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Open-Label Study to Assess the Effect of Long-Term Prolonged-Release Fampridine (BIIB041) on Quality of Life as Reported by Participants With Multiple Sclerosis (ENABLE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Biogen
ClinicalTrials.gov Identifier:
NCT01480076
First received: November 23, 2011
Last updated: September 14, 2016
Last verified: September 2016
  Purpose
The primary objective of the study is to assess the effect of long-term treatment with prolonged-release fampridine (BIIB041) 10 mg twice daily on the physical component scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) as reported by treatment responders. The secondary objectives of this study are to compare the change in the PCS of the SF-36 between treatment responders and non-responders, to evaluate change from baseline in additional quality of life measures among treatment responders as well as changes from baseline in treatment responders versus non-responders and to assess the safety and tolerability of prolonged-release fampridine 10 mg twice daily.

Condition Intervention Phase
Multiple Sclerosis
Drug: Fampridine
Phase 4

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Multicenter, Multinational Study to Assess the Effect of Long-Term Prolonged-Release Fampridine (BIIB041) 10 mg Twice Daily on Quality of Life as Reported by Subjects With Multiple Sclerosis

Resource links provided by NLM:


Further study details as provided by Biogen:

Primary Outcome Measures:
  • Change From Baseline in the Physical Component Scale (PCS) of the Short Form 36 Health Status Questionnaire (SF-36) At Months 3, 6, 9, and 12: Responders [ Time Frame: Baseline, Months 3, 6, 9, 12 ] [ Designated as safety issue: No ]
    The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. 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. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. Within-group least squares means are presented.


Secondary Outcome Measures:
  • Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12: Responders Versus Non-responders [ Time Frame: Baseline, Months 3, 6, 9, 12 ] [ Designated as safety issue: No ]
    The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12). In contrast to the primary endpoint, this analysis was done using data from both responder and non-responder groups; therefore, 'responder group' and 'visit by responder group interaction' were included as fixed effects.

