Clinical trial NCT01480076: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Multiple Sclerosis
Keywords: Quality of Life
Multiple Sclerosis
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2011-11-28
Enrollment: 901
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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.

Primary outcomes:
measure: 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
timeFrame: Baseline, Months 3, 6, 9, 12
Secondary outcomes:
measure: Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12: Responders Versus Non-responders
timeFrame: Baseline, Months 3, 6, 9, 12
measure: Change From Baseline in the MCS of the SF-36 At Months 3, 6, 9, and 12
timeFrame: Baseline, Months 3, 6, 9, 12
measure: Change From Baseline in the Multiple Sclerosis Impact Scale (MSIS-29) Physical Score at Months 3, 6, 9, and 12
timeFrame: Baseline, Months 3, 6, 9, 12
measure: Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12
timeFrame: Baseline, Months 3, 6, 9, 12
measure: Change From Baseline in the Activities Limitation Scale of the Patient-Reported Indices for Multiple Sclerosis (PRIMUS) at Months 3, 6, 9, and 12
timeFrame: Baseline, Months 3, 6, 9, 12
measure: 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
timeFrame: Baseline, Months 3, 6, 9, 12
measure: Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12
timeFrame: Baseline, Months 3, 6, 9, 12
measure: 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
timeFrame: Baseline, Months 3, 6, 9, 12
measure: Change From Baseline in Percent Impairment While Working Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12
timeFrame: Baseline, Months 3, 6, 9, 12
measure: Change From Baseline in Percent Overall Work Impairment Due to MS, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12
timeFrame: Baseline, Months 3, 6, 9, 12
measure: Change From Baseline in Regular Activity Productivity Loss, by the WPAI-SHP Questionnaire at Months 3, 6, 9, and 12
timeFrame: Baseline, Months 3, 6, 9, 12
measure: Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders
timeFrame: Baseline, Months 3, 6, 9, and 12
measure: Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by MS Disease Type: Responders
timeFrame: Baseline, Months 3, 6, 9, and 12
measure: Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders
timeFrame: Baseline, Months 3, 6, 9, and 12
measure: Change From Baseline in the MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders
timeFrame: Baseline, Months 3, 6, 9, and 12
measure: Change From Baseline in the Activity Limitation Scale (ALS) of PRIMUS Score at Months 3, 6, 9, and 12 by MS Disease Type: Responders
timeFrame: Baseline, Months 3, 6, 9, and 12
measure: Change From Baseline in Current Health State of the EQ-5D VAS at Months 3, 6, 9, and 12 by MS Disease Type: Responders
timeFrame: Baseline, Months 3, 6, 9, and 12
measure: Change From Baseline in EQ-5D Index Scores at Months 3, 6, 9, and 12 by MS Disease Type: Responders
timeFrame: Baseline, Months 3, 6, 9, and 12
measure: 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
timeFrame: Baseline, Months 3, 6, 9, and 12
measure: 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
timeFrame: Baseline, Months 3, 6, 9, and 12
measure: 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
timeFrame: Baseline, Months 3, 6, 9, and 12
measure: 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
timeFrame: Baseline, Months 3, 6, 9, and 12
measure: Change From Baseline in the PCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
timeFrame: Baseline, Months 3, 6, 9, 12
measure: Change From Baseline in the MCS of the SF-36 at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
timeFrame: Baseline, Months 3, 6, 9, 12
measure: Change From Baseline in the MSIS-29 Physical Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
timeFrame: Baseline, Months 3, 6, 9, and 12
measure: Change From Baseline in MSIS-29 Psychological Score at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
timeFrame: Months 3, 6, 9, and 12
measure: Change From Baseline in the Activities Limitation Scale of the PRIMUS at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
timeFrame: Baseline, Months 3, 6, 9, 12
measure: 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
timeFrame: Baseline, Months 3, 6, 9, 12
measure: Change From Baseline in the Index Scores of EQ-5D at Months 3, 6, 9, and 12 by Whether Taking Additional MS Therapy
timeFrame: Baseline, Months 3, 6, 9, 12
measure: 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
timeFrame: Baseline, Months 3, 6, 9, and 12
