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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Relapsing-Remitting Multiple Sclerosis

Intervention / Treatment
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* Drug: dimethyl fumarate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 58 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BG00012 plus placebo<br>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<br>* BG00012 capsules<br>* Other names: DMF;Drug: Placebo<br>* Capsules taken to maintain the blind in the 240 mg BID treatment group.<br>|
| Experimental: BG00012<br>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<br>* BG00012 capsules<br>* Other names: DMF;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) | 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. | Day 1 up to Week 561 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Had Relapses | Relapses were defined as new or recurrent neurologic symptoms not associated with fever or infection, lasting at least 24 hours. | Day 1 up to Week 384 | 
| Annualized Relapse Rate (ARR) | 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. | Day 1 up to Week 384 | 
| Change From Baseline in the Expanded Disability Status Scale (EDSS) at 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. | Baseline, Week 384 | 
| Number of Gadolinium (Gd)-Enhancing Lesions as Measured by Magnetic Resonance Imaging (MRI) | The Gd-enhancing lesions was evaluated using MRI technique. | Baseline up to Week 288 | 
| Volume of Gd-Enhancing Lesions as Measured by Magnetic Resonance Imaging (MRI) | The Gd-enhancing lesions was evaluated using MRI technique. | Baseline up to Week 288 | 
| Number of New or Newly Enlarging T2 Lesions as Measured by Magnetic Resonance Imaging (MRI) | The T2 lesions was evaluated using MRI technique. | Baseline up to Week 288 | 
| Volume of New or Newly Enlarging T2 Lesions as Measured by Magnetic Resonance Imaging (MRI) | The T2 lesions was evaluated using MRI technique. | Baseline up to Week 288 | 
| Number of T1 Hypointense Lesions as Measured by Magnetic Resonance Imaging (MRI) | The T1 hypointense lesions was evaluated using MRI technique. | Baseline up to Week 288 | 
| Volume of T1 Hypointense Lesions as Measured by Magnetic Resonance Imaging (MRI) | The T1 hypointense lesions was evaluated using MRI technique. | Baseline up to Week 288 | 
| Percent Change From Baseline in Brain Atrophy | Brain atrophy was measured using magnetic resonance imaging (MRI) technique. | Baseline up to Week 288 | 
| Percent Change From Baseline in Magnetization Transfer Ratio (MTR) | Magnetization Transfer Ratio (MTR) was measured using MRI technique. | Baseline up to Week 288 | 
| Change From Baseline in Short Form-36 Health Survey (SF-36®) at 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. | Baseline, Week 384 | 
| Change From Baseline in EuroQol 5 Dimensions Questionnaire (EQ-5D) Health Survey - EQ-5D Index Score at 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. | Baseline, Week 384 | 
| Change From Baseline in EuroQol 5 Dimensions Questionnaire (EQ-5D) Health Survey - Visual Analog Scale (VAS) at 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. | Baseline, Week 384 | 
| Change From Baseline in Visual Function Test Scores at 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. | Baseline, Week 384 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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relapsing, multiple sclerosis, remitting, oral