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TerminatedNCT05237284HIMALAYAUpdated Mar 21, 2025Results posted

Phase 2 Study for SAR443820 in Participants With Amyotrophic Lateral Sclerosis (ALS)

A Phase 2 interventional study of SAR443820 and Placebo in Amyotrophic Lateral Sclerosis, sponsored by Sanofi. Terminated at 63 sites in 13 countries. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2025-03-21.

Sponsored by Sanofi · Phase 2, Interventional, and Treatment

Why this study was terminated
The study was terminated as its Part A did not meet the primary endpoint.
Phase
Phase 2
Study type
Interventional
Enrollment
305
Allocation
Randomized
Ages
18 Years to 80 Years
Sex
All
01

Study summary

This was a parallel treatment, Phase 2, randomized, double-blind study to assess the efficacy, safety, tolerability, PK, and PD of twice daily (BID) oral SAR443820 compared with placebo in male and female participants, 18 to 80 years of age with ALS followed by an open-label, long-term extension period.

Study ACT16970 consisted of 2 parts (A and B) as follows:

Part A was a 24-week, double blind, placebo-controlled part, preceded by a screening period of up to 4 weeks before Day 1.

On Day 1 of Part A, participants were randomized in a 2:1 ratio to the SAR443820 treatment arm or matching placebo arm as listed below:

  • Treatment arm: SAR443820, BID
  • Placebo arm: Placebo, BID

Randomization was stratified by the geographic region of the study site, region of ALS onset (bulbar vs other areas), use of riluzole (yes vs no), use of edaravone (yes vs no) and use of the combination of sodium phenylbutyrate and taurursodiol (named Relyvrio in the United States of America [USA] and Albrioza in Canada) (yes vs no). Participants attended in-clinic study assessments at baseline (Day 1), Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, Week 16, Week 20, Week 21, Week 22, Week 23, and Week 24. All ongoing participants at Week 24 rolled to open-label extension Part B. The Week 24 Visit was the end of Part A and the beginning of Part B.

Part B was an open-label, long-term extension period that starts from Week 24 and continues up to Week 106. The objectives of Part B were to provide extended access to SAR443820 participants in Part A and to further evaluate the safety and efficacy of long-term SAR443820 treatment. The treatment assignment of participants at randomization in Part A remained blinded to Investigators, participants, and site personnel until the end of Part B. Every participant, except those who discontinued Investigational Medicinal Product (IMP) treatment permanently in Part A, received BID oral tablets of SAR443820 in Part B.

Read the detailed description

The study duration included an up to 4-week screening period, 24-week double-blind treatment period in Part A, 80-week open-label treatment period in Part B and 2-week post-treatment follow-up period, with a maximum total study duration of 110 weeks.

02

Conditions studied

  • Amyotrophic Lateral Sclerosis
03

In context

Motor Neuron Disease

717 studies on the registry are indexed under Motor Neuron Disease; 137 are open to participants now.

This study's enrollment of 305 is above the median of 35 across 461 interventional studies indexed under Motor Neuron Disease.

Browse Motor Neuron Disease studies →

Lead sponsor

Sanofi is the lead sponsor of 1,508 studies on the registry; 90 are open to participants now.

Of its 198 completed or terminated interventional studies of FDA-regulated products, 118 (60%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 80 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Diagnosis of possible, clinically probable ALS, clinically probable laboratory supported ALS, or clinically definite ALS according to the revised version of the El Escorial World Federation of Neurology criteria
  • Time since onset of first symptom of ALS ≤2 years.
  • Slow Vital Capacity (SVC) ≥60% of the predicted value.
  • Had to be able to swallow the study tablets at the screening visit.
  • Either not currently receiving riluzole or on a stable dose of riluzole for at least 4 weeks before the screening visit. Participants receiving riluzole were expected to remain on the same dose throughout the duration of the study.
  • Either not currently receiving edaravone or on the approved standard schedule of edaravone treatment. Participants receiving edaravone had to have completed at least 1 cycle of treatment before the screening visit and were expected to continue edaravone treatment throughout the duration of the study.
  • Either not currently receiving the combination of sodium phenylbutyrate and taurursodiol or on the approved standard schedule of the combination of sodium phenylbutyrate and taurursodiol treatment for at least 4 weeks before the screening visit. Participants receiving the combination of sodium phenylbutyrate and taurursodiol were expected to remain on the approved standard schedule throughout the duration of the study.
  • Participants with a body weight no less than 45 kg and body mass index no less than 18 kg/m2 at the screening visit
  • Female participants with childbearing potential were eligible to participate if they were not pregnant or breastfeeding and agreed to use adequate contraceptive method during study intervention period and for at least 32 days after the last dose of study drug.
  • Male participants had to agree to use highly effective contraceptive method during the study period and for at least 92 days following their last dose of the study drug. Male participants were not donate sperms for the duration of study and 92 days after last dose of study drug.