measure: 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
timeFrame: Baseline, Months 3, 6, 9, and 12
measure: 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
timeFrame: Baseline, Months 3, 6, 9, and 12
measure: 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
timeFrame: Baseline, Months 3, 6, 9, and 12
measure: Number of Participants With Adverse Events (AEs) and Serious AEs (SAEs)
timeFrame: 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)
Other outcomes:
Locations:
city: Concord
country: Australia
facility: Research Site
state: New South Wales
city: Kogarah
country: Australia
facility: Research Site
state: New South Wales
city: Liverpool
country: Australia
facility: Research Site
state: New South Wales
city: New Lambton Heights
country: Australia
facility: Research Site
state: New South Wales
city: Auchenflower
country: Australia
facility: Research Site
state: Queensland
city: Box Hill
country: Australia
facility: Research Site
state: Victoria
city: Clayton
country: Australia
facility: Research Site
state: Victoria
city: Fitzroy
country: Australia
facility: Research Site
state: Victoria
city: Heidelberg
country: Australia
facility: Research Site
state: Victoria
city: Brasschaat
country: Belgium
facility: Research Site
city: Brussels
country: Belgium
facility: Research Site
city: Diepenbeek
country: Belgium
facility: Research Site
city: Fraiture-en-Condroz
country: Belgium
facility: Research Site
city: Gent
country: Belgium
facility: Research Site
city: Liege
country: Belgium
facility: Research Site
city: Melsbroek
country: Belgium
facility: Research Site
city: Overpelt
country: Belgium
facility: Research Site
city: Sijsele-Damme
country: Belgium
facility: Research Site
city: Wilrijk
country: Belgium
facility: Research Site
city: Copenhagen
country: Denmark
facility: Research Site
city: Nice
country: France
facility: Research Site
state: Alpes-Maritimes
city: Strasbourg
country: France
facility: Research Site
state: Bas-Rhin
city: Caen
country: France
facility: Research Site
state: Calvados
city: Bordeaux Cedex
country: France
facility: Research Site
state: Gironde 5
city: Rennes
country: France
facility: Research Site
state: Ille-et-Vilaine
city: Nantes
country: France
facility: Research Site
state: Loire-Atlantique 6
city: Reims
country: France
facility: Research Site
state: Marne
city: Clemont-Ferrand
country: France
facility: Research Site
state: Rhone
city: Paris
country: France
facility: Research Site
state: Seine-Saint-Denis 14
city: Amiens
country: France
facility: Research Site
state: Somme
city: Paris
country: France
facility: Research Site
city: Heidenheim
country: Germany
facility: Research Site
state: Bad Wuerttemberg
city: Kassel
country: Germany
facility: Research Site
state: Hessen
city: Oldenburg
country: Germany
facility: Research Site
state: Niedersachsen
city: Muenster
country: Germany
facility: Research Site
state: Nordrhein-Westfalen
city: Berlin
country: Germany
facility: Research Site
city: Erbach
country: Germany
facility: Research Site
city: Hamburg
country: Germany
facility: Research Site
city: Jena
country: Germany
facility: Research Site
city: Osnabrueck
country: Germany
facility: Research Site
city: Schwendi
country: Germany
facility: Research Site
city: Bari
country: Italy
facility: Research Site
city: Firenze
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Padova
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Eindhoven
country: Netherlands
facility: Research Site
city: Hoorn
country: Netherlands
facility: Research Site
city: Nijmegen
country: Netherlands
facility: Research Site
city: Tilburg
country: Netherlands
facility: Research Site
city: Amadora
country: Portugal
facility: Research Site
city: Coimbra
country: Portugal
facility: Research Site
city: Lisboa
country: Portugal
facility: Research Site
city: Porto
country: Portugal
facility: Research Site
city: Salford
country: United Kingdom
facility: Research Site
state: Greater Manchester
city: Nottingham
country: United Kingdom
facility: Research Site
state: Northamptonshire
city: Glasgow
country: United Kingdom
facility: Research Site
state: Stirlingshire
city: Liverpool
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Macdonell R, Nagels G, Laplaud DA, Pozzilli C, de Jong B, Martins da Silva A, Nicholas R, Lechner-Scott J, Gaebler JA, Agarwal S, Wang P, Yeh M, Hovenden M, Soelberg Sorensen P. Improved patient-reported health impact of multiple sclerosis: The ENABLE study of PR-fampridine. Mult Scler. 2016 Jun;22(7):944-54. doi: 10.1177/1352458515606809. Epub 2015 Oct 7.