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Trial record 1 of 2 for:    SAR443820 | multiple sclerosis
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A Study to Evaluate the Effect of SAR443820 on Serum Neurofilament Levels in Male and Female Adult Participants With Multiple Sclerosis

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ClinicalTrials.gov Identifier: NCT05630547
Recruitment Status : Active, not recruiting
First Posted : November 29, 2022
Last Update Posted : November 3, 2023
Sponsor:
Information provided by (Responsible Party):
Sanofi

Brief Summary:

This is 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 is approximately 100 weeks and includes the following:

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


Condition or disease Intervention/treatment Phase
Multiple Sclerosis Drug: SAR443820 Other: Placebo Phase 2

Detailed Description:
Approximately 100 weeks

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 174 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double-blinded treatment (Part A) and open-label long-term extension period (Part B)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : December 19, 2022
Estimated Primary Completion Date : September 3, 2025
Estimated Study Completion Date : September 3, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: SAR443820
Oral SAR443820
Drug: SAR443820
Tablet by oral administration

Placebo Comparator: Placebo
Oral placebo
Other: Placebo
Tablet by oral administration




Primary Outcome Measures :
  1. Part A: Week 48 sNfL levels relative to baseline [ Time Frame: From baseline (Week 0) to Week 48 ]
  2. Part B: Week 96 sNfL levels relative to baseline [ Time Frame: From baseline (Week 0) to Week 96 ]

Secondary Outcome Measures :
  1. Part A: Cumulative number of new gadolinium (Gd)-enhancing T1 hyperintense lesions as detected by magnetic resonance imaging (MRI) [ Time Frame: Baseline (Week 0) to Week 48 ]
    The sum of the individual number of new Gd enhancing T1 hyperintense lesions at all scheduled visits starting after baseline up to and including the Week 48 visit.

  2. Part A: Cumulative number of new and/or enlarging T2 hyperintense lesions as detected by MRI [ Time Frame: Baseline (Week 0) to Week 48 ]
    The sum of the individual number of new and/or enlarging T2 lesions at all scheduled visits starting after baseline up to and including the Week 48 visit.

  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 [ Time Frame: Up to Week 48 ]
    Standard EDSS assessments of 7 functional domains (visual, brainstem, pyramidal [motor], cerebellar [coordination], sensory, cerebral, and bowel/bladder) scoring will be performed by assessing neurological symptoms in each of these domains. EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS), where higher scores indicats worst outcomes. Confirmed disease progressions (CDPs) are defined as an increase in EDSS score (defined as an increase of ≥1.0 point from the baseline EDSS score when the baseline score is ≤5.5 or an increase of ≥0.5 points from the baseline EDSS score when the baseline score is >5.5).

  4. Part A: Time to onset of sustained 20% increase in 9-Hole Peg Test (9-HPT) confirmed over at least 12 weeks [ Time Frame: Up to Week 48 ]
  5. Part A: Time to onset of sustained 20% increase in timed 25-foot walk test (T25-FW) confirmed over at least 12 weeks [ Time Frame: Up to Week 48 ]
  6. Part A: Change from baseline in EDSS Plus [ Time Frame: From baseline (Week 0) to Week 48 ]
    The EDSS-plus event is defined as disability progression on at least 1 of 3 components, EDSS score, or T25-FW test, or 9-HPT. Disability criteria for the individual components are defined as follows: 1) Disability progression on the EDSS is defined as an increase of ≥1.0 point from the baseline EDSS score when the baseline score is ≤5.5 or an increase of ≥0.5 points from the baseline EDSS score when the baseline score is >5.5. 2) Disability progression on the T25-FW test is defined as an increase (worsening) of ≥20% from the baseline score. 3) Disability progression on the 9-HPT is defined as an increase (worsening) of ≥20% from the baseline score.

