Multiple sclerosis Nervous System Diseases Patients with primary progressive or secondary progressive multiple sclerosis without relapse
Conditions
Interventions
There are 2 parallel arms: mansitinib and placebo. Patients will be treated for 96 weeks and will be offered an additional treatment extension to week 108 if they have benefit. The drug is administrat
Sponsors
Dokumeds
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients with either primary progressive or secondary progressive multiple sclerosis with onset of symptoms at least five years before inclusion and with no relapse diagnosed according to the 2017 revised McDonald’s criteria at least two years before screening 2. Patients with Expanded Disability Status Scale (EDSS) score between 3.0 to 6.0 (both inclusive) at screening and baseline 3. Patients with an EDSS score progression =1 point with no improvement during 2 years before screening 4. Absence of T1 Gadolinium-enhancing brain lesions at baseline as measured by MRI at screening
Exclusion criteria
Exclusion criteria: 1. Patients suffering from a disease other than MS that would better explain the patient’s neurological clinical signs and symptoms and/or MRI lesions observed at screening 2. Inability to complete screening MRI (contraindications for MRI) and/or any known allergy or hypersensitivity or any contra-indication to gadolinium macrocyclic 3. Patients treated with other disease modifying treatments in the time frames and conditions mentioned under previous treatment wash out period, assessed at baseline 4. Patients with lymphocytes <1.0 × 10^9/L at screening and at baseline
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Time to confirmed (12-weeks CDP [Confirmed Disability Progression]) Expanded Disability Status Scale (EDSS) progression. The EDSS progression is defined as 1-point worsening when EDSS baseline score =5.5 or 0.5 if baseline score >5.5 from randomization to Week 96. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Expanded Disability Status Scale (EDSS): 1.1. Time to confirmed (24-weeks CDP) EDSS progression. Progression is defined as 1-point worsening when EDSS score =5.5, or 0.5 if baseline score >5.5) 1.2. Expanded Disability Status Scale (EDSS): Absolute and ordinal change from baseline considering all measurements up to Week 96 2. Time to EDSS score of 7.0 Clinical Global Assessment Tools: 2.1. Timed 25-foot walk (T25-FW) from baseline up to Week 96 and 12 weeks confirmed worsening using 20% threshold 2.2. Nine-hole peg test (9-HPT), right and left hands sides (finger dexterity) from baseline up to Week 96 and 12 weeks confirmed worsening using 20% threshold 2.3. The Symbol Digit Modalities Test (SDMT) from baseline up to Week 96 and 12 weeks confirmed worsening using 4-point threshold 3. Brain MRI Assessments: 3.1. Brain Volume and Lesions will be measured and assessed at Baseline, Week 48 and Week 96, or early termination (only if patient discontinues after Week 48 and more than 24 weeks have elapsed since last MRI) for the following endpoints: Brain atrophy - Percent brain volume change (PBVC) from baseline at Week 96 or early termination 3.2. New/newly enlarged T2 lesion count (compared with baseline MRI scan) at Week 96 or early termination 4. Quality of Life assessment: 4.1. Multiple Sclerosis Quality of Life (MSQOL)-54 instrument from baseline up to Week 96 4.2. Modified Fatigue Impact Scale (MFIS) from baseline up to Week 96 4.3. Hamilton Depression Rating Scale (HAM-D) from baseline up to Week 96 4.4. Disability Impact Profile (DIP) from baseline up to Week 96 5. Relapses measured using patient records: 5.1. Occurrence of new or worsening neurological symptoms attributable to MS 5.2. Symptoms | — |
Countries
Argentina, Belgium, England, France, Germany, Greece, Hungary, Italy, Netherlands, Norway, Poland, Portugal, Romania, Russian Federation, South Africa, Spain, Sweden, Ukraine, United Kingdom
Outcome results
None listed