Trial Outcomes & Findings for Efficacy and Safety Study of Prolonged-Release Fampridine in Participants With Multiple Sclerosis (NCT NCT02219932)

NCT ID: NCT02219932

Last Updated: 2017-03-27

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

646 participants

Primary outcome timeframe

Baseline to 24 weeks

Results posted on

2017-03-27

Participant Flow

A total of 646 participants were enrolled. A single site in Poland was later closed due to serious Good Clinical Practice noncompliance issues observed during the conduct of the study. There were 10 participants randomized at this site (6 to fampridine and 4 to placebo). The data from this site were excluded from all analyses.

Participant milestones

Participant milestones
Measure	Placebo Placebo twice daily (BID) for up to 24 weeks	Fampridine 10 mg BID Prolonged-release fampridine 10 mg BID for up to 24 weeks
Overall Study STARTED	319	317
Overall Study Randomized, Not Treated	0	1
Overall Study COMPLETED	254	266
Overall Study NOT COMPLETED	65	51

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo Placebo twice daily (BID) for up to 24 weeks	Fampridine 10 mg BID Prolonged-release fampridine 10 mg BID for up to 24 weeks
Overall Study Other	5	11
Overall Study Death	1	1
Overall Study Investigator Decision	0	1
Overall Study Consent Withdrawn	11	7
Overall Study Lack of Efficacy (Subject Perception)	10	2
Overall Study Protocol Violation	10	6
Overall Study Pregnancy	1	0
Overall Study Lost to Follow-up	4	2
Overall Study Adverse Event	23	21

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=319 Participants Placebo BID for up to 24 weeks	Fampridine 10 mg BID n=316 Participants Prolonged-release fampridine 10 mg BID for up to 24 weeks	Total n=635 Participants Total of all reporting groups
Age, Continuous	48.8 years STANDARD_DEVIATION 10.50 • n=5 Participants	49.0 years STANDARD_DEVIATION 9.82 • n=7 Participants	48.9 years STANDARD_DEVIATION 10.16 • n=5 Participants
Sex: Female, Male Female	181 Participants n=5 Participants	187 Participants n=7 Participants	368 Participants n=5 Participants
Sex: Female, Male Male	138 Participants n=5 Participants	129 Participants n=7 Participants	267 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to 24 weeks

Population: Intent-to-treat population: participants who received at least 1 dose of study drug and had at least 1 postbaseline efficacy assessment.

Outcome measures

Outcome measures
Measure	Fampridine 10 mg BID n=315 Participants Prolonged-release fampridine 10 mg BID for up to 24 weeks	Placebo n=318 Participants Placebo BID for up to 24 weeks
Proportion of Participants Achieving a Mean Improvement of ≥ 8 Points From Baseline on the Multiple Sclerosis Walking Scale (MSWS-12) Over 24 Weeks	0.432 proportion of participants	0.336 proportion of participants

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: Intent-to-treat population: participants who received at least 1 dose of study drug and had at least 1 postbaseline efficacy assessment.

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.

Outcome measures

Outcome measures
Measure	Fampridine 10 mg BID n=315 Participants Prolonged-release fampridine 10 mg BID for up to 24 weeks	Placebo n=318 Participants Placebo BID for up to 24 weeks
Proportion of Participants Achieving a Mean Improvement From Baseline of ≥ 15% in Timed Up and Go (TUG) Speed Over 24 Weeks	0.434 proportion of participants	0.347 proportion of participants

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: Intent-to-treat population: participants who received at least 1 dose of study drug and had at least 1 postbaseline efficacy assessment.

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.

Outcome measures

Outcome measures
Measure	Fampridine 10 mg BID n=315 Participants Prolonged-release fampridine 10 mg BID for up to 24 weeks	Placebo n=318 Participants Placebo BID for up to 24 weeks
Change From Baseline in Multiple Sclerosis Impact Scale-29 (MSIS-29) Physical Score Over 24 Weeks	-8.00 units on a scale Standard Error 0.911	-4.68 units on a scale Standard Error 0.936

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: Intent-to-treat population: participants who received at least 1 dose of study drug and had at least 1 postbaseline efficacy assessment.

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.

