Primary Progressive Multiple Sclerosis MedDRA version: 21.1 Level: PT Classification code 10063401 Term: Primary progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Sponsors
Genzyme Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - 18 to 55 years of age inclusive - Diagnosis of PPMS according to the 2017 McDonald criteria - Expanded disability status scale (EDSS) score between 2.0 to 6.5 points, at screening inclusive - Positive cerebrospinal fluid oligoclonal bands and/or elevated Immunoglobulin G (IgG) index either during screening or documented previous history. - Contraceptive use consistent with local regulations for individuals 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 1320 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - Participant has conditions that would adversely affect study participation such as short life expectancy. - History of organ transplant. - Evidence of infection with human immunodeficiency virus (HIV), transplantation, progressive multifocal leukoencephalopathy (PML), active hepatitis B or C, active or latent tuberculosis or other active infection 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 |
|---|---|
| Main Objective: To determine the efficacy of SAR442168 compared to placebo in delaying disability progression in Primary Progressive Multiple Sclerosis (PPMS);Secondary Objective: To evaluate efficacy of SAR442168 compared to placebo on clinical endpoints, magnetic resonance 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 PPMS and its relationship to efficacy and safety To evaluate pharmacodynamics of SAR442168 ;Primary end point(s): 6 month Confirmed Disability Progression (CDP) ; Time to onset of 6 month CDP defined as follows: Increase of =1.0 point from the baseline expanded disability status scale (EDSS) score when the baseline score is =5.5, or Increase of =0.5 points when the baseline EDSS score is >5.5 ;Timepoint(s) of evaluation of this end point: Up to approximately 48 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1 - 3-month confirmed disability progression (CDP) ; Time to onset of 3-month CDP as assessed by EDSS score 2 - 3-month change in 9-hole peg test (9-HPT) ; Time to onset of sustained 20% increase in the 9-HPT test confirmed over at least 3 months 3 - 3-month change in timed 25 foot walk (T25-FW) ; Time to onset of sustained 20% increase in the T25-FW confirmed over at least 3 months 4 - Change in T2 hyperintense lesions by MRI ; Total number of new and/or enlarging T2 hyperintense lesions as detected by MRI after baseline up to and including the end of study (EOS) 5 - Time to onset of 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 6 - Percent change in Brain volume loss (BVL) ; Percent change in brain volume loss (BVL) as detected by brain MRI at the EOS compared to month 6 7 - Change in cognitive function ; Change in cognitive function at the EOS compared to baseline as assessed by the Symbol Digit Modalities Test (SDMT) 8 - Change in cognitive function ; Change in cognitive function at the EOS compared to baseline as assessed by the California Verbal Learning Test II (CVLT-II) where available 9 - Change in Multiple Sclerosis Quality of Life ; Change in Multiple Sclerosis Quality of Life-54 (MSQoL-54) at the EOS compared to baseline 10 - 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) 11 - Population pharmacokinetics ; Plasma concentration of SAR442168 (population PK assessment) at Months 6, 9, and 12 12 - Change in plasma neurofilament light chain (NfL) ; Change in NfL levels from at the EOS compared to baseline 13 - Change in lymphocyte phenotype subsets ; Change in lymphocyte phenotype subsets in whole blood at the EOS compared to baseline in a subset of participants 14 | — |
Countries
Argentina, Australia, Austria, Belarus, Belgium, Brazil, Bulgaria, Canada, Chile, China, Colombia, Croatia, Czechia, Czech Republic, Denmark, Egypt, Estonia, France, Georgia, Germany, Greece, Hungary, India, Ireland, Israel, Italy, Japan, Kuwait, Latvia, Mexico, Netherlands, Norway, Peru, Poland, Portugal, Romania, Russian Federation, Saudi Arabia, Serbia, South Africa, Spain, Sweden, Switzerland, Turkey, Ukraine, United Arab Emirates, United Kingdom, United States
Contacts
Public ContactClinical Study Unit
Sanofi AB
Outcome results
None listed