A Study of the Effectiveness of Fampridine in Improving Upper Limb Function in MS

NCT02208050 | Completed Phase 4 Results DMC

• 1 other identifier: SVUHneuro002
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to examine the effect of treatment with fampridine in patients with secondary progressive MS (SPMS) or primary progressive MS (PPMS) with upper limb dysfunction (as defined by a 9-HPT time of between 15-90 seconds) and Kurtzke EDSS scores in the range 4.0-7.0 on upper limb function assessed by the nine-hole peg test (9-HPT) and the Jebson Taylor Hand Function Test (JTT). Fampridine has been shown to be effective in improving motor function, specifically walking ability in prior studies in this patient population and is currently licensed for this use in Europe and the United States. Upper limb dysfunction is common in SPMS and PPMS and often underestimated. Fampridine effects action potential conduction in demyelinated nerve fibres and we would hypothesise that the improvement previously reported in walking ability would be similar to that on upper limb dysfunction. Our study aims to address this question using both independent and patient reported outcomes in the context of a randomised placebo controlled crossover trial.

Conditions

Secondary Progressive Multiple Sclerosis; Primary Progressive Multiple Sclerosis

Keywords

Secondary Progressive Multiple Sclerosis; Primary Progressive Multiple Sclerosis; Multiple Sclerosis; Upper limb function; Mobility; Fampridine; DASH; AMSQ; MSWS-12; MSIS-29; SF-36; 9HPT; 25FTW; JTT

Outcome Measures

Primary Outcomes (1)

• Number of Participants Classified as Upper Limb Responders on the 9 Hole Peg Test (9HPT)

  9 Hole Peg Test is a test of upper limb function. Participants place 9 pegs on pegboard and remove pegs - this is timed for each hand. Time recorded in seconds. Longer time indicates poorer upper limb function. 20% improvement is defined as 20% shorter time in seconds. An upper limb responder is defined as a patient with both of the two "on treatment" 9 Hole Peg Test (9-HPT) assessments measured in seconds (assessments 4 \& 5 or 7 \& 8) improving 20% from the average of the baseline assessments (1, 2 \& 3). Washout assessment not included in the analysis.

  20 weeks. Baseline assessments 1,2,3: weeks 0-2. Assessment 4 - midway through first treatment period; assessment 5: end of first treatment period. Assessment 7: midway through second treatment period, assessment 8: end of second treatment period.

Secondary Outcomes (6)

• Number of Participants Defined as Upper Limb Responders on the Jebsen Taylor Hand Function Test (JTT)

  20 weeks: Weeks 0-2: Assessment 1/2/3; Week 6: Assessment 4; Week 10: Assessment 5; Week 16: Assessment 7; Week 20: Assessment 8

• The Number of Mobility Responders to Fampridine as Measured by an Improvement in the 25 Foot Timed Walk (T25FW)

  20 weeks: Weeks 0-2: Assessment 1/2/3; Week 6: Assessment 4; Week 10: Assessment 5; Week 16: Assessment 7; Week 20: Assessment 8

• Mean Scores in DASH - Fampridine and Placebo.

  20 weeks: Assessments at Week 6 - midway through first treatment period, Week 10 - end of first treatment period, Week 16 - midway through second treatment period, Week 20 - end of second treatment period.

• Mean Scores in Multiple Sclerosis Walking Scale (MSWS-12) - Fampridine and Placebo.

  20 weeks: Assessments at Week 6 - midway through first treatment period, Week 10 - end of first treatment period, Week 16 - midway through second treatment period, Week 20 - end of second treatment period.

• Mean Scores in the Disabilities in Arm Function in Multiple Sclerosis Questionnaire (AMSQ) Score Between Fampridine and Placebo.

  20 weeks: Assessments at Week 6 - midway through first treatment period, Week 10 - end of first treatment period, Week 16 - midway through second treatment period, Week 20 - end of second treatment period.

Study Arms (2)

Group 1

OTHER

Patients will be randomised to a 8 week treatment period with the active drug followed by a 2 week washout period before an 8 week treatment period with placebo.

Drug: Fampridine; Drug: Placebo

Group 2

OTHER

Patients will be randomised to a 8 week treatment period with the placebo, followed by a 2 week washout period and a further 8 week treatment period with the active drug.

Drug: Fampridine; Drug: Placebo

Interventions

Fampridine DRUG

Also known as: Fampyra

Group 1; Group 2

Placebo DRUG

Group 1; Group 2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must be able and willing to give written informed consent and to comply with the requirements of this study protocol
• Subjects must be diagnosed with clinically definite SPMS or PPMS and be judged to be in generally good health by the investigator based upon the results of the medical history, laboratory tests (liver and renal function), physical examination, 12-lead electrocardiogram performed during Screening
• Subjects must be Male or female aged 18-70 at baseline
• Kurtzke EDSS scores in the range 4.0 to 7.0 inclusive
• Evidence of significant upper limb dysfunction as defined by a 9HPT of 15 - 90 seconds (dominant or non-dominant hand)
• Female subjects with reproductive capabilities must have a negative serum pregnancy test at baseline and agree to using an acceptable form of contraception for the duration of the study (barrier, coil or oral contraceptives only).

You may not qualify if:

• Allergy/sensitivity to study medications or their ingredients
• Female subjects who are pregnant or breast-feeding or considering becoming pregnant during the study.
• Subjects unable to provide written informed consent
• Subjects with a history of epilepsy or previous seizures (including provoked seizures).
• Subjects who have a history of drug or alcohol use that, in the opinion of the investigator, would interfere with adherence to study requirements.
• Subjects with an AST or ALT ≥ 3 x ULN on liver function tests
• Subjects have clinically significant ECG findings as judged by the investigator, in particular evidence of a cardiac conduction defect.
• Significant upper or lower limb arthritis as considered by the investigator to interfere with study assessments.
• Significant cognitive impairment as considered by the investigator to interfere with study assessments
• Subjects with clinically significant upper limb ataxia considered by the investigator to interfere with ability to complete study outcome measures.
• Patients with mild, moderate or severe renal impairment (creatinine clearance\<80ml/min) measured by 24-hour urine collection or estimated by the Cockcroft and Gault formula
• Subjects concomitantly using medicinal products that are inhibitors of Organic Cation Transporter 2 (OCT2) for example cimetidine
• Concurrent treatment with other medicinal products containing fampridine (4- aminopyridine)

Sponsors & Collaborators

• University College Dublin: lead

Study Sites (2)

St Vincent's University Hospital

Dublin, Dublin 4, Ireland

Location

St. Vincents University Hospital

Dublin, D4, Ireland

Location

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis

Interventions

4-Aminopyridine

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aminopyridines; Amines; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Professor Christopher McGuigan
• Organization: St. Vincent's University Hospital

C.McGuigan@svhg.ie

+35312214209

Study Officials

• Christopher McGuigan, MD

  University College Dublin, St Vincent's University Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant Neurologist

Study Record Dates

• First Submitted: May 19, 2014
• First Posted: August 4, 2014
• Study Start: February 21, 2014
• Primary Completion: February 16, 2016
• Study Completion: February 16, 2016
• Last Updated: July 9, 2021
• Results First Posted: July 9, 2021

Record last verified: 2021-07

Locations

IE (2)