Exclusion criteria

Exclusion Criteria:

  • A history of seizure (History of febrile seizure during childhood was allowed).
  • Having central IV lines, such as a peripherally inserted central catheter (PICC XE ' PICC ' \f Abbreviation \t 'peripherally inserted central catheter' ) or midline or portacath lines.
  • With significant cognitive impairment, psychiatric disease, other neurodegenerative disorder (eg, Parkinson disease or AD), substance abuse other causes of neuromuscular weakness, or any other condition 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.
  • History of recent serious infection (eg, pneumonia, septicemia) within 4 weeks of the screening visit; infection requiring hospitalization or treatment with IV antibiotics, antivirals, or antifungals within 4 weeks of screening; or chronic bacterial infection (such as tuberculosis) deemed unacceptable as per the Investigator's judgment.
  • With active herpes zoster infection within 2 months prior to the screening visit.
  • A documented history of attempted suicide within 6 months prior to the screening visit, present with suicidal ideation of category 4 or 5 on the Columbia Suicide Severity Rating Scale (CSSRS) , or in the Investigator's judgment are at risk for a suicide attempt.
  • History of unstable or severe cardiac, pulmonary, oncological, hepatic, or renal disease or another medically significant illness other than ALS precluding their safe participation in this study.
  • Participants who were pregnant or were currently breastfeeding.
  • A known history of allergy to any ingredients of SAR443820.
  • Currently or previously treated with any strong or moderate CYP3A4 inhibitors or strong CYP3A4 inducers within the specified washout period before the screening visit.
  • Received a live vaccine within 14 days before the screening visit.
  • Participants with concurrent participation in any other interventional clinical study or who had received treatment with another investigational drug (eg sodium phenylbutyrate or taurursodiol ) within 4 weeks or 5 halflives of the investigational agent before the screening visit, whichever is longer.
  • Participants who had received stem cell or gene therapy for ALS at any time in the past.
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3.0 × upper limit of normal (ULN)
  • Bilirubin >1.5 × ULN unless the participant had documented Gilbert syndrome (isolated bilirubin >1.5 × ULN was acceptable if bilirubin was fractionated and direct bilirubin is \<35%)
  • Serum albumin \<3.5 g/dL
  • Estimated glomerular filtration rate \<60 mL/min/1.73 m2 (Modification of Diet in Renal Disease [MDRD])

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Investigator, Outcomes assessor)
Enrollment
305 participants (actual)

Study arms

  • Experimental
    SAR443820

    twice daily (BID) oral SAR443820

    Drug: SAR443820

  • Placebo comparator
    Placebo

    twice daily (BID) oral placebo

    Drug: Placebo

Interventions

  • DrugSAR443820

    Tablet oral

  • DrugPlacebo

    Tablet

06

What researchers measure

Primary outcomes

  1. Part A: Change From Baseline to Week 24 in the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) Total Score

    The ALSFRS-R is an instrument to evaluate the functional status of participants with ALS. It consists of 12 items across 4 sub-domains of bodily function: bulbar, fine motor, gross motor, and breathing. Each item was scored on an ordinal scale from 0 (total loss of function) to 4 (no loss of function). The total scores was the sum of the individual items score and it ranges from 0 to 48, with a higher score indicating better function. The analysis was performed using mixed-effect model with repeated measures (MMRM). Baseline was defined as the Day 1 pre-dose value.

