Relapsing Multiple Sclerosis MedDRA version: 27.0 Level: PT Classification code 10080700 Term: Relapsing multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Sponsors
Genzyme Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - The participant must be 18 to 55 years of age, inclusive, at the time of signing the informed consent - The participant must have been diagnosed with RMS according to the 2017 revision of the McDonald diagnostic criteria - The participant has an expanded disability status scale (EDSS) score =5.5 at the first Screening Visit - The participant must have at least 1 of the following prior to screening: -- =1 documented relapse within the previous year OR -- =2 documented relapses within the previous 2 years, OR -- =1 documented Gd enhancing lesion on an MRI scan within the previous year - Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies - Male participants are eligible to participate if they agree to the following during the intervention period and until accelerated elimination procedure: Refrain from donating sperm Plus either: Be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agree to remain abstinent OR Must agree to use contraception/barrier as detailed below Agree to use a male condom and should also be advised of the benefit for a female partner to use a highly effective method of contraception as a condom may break or leak when having sexual intercourse with a woman of childbearing potential (WOCBP) who is not currently pregnant - A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions apply: Is not a Woman of child-bearing potential (WOCBP) OR Is a WOCBP and agrees to use a contraceptive method that is highly effective (with a failure rate of =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - The participant has been diagnosed with primary progressive multiplesclerosis (PPMS) according to the 2017 revision of the McDonald diagnostic criteria or with nonrelapsing secondary progressive multiplesclerosis (SPMS) - The participant has a history of infection or may be at risk for infection including but not limited to: HIV, transplantation, live attenuated vaccines, progressive multifocal leukoencephalopathy, tuberculosis, hepatitis B or C, any persistent chronic or active recurring infection -Clinically significant laboratory abnormalities (including evidence of liver injury) or electrocardiogram abnormalities at Screening - Confirmed screening ALT >2 × ULN - The participant has conditions or situations that would adversely affect participation in this study, including but not limited to: -- A short life expectancy due to pre-existing health condition(s) as determined by their treating neurologist -- Medical condition(s) or concomitant disease(s) making them nonevaluable for the primary efficacy endpoint or that would adversely affect participation in this study, as judged by the Investigator -- A requirement for concomitant treatment that could bias the primary evaluation - The participant has a history of or currently has concomitant medical or clinical conditions that would adversely affect participation in this study The participant has any of the following: -- A bleeding disorder or known platelet dysfunction at any time prior to the screening visit -- A platelet count <150 000/µL at the screening visit - The participant has a lymphocyte count below the lower limit of normal (LLN) at the screening visit - The presence of psychiatric disturbance or substance abuse Prior/concomitant therapy - The participant is receiving potent and moderate inducers of cytochrome P450 (CYP) 3A or potent inhibitors of CYP2C8 hepatic enzymes - The participant is receiving anticoagulant/antiplatelet therapies The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess efficacy of daily SAR442168 compared to a daily dose of 14 mg teriflunomide (Aubagio) measured by annualized adjudicated relapse rate (ARR) in participants with relapsing forms of MS;Secondary Objective: - To assess efficacy of SAR442168 compared to teriflunomide (Aubagio) on disability progression, MRI lesions, cognitive performance and quality of life - To evaluate the safety and tolerability of daily SAR442168 - To evaluate population pharmacokinetics (PK) of SAR442168 and relevant metabolites and its relationship to efficacy and safety - To evaluate pharmacodynamics (PD) of SAR442168 ;Primary end point(s): Annualized Adjudicated Relapse Rate : Number of confirmed protocol defined relapses ; Annualized Adjudicated Relapse Rate : Number of confirmed protocol defined adjudicated relapses;Timepoint(s) of evaluation of this end point: Up to approximately 36 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1 - Time to onset of confirmed disability worsening confirmed over at least 6 months ; Time to onset of confirmed disability worsening (CDW), confirmed over at least 6 months, defined as follows: -- increase of =1.5 points from the baseline expanded disability status scale (EDSS) score when the baseline score is 0 OR -- increase of =1.0 point from the baseline EDSS score when the baseline score is 0.5 to =5.5 OR -- increase of =0.5 point from the baseline EDSS score when the baseline score is >5.5 2 - Time to onset of CDW, assessed by the EDSS score and confirmed over at least 3 month 3 - Total number of new and/or enlarging T2 hyperintense lesions as detected by MRI from Month 6 through the end of study 4 - Total of Gd-enhancing T1 hyperintense lesions as detected by MRI from 6 months through the EOS 5 - Change in cognitive function ; Change in cognitive function from baseline to the EOS as assessed by SDMTand by CVLT-II where available 6 - Time to confirmed disability improvement ; Time to confirmed disability improvement (CDI), defined as a =1.0 point decrease on the EDSS from the baseline EDSS score confirmed over at least 6 months 7 - Percent Change in Brain volume loss (BVL) ; Brain volume loss (BVL) rate as detected by brain MRI from Month 6 to the EOS 8 - Change in Multiple Sclerosis Quality of Life ; Change in Multiple Sclerosis Quality of Life-54 (MSQoL-54) from the baseline through the EOS 9 - Number of participants with adverse events (AEs) leading to permanent study intervention discontinuation, and adverse events of special interest (AESI) 10 - Population Pharmacokinetics ; Plasma concentration of SAR442168 (population PK assessment) at 6 Months Plasma concentration of SAR442168 (population PK assessment) at 9 Months Plasma concentration of SAR442168 (population PK assessment) at 12 Months 11 - Change in plasma NfL ; Change in plasma neurofilament light chain (NfL) levels at the EOS compared to baseline 12 - Change in lymph | — |
Countries
Austria, Belarus, Bulgaria, Canada, China, Czechia, Czech Republic, Denmark, Estonia, Finland, Germany, Hong Kong, Italy, Japan, Lithuania, Mexico, Poland, Romania, Russian Federation, Spain, Sweden, Taiwan, Türkiye, Ukraine, United States
Outcome results
None listed