Outcome measures

Outcome measures
Measure	Fampridine 10 mg BID n=315 Participants Prolonged-release fampridine 10 mg BID for up to 24 weeks	Placebo n=318 Participants Placebo BID for up to 24 weeks
Change From Baseline in Berg Balance Scale (BBS) Over 24 Weeks	1.75 units on a scale Standard Error 0.278	1.34 units on a scale Standard Error 0.284

SECONDARY outcome

Timeframe: Baseline to Week 24

Population: Intent-to-treat population: participants who received at least 1 dose of study drug and had at least 1 postbaseline efficacy assessment and available data.

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.

Outcome measures

Outcome measures
Measure	Fampridine 10 mg BID n=312 Participants Prolonged-release fampridine 10 mg BID for up to 24 weeks	Placebo n=315 Participants Placebo BID for up to 24 weeks
Change From Baseline in ABILHAND Score Over 24 Weeks	1.49 units on a scale Standard Error 0.574	0.75 units on a scale Standard Error 0.593

Adverse Events

Placebo

Serious events: 21 serious events

Other events: 93 other events

Deaths: 0 deaths

Fampridine 10mg BID

Serious events: 25 serious events

Other events: 100 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=319 participants at risk Placebo twice daily (BID) for up to 24 weeks	Fampridine 10mg BID n=316 participants at risk Prolonged-release fampridine 10 mg BID for up to 24 weeks
Infections and infestations Nasopharyngitis	5.6% 18/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	4.7% 15/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.
Infections and infestations Urinary tract infection	9.1% 29/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	12.7% 40/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.
Injury, poisoning and procedural complications Fall	5.3% 17/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	7.0% 22/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.
Musculoskeletal and connective tissue disorders Back pain	3.4% 11/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	5.1% 16/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.
Nervous system disorders Multiple sclerosis relapse	9.7% 31/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	9.8% 31/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.

Additional Information

Biogen Study Medical Director

Biogen

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
Publication restrictions are in place

Restriction type: OTHER

Measure	Placebo n=319 participants at risk Placebo twice daily (BID) for up to 24 weeks	Fampridine 10mg BID n=316 participants at risk Prolonged-release fampridine 10 mg BID for up to 24 weeks
Cardiac disorders Acute myocardial infarction	0.31% 1/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	0.00% 0/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.
Cardiac disorders Atrioventricular block second degree	0.31% 1/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	0.00% 0/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.
Cardiac disorders Coronary artery stenosis	0.00% 0/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	0.32% 1/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.
Ear and labyrinth disorders Vertigo positional	0.00% 0/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	0.32% 1/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.
General disorders Chest pain	0.00% 0/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	0.32% 1/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.
Infections and infestations Diverticulitis	0.00% 0/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	0.32% 1/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.
Infections and infestations Gallbladder empyema	0.00% 0/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	0.32% 1/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.
Infections and infestations Injection site infection	0.31% 1/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	0.00% 0/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.
Infections and infestations Urinary tract infection	0.31% 1/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	0.63% 2/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.
Injury, poisoning and procedural complications Ankle fracture	0.31% 1/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	0.00% 0/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.
Injury, poisoning and procedural complications Fall	0.63% 2/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	0.63% 2/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.
Injury, poisoning and procedural complications Femur fracture	0.31% 1/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	0.00% 0/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.
Injury, poisoning and procedural complications Humerus fracture	0.00% 0/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	0.32% 1/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.
Injury, poisoning and procedural complications Joint dislocation	0.00% 0/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	0.32% 1/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.
Musculoskeletal and connective tissue disorders Intervertebral disc disorder	0.31% 1/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	0.00% 0/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Bladder cancer	0.00% 0/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	0.32% 1/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	0.32% 1/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Ovarian endometrioid carcinoma	0.31% 1/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	0.00% 0/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Uterine leiomyoma	0.00% 0/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	0.32% 1/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.
Nervous system disorders Dizziness	0.31% 1/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	0.00% 0/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.
Nervous system disorders Multiple sclerosis relapse	3.1% 10/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	4.4% 14/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.31% 1/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	0.00% 0/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.
Psychiatric disorders Anxiety	0.31% 1/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	0.00% 0/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.
Psychiatric disorders Mental disorder	0.31% 1/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	0.00% 0/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.
Reproductive system and breast disorders Endometrial atrophy	0.31% 1/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	0.00% 0/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.
Reproductive system and breast disorders Metrorrhagia	0.31% 1/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	0.00% 0/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.
Vascular disorders Peripheral ischaemia	0.00% 0/319 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.	0.32% 1/316 • Collected through follow-up (14 [±3] days following Week 24/Early Termination). Serious adverse events collected from signing of informed consent; adverse events collected from first dose of study treatment.