Primary: The primary objective of the study is to assess the effect of long term treatment with prolonged release fampridine 10 mg twice daily on the physical component scale (PCS) of the Short Form (36) Health Status Questionnaire (SF 36) as…
ID
Source
Brief title
Condition
- Central nervous system infections and inflammations
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
• Change from baseline in the PCS of the SF 36 measured over Months 3, 6, 9,
and 12 among subjects who respond to treatment with prolonged release
fampridine.
Secondary outcome
• Comparison of the change from baseline in the PCS of the SF 36 measured over
Months 3, 6, 9, and 12 among subjects who respond to treatment with prolonged
release fampridine and those who do not.
• Change from baseline in additional QoL measures over Months 3, 6, 9, and 12
among responders as well as comparisons in change from baseline between
responders and non responders:
- Total and mental component scale (MCS) of the SF 36
- Multiple Sclerosis Impact Scale (MSIS 29) Physical and Psychological Score
- EuroQoL descriptive system of health-related quality of life states
consisting of 5 dimensions (questionnaire; EQ 5D)
- Work Productivity and Activity Impairment (WPAI) Specific Health Problem
(SHP) questionnaire
• Change in QoL measures among responders stratified by disease type.
• Change in QoL measures between responders and non responders not taking
additional MS therapy.
• Safety of prolonged-release fampridine will be assessed by:
- the number and proportion of subjects with adverse events (AEs) and serious
adverse events (SAEs)
Background summary
Walking impairment is a prominent manifestation of MS. With the exception of
anti spasticity agents, no functional modifying therapies are currently
available to treat walking impairment. Walking disability has also been ranked
by both MS patients and neurologists as having the greatest negative impact on
quality of life (QoL). This was demonstrated by an increase in walking speed.
Fampridine has also been approved under the brand name Fampyra* in Australia
(May 2011) and in the European Union (EU; July 2011). Approval in the EU is
*conditional approval,* which means that further evidence on this medicinal
product is awaited, in particular about prolonged released fampridine*s
benefits beyond its effects on walking speed and with respect to early
identification of responders.
Study objective
Primary:
The primary objective of the study is to assess the effect of long term
treatment with prolonged release fampridine 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.
Secondary:
The secondary objectives of this study are as follows:
•Compare the change in the PCS of the SF 36 between treatment responders and
non responders (treatment discontinued at Week 4).
•Evaluate change from baseline in additional QoL measures among treatment
responders as well as changes from baseline in treatment responders versus non
responders.
•Assess the safety and tolerability of prolonged release fampridine 10 mg twice
daily.
Study design
A multicenter, open label study to assess subject QoL as reported by responders
to long term treatment with prolonged release fampridine 10 mg twice daily.
Subjects classified as non responders (those who did not meet criteria for
continued fampridine treatment in this study) at Week 4 will stop treatment but
will continue to provide QoL data for comparative purposes.
Intervention
Open label run-in period of 4 weeks to assess treatment response:
All eligible subjects will receive prolonged release fampridine 10 mg orally
twice daily for 4 weeks.
Observational period of 44 weeks (Treatment or No Treatment during Weeks 5 48):
• Group 1 (Treatment, Weeks 5-48): Subjects who improved in overall score on
the MS Walking Scale (MSWS 12) at the 4 week on treatment visit of the run in
period over baseline AND who have both on treatment T25FWs (Week 2 and Week 4)
> mean pretreatment T25FW, will be considered treatment responders in this
study and will continue to receive prolonged release fampridine 10 mg twice
daily for the next 44 weeks. It is estimated that approximately 300 subjects
will qualify for Group 1.
• Group 2 (No Treatment, Weeks 5 48): Subjects who do not meet the above
criteria will be considered non responders in this study. It is estimated that
approximately 500 subjects will be offered the opportunity to continue study
participation via quarterly QoL assessments.
Study burden and risks
The PR fampridine dose and regimen to be used in this study will be 10 mg twice
daily, given orally, which is the commercially approved dose/regimen in the EU.
Phase 3 studies have demonstrated that the effect of PR fampridine with respect
to an improvement in T25FW was observed 2 to 4 weeks after initiation of
therapy allowing for the early identification of responders to therapy.
Responders to treatment will be identified at week 4 based on objective (Timed
25 foot walk, T25FW) and subjective MS walking scale score (MSWS-12).
PR fampridine 10 mg twice daily has been well tolerated in clinical studies to
date. Of the adverse events (AEs) observed in the placebo-controlled studies,
94% were assessed as either mild or moderate in intensity and rarely caused
withdrawal of treatment.
Based on the current benefit/risk profile of PR fampridine, the potential
benefit of treatment in responders to therapy is likely to outweigh any risks
of treatment at the proposed dose and regimen. Physical burden to patients is
limited to a one time blood collected. Furthermore are several questionnaire
used and walking ability assessed.
Biogen Idec Research Limited, Innovation House, 70 Norden Road
Maidenhead, Berkshire, SI6 4AY
GB
Biogen Idec Research Limited, Innovation House, 70 Norden Road
Maidenhead, Berkshire, SI6 4AY
GB
Listed location countries
Age
Inclusion criteria
1. Male or female subjects, 18 to 75 years old, inclusive, at the time of informed consent.
2. Must have a diagnosis of primary progressive, secondary progressive, progressive remitting, or relapsing remitting MS per revised McDonald Committee criteria as defined by Lublin and Reingold of at least 3 months duration.
3. Have a walking impairment as determined by the Investigator.
4. Able to perform the T25FW test with or without a walking aid.
5. 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.
Exclusion criteria
1. Known allergy to pyridine-containing substances or to any of the inactive ingredients in the prolonged release fampridine tablet.
2. Any history of seizure, epilepsy, or other convulsive disorder, with the exception of febrile seizures in childhood.
3. An estimated CrCl of <80 mL/minute.
4.Subject needs to take medicinal products that are inhibitors of organic cation transporter 2 (OCT2 [e.g., cimetidine]).
5.Previous exposure to fampridine.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-003507-38-NL |
| CCMO | NL38261.060.11 |