Effect of MD1003 in Spinal Progressive Multiple Sclerosis

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to demonstrate the superiority of MD1003 over placebo in the disability of patients suffering from progressive multiple sclerosis and especially those with gait impairment.

Official Title
-----------------
Effect of MD1003 in Spinal Progressive Multiple Sclerosis: a Pivotal Randomized Double Blind Placebo Controlled Study

Conditions
-----------------
Multiple Sclerosis

Intervention / Treatment
-----------------
* Drug: MD1003 100mg capsule
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis criteria of secondary or primary progressive MS with clinical evidence of spastic paraparesis fulfilling revised McDonald criteria (2010) and Lublin criteria (1996) Progression of the EDSS during the past two years of at least 1 point if EDSS from 4.5 to 5.5 and at least 0.5 point if EDSS from 6 to 7 EDSS score from 4.5 to 7 (measured away from a relapse and confirmed at 6 months) Informed consent prior to any study procedure Patient aged 18-75 years Exclusion Criteria: Any general chronic handicapping disease other than MS Intensive physical therapy program within the 3 months prior to inclusion Impossibility to perform the TW25 test New treatment introduced less than 3 months prior to inclusion or less than 1 month for Fampridine Pregnancy or woman with childbearing potential without contraception Evidence of inflammatory activity of the disease defined as clinical evidence of a relapse during the year before inclusion or evidence of new gadolinium-enhanced lesions on a brain MRI performed the year before inclusion.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MD1003<br>MD1003 100mg capsules, 1 capsule tid for 24 months | Drug: MD1003 100mg capsule<br> <br> |
| Placebo Comparator: Placebo<br>Placebo capsule, 1 capsule tid for 12 months, then switch to MD1003 100mg capsule, 1 capsule tid for 12 months | Drug: MD1003 100mg capsule<br> <br> Drug: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients improved on either Expanded Disability Status Scale (EDSS) or time to walk 25 feet (TW25) | Proportions of patients in each treatment arm: - with decreased EDSS at M9 confirmed at Month12 (where decreased EDSS is defined as a decrease of at least 0.5 point if initial EDSS from 6 to 7 and a decrease of at least 1 point if initial EDSS from 4.5 to 5.5) or - with improved TW25 of at least 20% at Month 9 and Month12 compared to the best EDSS and TW25 scores among screening visit (Month-1) and randomization visit (baseline) | up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Multiple Sclerosis Walking Scale (MSWS) | The 12-item multiple sclerosis walking scale (MSWS-12) is a self-report measure of the impact of MS on the individual's walking ability. | Baseline, 12 months, 24 months | 
| Clinical Global Impression / Subject Global Impression (CGI / SGI) | The Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. The clinical global impression will be assessed by the patient (subject global impression, SGI) and by the clinician (clinician global impression, CGI). | 12 months, 24 months | 
| Unidimensional Fatigue Impact Scale (U-FIS) | The U-FIS has 22-items measuring the impact of fatigue. | Baseline, 12 months, 24 months | 
| Multiple Sclerosis Quality of Life Scale (SEP-59) | The SEP-59 is a multidimensional health-related quality of life measure that combines 36 generic items and 29 MS-specific items into a single instrument. | Baseline, 12 months, 24 months | 
| Hole Peg Test (9-HPT) | The 9-HPT apparatus comprises a container with nine pegs and an empty pegboard with nine holes, set three by three. The pegs must be picked up one at a time and placed in the holes as quickly as possible until all holes are filled. Then, without pausing, the pegs should be removed one at a time, again as quickly as possible. This should be performed twice for each hand. If a peg falls onto the table, the peg should be picked up with the hand which is being tested. If a peg falls onto the floor, it is picked up by the examiner. The time is recorded in seconds, starting as the patient picks up the first peg and ending when the last peg drops into the container. | Baseline, 3 months, 6 months, 9 months, 12 months, 18 months, 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
MS, Multiple Sclerosis, EDSS