A Study to Evaluate the Effect of SAR443820 on Serum Neurofilament Levels in Male and Female Adult Participants With Multiple Sclerosis

Sanofi

Status and phase: Terminated; Phase 2

Conditions: Multiple Sclerosis

Treatments: Other: Placebo; Drug: SAR443820

Study type: Interventional

Funder types: Industry

Identifiers

NCT05630547

2023-509078-45-00 (Registry Identifier)

U1111-1271-1257 (Registry Identifier)

ACT16753

2022-000049-34 (EudraCT Number)

Details and patient eligibility

About

This was a Phase 2, randomized, double-blind, placebo-controlled 2 parallel-arm study to assess the effect on serum neurofilament light chain (sNfL), safety and tolerability of oral SAR443820 compared to placebo in male and female participants aged 18 to 60 years with relapsing-remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS) (relapsing or non-relapsing), or primary progressive multiple sclerosis (PPMS) followed by an open-label long-term extension period.

The total study duration was approximately 100 weeks and included the following:

4-week screening period 48-week double-blind treatment period (Part A) 48-week open-label long-term extension period (Part B)

The study was terminated prior to completion (of Week 96) as primary endpoint was not met. Therefore final duration was less than 96 weeks.

Full description

Approximately 100 weeks

Enrollment: 174 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

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 to 6 inclusive at screening.
• Participants who were either untreated or in the opinion of the Investigator were 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 was 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 was consistent with local regulations regarding the methods of contraception for those participating in clinical studies.

Exclusion criteria

• 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 was 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 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 had significant cognitive impairment, psychiatric disease, other neurodegenerative disorders (eg, Parkinson disease or Alzheimer disease), substance abuse, or any other conditions that made the participants unsuitable for participating in the study or interfered 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 (CSSRS), or if in the Investigator's judgment, the participant was 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).
• Participants who used any medications that are moderate or strong inhibitors or strong inducers of cytochrome P450 3A4 (CYP3A4).
• Participants who used 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 were not allowed within 5 half-lives before the Screening Visit and for the duration of Part A and Part B.
• Participants who had prior/concurrent clinical study enrollment, ie, the participant had taken other investigational drugs within 4 weeks or 5 half-lives, whichever was longer, before the first Screening Visit; concurrent or recent participation in non-interventional studies may be permitted.

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
• The above information is not intended to contain all considerations relevant to a potential participation in a clinical trial

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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174 participants in 2 patient groups, including a placebo group

SAR443820

Experimental group

Description:

Oral SAR443820

Treatment:

Drug: SAR443820

Placebo

Placebo Comparator group

Description:

Oral placebo

Treatment:

Other: Placebo