  • Change From Baseline in the MCS of the SF-36 At Months 3, 6, 9, and 12 [ Time Frame: Baseline, Months 3, 6, 9, 12 ] [ Designated as safety issue: No ]
    The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Change From Baseline in the Multiple Sclerosis Impact Scale (MSIS-29) Physical Score at Months 3, 6, 9, and 12 [ Time Frame: Baseline, Months 3, 6, 9, 12 ] [ Designated as safety issue: No ]
    The MSIS-29 is a disease specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 20 physical condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less physically-related impact while a higher total score indicates greater physically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 [ Time Frame: Baseline, Months 3, 6, 9, 12 ] [ Designated as safety issue: No ]
    The MSIS-29 is a disease specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 9 psychological condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less psychologically-related impact while a higher total score indicates greater psychologically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Change From Baseline in the Activities Limitation Scale of the Patient-Reported Indices for Multiple Sclerosis (PRIMUS) at Months 3, 6, 9, and 12 [ Time Frame: Baseline, Months 3, 6, 9, 12 ] [ Designated as safety issue: No ]
    The PRIMUS activity measure is a 15-item assessment of patient-reported activities of daily living. The total score was calculated as sum of all 15 items converted into a 0-30 range, where missing items were imputed by average of non-missing total when no more than 50% of items were missing (otherwise, the total score is missing). Higher score indicates worse condition. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Change From Baseline in the Current Health State of EuroQoL Descriptive System of Health-related Quality of Life States Consisting of 5 Dimensions (EQ-5D) Visual Analog Scale (VAS) at Months 3, 6, 9, And 12 [ Time Frame: Baseline, Months 3, 6, 9, 12 ] [ Designated as safety issue: No ]
    EQ-5D is a participant-answered questionnaire containing a descriptive system of 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The EQ-5D VAS ranges from 0 (worst health state) to 100 (best health state). An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 [ Time Frame: Baseline, Months 3, 6, 9, 12 ] [ Designated as safety issue: No ]
    EQ-5D is a participant-answered questionnaire containing a descriptive system on 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The scores on the 5 dimensions of descriptive system can be converted into an index score by applying United Kingdom (UK) weights. EQ-5D index score ranges from 1 to -0.59, and 1 reflects the best outcome. An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Change From Baseline in Percent Work Time Missed Due to MS, by the Work Productivity and Activity Impairment-Specific Health Problem (WPAI-SHP) Questionnaire at Months 3, 6, 9, and 12 [ Time Frame: Baseline, Months 3, 6, 9, 12 ] [ Designated as safety issue: No ]
    WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Change From Baseline in Percent Impairment While Working Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 [ Time Frame: Baseline, Months 3, 6, 9, 12 ] [ Designated as safety issue: No ]
    WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Change From Baseline in Percent Overall Work Impairment Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 [ Time Frame: Baseline, Months 3, 6, 9, 12 ] [ Designated as safety issue: No ]
    WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Change From Baseline in Regular Activity Productivity Loss, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 [ Time Frame: Baseline, Months 3, 6, 9, 12 ] [ Designated as safety issue: No ]
    WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders [ Time Frame: Baseline, Months 3, 6, 9, and 12 ] [ Designated as safety issue: No ]
    The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders [ Time Frame: Baseline, Months 3, 6, 9, and 12 ] [ Designated as safety issue: No ]
    The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders [ Time Frame: Baseline, Months 3, 6, 9, and 12 ] [ Designated as safety issue: No ]
    The MSIS-29 is a disease-specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 20 physical condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less physically-related impact while a higher total score indicates greater physically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Change From Baseline in the MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders [ Time Frame: Baseline, Months 3, 6, 9, and 12 ] [ Designated as safety issue: No ]
    The MSIS-29 is a disease-specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 9 psychological condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less psychologically-related impact while a higher total score indicates greater psychologically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Change From Baseline in the Activity Limitation Scale (ALS) of PRIMUS Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders [ Time Frame: Baseline, Months 3, 6, 9, and 12 ] [ Designated as safety issue: No ]
    The PRIMUS activity measure is a 15-item assessment of patient-reported activities of daily living. The total score was calculated as sum of all 15 items converted into a 0-30 range, where missing items were imputed by average of non-missing total when no more than 50% of items were missing (otherwise, the total score is missing). Higher score indicates worse condition. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Change From Baseline in Current Health State of the EQ-5D VAS at Months 3, 6, 9, and 12 by MS Disease Type: Responders [ Time Frame: Baseline, Months 3, 6, 9, and 12 ] [ Designated as safety issue: No ]
    EQ-5D is a participant-answered questionnaire containing a descriptive system of 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The EQ-5D VAS ranges from 0 (worst health state) to 100 (best health state). An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Change From Baseline in EQ-5D Index Scores at Months 3, 6, 9, and 12 by MS Disease Type: Responders [ Time Frame: Baseline, Months 3, 6, 9, and 12 ] [ Designated as safety issue: No ]
