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

NCT05630547 | Terminated Phase 2 Results DMC FDA Drug

• 4 other identifiers: ACT16753U1111-1271-12572023-509078-45-002022-000049-34
• Study Type: interventional
• Target: 174
• Locations: 10 countries
• Sites: 35

Brief Summary

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.

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (2)

• Part A: Change From Baseline to Week 48 in Serum Neurofilament Light Chain (sNfL) Levels

  Serum blood samples were collected at indicated time points to measure changes in NfL, a marker of neuronal damage. Baseline was defined as the average value of the assessments on screening and Day 1 visits prior to the first dose of the study treatment unless the number of Gadolinium (Gd)-enhancing T1 lesion at Day 1 was greater than zero in which case baseline was the lower value of screening and Day 1 visits.

  Baseline (up to Day 1, pre-dose) and Week 48

• Part B: Change From Baseline to Week 72 in Serum Neurofilament Light Chain Levels

  Serum blood samples were collected at indicated time points to measure changes in NfL, a marker of neuronal damage. Baseline was defined as the average value of the assessments on screening and Day 1 visits prior to the first dose of the study treatment unless the number of Gd-enhancing T1 lesion at Day 1 was greater than zero in which case baseline was the lower value of screening and Day 1 visits.

  Baseline (up to Day 1, pre-dose) and Week 72

Secondary Outcomes (27)

• Part A: Number of New Gadolinium-Enhancing T1 Hyperintense Lesions as Detected by Magnetic Resonance Imaging (MRI)

  Post-baseline (Baseline: Day 1, pre-dose) and up to Week 48

• Part B: Number of New Gadolinium-Enhancing T1 Hyperintense Lesions as Detected by MRI

  From Week 48 to approximately up to Week 72

• Part A: Number of New, Enlarging T2 Hyperintense Lesions as Detected by MRI

  Post-baseline (Baseline: Day 1, pre-dose) and up to Week 48

• Part B: Number of New, Enlarging T2 Hyperintense Lesions as Detected by MRI

  From Week 48 to approximately up to Week 72

• Part A: Time to Onset of 12 Weeks Confirmed Disability Progression (CDP) From Baseline as Assessed by the Expanded Disability Status Scale (EDSS) Score

  Baseline (Day 1, pre-dose) and Week 48

Study Arms (2)

SAR443820

EXPERIMENTAL

Oral SAR443820

Drug: SAR443820

Placebo

PLACEBO COMPARATOR

Oral placebo

Other: Placebo

Interventions

SAR443820 DRUG

Tablet by oral administration

SAR443820

Placebo OTHER

Tablet by oral administration

Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Sanofi: lead

Study Sites (35)

Investigational Site Number : 0560001

Brussels, BE-1200, Belgium

Location

Investigational Site Number : 0560002

Ghent, 9000, Belgium

Location

Investigational Site Number : 0560003

Overpelt, 3900, Belgium

Location

Investigational Site Number : 1000001

Sofia, 1407, Bulgaria

Location

Investigational Site Number : 1000002

Sofia, 1431, Bulgaria

Location

Investigational Site Number : 1000003

Sofia, 1680, Bulgaria

Location

Investigational Site Number : 1240002

Ottawa, Ontario, K1H 8L6, Canada

Location

Investigational Site Number : 1240004

Toronto, Ontario, M5B 1W8, Canada

Location

Investigational Site Number : 1240001

Gatineau, Quebec, J8Y 1W2, Canada

Location

Investigational Site Number : 1240003

Lévis, Quebec, G6W0M5, Canada

Location

Investigational Site Number : 1520001

Santiago, Reg Metropolitana de Santiago, 8380456, Chile

Location

Investigational Site Number : 1560003

Chengdu, 610041, China

Location

Investigational Site Number : 1560002

Shanghai, 200040, China

Location

Investigational Site Number : 1560001

Tianjin, 300052, China

Location

Investigational Site Number : 1560004

Xi'an, 710038, China

Location

Investigational Site Number : 2500004

Caen, 14033, France

Location

Investigational Site Number : 2500002

Nice, 06001, France

Location

Investigational Site Number : 2500001

Paris, 75013, France

Location

Investigational Site Number : 2500003

Strasbourg, 67098, France

Location

Investigational Site Number : 2760002

Würzburg, 97074, Germany

Location

Investigational Site Number : 3800001

Pozzilli, Isernia, 86077, Italy

Location

Investigational Site Number : 3800005

Cagliari, 09126, Italy

Location

Investigational Site Number : 3800002

Milan, 20132, Italy

Location

Investigational Site Number : 3800003

Milan, 20133, Italy

Location

Investigational Site Number : 6160004

Plewiska, Greater Poland Voivodeship, 62-064, Poland

Location

Investigational Site Number : 6160002

Katowice, Silesian Voivodeship, 40-571, Poland

Location

Investigational Site Number : 6160005

Katowice, Silesian Voivodeship, 40-686, Poland

Location

Investigational Site Number : 6160001

Krakow, 31-503, Poland

Location

Investigational Site Number : 6160006

Zabrze, 41-800, Poland

Location

Investigational Site Number : 7240002

Seville, Andalusia, 41009, Spain

Location

Investigational Site Number : 7240001

Barcelona, Barcelona [Barcelona], 08035, Spain

Location

Investigational Site Number : 7240003

Madrid, Madrid, Comunidad de, 28040, Spain

Location

Investigational Site Number : 7240004

Madrid / Madrid, Madrid, Comunidad de, 28007, Spain

Location

Investigational Site Number : 7240006

Madrid, 28034, Spain

Location

Investigational Site Number : 7240005

Murcia, 30120, Spain

Location

Related Publications (1)

• Hincelin-Mery A, Nicolas X, Cantalloube C, Pomponio R, Lewanczyk P, Benamor M, Ofengeim D, Krupka E, Hsiao-Nakamoto J, Eastenson A, Atassi N. Safety, pharmacokinetics, and target engagement of a brain penetrant RIPK1 inhibitor, SAR443820 (DNL788), in healthy adult participants. Clin Transl Sci. 2024 Jan;17(1):e13690. doi: 10.1111/cts.13690. Epub 2023 Dec 11.

  PMID: 38010108 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Limitations and Caveats

The study was terminated as it did not meet its primary and key secondary endpoints, therefore Week 96 data was not collected.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement

Contact-US@sanofi.com

8006331610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blinded treatment (Part A) and open-label long-term extension period (Part B)
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2022
• First Posted: November 29, 2022
• Study Start: December 19, 2022
• Primary Completion: November 21, 2024
• Study Completion: November 21, 2024
• Last Updated: October 15, 2025
• Results First Posted: October 15, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

ES (6); CA (4); CL (1); IT (4); CN (4); FR (4); BU (3); PL (5); BE (3); DE (1)