BG00012 and Delay of Disability Progression in Secondary Progressive Multiple Sclerosis

Study Overview
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Brief Summary
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The primary objective of the study is to investigate whether treatment with BG00012 (dimethyl fumarate) compared with placebo slows the accumulation of disability not related to relapses in participants with secondary progressive multiple sclerosis (SPMS). The secondary objective of the study is to assess the effect of BG00012 compared with placebo on patient-reported outcomes, brain atrophy, and cognitive function.

Official Title
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A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy and Safety of BG00012 in Delaying Disability Progression in Subjects With Secondary Progressive Multiple Sclerosis

Conditions
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Multiple Sclerosis, Secondary Progressive

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


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Onset of SPMS at least 1 to 2 years prior to randomization. SPMS is defined as relapsing-remitting disease followed by progression of disability independent of or not explained by relapses. Have documented confirmed evidence of disease progression independent of clinical relapses over the 1 year prior to randomization. Have an Expanded Disability Status Scale score of 3.0 to 6.5, inclusive. Have a Multiple Sclerosis (MS) Severity Score of 4 or higher. Key Exclusion Criteria: Have a diagnosis of relapsing remitting multiple sclerosis or primary progressive MS as defined by the revised McDonald criteria. Had a recent clinical relapse (within 3 months) prior to randomization. Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection; symptomatic congestive heart failure; unstable angina pectoris; cardiac arrhythmia; serious or acute liver, kidney, or bone marrow dysfunction; uncontrolled diabetes; serious or acute psychiatric illness that would limit compliance with study requirements. Note: Other protocol-defined Inclusion/Exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dimethyl fumarate<br>BG00012 120 mg (1 BG00012 120 mg capsule + 1 matching placebo capsule) orally twice daily (BID) for 1 week, followed by BG00012 240 mg orally BID thereafter. | Drug: dimethyl fumarate<br>* capsule<br>* Other names: Tecfidera;Other: Placebo<br>* matched placebo capsule<br>|
| Experimental: Placebo<br>BG00012 120 mg capsule orally once a day supplemented with matching placebo capsules for the first 4 weeks of treatment, as an additional blinding measure. Matched placebo capsules only thereafter. | Drug: dimethyl fumarate<br>* capsule<br>* Other names: Tecfidera;Other: Placebo<br>* matched placebo capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Disability Progression Independent of Relapse | Time to onset of confirmed progression of disability is defined as 1 or more of the following criteria, confirmed at ≥ 6 months after start of treatment and at Week 108 using 1 or more of the following assessments: Expanded Disability Status Scale (EDSS) score increased from Baseline of ≥ 1 point if baseline EDSS ≤ 5.5, or ≥ 0.5 point if Baseline EDSS ≥ 6.0; Timed 25-Foot Walk (T25FW) ≥ 20% increase from Baseline in the time taken for the 25-foot walk; worsening on the 9-Hole Peg Test (9HPT; ≥ 20% increase from Baseline in the time taken for the 9HPT, confirmed in the same hand). The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. The T25FW is a quantitative mobility and leg function performance test where the participant is timed while walking for 25 feet. The 9HPT is a quantitative test of upper extremity function that measures the time it takes to place 9 pegs into 9 holes and then remove the pegs. | Up to 108 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to 2 Years on the 12-Item Multiple Sclerosis Walking Scale (MSWS-12) | MSWS-12 is a participant self-assessment of walking limitations due to multiple sclerosis (MS) during the past 2 weeks. It contains 12 items that measure the impact of MS on walking. Items are summed to generate a total score and transformed to a scale with a range of 0 to 100, where high scores indicate greater negative impact on walking. | Baseline, 2 years | 
| Change From Baseline to Week 108 in ABILHAND Questionnaire Score | The ABILHAND Questionnaire measures the participant's perceived difficulty in performing everyday manual activities in the last 3 months. Participants fill in the 56-item questionnaire by estimating their own difficulty or ease in performing each of the 56 activities. Items are summed to generate a total score and transformed to a scale with a range of 0 to 100, where high scores indicate greater impact on manual ability. | Baseline, Week 108 | 
| Percentage Change From Baseline to Week 108 in Whole Brain Volume | Whole brain volume is measured by magnetic resonance imaging (MRI). | Baseline, Week 108 | 
| Change From Baseline to Week 108 in Cognitive Function as Measured by the Symbol Digit Modalities Test (SDMT) | The SDMT measures the time to pair abstract geometric symbols with specific numbers. The score is the number of correctly coded items from 0-110 in 90 seconds. A higher score indicates a better outcome. | Baseline, Week 108 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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INSPIRE, SPMS, Tecfidera, BG00012