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)

• Register: EUCTR
• Last refreshed on: 2 May 2016
• Main ID: EUCTR2013-003600-40-FI
• Date of registration: 21/07/2014
• Prospective Registration: Yes
• Primary sponsor: Biogen Idec Research Limited
• Public title: 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)
• Scientific 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)
• Date of first enrolment: 05/08/2014
• Target sample size: 590
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-003600-40
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2

Countries of recruitment

Bulgaria, Czech Republic, Finland, Italy, Lithuania, Netherlands, Poland, Russian Federation, Serbia, Switzerland, United Kingdom, United States

Contacts

• Name: Not Available
• Affiliation: Biogen Idec Research Limited

• Name: Not Available
• Affiliation: Biogen Idec Research Limited

Key inclusion & exclusion criteria

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.
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.
5. Must have an EDSS score of 4 to 7, inclusive.
6. Must have walking impairment, as deemed by the Investigator.
7. Subjects must be able to understand and comply with the requirements of the protocol.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 560
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion criteria:
1. History of human immunodeficiency virus (HIV).
2. 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.
3. Known allergy to fampridine, pyridine-containing substances or any of the inactive ingredients in the prolonged-release fampridine tablet.
4. Any history of seizure, epilepsy or other convulsive disorder, with the exception of febrile seizures in childhood.
5. CrCl of <80 mL/min.
6. History of malignant disease, including solid tumors and hematologic malignancies (with the exception of basal cell and squamous cell carcinomas of the skin that have been completely excised and are considered cured) within the 5 years prior to the Screening Visit or at any time during the screening period.
7. Onset of MS exacerbation within 60 days prior to the Screening Visit, or at any time during the screening period.
8. History of any major surgical intervention (with the exception of skin biopsy) within the 30 days prior to the Screening Visit or Day 1 or at any time during the screening period.
9. Any non-MS-related condition or factor (as determined by the Investigator) that is likely to interfere with walking ability including, but not limited to, previous major surgery of the foot, leg or hip; any significant trauma; or known peripheral neuropathy of the lower limb.
10. Presence of pulmonary disease including, but not limited to, chronic obstructive pulmonary disease that can impede the subject’s daily activities (as determined by the Investigator).
11. Presence of any psychiatric disorder, including clinical depression, that is likely to interfere with the subject’s participation in the study (as determined by the Investigator).
12. Uncontrolled hypertension (as determined by the Investigator) at the Screening Visit or at any time during the screening period.
13. History of any clinically significant cardiac, endocrinologic, hematologic, immunologic, metabolic, urologic, neurologic (except for MS, but including events indicative of a potentially lower seizure threshold), dermatologic or other major disease (as determined by the Investigator).
14. Clinically significant abnormal laboratory values.
15. A body mass index (BMI) =40 (BMI formula: BMI=mass [kg]/[height(m)]2)
16. History of severe allergic or anaphylactic reactions.
17. Use of off-label MS treatment including rituximab, daclizumab or antibody (except natalizumab) within 3 months prior to the Screening Visit, at any time during the screening period or scheduled for use during study participation.
18. Use of mitoxantrone or cyclophosphamide within 3 months prior to the Screening Visit, at any time during the screening period or scheduled for use during study participation.
19. Initiation of natalizumab or alemtuzumab treatment or any change in the subject’s dose or regimen of natalizumab or alemtuzumab, within 3 months prior to the Screening Visit or at any time during the screening period.
20. Initiation of treatment with, or any change in the subject’s dose or regimen of, interferon ß-1b, interferon ß-1a, fingolimod, teriflunomide, glatiramer acetate or dimethyl fumarate within the 30 days prior to the Screening Visit or at any time during the screening period.
21. Pulsed steroid treatment within the 60 days prior to the Screening Visit or at any time during the screening period.
22. Any change in the subject’s medication dos

Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Multiple Sclerosis
MedDRA version: 17.1 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

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

Primary Outcome(s)

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.

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 Outcome(s)

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

Secondary ID(s)

218MS305

2013-003600-40-GB

Source(s) of Monetary Support

Biogen Idec Research Limited