  7. Part A: Annualized relapse rate (ARR) of RMS population (relapsing SPMS and RRMS) [ Time Frame: Up to Week 48 ]
  8. Part A: Percent change from baseline in brain volume loss (BVL) as detected by brain MRI [ Time Frame: From baseline (Week 0) to Weeks 48 ]
  9. Part A: Change from baseline in the volume of slowly expanding lesions (SELs) [ Time Frame: From baseline (Week 0) to Weeks 12, 24, 36 and 48 ]
  10. Part A: Change from baseline in the number of SELs [ Time Frame: From baseline (Week 0) to Weeks 12, 24, 36 and 48 ]
  11. Part A: Change from baseline in the intensity (T1) of SELs [ Time Frame: From baseline (Week 0) to Weeks 12, 24, 36 and 48 ]
  12. Part A: Change from baseline in the normalized T1 intensity in lesions [ Time Frame: From baseline (Week 0) to Weeks 12, 24, 36 and 48 ]
  13. Part A: Change from baseline in the total number of non-enhancing lesions [ Time Frame: From baseline (Week 0) to Weeks 12, 24, 36 and 48 ]
  14. Part A: Change from baseline in the volume of non-enhancing lesions [ Time Frame: From baseline (Week 0) to Weeks 12, 24, 36 and 48 ]
  15. Part A: Change from baseline in the number of phase rim lesions (PRL) will be conducted at 3 Tesla (3T) capable sites [ Time Frame: From baseline (Week 0) to Weeks 12, 24, 36 and 48 ]
  16. Part A: Incidence of adverse event (AE) [ Time Frame: Week 0 to Week 48 ]
  17. Part A: Incidence of serious adverse event (SAE) [ Time Frame: Week 0 to Week 48 ]
  18. Part A: Incidence of treatment emergent adverse event (TEAE) [ Time Frame: Week 0 to Week 48 ]
  19. Part A: Incidence of potentially clinically significant abnormality (PCSA) in laboratory tests [ Time Frame: Week 0 to Week 48 ]
  20. Part A: Plasma concentration of SAR443820 [ Time Frame: Up to Week 36 ]
    Pre-dose concentration at steady state (Ctrough,ss)

  21. Part B: Percent change from baseline in BVL as detected by brain MRI [ Time Frame: From baseline (Week 0) to Week 96 ]
  22. Part B: Change from baseline in the volume of slowly expanding lesions (SELs) [ Time Frame: From baseline (Week 0) to Weeks 96 ]
  23. Part B: Change from baseline in the number of SELs [ Time Frame: From baseline (Week 0) to Weeks 96 ]
  24. Part B: Change from baseline in the intensity (T1) of SELs [ Time Frame: From baseline (Week 0) to Weeks 96 ]
  25. Part B: Change from baseline in the normalized T1 intensity in lesions [ Time Frame: From baseline (Week 0) to Weeks 96 ]
  26. Part B: Change from baseline in the total number of non-enhancing lesions [ Time Frame: From baseline (Week 0) to Weeks 96 ]
  27. Part B: Change from baseline in the volume of non-enhancing lesions [ Time Frame: From baseline (Week 0) to Weeks 96 ]
  28. Part B: Change from baseline in the number of PRLs (same participants/centers from Part A with 3T capability) [ Time Frame: From baseline (Week 0) to Weeks 96 ]
  29. Part B: Incidence of AE [ Time Frame: Week 48 to Week 96 ]
  30. Part B: Incidence of SAE [ Time Frame: Week 48 to Week 96 ]
  31. Part B: Incidence of TEAE [ Time Frame: Week 48 to Week 96 ]
  32. Part B: Incidence of potentially clinically significant abnormality (PCSA) in laboratory tests [ Time Frame: Week 48 to Week 96 ]
  33. Part B: Incidence of PCSA in ECG [ Time Frame: Week 48 to Week 96 ]
  34. Part B: Incidence of PCSA in vital signs [ Time Frame: Week 48 to Week 96 ]
  35. Part B: Cumulative number of new Gd-enhancing lesions as detected by T1-weighted MRI [ Time Frame: Week 48 to Week 96 ]
  36. Part B: number of new or enlarging T2-hyperintense lesions on MRI [ Time Frame: Week 48 to Week 96 ]
  37. Part B: ARR of RMS population (relapsing SPMS and RRMS) [ Time Frame: Up to Week 96 ]
  38. Part B: Time to onset of composite CDP (CCDP), confirmed over at least 12 weeks (3-month CCDP), by the EDSS Plus composite (EDSS score increase, OR 20% increase in the T25-FW test, OR 20% increase in the 9-HPT) [ Time Frame: Up to Week 96 ]
    The EDSS-plus event is defined as disability progression on at least 1 of 3 components, EDSS score, or T25-FW test, or 9-HPT. Disability criteria for the individual components are defined as follows: 1) Disability progression on the EDSS is defined as an increase of ≥1.0 point from the baseline EDSS score when the baseline score is ≤5.5 or an increase of ≥0.5 points from the baseline EDSS score when the baseline score is >5.5. 2) Disability progression on the T25-FW test is defined as an increase (worsening) of ≥20% from the baseline score. 3) Disability progression on the 9-HPT is defined as an increase (worsening) of ≥20% from the baseline score.

