BG00012 and Delay of Disability Progression in Secondary Progressive Multiple Sclerosis (INSPIRE)

• ClinicalTrials.gov Identifier: NCT02430532
• Recruitment Status: Terminated
• First Posted: April 30, 2015
• Results First Posted: March 27, 2017
• Last Update Posted: April 26, 2017
• Sponsor: Biogen
• Information provided by (Responsible Party): Biogen

Tracking Information

• First Submitted Date: April 27, 2015
• First Posted Date: April 30, 2015
• Results First Submitted Date: December 12, 2016
• Results First Posted Date: March 27, 2017
• Last Update Posted Date: April 26, 2017
• Study Start Date: May 2015
• Actual Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: February 7, 2017)

Time to Disability Progression Independent of Relapse [ Time Frame: 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.

Original Primary Outcome Measures (submitted: April 27, 2015)

Time to onset of confirmed progression of disability as measured by worsening on one or more of the Expanded Disability Status Scale (EDSS), Timed 25-Foot Walk (T25FW) or 9-Hole Peg Test (9HPT) [ Time Frame: Up to 108 weeks ]

Confirmed progression of disability is defined as one or more of the following criteria, confirmed at a second visit ≥6 months later and at week 108 using one or more of the following assessments: 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 (increase must be 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.

Current Secondary Outcome Measures (submitted: February 7, 2017)

• Change From Baseline to 2 Years on the 12-Item Multiple Sclerosis Walking Scale (MSWS-12) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: April 27, 2015)

• Change from Baseline to 2 years on the 12-Item Multiple Sclerosis Walking Scale (MSWS-12) [ Time Frame: Up to 108 weeks ]
  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 [ Time Frame: Up to 108 weeks ]
  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 [ Time Frame: Up to 108 weeks ]
  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) [ Time Frame: Up to 108 weeks ]
  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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: BG00012 and Delay of Disability Progression in Secondary Progressive Multiple Sclerosis
• Official Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Multiple Sclerosis, Secondary Progressive

Intervention

• Drug: dimethyl fumarate
  capsule
  Other Names:

  • DMF
  • BG00012
  • Tecfidera
• Other: Placebo
  matched placebo capsule

Study Arms

• Experimental: Dimethyl fumarate
  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.
  Interventions:

  • Drug: dimethyl fumarate
  • Other: Placebo
• Experimental: Placebo
  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.
  Interventions:

  • Drug: dimethyl fumarate
  • Other: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: November 12, 2015): 58
• Original Estimated Enrollment (submitted: April 27, 2015): 1170
• Actual Study Completion Date: January 2016
• Actual Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)

Eligibility 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/Exclusion criteria may apply

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 58 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Czech Republic, Netherlands, Poland, Slovakia, United States
• Removed Location Countries: Austria, Sweden

Administrative Information

• NCT Number: NCT02430532
• Other Study ID Numbers: 109MS308; 2014-003021-18 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Biogen
• Original Responsible Party: Same as current
• Current Study Sponsor: Biogen
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Biogen

• PRS Account: Biogen
• Verification Date: March 2017