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

February 6, 2017 updated by: Biogen

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)

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

646

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Bulgaria
      • Pleven, Bulgaria, 5800
        • Research Site
      • Plovdiv, Bulgaria, 4002
        • Research Site
      • Sofia, Bulgaria, 1431
        • Research Site
      • Sofia, Bulgaria, 1407
        • Research Site
      • Sofia, Bulgaria, 1142
        • Research Site
      • Sofia, Bulgaria, 1606
        • Research Site
      • Sofia, Bulgaria, 1797
        • Research Site
      • Sofia, Bulgaria, 1113
        • Research Site
  • Czech Republic
      • Brno, Czech Republic, 62500
        • Research Site
      • Brno, Czech Republic, 65691
        • Research Site
      • Chocen, Czech Republic, 56501
        • Research Site
      • Havirov, Czech Republic, 73601
        • Research Site
      • Jihlava, Czech Republic, 58633
        • Research Site
      • Pardubice, Czech Republic, 53203
        • Research Site
      • Praha 2, Czech Republic, 12808
        • Research Site
      • Praha 5, Czech Republic, 15006
        • Research Site
      • Teplice, Czech Republic, 41501
        • Research Site
  • Finland
      • Helsinki, Finland, 00100
        • Research Site
      • Oulu, Finland, 90220
        • Research Site
      • Tampere, Finland, 33520
        • Research Site
      • Turku, Finland, 20520
        • Research Site
  • Italy
      • Gallarate, Italy
        • Research Site
      • Messina, Italy, 98121
        • Research Site
      • Milano, Italy, 20133
        • Research Site
      • Napoli, Italy, 80138
        • Research Site
      • Rome, Italy, 00189
        • Research Site
  • Lithuania
      • Kaunas, Lithuania, 50009
        • Research Site
      • Klaipeda, Lithuania, 92288
        • Research Site
      • Vilnius, Lithuania, 08661
        • Research Site
  • Netherlands
      • Breda, Netherlands, 4818
        • Research Site
      • Sittard-Geleen, Netherlands, 6162
        • Research Site
      • s-Hertogenbosch, Netherlands, 5223
        • Research Site
  • Poland
      • Bialystok, Poland, 15-276
        • Research Site
      • Gdansk, Poland, 80-803
        • Research Site
      • Grudziadz, Poland, 86-300
        • Research Site
      • Katowice, Poland, 40-749
        • Research Site
      • Katowice, Poland, 40-752
        • Research Site
      • Katowice, Poland, 40-595
        • Research Site
      • Kielce, Poland, 25-726
        • Research Site
      • Krakow, Poland, 31-505
        • Research Site
      • Krakow, Poland, 31-637
        • Research Site
      • Lodz, Poland, 90-324
        • Research Site
      • Olsztyn, Poland, 10-561
        • Research Site
      • Plewiska, Poland, 62064
        • Research Site
      • Rzeszow, Poland, 35055
        • Research Site
      • Warsaw, Poland, 00-669
        • Research Site
      • Warsaw, Poland, 01-697
        • Research Site
      • Warsaw, Poland, 04-749
        • Research Site
  • Russian Federation
      • Kazan, Russian Federation, 420021
        • Research Site
      • Kemerovo, Russian Federation, 650066
        • Research Site
      • Krasnoyarsk, Russian Federation, 660037
        • Research Site
      • Moscow, Russian Federation, 129128
        • Research Site
      • Moscow, Russian Federation, 127015
        • Research Site
      • Nizhny Novgorod, Russian Federation, 60155
        • Research Site
  • Serbia
      • Belgrade, Serbia, 11000
        • Research Site
      • Kragujevac, Serbia, 34000
        • Research Site
      • Nis, Serbia, 18000
        • Research Site
  • United Kingdom
      • London, United Kingdom, NW3 2QG
        • Research Site
      • London, United Kingdom, WC1N 3BG
        • Research Site
      • London, United Kingdom, E1 2AT
        • Research Site
      • Nottingham, United Kingdom, NG7 2UH
        • Research Site
    • Devon
      • Exeter, Devon, United Kingdom, EX2 5DW
        • Research Site
      • Plymouth, Devon, United Kingdom, PL6 8DH
        • Research Site
    • Essex
      • Romford, Essex, United Kingdom, RM7 0AG
        • Research Site
    • Greater Manchester
      • Salford, Greater Manchester, United Kingdom, M6 8HD
        • Research Site
    • Norfolk
      • Norwich, Norfolk, United Kingdom, NR4 7UY
        • Research Site
    • Scotland
      • Glasgow, Scotland, United Kingdom, G51 4TF
        • Research Site
    • Surrey
      • Chertsey, Surrey, United Kingdom, KT16 0PZ
        • Research Site
    • Swansea
      • Cardiff, Swansea, United Kingdom, SA6 6NL
        • Research Site
    • West Midlands
      • Birmingham, West Midlands, United Kingdom, B15 2WB
        • Research Site
  • United States
    • Alabama
      • Cullman, Alabama, United States, 35058
        • Research Site
    • Arizona
      • Phoenix, Arizona, United States, 85013
        • Research Site
    • California
      • San Diego, California, United States, 92108
        • Research Site
    • Florida
      • Bradenton, Florida, United States, 34205
        • Research Site
      • Orlando, Florida, United States, 32806
        • Research Site
      • Tampa, Florida, United States, 33612
        • Research Site
      • Tampa, Florida, United States, 33634
        • Research Site
      • West Palm Beach, Florida, United States, 33407
        • Research Site
    • Kentucky
      • Lexington, Kentucky, United States, 40513
        • Research Site
    • Massachusetts
      • New Bedford, Massachusetts, United States, 02740
        • Research Site
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Research Site
    • Missouri
      • Chesterfield, Missouri, United States, 63017
        • Research Site
    • New York
      • Rochester, New York, United States, 14642
        • Research Site
    • North Carolina
      • Charlotte, North Carolina, United States, 28207
        • Research Site
      • Charlotte, North Carolina, United States, 28210
        • Research Site
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Research Site
    • Virginia
      • Roanoke, Virginia, United States, 24018
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / 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:
  • Ampyra
  • dalfampridine
  • Fampyra
  • BIIB041
  • fampridine prolonged-release tablets
PLACEBO_COMPARATOR: Placebo
Matched placebo 10 mg BID for up to 24 weeks
Drug: Placebo
Matched placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline to 24 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline to Week 24
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.
Baseline to Week 24
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.
Baseline to Week 24
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.
Baseline to Week 24

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Biogen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2014

Primary Completion (ACTUAL)

February 1, 2016

Study Completion (ACTUAL)

February 1, 2016

Study Registration Dates

First Submitted

August 18, 2014

First Submitted That Met QC Criteria

August 18, 2014

First Posted (ESTIMATE)

August 19, 2014

Study Record Updates

Last Update Posted (ACTUAL)

March 27, 2017

Last Update Submitted That Met QC Criteria

February 6, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 218MS305
  • 2013-003600-40 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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