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BG00012 Monotherapy Safety and Efficacy Extension Study in Multiple Sclerosis (MS) (ENDORSE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00835770
Recruitment Status : Completed
First Posted : February 4, 2009
Results First Posted : December 31, 2020
Last Update Posted : December 31, 2020
Sponsor:
Information provided by (Responsible Party):
Biogen

Study Description
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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.

Condition or disease Intervention/treatment Phase
Relapsing-Remitting Multiple Sclerosis Drug: dimethyl fumarate Drug: Placebo Phase 3

Detailed Description:
The initial BG00012 dosage for the extension study (240 mg BID or 240 mg TID) was the same as that used in the Phase 3 Studies 109MS301 (NCT00420212) and 109MS302 (NCT00451451). Subsequent to the initiation of this study, BG00012 was approved in several countries for the treatment of MS at a dose of 240 mg BID. For this reason, all participants continuing in this study will receive the currently marketed dose of 240 mg BID.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1736 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official 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
Actual Study Start Date : February 3, 2009
Actual Primary Completion Date : November 8, 2019
Actual Study Completion Date : November 8, 2019

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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.
 Drug: dimethyl fumarate
BG00012 capsules
Other Names:
  • BG00012
  • Tecfidera
  • DMF

Drug: Placebo
Capsules taken to maintain the blind in the 240 mg BID treatment group.
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.
 Drug: dimethyl fumarate
BG00012 capsules
Other Names:
  • BG00012
  • Tecfidera
  • DMF


Outcome Measures
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Primary Outcome Measures :
  1. Number of Participants With Treatment-Emergent Adverse Events (AEs) [ Time Frame: Day 1 up to Week 561 ]
    An adverse event (AE) is any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment.


Secondary Outcome Measures :
  1. Percentage of Participants Who Had Relapses [ Time Frame: Day 1 up to Week 384 ]
    Relapses were defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting at least 24 hours.

  2. Annualized Relapse Rate (ARR) [ Time Frame: Day 1 up to Week 384 ]
    The annualized relapse rate is calculated as the total number of relapses occurred during the period for all participants, divided by the total number of participant-years followed in the period.

  3. Change From Baseline in the Expanded Disability Status Scale (EDSS) at Week 384 [ Time Frame: Baseline, Week 384 ]
    EDSS scale ranges from 0 (Normal neurological exam, no disability) to 10 (Death) in 0.5 unit increments that represent higher levels of disability. Scoring is based on an examination by a neurologist. Sustained disability progression was defined as at least a 1.0 point increase on the EDSS from a baseline EDSS ≥1.0 that was sustained for at least 24 weeks, or a 1.5 point increase on the EDSS from a baseline EDSS =0 that was sustained for at least 24 weeks.

  4. Number of Gadolinium (Gd)-Enhancing Lesions as Measured by Magnetic Resonance Imaging (MRI) [ Time Frame: Baseline up to Week 288 ]
    The Gd-enhancing lesions was evaluated using MRI technique.

  5. Volume of Gd-Enhancing Lesions as Measured by Magnetic Resonance Imaging (MRI) [ Time Frame: Baseline up to Week 288 ]
    The Gd-enhancing lesions was evaluated using MRI technique.

  6. Number of New or Newly Enlarging T2 Lesions as Measured by Magnetic Resonance Imaging (MRI) [ Time Frame: Baseline up to Week 288 ]
    The T2 lesions was evaluated using MRI technique.

  7. Volume of New or Newly Enlarging T2 Lesions as Measured by Magnetic Resonance Imaging (MRI) [ Time Frame: Baseline up to Week 288 ]
    The T2 lesions was evaluated using MRI technique.

  8. Number of T1 Hypointense Lesions as Measured by Magnetic Resonance Imaging (MRI) [ Time Frame: Baseline up to Week 288 ]
    The T1 hypointense lesions was evaluated using MRI technique.

  9. Volume of T1 Hypointense Lesions as Measured by Magnetic Resonance Imaging (MRI) [ Time Frame: Baseline up to Week 288 ]
    The T1 hypointense lesions was evaluated using MRI technique.

  10. Percent Change From Baseline in Brain Atrophy [ Time Frame: Baseline up to Week 288 ]
    Brain atrophy was measured using magnetic resonance imaging (MRI) technique.

  11. Percent Change From Baseline in Magnetization Transfer Ratio (MTR) [ Time Frame: Baseline up to Week 288 ]
    Magnetization Transfer Ratio (MTR) was measured using MRI technique.

  12. Change From Baseline in Short Form-36 Health Survey (SF-36®) at Week 384 [ Time Frame: Baseline, Week 384 ]
    The SF-36 is a brief (36-item) scale reflecting the impact of both dysfunctions and general health perception the questionnaire measures: 1.physical function (PF),2. role physical (RF),3. bodily pain (BP),4. role emotional (RE),5. social function (SF), 6. general health (GH),7. vitality (VT), 8. mental health (MH). Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the mental component summary (MCS) score of the SF-36. The questions related to each dimension are scored on a scale from 0 (worst score) to 100 (best score), with higher scores indicating better function.

  13. Change From Baseline in EuroQol 5 Dimensions Questionnaire (EQ-5D) Health Survey - EQ-5D Index Score at Week 384 [ Time Frame: Baseline, Week 384 ]
    The EQ-5D is a generic health-related quality of life instrument consisting of 2 components, EQ-5D index score and EQ-VAS. The EQ-5D provides a profile of the participant's health state in 5 dimensions (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression). For each dimension, the participant is instructed to indicate whether he or she has (1) "no problems", (2) "some problems", or (3) "severe problems". A positive change from baseline indicates improvement.

  14. Change From Baseline in EuroQol 5 Dimensions Questionnaire (EQ-5D) Health Survey - Visual Analog Scale (VAS) at Week 384 [ Time Frame: Baseline, Week 384 ]
    The EQ-5D is a generic health-related quality of life instrument consisting of 2 components, EQ-5D index score and EQ-VAS. In EQ-VAS participants are asked to rate their current health on a 20 centimeter (cm) scale from 0 to 100 where 0 represents "worst imaginable health state" and 100 represents "best imaginable health state". A positive change from baseline indicates improvement.

  15. Change From Baseline in Visual Function Test Scores at Week 384 [ Time Frame: Baseline, Week 384 ]
    Participants were tested using the contrast level of 100%, 2.5%, and 1.25% charts, and the scores were defined as the number of letters identified correctly for each chart (the maximum score was 60). Higher scores indicate better functioning. A positive change from baseline indicates better functioning.


Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   19 Years to 58 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00835770


Locations
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Sponsors and Collaborators
Biogen
Investigators
Layout table for investigator information
Study Director: Medical Director Biogen
  Study Documents (Full-Text)

Documents provided by Biogen:
Study Protocol  [PDF] February 12, 2018
Statistical Analysis Plan  [PDF] June 14, 2019

More Information
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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT00835770    
Other Study ID Numbers: 109MS303
2008-004753-14 ( EudraCT Number )
First Posted: February 4, 2009    Key Record Dates
Results First Posted: December 31, 2020
Last Update Posted: December 31, 2020
Last Verified: December 2020
Keywords provided by Biogen:
relapsing
multiple sclerosis
remitting
oral
Additional relevant MeSH terms:
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Multiple Sclerosis
Multiple Sclerosis, Relapsing-Remitting
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
 Autoimmune Diseases
Immune System Diseases
Dimethyl Fumarate
Dermatologic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs