BG00012 Monotherapy Safety and Efficacy Extension Study in Multiple Sclerosis (MS) - Full Text View

Purpose

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	Intervention	Phase
Relapsing-Remitting Multiple Sclerosis	Drug: dimethyl fumarate Drug: Placebo	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: 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

Resource links provided by NLM:

Genetics Home Reference related topics: multiple sclerosis

MedlinePlus related topics: Multiple Sclerosis

Drug Information available for: Dimethyl fumarate

U.S. FDA Resources

Further study details as provided by Biogen:

Primary Outcome Measures:

Number of Participants with Adverse Events [ Time Frame: Day 1 up to 12 years ]

Secondary Outcome Measures:

Number of Participants Who Had Relapses [ Time Frame: Day 1 up to 12 years ]
Annualized Relapse Rate (ARR) [ Time Frame: Day 1 up to 12 years ]
Change from Baseline in the Expanded Disability Status Scale (EDSS) up to 12 years [ Time Frame: Day 1 up to 12 years ]
Progression of disability is defined as at least a 1.0 point increase on the EDSS from baseline EDSS 1.0 that is sustained for 24 weeks or at least a 1.5 point increase on the EDSS from baseline EDSS =0 that is sustained for 24 weeks. The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist.
Number and volume of Gd-enhancing lesions as Measured by Magnetic Resonance Imaging (MRI) [ Time Frame: Day 1 up to 12 years ]
Number and volume of new or newly-enlarging T2 lesions as Measured by Magnetic Resonance Imaging (MRI) [ Time Frame: Day 1 up to 12 years ]
Number and volume of T1 hypointense lesions [ Time Frame: Day 1 to 12 years ]
Change from Baseline in Brain atrophy up to 12 years [ Time Frame: Day 1 to 12 years ]
Summary of Magnetization Transfer Ratio (MTR) [ Time Frame: Day 1 to 12 years ]
MTR is used in neuroradiology to highlight abnormalities in brain structures
Change from Baseline in EQ-5D Health Survey (EQ-5D) up to 12 years [ Time Frame: Day 1 to 12 years ]
EQ-5D is a self-administered questionnaire consisting of 5 sets of 3 questions pertaining to specific health states (i.e., mobility, self-care, pain, usual activities, anxiety), a health status rating scale, and demographic questions.
Change from baseline in SF-36® Health Survey (SF-36) up to 12 years [ Time Frame: Day 1 to 12 years ]
The SF-36 is a self-administered, generic health status questionnaire consisting of 36 questions that measure 8 health concepts: physical functioning, role limitations due to physical problems, bodily pain, general health perception, vitality, social functioning, role limitations due to emotional problems and mental health.
Change from Baseline in Visual Function test scores up to 12 years [ Time Frame: Day 1 to 12 years ]


Enrollment:	1738
Actual Study Start Date:	February 28, 2009
Estimated Study Completion Date:	February 6, 2023
Estimated Primary Completion Date:	February 6, 2023 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 up to 12 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 up to 12 years.	Drug: dimethyl fumarate BG00012 capsules Other Names: BG00012 Tecfidera DMF

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.

Eligibility


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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00835770

Show 245 Study Locations

Sponsors and Collaborators

Biogen

Investigators


Study Director:	Medical Director	Biogen

More Information

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

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.


Responsible Party:	Biogen
ClinicalTrials.gov Identifier:	NCT00835770 History of Changes
Other Study ID Numbers:	109MS303 2008-004753-14 ( EudraCT Number )
Study First Received:	February 2, 2009
Last Updated:	May 4, 2017

Keywords provided by Biogen:


relapsing multiple sclerosis remitting oral

Additional relevant MeSH terms:


Sclerosis Multiple Sclerosis Multiple Sclerosis, Relapsing-Remitting 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

ClinicalTrials.gov processed this record on July 17, 2017

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