Non-relapsing Secondary Progressive Multiple Sclerosis MedDRA version: 21.1 Level: PT Classification code 10063400 Term: Secondary progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Sponsors
Genzyme Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - 18 to 60 years of age inclusive - Diagnosis of nonrelapsing secondary progressive multiple sclerosis according to the 2017 McDonald criteria - Expanded disability status scale (EDSS) between 3.0 to 6.5 points inclusive, at screening - The participant must have documented evidence of disability progression observed during the 12 months before screening - Absence of clinical relapses for at least 24 months - Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies - Participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: - Is not a woman of child bearing potential (WOCBP) OR - Is a WOCBP and agrees to use an acceptable contraceptive method 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 1700 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - The participant has conditions that would adversely affect study participation such as short life expectancy. - History of organ transplant. - Evidence of infection with human immuodeficiency virus (HIV), transplantation, progressive multifocal leukoencephalopathy (PML), active hepatitis B or C, active or latent tuberculosis or other active infections that would adversely affect study participation. - Persistent chronic or active or recurring system infection, that may adversely affect participation or IMP administration in this study, as judged by the Investigator. - History of malignancy within 5 years prior to screening. - History of alchohol or drug abuse within 1 year prior to screening. - Hospitalized for psychiatric disease within 2 years prior to screening. - Clinically significant laboratory abnormalities (including evidence of liver injury) or electrocardiogram abnormalities at screening - A bleeding disorder or known platelet dysfunction at any time prior to the screening visit. - A platelet count 81mg/day, clopidogrel, warfarin). - Contraindications to magnetic resonance imaging (MRI). NOTE: Other Inclusion/Exclusion criteria may apply.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: - To evaluate efficacy of SAR442168 compared to placebo on clinical endpoints, magnetic resonsnce imaging (MRI) lesions, cognitive performance, physical function, and quality of life - To evaluate safety and tolerability of SAR442168 - To evaluate population pharmacokinetics (PK) of SAR442168 in NRSPMS and its relationship to efficacy and safety - To evaluate pharmacodynamics (PD) of SAR442168;Primary end point(s): 6-month confirmed disability progression (CDP) ; Time to onset of 6 months CDP defined as follows: -Increase of =1.0 point from the baseline expanded disability status scale (EDSS) score when the baseline score is =5.0, or -Increase of =0.5 point when the baseline EDSS score is >5.0;Timepoint(s) of evaluation of this end point: Up to approximately 48 months;Main Objective: To determine the efficacy of SAR442168 compared to placebo in delaying disability progression in NRSPMS | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1 - 3-months change in T25-FW and 9-HPT ; Time to onset of sustained 20% increase in the timed 25 foot walk (T25-FW) and the 9-hole peg test (9-HPT) for at least 3 months 2 - 3-month CDP ; Time to onset of 3-month CDP as assessed by EDSS score 3 - T2 hyperintense lesion by MRI ; Total number of new or enlarging T2 hyperintense lesions as detected by MRI 4 - Time to confirmed disability improvement (CDI) ; Time to onset of CDI defined as =1.0 point decrease on the EDSS score from baseline confirmed over at least 6 months 5 - Brain volume loss (BVL) ; Percent change in Brain volume loss (BVL) as detected by brain MRI at the EOS compared to month 6 6 - Change in cognitive function ; Change in cognitive function at the EOS compared to baseline as assessed by the Symbol Digit Modalities Test (SDMT) and by the California Verbal Learning Test (CVLT-II) 7 - Change in Multiple Sclerosis Quality of Life-54 (MSQoL-54) ; Change in Multiple Sclerosis Quality of Life-54 (MSQoL-54) from the baseline through the EOS 8 - Safety and Tolerability ; Number of participants with adverse events (AEs), Serious AEs, AEs leading to permanent study intervention discontinuation, and adverse events of special interest (AESI) 9 - Population pharmacokinetics ; Plasma concentration of SAR442168 and relevant metabolites (population PK assessment) at Months 6, 9, and 12 10 - Change in plasma neurofilament light chain (NfL) ; Change in NfL levels at the EOS compared to baseline 11 - Changes in serum Immunoglobulin level ; Changes in serum Immunoglobulin level at the EOS compared to baseline 12 - Change in lymphocyte phenotype subsets ; Change in lymphocyte phenotype subsets in whole blood at the EOS compared to baseline in a subset of participants 13 - Change in serum chitinase-3 like protein 1 (Chi3L1) ; Change in serum chitinase-3 like protein 1 (Chi3L1) at the EOS compared to baseline;Timepoint(s) of evaluation of this end point: 1, 2 : Up to approximately 48 months 3, 4, 5 | — |
Countries
Argentina, Australia, Austria, Belarus, Belgium, Bulgaria, Canada, Chile, China, Czechia, Czech Republic, Denmark, Finland, France, Germany, Greece, Hungary, India, Israel, Italy, Japan, Lithuania, Netherlands, Norway, Poland, Portugal, Romania, Russian Federation, Spain, Türkiye, Ukraine, United Kingdom, United States
Outcome results
None listed