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)

INTERVENTION: Trade Name: Fampyra Product Name: Fampridine Product Code: BIIB041 Pharmaceutical Form: Prolonged‐release tablet INN or Proposed INN: FAMPRIDINE CAS Number: 504‐24‐5 Current Sponsor code: BIIB041 Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 10‐ Pharmaceutical form of the placebo: Coated tablet Route of administration of the placebo: Oral use CONDITION: Multiple Sclerosis ; MedDRA version: 17.0 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 ‐ Nervous system disorders Therapeutic area: Diseases [C] ‐ Nervous System Diseases [C10] PRIMARY OUTCOME: Main Objective: The primary objective of Study 218MS305 is to determine whether prolonged‐release fampridine (10 mg BID) has a clinically meaningful effect on patient‐reported walking ability over a 24‐week study period. Primary end point(s): The primary endpoint of this study is the proportion of subjects who achieve a mean improvement on the MSWS‐12 of =8‐points from baseline over a 24‐week treatment period. Secondary Objective: The secondary objectives are as follows:; o To determine whether prolonged‐release fampridine 10 mg BID has a clinically meaningful effect on dynamic and static balance, physical impact of MS, and upper extremity function over a 24‐week study period; o To evaluate criteria for early assessment of response to fampridine that can predict clinically meaningful benefits in walking ability and balance; o To assess the safety and tolerability of prolonged‐release fampridine 10 mg BID over a 24‐week treatment period. Timepoint(s) of evaluation of this end point: Screening, Day 1, Week 2, Weeks 4, 8, 12, 16, 20 and 24/early termination and during follow up. SECONDARY OUTCOME: Secondary end point(s): Proportion of subjects who achieve a mean improvement in TUG speed of =15% from baseline over a 24‐week period ; Change from baseline over a 24‐week treatment period in the following ; o MSIS‐29 physical score ; o BBS ; o ABILHAND Timepoint(s) of evaluation of this end point: Proportion of subjects who achieve a mean improvement in TUG speed of =15% from baseline over a 24‐week period = Screening, Day 1, Week 2, Weeks 4, 8, 12, 16, 20 and 24/early termination and during follow up. ; Change from baseline over a 24‐week treatment period in the following ; o MSIS‐29 physical score = Screening, Day 1, Week 2, Weeks 4, 8, 12, 16, 20 and 24/early termination ; o BBS = Screening, Day 1, Week 2, Weeks 12 and 24/early termination ; o ABILHAND = Day 1, Week 2, Weeks 8 and 20 INCLUSION CRITERIA: 1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local subject privacy regulations 2. Aged 18 to 70 years, inclusive, at the time of informed consent. 3. Female subjects of childbearing potential must have a negative urine pregnancy test at the Screening Visit and on Day 1. All subjects must agree to practice effective contraception during the study, and be willing and able to continue contraception for 30 days after their last dose of study treatment. For effective contraception methods, see Section 15.5.3. 5. Must have an 4. 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.