Multiple SclerosisPhase 3ENHANCENCT02219932
Efficacy and Safety Study of Prolonged-Release Fampridine in Participants With Multiple Sclerosis
A Phase 3 study testing fampridine in people with Multiple Sclerosis, run by Biogen at 87 sites in 11 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- fampridine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 646 participants
- Where
- 87 sitesin 11 countries
- Study dates
- Sep 2014to Feb 2016
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
87 sites in 11 countries.
87 sites in 11 countries
United States17 sites
Research site
Bradenton, Florida, 34205
Research site
Charlotte, North Carolina, 28207
Research site
Charlotte, North Carolina, 28210
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Chesterfield, Missouri, 63017
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Columbus, Ohio, 43210
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Cullman, Alabama, 35058
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Detroit, Michigan, 48201
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Lexington, Kentucky, 40513
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New Bedford, Massachusetts, 02740
Research Site
Orlando, Florida, 32806
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Phoenix, Arizona, 85013
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Roanoke, Virginia, 24018
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Rochester, New York, 14642
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San Diego, California, 92108
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Tampa, Florida, 33612
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Tampa, Florida, 33634
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West Palm Beach, Florida, 33407
Poland16 sites
Research Site
Bialystok, 15-276
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Gdansk, 80-803
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Grudziądz, 86-300
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Katowice, 40-595
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Katowice, 40-749
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Katowice, 40-752
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Kielce, 25-726
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Krakow, 31-505
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Krakow, 31-637
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Lodz, 90-324
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Olsztyn, 10-561
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Plewiska, 62064
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Rzeszów, 35055
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Warsaw, 00-669
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Warsaw, 01-697
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Warsaw, 04-749
United Kingdom13 sites
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Birmingham, West Midlands, B15 2WB
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Cardiff, Swansea, SA6 6NL
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Chertsey, Surrey, KT16 0PZ
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Exeter, Devon, EX2 5DW
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Glasgow, Scotland, G51 4TF
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London, E1 2AT
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London, NW3 2QG
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London, WC1N 3BG
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Norwich, Norfolk, NR4 7UY
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Nottingham, NG7 2UH
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Plymouth, Devon, PL6 8DH
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Romford, Essex, RM7 0AG
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Salford, Greater Manchester, M6 8HD
Czechia9 sites
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Brno, 62500
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Brno, 65691
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Choceň, 56501
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Havířov, 73601
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Jihlava, 58633
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Pardubice, 53203
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Prague, 12808
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Prague, 15006
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Teplice, 41501
Bulgaria8 sites
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Pleven, 5800
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Plovdiv, 4002
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Sofia, 1113
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Sofia, 1142
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Sofia, 1407
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Sofia, 1431
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Sofia, 1606
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Sofia, 1797
Russia6 sites
Research Site
Kazan', 420021
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Kemerovo, 650066
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Krasnoyarsk, 660037
Research Site
Moscow, 127015
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Moscow, 129128
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Nizhny Novgorod, 60155
Italy5 sites
Research Site
Gallarate
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Messina, 98121
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Milan, 20133
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Naples, 80138
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Rome, 00189
Finland4 sites
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Helsinki, 00100
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Oulu, 90220
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Tampere, 33520
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Turku, 20520
Lithuania3 sites
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Kaunas, 50009
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Klaipėda, 92288
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Vilnius, 08661
Netherlands3 sites
Research Site
's-Hertogenbosch, 5223
Research Site
Breda, 4818
Research Site
Sittard-Geleen, 6162
Serbia3 sites
Research site
Belgrade, 11000
Research site
Kragujevac, 34000
Research site
Niš, 18000
About this study
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)
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.
- Conditions
- Multiple Sclerosis
- Being tested
- fampridine, Placebo
- Keywords
- Fampridine
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
fampridineDrug
Also called dalfampridine, Ampyra, Fampyra, fampridine prolonged-release tablets
PlaceboDrug
Matched placebo
| Study group | Role | What they receive |
|---|---|---|
| Fampridine 10 mg BID | Experimental | Prolonged-release fampridine 10 mg twice daily (BID) for up to 24 weeks Receives: Drug: fampridine |
| Placebo | Placebo comparator | Matched placebo 10 mg BID for up to 24 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of Participants Achieving a Mean Improvement of ≥ 8 Points From Baseline on the Multiple Sclerosis Walking Scale (MSWS-12) Over 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.
