E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Nervous System Diseases [C10] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 17.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10028245 |
E.1.2 | Term | Multiple sclerosis |
E.1.2 | System Organ Class | 10029205 - Nervous system disorders |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
|
E.2.2 | Secondary objectives of the trial |
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. |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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. |
|
E.4 | Principal 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 the 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 the 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 the 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 β-1b, interferon β-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 dose or regimen for the treatment of fatigue or depression within the 30 days prior to the Screening Visit or at any time during the screening period.
23. Any change in prophylactic treatment for pain with antidepressants or anticonvulsants prescribed for this purpose within 30 days prior to the Screening Visit or at any time during the screening period.
24.Any change in the subject’s dose or regimen of antispastic agents within the 7 days prior to the Screening Visit or at any time during the screening period.
25.Treatment with an investigational drug within the 30 days (or 7 half-lives, whichever is longer) prior to the Screening Visit or at any time during the screening period.
26. Treatment with any aminopyridine (fampridine, 4-AP, or 3,4-diaminopyridine [DAP] in any formulation) within the 30 days prior to the Screening Visit or at any time during the screening period.
27.Treatment with organic cation transporter 2 (OCT2) inhibitors within 5 half-lives prior to the Screening Visit or at any time during the screening period
28.History of drug or alcohol abuse within the 2 years prior to the Screening Visit.
29.Female subjects who are currently pregnant or who are considering becoming pregnant while participating in the study.
30. Female subjects who are currently breastfeeding.
31.Inability to comply with study requirements.
32. Subject who plan to participate in another clinical study (including any observational studies) during the course of the current study.
|
|
E.5 End points |
E.5.1 | 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. |
|
E.5.1.1 | 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. |
|
E.5.2 | 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 |
|
E.5.2.1 | 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 |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 9 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 74 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Bulgaria |
Czech Republic |
Finland |
Italy |
Lithuania |
Netherlands |
Poland |
Russian Federation |
Serbia |
Switzerland |
United Kingdom |
United States |
|
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
The end of study is last subject, last visit for final collection of data for the primary outcome. |
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 8 |
E.8.9.2 | In all countries concerned by the trial days | 0 |