randomization, with a prior cranial MRI demonstrating lesion(s) consistent with MS OR show evidence of Gd-enhancing lesions of the brain on an MRI performed within the 6 weeks.
5. Male and female subjects must be willing to take appropriate measures to prevent pregnancy.

Exclusion Criteria:

1. Primary progressive, secondary progressive, or progressive relapsing MS (as defined by Lublin and Reingold, 1996 \[Appendix 3\]).
2. History of malignancy.
3. History of severe allergic or anaphylactic reactions or known drug hypersensitivity.
4. History of abnormal laboratory results indicative of any significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, gastrointestinal, dermatologic, psychiatric, renal, neurologic (other than MS), and/or other major disease.
5. History of human immunodeficiency virus (HIV).
6. History of drug or alcohol abuse (as defined by the Investigator) within the 2 years prior to randomization.
7. An MS relapse that has occurred within the 50 days prior to randomization AND/OR the subject has not stabilized from a previous relapse prior to randomization.
8. Body weight \>100 kg.
9. Positive for hepatitis C antibody and/or positive for hepatitis B surface antigen (HBsAg) at screening.
10. Any of the following abnormal blood tests at screening.
11. Any previous treatment with FUMADERM®, FAG-201, or BG00012.
12. A medication history that precludes entry into the study.
13. Female subjects who are currently pregnant or breast-feeding.

Primary outcomes:
measure: The primary endpoint for the primary objective is the total number of MRI lesions at Weeks 12, 16, 20, and 24.
timeFrame: Weeks 12, 16, 20, and 24
Secondary outcomes:
measure: The secondary endpoints will include measuring the changes in MRIs from baseline until Week 24, changes in other MS measurements q12 weeks, and the annualized relapse rate and proportion of changes at Weeks 24 and 48.
timeFrame: Weeks 24 and 48
Other outcomes:
Locations:
city: Bmo
country: Czechia
facility: Faculty Hospital St. Anne
city: Hradec Kralove
country: Czechia
facility: Faculty Hospital
city: Pardupice
country: Czechia
facility: Hospital of Pardubice
city: Plzen
country: Czechia
facility: Faculty Hospital of Plzen
city: Prague
country: Czechia
facility: General Teaching Hospital
city: Bochum
country: Germany
facility: Bochum am St. Josef-Hospital
city: Dusseldorf
country: Germany
facility: Heinrich-Heine-Universitat
city: Goettigen
country: Germany
facility: George-August-Universitat Goettigen
city: Budapest
country: Hungary
facility: Uzsoki Hospital
city: Debrecen
country: Hungary
facility: University of Debrecen
city: Gyor
country: Hungary
facility: Petz Aladar County Hospital
city: Amsterdam
country: Netherlands
facility: VUMC
city: Rotterdam
country: Netherlands
facility: Academic Hospital Rotterdam
city: Bialystok
country: Poland
facility: SamodzielnyPubliczny Szpital Kliniczny
city: Bialystok
country: Poland
facility: Niesalezny Zespol Opieki Zdrowognej
city: Bydgoszcz
country: Poland
facility: 10 Wojskowy Szpital Kliniczny z Poliklinika
city: Gdansk
country: Poland
facility: Wojewodzki Szpital Specjalistczny
city: Katowice-Ligota
country: Poland
facility: Slaskiej Akademii Medycznej
city: Krakow
country: Poland
facility: Szpital Uniwersytecki w Krakowie
city: Lodz
country: Poland
facility: Panstwowy Szpital Kliniczny
city: Warszawa
country: Poland
facility: Samodzielny Publiczny Centralny Szpital
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Moscow
country: Russian Federation
city: Novgorod
country: Russian Federation
city: Novosibirsk
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Molndal
country: Sweden
facility: MS Centrum
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
city: Basel
country: Switzerland
facility: Kantonsspital Basel
city: Ankara
country: Turkey
facility: Hacettepe Unisersitesi
city: Istanbul
country: Turkey
facility: Istanbul University
city: Istanbul
country: Turkey
facility: University of Instanbul
city: London
country: United Kingdom
facility: Multiple Sclerosis Reseach Clinic
city: London
country: United Kingdom
facility: Institute of Neurology
city: Sheffield
country: United Kingdom
facility: Royal Hampshire Hospital
city: Stoke-on-Trent
country: United Kingdom
facility: University Hospital of North Staffordshire
Study officials:
affiliation: Kantonsspital Basel
name: Ludwig Kappos, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Biogen
name: Gilmore O'Neill, MB,MRCPI,MMedSc
role: STUDY_DIRECTOR
References:
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, 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: Kappos L, Gold R, Miller DH, Macmanus DG, Havrdova E, Limmroth V, Polman CH, Schmierer K, Yousry TA, Yang M, Eraksoy M, Meluzinova E, Rektor I, Dawson KT, Sandrock AW, O'Neill GN; BG-12 Phase IIb Study Investigators. 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 Oct 25;372(9648):1463-72. doi: 10.1016/S0140-6736(08)61619-0.