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Efficacy and Safety Study of Prolonged-Release Fampridine in Participants With Multiple Sclerosis (ENHANCE)

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ClinicalTrials.gov Identifier: NCT02219932
Recruitment Status : Completed
First Posted : August 19, 2014
Results First Posted : March 27, 2017
Last Update Posted : March 27, 2017
Sponsor:
Information provided by (Responsible Party):
Biogen

Brief Summary:

The primary objective is to determine whether prolonged-release fampridine (10 mg twice daily) has a clinically meaningful effect on participant-reported walking ability over a 24-week study period.

The secondary objectives are: to determine whether prolonged-release fampridine 10 mg taken twice daily (BID) has a clinically meaningful effect on dynamic and static balance, physical impact of multiple sclerosis (MS), and upper extremity function over a 24-week study period; to evaluate criteria for early assessment of response to fampridine that can predict clinically meaningful benefits in walking ability and balance; to assess the safety and tolerability of prolonged-release fampridine 10 mg twice daily over a 24-week treatment period.


Condition or disease Intervention/treatment Phase
Multiple Sclerosis Drug: fampridine Drug: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 646 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double Blind, Placebo Controlled Study to Assess the Long-Term Efficacy and Safety of Prolonged Release Fampridine (BIIB041) 10 mg, Administered Twice Daily in Subjects With Multiple Sclerosis (ENHANCE)
Study Start Date : September 2014
Actual Primary Completion Date : February 2016
Actual Study Completion Date : February 2016

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Fampridine 10 mg BID
Prolonged-release fampridine 10 mg twice daily (BID) for up to 24 weeks
Drug: fampridine
Other Names:
  • dalfampridine
  • Ampyra
  • Fampyra
  • fampridine prolonged-release tablets
  • BIIB041

Placebo Comparator: Placebo
Matched placebo 10 mg BID for up to 24 weeks
Drug: Placebo
Matched placebo




Primary Outcome Measures :
  1. Proportion of Participants Achieving a Mean Improvement of ≥ 8 Points From Baseline on the Multiple Sclerosis Walking Scale (MSWS-12) Over 24 Weeks [ Time Frame: Baseline to 24 weeks ]

    MSWS-12 is a participant self-assessment of the walking limitations due to 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 higher scores indicate greater impact on walking.

    A responder is defined as a participant with a mean improvement of at least 8 points over 24 weeks compared to baseline. Baseline is defined as the mean at Screening and Day 1 visits. If a participant has a mean MSWS-12 score of < 0.5 over the double-blind period, and a baseline MSWS-12 score of < 8 points, the participant is counted as a responder. A participant who indicates they cannot walk at all on MSWS-12 during any double-blind visit, and who shows severe disability and an inability to walk on other efficacy assessments is counted as a non-responder. Estimated proportion obtained from binomial proportions.



Secondary Outcome Measures :
  1. Proportion of Participants Achieving a Mean Improvement From Baseline of ≥ 15% in Timed Up and Go (TUG) Speed Over 24 Weeks [ Time Frame: Baseline to Week 24 ]

    TUG is a timed walking test designed to measure gait performance and balance. It measures in seconds the time taken by an individual to stand up from a standard arm chair (approximate seat height of 46 cm [18in], arm height 65 cm [25.6 in]), walk a distance of 3 meters (118 inches, approximately 10 feet), turn, walk back to the chair, and sit down.

    A responder is defined as a participant with a mean improvement of at least 15% in TUG speed over 24 weeks compared to baseline. Baseline is defined as the mean at Screening and Day 1 visits. Estimated proportion obtained from binomial proportions. There are 2 TUG tests given, and the average across the 2 tests is used to calculate average speed. Healthy participants below the age of 79 are expected to complete this task in 7-10 seconds (American College of Rheumatology). Missing data are handled using multiple imputation and baseline is defined as the mean over Screening and Day 1.


