Multiple sclerosis MedDRA version: 20.1 Level: PT Classification code 10028245 Term: Multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: SAR443820
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: SAR443820
CAS Number: 2252271-93-3
Current Sponsor code: SAR443820
Other descriptive name: RA15804589, C19061501-F,
Sponsors
Sanofi-aventis recherche & développement
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Male or female, 18 to 60 years (inclusive) of age, at the time of signing the informed consent. - Participants with diagnosis of RRMS, SPMS (relapsing or non-relapsing) or primary progressive subtype according to the 2017 revision of the McDonald diagnostic criteria (SPMS diagnostic criteria according to initial relapsing remitting disease course followed by progression with or without occasional relapses, minor remissions, and plateaus; progression denotes the continuous worsening of neurological impairment over at least 6 months). - Participants with Expanded Disability Status Scale (EDSS) score of 2-6 inclusive at screening. - Participants who in the opinion of the Investigator are stable on their disease-modifying therapy (DMT) (past 3 months), and do not require a change in multiple sclerosis (MS) treatment for the duration of Part A (through Week 48). - Participants with body weight at least 45 kg and body mass index (BMI) at least 18.0 kg/m^2. - Contraceptive use by men and women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. 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 280 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Participants are excluded from the study if any of the following criteria apply: Medical conditions - Participants with a history of seizures or epilepsy (history of febrile seizure during childhood is allowed). - Participants with known clinical relapse (acute or subacute episodes of new or increasing neurological dysfunction followed by full or partial recovery, in absence of fever or infection) within 8 weeks of study enrollment. - Participants with neurological disease history other than MS, eg, head trauma within 3 months, cerebrovascular disease, and vascular dementia. - Participants with a history of recent serious infection (eg, pneumonia,septicemia) within 4 weeks of screening; an infection requiring hospitalization or intravenous antibiotics, antivirals, or antifungals within 4 weeks of screening; or chronic bacterial infections (such as tuberculosis) deemed unacceptable, as per Investigator’s judgment. - Participants who have significant cognitive impairment, psychiatric disease, other neurodegenerative disorders (eg, Parkinson disease or Alzheimer disease), substance abuse, or any other conditions that would make the participants unsuitable for participating in the study or could interfere with assessment or completing the study in the opinion of the Investigator. - Participants with a documented history of attempted suicide over the 24 weeks prior to the Screening Visit, presents with suicidal ideation of category 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS),or if in the Investigator's judgment, the participant is at risk for a suicide attempt. - Participants with a history of unstable or severe cardiac, pulmonary, oncological, hepatic, or renal disease or another medically significant illness other than MS precluding their safe participation in this study. - Participants who received a live vaccine within 14 days before the Screening Visit. - Participants with a known history of allergy to any ingredients of SAR443820 (mannitol, lactose monohydrate, sodium starch glycolate, colloidal silicon dioxide, magnesium stearate, hypromellose, titanium dioxide, polyethylene glycol, and microcrystalline cellulose). Prior/concomitant therapy - Participants with a current use of any medications that are moderate or strong inhibitors or strong inducers of cytochrome P450 3A4 (CYP3A4). - Participants with a current use of any of the following medications/treatments: fampridine/dalfampridine, ofatumumab, fingolimod, cladribine, siponimod, ponesimod, ozanimod, alemtuzumab, mitoxantrone, ocrelizumab, natalizumab, or similar approved compounds but with different trade names and any unapproved treatments or therapies for MS. Any DMTs newly approved after July 2022 that are marketed at any time during the course of the double-blind study period. These medications are not allowed within 5 half-lives before the Screening Visit and for the duration of Part A. Prior/concurrent clinical study experience - Participants who have prior/concurrent clinical study enrollment, ie, the participant has taken other investigational drugs within 4 weeks or 5 halflives, whichever is longer, before the first Screening Visit; concurrent or recent participation in non-interventional studies may be permitted. Diagnostic assessments Participants with abnormal laboratory test(s) at the Screening Visit: - Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) more than 3.0 x upper limit of normal (ULN) - Bilirubin more than 1.5 x ULN;
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: - Part A: To assess the effect of SAR443820 compared to placebo on serum neurofilament (sNfL) - Part B: To assess long-term trends in durability of sNfL;Primary end point(s): 1)Part A: Week 48 sNfL levels relative to baseline 2)Part B: Week 96 sNfL levels relative to baseline;Secondary Objective: - Part A: To evaluate efficacy of SAR443820 compared to placebo on imaging and clinical endpoints - Part A: To explore effect of SAR443820 compared to placebo on brain volume and chronic lesions - Part A: To assess the safety and tolerability of SAR443820 - Part A: To assess pharmacokinetic (PK) of SAR443820 - Part B: To explore the effect of SAR443820 on brain volume and chronic lesions - Part B: To assess the long-term safety and tolerability of SAR443820 - Part B: To evaluate long-term effect of SAR443820 on disease progression and activity assessed by other clinical and imaging measures on physical function and patient reported outcomes (PROs);Timepoint(s) of evaluation of this end point: 1)2)From baseline (Week 0) to Week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1)Part A: Cumulative number of new gadolinium (Gd)-enhancing T1 hyperintense lesions as detected by magnetic resonance imaging (MRI) 2)Part A: Cumulative number of new and/or enlarging T2 hyperintense lesions as detected by MRI 3)Part A: Time to onset of 12 weeks confirmed disability progression (CDP) from baseline as assessed by the Expanded Disability Status Scale (EDSS) score 4)Part A: Time to onset of sustained 20% increase in 9-Hole Peg Test (9-HPT) confirmed over at least 12 weeks 5)Part A: Time to onset of sustained 20% increase in timed 25-foot walk test (T25-FW) confirmed over at least 12 weeks 6)Part A: Change from baseline in EDSS Plus 7)Part A: Annualized relapse rate (ARR) of RMS population (relapsing SPMS and RRMS) 8)Part A: Percent change from baseline in brain volume loss (BVL) as detected by brain MRI 9)Part A: Change from baseline in the volume, number, and intensity (T1) of slowly expanding lesions (SELs), and normalized T1 intensity in lesions 10)Part A: Change from baseline in the total number and volume of non-enhancing lesions 11)Part A: Change from baseline in the number of phase rim lesions (PRL) (subset of centers with 3T capacity, 25% of participants) 12)Part A and Part B: Incidence of adverse event(AE), serious adverse event (SAE), treatment emergent adverse event (TEAE), potentially clinically significant abnormality (PCSA) in laboratory tests, electrocardiogram (ECG) and vital signs 13)Part A: Plasma concentration of SAR443820 14)Part B: Percent change from baseline in BVL as detected by brain MRI 15)Part B: Change from baseline in volume, number and intensity (T1) in SEL and normalized T1 intensity in lesions 16)Part B: Change from baseline in the total number and volume of non-enhancing lesions 17)Part B: Change from baseline in the number of PRLs (same participants/centers from Part A with 3T capacity, 25% of participants) 18)Part B: Cumulative number of new Gd enhancing lesions as detected by T1-weighted MRI | — |
Countries
Belgium, Canada, China, Czechia, France, Germany, Italy, Poland, Spain, United States
Contacts
Public ContactUnidad de Estudios Clínicos
Sanofi-Aventis, S.A
Outcome results
None listed