ENDORSE
What it found
The main measure was safety, drug levels or similar, not whether the treatment works.
“Overall, 551 (32%) patients experienced serious adverse events (mostly multiple sclerosis (MS) relapse or fall; one progressive multifocal leukoencephalopathy); 243 (14%) discontinued treatment due to adverse events (4% gastrointestinal (GI) disorders).”Read by software from the paper's abstract
Total participants: 1736
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
Number of Participants With Treatment-Emergent Adverse Events (AEs)
Day 1 up to Week 561
| Group | Value | Interval | Number analysed |
|---|---|---|---|
| BG00012 240 mg BID | 824 Participants | 868 | |
| BG00012 240 mg TID | 814 Participants | 868 |
BG00012 240 mg BID
BG00012 240 mg 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 |
|---|---|---|---|
| BG00012 240 mg BID | 868 | 279 (32.1%) | 5 |
| BG00012 240 mg TID | 868 | 272 (31.3%) | 6 |
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
Number of Participants With Treatment-Emergent Adverse Events (AEs)
Day 1 up to Week 561
SafetyThe primary objective and endpoint is to evaluate the long-term safety profile of BG00012.
Safety
Other measures (16)
Percentage of Participants Who Had Relapses
Day 1 up to Week 384
RelapsesAnnualized Relapse Rate (ARR)
Day 1 up to Week 384
RelapsesChange From Baseline in the Expanded Disability Status Scale (EDSS) at Week 384
Baseline, Week 384
Disability progressionNumber of Gadolinium (Gd)-Enhancing Lesions as Measured by Magnetic Resonance Imaging (MRI)
Baseline up to Week 288
MRI lesionsVolume of Gd-Enhancing Lesions as Measured by Magnetic Resonance Imaging (MRI)
Baseline up to Week 288
MRI lesionsNumber of New or Newly Enlarging T2 Lesions as Measured by Magnetic Resonance Imaging (MRI)
Baseline up to Week 288
MRI lesionsVolume of New or Newly Enlarging T2 Lesions as Measured by Magnetic Resonance Imaging (MRI)
Baseline up to Week 288
MRI lesionsNumber of T1 Hypointense Lesions as Measured by Magnetic Resonance Imaging (MRI)
Baseline up to Week 288
MRI lesionsVolume of T1 Hypointense Lesions as Measured by Magnetic Resonance Imaging (MRI)
Baseline up to Week 288
MRI lesionsPercent Change From Baseline in Brain Atrophy
Baseline up to Week 288
MRI lesionsBrain volume loss
Who could take part
Relapsing MS · 19 to 58
Key Inclusion Criteria: -Subjects who participated in and completed as per protocol previous BG00012 clinical studies 109MS301 (NCT00420212) or 109MS302 (NCT00451451). Key Exclusion Criteria: * Any significant change in medical history from 109MS301 or 109MS302 that would have excluded subject's participation from their previous study. * Subjects from 109MS301 or 109MS302 who discontinued oral study treatment due to an AE or due to reasons other than protocol-defined relapse/disability progression. * Subjects from 109MS301 or 109MS302 who discontinued study treatment due to disability progression or relapses and did not follow the modified visit schedule up to Week 96. 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
The primary objective of this study is to evaluate the long-term safety profile of BG00012 (dimethyl fumarate). Secondary objectives of this study are to evaluate the long-term efficacy of BG00012 using clinical endpoints and disability progression, to evaluate further the long-term effects of BG00012 on multiple sclerosis (MS) brain lesions on magnetic resonance imaging (MRI) scans in participants who had MRI scans as part of Studies 109MS301 (NCT00420212) and 109MS302 (NCT00451451) and to evaluate the long-term effects of BG00012 on health economics assessments and the visual function test.
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
Overall, 551 (32%) patients experienced serious adverse events (mostly multiple sclerosis (MS) relapse or fall; one progressive multifocal leukoencephalopathy); 243 (14%) discontinued treatment due to adverse events (4% gastrointestinal (GI) disorders).
Read by software from the paper's abstract
Results
Long-term effects of delayed-release dimethyl fumarate in multiple sclerosis: Interim analysis of ENDORSE, a randomized extension study.Mult Scler · 2017
Results
Time course of clinical and neuroradiological effects of delayed-release dimethyl fumarate in multiple sclerosis.Eur J Neurol · 2015
Results
Amezcua L, Mao-Draayer Y, Vargas WS, Farber R, Schaefer S, Branco F, England SM, Belviso N, Lewin JB, Mendoza JP, Shankar SL; ENDORSE Study Investigators. Efficacy of Dimethyl Fumarate in Young Adults with Relapsing-Remitting Multiple Sclerosis: Analysis of the DEFINE, CONFIRM, and ENDORSE Studies. Neurol Ther. 2023 Jun;12(3):883-897. doi: 10.1007/s40120-023-00475-8. Epub 2023 Apr 15.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.Results
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.
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History
Started
Feb 2009
Main results due
Nov 2019
Finished
Nov 2019
Results posted
Dec 2020
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