  2. Change From Baseline in Multiple Sclerosis Impact Scale-29 (MSIS-29) Physical Score Over 24 Weeks [ Time Frame: Baseline to Week 24 ]

    The 29-item MSIS-29 is a participant-reported outcome measure to assess the impact of MS on day-to-day life during the past 2 weeks from a participant's perspective; it measures 20 physical items and 9 psychological items. The physical score is generated by summing individual items and then transforming to a scale with a range of 0 (no impact of MS) to 100 (extreme impact of MS); a negative change indicates an improvement in function.

    Data are based on a mixed model for repeated measures (MMRM) model using a common variance AR(1) variance-covariance matrix structure. Treatment, visit and treatment by visit interaction were included in the model as explanatory variables, adjusting for screening EDSS, baseline MSIS-29 physical score and prior aminopyridine as covariates. Missing data are handled using multiple imputation and baseline is defined as the mean over screening and Day 1.


  3. Change From Baseline in Berg Balance Scale (BBS) Over 24 Weeks [ Time Frame: Baseline to Week 24 ]

    The BBS is a widely used assessment tool to identify balance impairment. Functional activities such as reaching, bending, transferring, and standing are evaluated on the test to evaluate balance. Participants are asked to complete 14 tasks that are rated from 0 (cannot perform) to 4 (normal performance) for a total of 56 points. BBS scores range from 0 (poor balance) to 56 (good balance); a positive change indicates improvement.

    Data are based on an MMRM model using a common variance AR(1) variance-covariance matrix structure. Treatment, visit and treatment by visit interaction were included in the model as explanatory variables, adjusting for screening EDSS, baseline BBS and prior aminopyridine as covariates. Missing data are handled using multiple imputation and baseline is defined as the mean over screening and Day 1.


  4. Change From Baseline in ABILHAND Score Over 24 Weeks [ Time Frame: Baseline to Week 24 ]

    The ABILHAND Questionnaire measures a participant's perceived difficulty in performing everyday manual activities in the last 3 months. The participant completes a 56-item questionnaire by estimating their own difficulty or ease in performing each of 56 activities. Items are summed to generate a total score and transformed to a scale with a range of 0 (poor manual ability) to 100 (good manual ability); a positive change indicates an improvement in manual ability.

    Data are based on an MMRM model using a common variance AR(1) variance-covariance matrix structure. Treatment, visit and treatment by visit interaction were included in the model as explanatory variables, adjusting for screening EDSS, baseline ABILHAND and prior aminopyridine as covariates. Missing data are handled using multiple imputation and baseline is defined as the Day 1 assessment.




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Must have a diagnosis of primary-progressive, secondary-progressive, progressive-relapsing, or relapsing-remitting MS per revised McDonald Committee criteria [McDonald 2001; Polman 2005] as defined by Lublin and Reingold [Lublin and Reingold 1996] of at least 3 months duration
  • Must have an Expanded Disability Status Scale (EDSS) score of 4 to 7, inclusive
  • Must have walking impairment, as deemed by the Investigator

Key Exclusion Criteria:

  • History of human immunodeficiency virus (HIV)
  • Presence of acute or chronic hepatitis. Subjects who have evidence of prior hepatitis infection that has been serologically confirmed as resolved are not excluded from study participation
  • Known allergy to fampridine, pyridine-containing substances, or any of the inactive ingredients in the prolonged-release fampridine tablet
  • Creatinine clearance (CrCl) of <80 mL/min
  • History of malignant disease
  • Presence of pulmonary disease
  • A body mass index (BMI) ≥40 (BMI formula: BMI = mass [kg]/[height(m)]2)

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02219932


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Sponsors and Collaborators
Biogen
Investigators
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Study Director: Medical Director Biogen

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT02219932     History of Changes
Other Study ID Numbers: 218MS305
2013-003600-40 ( EudraCT Number )
First Posted: August 19, 2014    Key Record Dates
Results First Posted: March 27, 2017
Last Update Posted: March 27, 2017
Last Verified: January 2017

Keywords provided by Biogen:
Fampridine

Additional relevant MeSH terms:
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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