Multiple Sclerosis, Secondary Progressive
Conditions
Keywords
INSPIRE, SPMS, Tecfidera, BG00012
Brief summary
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.
Interventions
DRUGdimethyl fumarate
capsule
OTHERPlacebo
matched placebo capsule
Sponsors
Biogen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 58 Years
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Disability Progression Independent of Relapse | Up to 108 weeks | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to 2 Years on the 12-Item Multiple Sclerosis Walking Scale (MSWS-12) | Baseline, 2 years | 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. |
| Change From Baseline to Week 108 in ABILHAND Questionnaire Score | Baseline, Week 108 | 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. |
| Percentage Change From Baseline to Week 108 in Whole Brain Volume | Baseline, Week 108 | Whole brain volume is measured by magnetic resonance imaging (MRI). |
| Change From Baseline to Week 108 in Cognitive Function as Measured by the Symbol Digit Modalities Test (SDMT) | Baseline, Week 108 | 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. |
Countries
Belgium, Czechia, Netherlands, Poland, Slovakia, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo BG00012 120 mg capsule orally QD supplemented with matching placebo capsules for the first 4 weeks of treatment. Matched placebo capsules only thereafter for up to 108 weeks. | 30 |
| Tecfidera 240 mg BID BG00012 120 mg orally BID for 1 week, followed by BG00012 240 mg orally BID beginning on Day 8 for up to 108 weeks. | 28 |
| Total | 58 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Consent Withdrawn | 0 | 2 |
| Overall Study | Sponsor Decision to Stop Study Early | 30 | 25 |
Baseline characteristics
| Characteristic | Placebo | Tecfidera 240 mg BID | Total |
|---|---|---|---|
| Age, Continuous | 50.7 years STANDARD_DEVIATION 6.67 | 49.6 years STANDARD_DEVIATION 8.05 | 50.2 years STANDARD_DEVIATION 7.33 |
| Age, Customized 20 to 29 years | 0 participants | 0 participants | 0 participants |
| Age, Customized < 20 years | 0 participants | 0 participants | 0 participants |
| Age, Customized 30 to 39 years | 1 participants | 4 participants | 5 participants |
| Age, Customized 40 to 49 years | 10 participants | 8 participants | 18 participants |
| Age, Customized >= 50 years | 19 participants | 16 participants | 35 participants |
| Sex: Female, Male Female | 19 Participants | 17 Participants | 36 Participants |
| Sex: Female, Male Male | 11 Participants | 11 Participants | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 9 / 30 | 9 / 28 |
| serious Total, serious adverse events | 0 / 30 | 5 / 28 |
Outcome results
Primary
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.
Time frame: Up to 108 weeks
Population: The limited number of participants enrolled and the early termination of the study resulted in efficacy data not collected, and efficacy outcomes not analyzed, as per the pre-specified plan of analysis.
Secondary
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.
Time frame: Baseline, 2 years
Population: The limited number of participants enrolled and the early termination of the study resulted in efficacy data not collected, and efficacy outcomes not analyzed, as per the pre-specified plan of analysis.
Secondary
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.
Time frame: Baseline, Week 108
Population: The limited number of participants enrolled and the early termination of the study resulted in efficacy data not collected, and efficacy outcomes not analyzed, as per the pre-specified plan of analysis.
Secondary
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.
Time frame: Baseline, Week 108
Population: The limited number of participants enrolled and the early termination of the study resulted in efficacy data not collected, and efficacy outcomes not analyzed, as per the pre-specified plan of analysis.
Secondary
Percentage Change From Baseline to Week 108 in Whole Brain Volume
Whole brain volume is measured by magnetic resonance imaging (MRI).
Time frame: Baseline, Week 108
Population: The limited number of participants enrolled and the early termination of the study resulted in efficacy data not collected, and efficacy outcomes not analyzed, as per the pre-specified plan of analysis.