    Time frame: Baseline (Day 1, pre-dose) and Week 24

  2. Part B: Combined Assessment of the Function and Survival (CAFS) Score at Week 52

    The CAFS at Week 52 is a composite endpoint based on time to earlier occurrence of death or permanent assisted ventilation (\>22 hours a day for \>7 consecutive days) and change from baseline in ALSFRS-R score up to Week 52. ALSFRS-R is a rating scale where 12 functions are rated on 5-point scales (from 0 to 4) with a maximum score of 48 (sum of all 12 items), with a higher score indicating better function. Each participant's outcome was compared to every other participant's outcome by time to death or permanent assisted ventilation and change on ALSFRS-R if survived without permanent assisted ventilation, assigned a score which is sum of comparisons (+1 \[better\], 0 \[tie\], -1 \[worse\]), and summed scores were ranked, from 1 to 296 (modified ITT\[mITT\] population) lowest rank corresponds to participant who died first and highest rank to 1 with best ALSFRS-R outcome among those who survived. A higher rank is considered a better outcome.

    Time frame: Week 52

Secondary outcomes

  1. Part A: Combined Assessment of the Function and Survival Score at Week 24

    The CAFS at Week 24 is a composite endpoint based on time to earlier occurrence of death or permanent assisted ventilation (\>22 hours a day for \>7 consecutive days) and change from baseline in ALSFRS-R score up to Week 24. ALSFRS-R is a rating scale where 12 functions are rated on 5-point scales (from 0 to 4) with a maximum score of 48 (sum of all 12 items), with a higher score indicating better function. Each participant's outcome was compared to every other participant's outcome by time to death or permanent assisted ventilation and change on ALSFRS-R if survived without permanent assisted ventilation, assigned a score which is sum of comparisons (+1 \[better\], 0 \[tie\], -1 \[worse\]), and summed scores were ranked, from 1 to 296 (mITT population) lowest rank corresponds to participant who died first and highest rank to 1 with best ALSFRS-R outcome among those who survived. A higher rank is considered a better outcome.

    Time frame: Week 24

  2. Combined Assessment of the Function and Survival Score at Weeks 76 and 104

    The CAFS at Weeks 76 and 106 is a composite endpoint based on time to earlier occurrence of death or permanent assisted ventilation (\>22 hours a day for \>7 consecutive days) and change from baseline in ALSFRS-R score up to Weeks 76 and 104. ALSFRS-R is a rating scale where 12 functions are rated on 5-point scales (from 0 to 4) with a maximum score of 48 (sum of all 12 items), with a higher score indicating better function. Each participant's outcome was compared to every other participant's outcome by time to death or permanent assisted ventilation and change on ALSFRS-R if survived without permanent assisted ventilation, assigned a score which is sum of comparisons (+1 \[better\], 0 \[tie\], -1 \[worse\]), and summed scores were ranked, from 1 to 296 (mITT population) lowest rank corresponds to participant who died first and highest rank to 1 with best ALSFRS-R outcome among those who survived. A higher rank is considered a better outcome.

    Time frame: Weeks 76 and 104

  3. Part B:Change From Baseline to Weeks 52, 76, and 104 in the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) Total Score

    The ALSFRS-R is an instrument to evaluate the functional status of participants with ALS. It consists of 12 items across 4 sub-domains of bodily function: bulbar, fine motor, gross motor, and breathing. Each item was scored on an ordinal scale from 0 (total loss of function) to 4 (no loss of function). The total scores was the sum of the individual items score and it ranges from 0 to 48, with a higher score indicating better function. Baseline was defined as the Day 1 pre-dose value.

    Time frame: Baseline (Day 1, pre-dose) and Weeks 52, 76 and 104

  4. Parts A and B: Change From Baseline to Weeks 24, 52, 76, and 104 in Amyotrophic Lateral Sclerosis Assessment Questionnaire 5 Items (ALSAQ-5)

    The ALSAQ-5 is a patient-reported outcome that consists of 5 items derived from the ALSAQ-40. The 5 items closely resemble those of the 5-dimension scores of the ALSAQ-40: eating and drinking; communication; activities of daily living/independence; physical mobility; and emotional functioning. Each item was scored on a 5-point Likert scale ranging from 0 (never) to 4 (always or cannot do at all) according to the frequency of a particular problem. The total scores was the sum of the individual items score and it ranges from 0 to 20, with higher scores indicative of greater physical and emotional limitations. Baseline was defined as the Day 1 pre-dose value.

    Time frame: Baseline (Day 1, pre-dose) and Part A: Week 24, Part B: Weeks 52, 76 and 104

  5. Parts A and B: Change From Baseline to Weeks 24, 52, 76, and 104 in Percent Predicted Slow Vital Capacity (SVC)

    SVC is the maximum volume of air that can be slowly exhaled after slow, maximal inhalation. SVC is measured in participants while they are in an upright position at least 3 trials per assessment or up to 5 trials when the highest and second highest of the first 3 measurements differ by 10% or more. Baseline was defined as the Day 1 pre-dose value.

    Time frame: Baseline (Day 1, pre-dose) and Part A: Week 24, Part B: Weeks 52, 76 and 104

  6. Parts A and B: Change From Baseline to Weeks 24 and 52 in Serum Neurofilament Light Chain (NfL)

    Serum blood samples were collected at indicated time points to measure changes in NfL, a marker of neuronal injury. Baseline was defined as the Day 1 pre-dose value.

    Time frame: Baseline (Day 1, pre-dose) and Part A: Week 24 and Part B: Week 52

  7. Part A: Change From Baseline to Week 24 in Muscle Strength

    The muscles measured in the study included upper limb and lower-limb muscle groups. Bilateral hand grip were measured using a grip dynamometer and all other muscles were measured using a handheld dynamometer (HHD). Nine upper and lower extremity muscles or muscle groups were examined: shoulder flexion, elbow flexion, wrist extension, first dorsal interosseous contraction, hip flexion, knee extension, and ankle dorsiflexion. Each group was measured at least twice bilaterally and the average of the 2 highest measurements were analyzed. Individual muscles are standardized into the corresponding Z-scores using data from standard sample of healthy participants. A Z-score of 0 in a muscle measurement is equal to the mean of that measurement from the standard sample. Negative numbers indicate decreased muscle strength. For analysis, individual Z-scores were averaged to produce a total megascore including all available muscle groups. Baseline was defined as the Day 1 pre-dose value.

    Time frame: Baseline (Day 1, pre-dose) and Week 24

  8. Part B: Time From Baseline to Occurrence of Either Death or Permanent Assisted Ventilation

    The survival endpoint was defined as the time to death or permanent assisted ventilation (\>22 hours a day for \>7 consecutive days), whichever comes first. Baseline was defined as the Day 1 pre-dose value.

    Time frame: Baseline (Day 1, pre-dose) up to early termination of study, approximately 84 weeks

  9. Part B: Time From Baseline to the Occurrence of Death

    Time to the occurrence of death from baseline due to any reason has been reported. Baseline was defined as the Day 1 pre-dose value.

    Time frame: Baseline (Day 1, pre-dose) up to early termination of study, approximately 84 weeks

  10. Parts B and A+B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) After SAR443820 Initiation

    An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs were defined as the AEs that developed, worsened or became serious during the treatment-emergent period (defined as time from first administration of study treatment (Day 1) to last administration of study treatment + 14 days). Serious adverse events (SAE): Any AE that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. All TEAE occurring after SAR443820 initiation are provided for both randomized treatment arms in this endpoint.

    Time frame: From first dose of SAR443820 up to 14 days after last dose of SAR443820 administration in Part B, approximately 82 weeks for Parts A+B combined Arm (SAR443820/SAR443820), approximately 58 weeks for Part B Arm (Placebo/SAR443820)

  11. Parts A and B: Plasma Concentration of SAR443820

    Plasma samples were collected at specified timepoints to determine plasma concentrations of SAR443820.

    Time frame: Part A: Day 1: 0.25- 1 hour and 1-3 hours post-dose; Weeks 2 and 8: pre-dose; Week 8: 0.25-3 hours post-dose; Part B: Week 28: pre-dose

07

Results

Posted Mar 21, 2025
Limitations and caveats
The study was terminated prematurely since the Part A did not meet the primary endpoint.

Participant flow

This study is double-blind followed by an open-label extension, 2 parts: Part (A and B) conducted at 63 investigational sites in 13 countries. A total of 397 participants were screened between 13 Apr 2022 and 17 July 2023, of which 92 were screen failures. Screen failures were due to not meeting the eligibility criteria.