  39. Part B: Time to onset of 12 weeks CDP as assessed by the EDSS score [ Time Frame: Up to Week 96 ]
  40. Part B: Time to onset of sustained 20% increase in 9-HPT confirmed over at least 12 weeks [ Time Frame: Up to Week 96 ]
  41. Part B: Time to onset of sustained 20% increase T25-FW test confirmed over at least 12 weeks [ Time Frame: Up to Week 96 ]
  42. Part B: Change from baseline in EDSS Plus [ Time Frame: From baseline (Week 0) to Week 96 ]
    The EDSS-plus event is defined as disability progression on at least 1 of 3 components, EDSS score, or T25-FW test, or 9-HPT. Disability criteria for the individual components are defined as follows: 1) Disability progression on the EDSS is defined as an increase of ≥1.0 point from the baseline EDSS score when the baseline score is ≤5.5 or an increase of ≥0.5 points from the baseline EDSS score when the baseline score is >5.5. 2) Disability progression on the T25-FW test is defined as an increase (worsening) of ≥20% from the baseline score. 3) Disability progression on the 9-HPT is defined as an increase (worsening) of ≥20% from the baseline score.

  43. Part B: Change in Multiple Sclerosis Impact Scale -29 version 2 (MSIS-29v2) physical and psychological domains scoring [ Time Frame: From baseline (Week 0) to Week 96 ]
    The Multiple Sclerosis Impact Scale with 29 items (MSIS-29m) evaluates the specific physical and psychological impact of MS from a patient's perspective. This patient reported outcome (PRO) instrument has 2 subscales: 1) a physical impact score (20 items) and 2) a psychological impact score (9 items). The physical and psychological impact subscales of the MSIS-29v2m range from 0 to 100, with higher scores indicating greater physical or psychological impact.

  44. Part B: Change in Multiple Sclerosis Walking Scale 12 items (MSWS-12 [ Time Frame: From baseline (Week 0) to Week 96 ]
    The Multiple Sclerosis Walking Scale (MSWS-12m) measures the impact of walking impairment in patients with MS. This PRO instrument has 12 items with a global score ranging from 0 to 100. A higher score indicates better quality of life.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 26 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 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 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 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 (CSSRS), 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). - 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 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05630547


Locations
Show Show 41 study locations
Sponsors and Collaborators
Sanofi
Investigators
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Study Director: Clinical Sciences & Operations Sanofi
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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT05630547    
Other Study ID Numbers: ACT16753
U1111-1271-1257 ( Registry Identifier: ICTRP )
First Posted: November 29, 2022    Key Record Dates
Last Update Posted: November 3, 2023
Last Verified: November 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Multiple Sclerosis
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases