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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00835770




Registration number
NCT00835770
Ethics application status
Date submitted
2/02/2009
Date registered
4/02/2009
Date last updated
31/12/2020

Titles & IDs
Public title
BG00012 Monotherapy Safety and Efficacy Extension Study in Multiple Sclerosis (MS)
Scientific title
A Dose-Blind, Multicenter, Extension Study to Determine the Long-Term Safety and Efficacy of Two Doses of BG00012 Monotherapy in Subjects With Relapsing-Remitting Multiple Sclerosis
Secondary ID [1] 0 0
2008-004753-14
Secondary ID [2] 0 0
109MS303
Universal Trial Number (UTN)
Trial acronym
ENDORSE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Relapsing-Remitting Multiple Sclerosis 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - dimethyl fumarate
Treatment: Drugs - Placebo

Experimental: BG00012 plus placebo - In the first phase, participants will receive BG00012 240 mg (two 120 mg capsules) twice a day (BID) and 2 placebo capsules once a day. In the second phase participants will receive open-label BG00012 240 mg BID, for atleast 8 years.

Experimental: BG00012 - In the first phase participants will receive BG00012 240 mg (two 120 mg capsules) three times a day (TID). In the second phase participants will receive open-label BG00012 240 mg BID for atleast 8 years.


Treatment: Drugs: dimethyl fumarate
BG00012 capsules

Treatment: Drugs: Placebo
Capsules taken to maintain the blind in the 240 mg BID treatment group.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of Participants With Treatment-Emergent Adverse Events (AEs)
Timepoint [1] 0 0
Day 1 up to Week 561
Secondary outcome [1] 0 0
Percentage of Participants Who Had Relapses
Timepoint [1] 0 0
Day 1 up to Week 384
Secondary outcome [2] 0 0
Annualized Relapse Rate (ARR)
Timepoint [2] 0 0
Day 1 up to Week 384
Secondary outcome [3] 0 0
Change From Baseline in the Expanded Disability Status Scale (EDSS) at Week 384
Timepoint [3] 0 0
Baseline, Week 384
Secondary outcome [4] 0 0
Number of Gadolinium (Gd)-Enhancing Lesions as Measured by Magnetic Resonance Imaging (MRI)
Timepoint [4] 0 0
Baseline up to Week 288
Secondary outcome [5] 0 0
Volume of Gd-Enhancing Lesions as Measured by Magnetic Resonance Imaging (MRI)
Timepoint [5] 0 0
Baseline up to Week 288
Secondary outcome [6] 0 0
Number of New or Newly Enlarging T2 Lesions as Measured by Magnetic Resonance Imaging (MRI)
Timepoint [6] 0 0
Baseline up to Week 288
Secondary outcome [7] 0 0
Volume of New or Newly Enlarging T2 Lesions as Measured by Magnetic Resonance Imaging (MRI)
Timepoint [7] 0 0
Baseline up to Week 288
Secondary outcome [8] 0 0
Number of T1 Hypointense Lesions as Measured by Magnetic Resonance Imaging (MRI)
Timepoint [8] 0 0
Baseline up to Week 288
Secondary outcome [9] 0 0
Volume of T1 Hypointense Lesions as Measured by Magnetic Resonance Imaging (MRI)
Timepoint [9] 0 0
Baseline up to Week 288
Secondary outcome [10] 0 0
Percent Change From Baseline in Brain Atrophy
Timepoint [10] 0 0
Baseline up to Week 288
Secondary outcome [11] 0 0
Percent Change From Baseline in Magnetization Transfer Ratio (MTR)
Timepoint [11] 0 0
Baseline up to Week 288
Secondary outcome [12] 0 0
Change From Baseline in Short Form-36 Health Survey (SF-36®) at Week 384
Timepoint [12] 0 0
Baseline, Week 384
Secondary outcome [13] 0 0
Change From Baseline in EuroQol 5 Dimensions Questionnaire (EQ-5D) Health Survey - EQ-5D Index Score at Week 384
Timepoint [13] 0 0
Baseline, Week 384
Secondary outcome [14] 0 0
Change From Baseline in EuroQol 5 Dimensions Questionnaire (EQ-5D) Health Survey - Visual Analog Scale (VAS) at Week 384
Timepoint [14] 0 0
Baseline, Week 384
Secondary outcome [15] 0 0
Change From Baseline in Visual Function Test Scores at Week 384
Timepoint [15] 0 0
Baseline, Week 384

Eligibility
Key inclusion criteria
Key

-Subjects who participated in and completed as per protocol previous BG00012 clinical studies 109MS301 (NCT00420212) or 109MS302 (NCT00451451).

Key
Minimum age
19 Years
Maximum age
58 Years
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
3/02/2009
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
8/11/2019
Sample size
Target
Accrual to date
Final
1736
Recruitment in Australia
Recruitment state(s)
NSW,VIC
Recruitment hospital [1] 0 0
Research Site - Kogarah
Recruitment hospital [2] 0 0
Research Site - New Lambton Heights
Recruitment hospital [3] 0 0
Research Site - Melbourne
Recruitment hospital [4] 0 0
Research Site - Box Hill
Recruitment hospital [5] 0 0
Research Site - Chatswood
Recruitment hospital [6] 0 0
Research Site - Fitzroy
Recruitment hospital [7] 0 0
Research Site - Geelong
Recruitment hospital [8] 0 0
Research Site - Sydney
Recruitment postcode(s) [1] 0 0
2217 - Kogarah
Recruitment postcode(s) [2] 0 0
2305 - New Lambton Heights
Recruitment postcode(s) [3] 0 0
3084 - Melbourne
Recruitment postcode(s) [4] 0 0
3128 - Box Hill
Recruitment postcode(s) [5] 0 0
2067 - Chatswood
Recruitment postcode(s) [6] 0 0
3065 - Fitzroy
Recruitment postcode(s) [7] 0 0
3220 - Geelong
Recruitment postcode(s) [8] 0 0
2000 - Sydney
Recruitment outside Australia
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Stoke on Trent

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Biogen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
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.
Trial website
https://clinicaltrials.gov/study/NCT00835770
Trial related presentations / publications
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. Erratum In: Ther Adv Neurol Disord. 2020 Oct 21;13:1756286420968357. doi: 10.1177/1756286420968357.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Biogen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00835770