DEFINE
What it found
The main measure showed a statistically significant benefit.
“The estimated proportion of patients who had a relapse was significantly lower in the two BG-12 groups than in the placebo group (27% with BG-12 twice daily and 26% with BG-12 thrice daily vs. 46% with placebo, P<0.001 for both comparisons).”Read by software from the paper's abstract
Proportion of patients who had a relapse by 2 years · 2 years
| Group | n | Value |
|---|---|---|
| Placebo | 46% |
p = <0.001 for both comparisons
Read by software from the paper's abstract
What was tested
Treatment tested
- Dimethyl fumarate
Kelch-like ECH-associated protein 1 inhibitor
Placebo or sham
- Placebo
Results by group
Proportion of Subjects Relapsed
2 years
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| Placebo | 0.461 Proportion of subjects,confirmed relapse | 408 | |
| BG00012 240 mg Twice Daily (BID) | 0.270 Proportion of subjects,confirmed relapse | 410 | |
| BG00012 240 mg 3 Times Daily (TID) | 0.260 Proportion of subjects,confirmed relapse | 416 |
Placebo
BG00012 240 mg Twice Daily (BID)
BG00012 240 mg 3 Times Daily (TID)
Values as posted on ClinicalTrials.gov. Outcomes measured differently across trials are not directly comparable.
Safety
| Group | Participants at risk | Serious adverse events | Deaths |
|---|---|---|---|
| Placebo | 408 | 86 (21.1%) | |
| BG00012 240 mg Twice Daily (BID) | 410 | 74 (18.0%) | |
| BG00012 240 mg 3 Times Daily (TID) | 416 | 65 (15.6%) | |
| Total BG00012 | 826 | 139 (16.8%) |
As posted on ClinicalTrials.gov. Serious adverse events include any serious health event during the trial, whether or not the treatment caused it.
What it measured
Main measures
Proportion of Subjects Relapsed
2 years
RelapsesProportion of subjects relapsed at 2 years
Relapses
Other measures (5)
Number of New or Newly Enlarging T2 Hyperintense Lesions
2 years
MRI lesionsNumber of Gadolinium-enhancing T1-weighted Lesions
2 years
MRI lesionsNumber of Subjects With Gadolinium (Gd)-Enhancing Lesions
2 years
MRI lesionsAnnualized Relapse Rate
2 years
Disability progressionRelapsesProportion of Subjects Experiencing Progression of Disability Assessed Using the Expanded Disability Status Scale (EDSS)
2 years
Disability progression
Who could take part
Relapsing MS · 18 to 55
Key Inclusion 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: * Must have a 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: * Unless otherwise specified, candidates will be excluded from study entry if any of the following exclusion criteria exist at randomization: * Other chronic disease of the immune system, malignancies, acute urologic, pulmonary, gastrointestinal disease. * Pregnant or nursing women. Note: Other protocol-defined inclusion/exclusion criteria may apply.
As registered. Criteria can change, so ask the trial team or your neurologist.
About this trial
In the sponsor's words
To determine if treatment with BG00012 can decrease the number of MS relapses during a certain time period. 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 the disease to get worse. The purpose of this study is also to determine the safety of BG00012 and how well it is tolerated. Another goal is to see what effect BG00012 may have on tests and evaluations used to assess MS.
Papers
Results
Long-term safety and efficacy of dimethyl fumarate for up to 13 years in patients with relapsing-remitting multiple sclerosis: Final ENDORSE study results.Mult Scler · 2022
Results
Dimethyl fumarate treatment shifts the immune environment toward an anti-inflammatory cell profile while maintaining protective humoral immunity.Mult Scler · 2021
Results
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
Results
Effect of delayed-release dimethyl fumarate on no evidence of disease activity in relapsing-remitting multiple sclerosis: integrated analysis of the phase III DEFINE and CONFIRM studies.Eur J Neurol · 2017
Results
Comparing outcomes from clinical studies of oral disease-modifying therapies (dimethyl fumarate, fingolimod, and teriflunomide) in relapsing MS: Assessing absolute differences using a number needed to treat analysis.Mult Scler Relat Disord · 2016
Results
Time course of clinical and neuroradiological effects of delayed-release dimethyl fumarate in multiple sclerosis.Eur J Neurol · 2015
Results
Effects of delayed-release dimethyl fumarate on MRI measures in the Phase 3 DEFINE study.J Neurol · 2014
Results
Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis.N Engl J Med · 2012
The estimated proportion of patients who had a relapse was significantly lower in the two BG-12 groups than in the placebo group (27% with BG-12 twice daily and 26% with BG-12 thrice daily vs. 46% with placebo, P<0.001 for both comparisons).
Read by software from the paper's abstract
Results
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.Results
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.
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History
Started
Jan 2007
Main results due
Feb 2011
Finished
Feb 2011
Results posted
Jun 2014
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