A Phase 2 double-blind, randomized, placebo-controlled study evaluating the effect of SAR443820 on serum neurofilament levels in participants with multiple sclerosis, followed by an open-label long-term extension period

Trial details

Who runs it

Sanofi-Aventis Recherche & Developpement

Trial code

EU 2023-509078-45-00

Record updated

2024. október 18.

Original description

- 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 sNfLRead full original descriptionShow less

A Phase 2 double blind, randomized, placebo controlled study evaluating the effect of SAR443820 on serum neurofilament levels in participants with multiple sclerosis, followed by an open-label long-term extension period

- 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

Inclusion: 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 are either untreated or in the opinion of the Investigator are stable on an allowed disease-modifying therapy (DMT) (interferons, glatiramer acetate, fumarates, or teriflunomide) for at least the past 3 months, AND not anticipated to require a change in multiple sclerosis (MS) treatment for the duration of Part A and Part B (through Week 96); in Part B changes in dose of allowed DMTs or transition to other allowed DMTs is permitted); 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.

Exclusion: 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 January 2023 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 and Part B; Participants who have prior/concurrent clinical study enrollment, ie, the participant has taken other investigational drugs within 4 weeks or 5 half-lives, whichever is longer, before the first Screening Visit; concurrent or recent participation in non-interventional studies may be permitted; 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 who received a live vaccine within 14 days before the Screening Visit; Participants with immunodeficiency syndromes or other autoimmune diseases requiring immunosuppressive therapy; 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 screening; Participants with a 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 (including a history of alcohol 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 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 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); 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; unless the participant has documented Gilbert syndrome (isolated bilirubin more than 1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35%) - Serum albumin less than 3.5 g/dL - Estimated Glomerular filtration rate less than 60 mL/min/1.73 m^2 (Modification of Diet in Renal Disease [MDRD]) - Other abnormal laboratory values or electrocardiogram (ECG) changes that are deemed clinically significant as per Investigator’s judgment.

EU CTIS 2023-509078-45-00