    EQ-5D is a participant-answered questionnaire containing a descriptive system on 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The scores on the 5 dimensions of descriptive system can be converted into an index score by applying UK weights. EQ-5D index score ranges from 1 to -0.59, and 1 reflects the best outcome. An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders [ Time Frame: Baseline, Months 3, 6, 9, and 12 ] [ Designated as safety issue: No ]
    WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders [ Time Frame: Baseline, Months 3, 6, 9, and 12 ] [ Designated as safety issue: No ]
    WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders [ Time Frame: Baseline, Months 3, 6, 9, and 12 ] [ Designated as safety issue: No ]
    WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by MS Disease Type: Responders [ Time Frame: Baseline, Months 3, 6, 9, and 12 ] [ Designated as safety issue: No ]
    WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy [ Time Frame: Baseline, Months 3, 6, 9, 12 ] [ Designated as safety issue: No ]
    The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy [ Time Frame: Baseline, Months 3, 6, 9, 12 ] [ Designated as safety issue: No ]
    The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Items 1-4 primarily contribute to the PCS score of the SF-36. Items 5-8 primarily contribute to the MCS score of the SF-36. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy [ Time Frame: Baseline, Months 3, 6, 9, and 12 ] [ Designated as safety issue: No ]
    The MSIS-29 is a disease specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 20 physical condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less physically-related impact while a higher total score indicates greater physically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy [ Time Frame: Months 3, 6, 9, and 12 ] [ Designated as safety issue: No ]
    The MSIS-29 is a disease-specific patient-reported outcome measure that has been developed and validated to examine the physical and psychological impact of MS from a patient's perspective; it measures 20 physical items and 9 psychological items. Sum of 9 psychological condition items converted into a 0-100 score range, where missing items are imputed by average of total of non-missing items when no more than 50% are missing (otherwise the total score is missing). A lower total score indicates less psychologically-related impact while a higher total score indicates greater psychologically-related impact on a participant's functioning. Decreases from Baseline indicate improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Change From Baseline in the Activities Limitation Scale of the PRIMUS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy [ Time Frame: Baseline, Months 3, 6, 9, 12 ] [ Designated as safety issue: No ]
    The PRIMUS activity measure is a 15-item assessment of patient-reported activities of daily living. The total score was calculated as sum of all 15 items converted into a 0-30 range, where missing items were imputed by average of non-missing total when no more than 50% of items were missing (otherwise, the total score is missing). Higher score indicates worse condition. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Change From Baseline in the Current Health State of EQ-5D VAS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy [ Time Frame: Baseline, Months 3, 6, 9, 12 ] [ Designated as safety issue: No ]
    EQ-5D is a participant-answered questionnaire containing a descriptive system of 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The EQ-5D VAS ranges from 0 (worst health state) to 100 (best health state). An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy [ Time Frame: Baseline, Months 3, 6, 9, 12 ] [ Designated as safety issue: No ]
    EQ-5D is a participant-answered questionnaire containing a descriptive system on 5 dimensions - mobility, self-care, usual activities, pain/discomfort and anxiety/depression and a VAS on health state. The scores on the 5 dimensions of descriptive system can be converted into an index score by applying UK weights. EQ-5D index score ranges from 1 to -0.59, and 1 reflects the best outcome. An increase from baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Change From Baseline in Percent Work Time Missed Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy [ Time Frame: Baseline, Months 3, 6, 9, and 12 ] [ Designated as safety issue: No ]
    WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Change From Baseline in Percent Impairment While Working Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy [ Time Frame: Baseline, Months 3, 6, 9, and 12 ] [ Designated as safety issue: No ]
    WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Change From Baseline in Percent Overall Work Impairment Due to MS on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy [ Time Frame: Baseline, Months 3, 6, 9, and 12 ] [ Designated as safety issue: No ]
    WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Change From Baseline in Regular Activity Productivity Loss on the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy [ Time Frame: Baseline, Months 3, 6, 9, and 12 ] [ Designated as safety issue: No ]
    WPAI-SHP is a 6-question participant-rated questionnaire to determine degree to which a specific health problem affected work productivity while at work and outside of work. Four scores are derived: percentage of absenteeism (percentage of work time missed) and presenteeism (reduced productivity while at work), overall work impairment score combining absenteeism and presenteeism, and percentage of impairment in activities performed outside of work. Score range: 0 (not affected/no impairment) to 100 (completely affected/impaired). WPAI outcomes are expressed as impairment percentages with higher numbers indicating greater impairment and less productivity. A decrease from Baseline indicates improvement. A mixed effect model for repeated measures was used for this analysis. An unstructured covariance was used to model within-participant error. The 'overall' estimate is the average change from baseline over the whole time period (through Month 12).

  • Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs) [ Time Frame: From signing of Informed Consent (SAEs) or from first dose of study treatment (AEs) through Week 50 or Early Termination (14 +/- 7 days after last dose) ] [ Designated as safety issue: No ]
    AE: any untoward medical occurrence that did not necessarily have a causal relationship with study treatment. SAE: any untoward medical occurrence that at any dose: resulted in death; in the view of the Investigator, placed the subject at immediate risk of death (a life threatening event); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity; resulted in a congenital anomaly/birth defect; any other medically important event that, in the opinion of the Investigator, could have jeopardized the subject or may have required intervention to prevent one of the other outcomes listed in the definition above.


Enrollment: 901
Study Start Date: February 2012
Study Completion Date: August 2013
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: (BIIB041) Fampridine
All participants take 10 mg fampridine twice daily for the first 4 weeks. If deemed a treatment responder, a participant continues 10 mg fampridine twice daily for 44 weeks. Treatment non-responders can continue without treatment by completing quality of life questionnaires.
Drug: Fampridine
Supplied as a 10 mg twice daily tablet and taken twice daily. Doses must be spaced at least 12 hours apart.
Other Names:
  • Fampyra
  • BIIB041
  • Ampyra
  • dalfampridine
  • fampridine prolonged-release tablets

Detailed Description:
This study has 2 components: a 4-week run-in period during which participants are treated with prolonged-release fampridine and undergo subjective and objective assessments of walking ability, the results of which are used to determine who responded to study treatment, and an observational period, during which treatment responders will continue prolonged-release fampridine treatment. The participants who do not meet the criteria to continue study treatment will be offered the opportunity to continue study participation but will not continue prolonged-release fampridine treatment.
  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information in accordance with national and local subject privacy regulations.
  • Must have a diagnosis of primary-progressive, secondary-progressive, progressive-remitting, or relapsing-remitting multiple sclerosis (MS) per revised McDonald Committee criteria ([Polman et al, 2011]) as defined by Lublin and Reingold [Lublin and Reingold 1996] of at least 3 months duration.
  • Have a walking impairment as determined by the Investigator.
  • Able to perform the Timed 25-foot Walk Test with or without a walking aid.
  • Female subjects of childbearing potential must practice effective contraception during the study and be willing and able to continue contraception for 30 days after their last dose of study treatment.
  • Able to understand and comply with the requirements of the protocol.

Key Exclusion Criteria:

  • Known allergy to pyridine-containing substances or to any of the inactive ingredients in the prolonged-release fampridine tablet.
  • Any history of seizure, epilepsy, or other convulsive disorder, with the exception of febrile seizures in childhood.
  • An estimated creatinine clearance of <80 mL/minute.
  • Subject needs to take medicinal products that are inhibitors of organic cation transporter 2 (OCT2 [e.g., cimetidine]).
  • Female subjects who are currently pregnant or who are considering becoming pregnant while participating in the study.
  • Female subjects who are currently breastfeeding.
  • Previous exposure to fampridine.

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: NCT01480076

  Show 59 Study Locations
Sponsors and Collaborators
Biogen
Investigators
Study Director: Medical Director Biogen
  More Information

Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT01480076     History of Changes
Other Study ID Numbers: 218MS403 
Study First Received: November 23, 2011
Results First Received: July 11, 2016
Last Updated: September 14, 2016
Health Authority: Belgium: Federal Agency for Medicinal Products and Health Products
Denmark: Danish Medicines Agency
Italy: Ethics Committee
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Portugal: Ethics Committee for Clinical Research
France: Institutional Ethical Committee
Greece: Ethics Committee
Denmark: Ethics Committee
Portugal: National Pharmacy and Medicines Institute
Netherlands: Independent Ethics Committee
Netherlands: Medical Ethics Review Committee (METC)
Germany: Federal Institute for Drugs and Medical Devices
Australia: Human Research Ethics Committee
France: Agence Nationale de Sécurité du Médicament et des produits de santé (ANSM)
United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Biogen:
Quality of Life
Multiple Sclerosis

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
4-Aminopyridine
Potassium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on December 09, 2016