Measured: Baseline to 24 weeks
Secondary outcomes (4)
Proportion of Participants Achieving a Mean Improvement From Baseline of ≥ 15% in Timed Up and Go (TUG) Speed Over 24 Weeks
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.
Measured: Baseline to Week 24
Change From Baseline in Multiple Sclerosis Impact Scale-29 (MSIS-29) Physical Score Over 24 Weeks
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.
Measured: Baseline to Week 24
Change From Baseline in Berg Balance Scale (BBS) Over 24 Weeks
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.
Measured: Baseline to Week 24
Change From Baseline in ABILHAND Score Over 24 Weeks
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.
Measured: Baseline to Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2014 (estimated)
- Study startSep 2014
- Primary completionFeb 2016
- Study completionFeb 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by BiogenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 646 participants (actual)
Sponsor and investigators
- Lead sponsor
- Biogen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Medical Director, Study director, Biogen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02219932
- Sponsor's protocol ID
- 218MS305
- Other IDs
- 2013-003600-40
- Acronym
- ENHANCE
- Status last verified
- Jan 2017
- First submitted
- 18 Aug 2014
- Last updated
- 27 Mar 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Hobart J, Ziemssen T, Feys P, Linnebank M, Goodman AD, Farrell R, Hupperts R, Blight AR, Englishby V, McNeill M, Chang I, Lima G, Elkins J; ENHANCE study investigators. Assessment of Clinically Meaningful Improvements in Self-Reported Walking Ability in Participants with Multiple Sclerosis: Results from the Randomized, Double-Blind, Phase III ENHANCE Trial of Prolonged-Release Fampridine. CNS Drugs. 2019 Jan;33(1):61-79. doi: 10.1007/s40263-018-0586-5.
PubMed 30535670
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT02219932
- Acronym / sponsor ID
- ENHANCE / 218MS305
- Conditions
- Multiple Sclerosis
- Keywords
- Fampridine
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 646 participants (actual)
- Lead sponsor
- BiogenIndustry (pharma, biotech, devices)
- Study start
- Sep 2014
- Primary completion
- Feb 2016 (actual)
- Study completion
- Feb 2016 (actual)
- First posted
- 19 Aug 2014 (estimated)
- Results
- Posted 27 Mar 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Fampridine 10 mg BID | Experimental | Drug: fampridineProlonged-release fampridine 10 mg twice daily (BID) for up to 24 weeks |
| Placebo | Placebo comparator | Drug: PlaceboMatched placebo 10 mg BID for up to 24 weeks |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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 (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| fampridineAlso: dalfampridine, Ampyra, Fampyra, fampridine prolonged-release tablets | Drug | Fampridine 10 mg BID |
| PlaceboMatched placebo | Drug | Placebo |
Primary outcome
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.
4 secondary outcomes
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
Change From Baseline in Multiple Sclerosis Impact Scale-29 (MSIS-29) Physical Score Over 24 Weeks
Time frame: Baseline to Week 24
Change From Baseline in Berg Balance Scale (BBS) Over 24 Weeks
Time frame: Baseline to Week 24
Change From Baseline in ABILHAND Score Over 24 Weeks
Time frame: Baseline to Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30535670Hobart J, Ziemssen T, Feys P, Linnebank M, Goodman AD, Farrell R, Hupperts R, Blight AR, Englishby V, McNeill M, Chang I, Lima G, Elkins J; ENHANCE study investigators. Assessment of Clinically Meaningful Improvements in Self-Reported Walking Ability in Participants with Multiple Sclerosis: Results from the Randomized, Double-Blind, Phase III ENHANCE Trial of Prolonged-Release Fampridine. CNS Drugs. 2019 Jan;33(1):61-79. doi: 10.1007/s40263-018-0586-5.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Medical Director study director
Biogen
87 sites in 11 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing fampridine in people with Multiple Sclerosis, run by Biogen at 87 sites in 11 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Mar 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 87 sites in United States, Poland, United Kingdom, Czechia, Bulgaria and 6 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Mar 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02219932, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2017.