Part A (Double-blind Period: 24 Weeks)
Participant flow — Part A (Double-blind Period: 24 Weeks)
MilestonePart A: PlaceboPart A: SAR443820Part B: Placebo/SAR443820Part B: SAR443820/SAR443820
Started10220300
Randomized and treated10220200
Completed8816700
Not completed143600
Withdrew: Other0200
Withdrew: Withdrawal by subject81300
Withdrew: Poor compliance to protocol0100
Withdrew: Adverse event62000
Part B (Open-label Period: 80 Weeks)
Participant flow — Part B (Open-label Period: 80 Weeks)
MilestonePart A: PlaceboPart A: SAR443820Part B: Placebo/SAR443820Part B: SAR443820/SAR443820
Started0088167
Treated0079136
Completed0000
Not completed0088167
Withdrew: Other0003
Withdrew: Study terminated by sponsor0064126
Withdrew: Withdrawal by subject001121
Withdrew: Poor compliance to protocol0001
Withdrew: Adverse event001316

Outcome measures

SecondaryPart A: Combined Assessment of the Function and Survival Score at Week 24

The CAFS at Week 24 is a composite endpoint based on time to earlier occurrence of death or permanent assisted ventilation (\>22 hours a day for \>7 consecutive days) and change from baseline in ALSFRS-R score up to Week 24. ALSFRS-R is a rating scale where 12 functions are rated on 5-point scales (from 0 to 4) with a maximum score of 48 (sum of all 12 items), with a higher score indicating better function. Each participant's outcome was compared to every other participant's outcome by time to death or permanent assisted ventilation and change on ALSFRS-R if survived without permanent assisted ventilation, assigned a score which is sum of comparisons (+1 \[better\], 0 \[tie\], -1 \[worse\]), and summed scores were ranked, from 1 to 296 (mITT population) lowest rank corresponds to participant who died first and highest rank to 1 with best ALSFRS-R outcome among those who survived. A higher rank is considered a better outcome.

Time frame:
Week 24
Reported as:
Mean · score on a scale
Part A: Combined Assessment of the Function and Survival Score at Week 24
score on a scalePart A: PlaceboPart A: SAR443820
Part A: Combined Assessment of the Function and Survival Score at Week 24151.19 ± 90.71147.13 ± 83.06
Statistical analysis
  • Part A: Placebo vs Part A: SAR443820 · Wilcoxon (Mann-Whitney) · p = 0.6999
SecondaryCombined Assessment of the Function and Survival Score at Weeks 76 and 104

The CAFS at Weeks 76 and 106 is a composite endpoint based on time to earlier occurrence of death or permanent assisted ventilation (\>22 hours a day for \>7 consecutive days) and change from baseline in ALSFRS-R score up to Weeks 76 and 104. ALSFRS-R is a rating scale where 12 functions are rated on 5-point scales (from 0 to 4) with a maximum score of 48 (sum of all 12 items), with a higher score indicating better function. Each participant's outcome was compared to every other participant's outcome by time to death or permanent assisted ventilation and change on ALSFRS-R if survived without permanent assisted ventilation, assigned a score which is sum of comparisons (+1 \[better\], 0 \[tie\], -1 \[worse\]), and summed scores were ranked, from 1 to 296 (mITT population) lowest rank corresponds to participant who died first and highest rank to 1 with best ALSFRS-R outcome among those who survived. A higher rank is considered a better outcome.

Time frame:
Weeks 76 and 104
Reported as:
Mean · score on a scale
Combined Assessment of the Function and Survival Score at Weeks 76 and 104
score on a scalePlacebo/SAR443820SAR443820/SAR443820
Week 76155.54 ± 92.17144.91 ± 82.04
SecondaryPart B:Change From Baseline to Weeks 52, 76, and 104 in the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) Total Score

The ALSFRS-R is an instrument to evaluate the functional status of participants with ALS. It consists of 12 items across 4 sub-domains of bodily function: bulbar, fine motor, gross motor, and breathing. Each item was scored on an ordinal scale from 0 (total loss of function) to 4 (no loss of function). The total scores was the sum of the individual items score and it ranges from 0 to 48, with a higher score indicating better function. Baseline was defined as the Day 1 pre-dose value.

Time frame:
Baseline (Day 1, pre-dose) and Weeks 52, 76 and 104
Reported as:
Mean · score on a scale
Part B:Change From Baseline to Weeks 52, 76, and 104 in the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) Total Score
score on a scalePart B: Placebo/SAR443820Part B: SAR443820/SAR443820
Week 52-11.9 ± 7.8-12.1 ± 8.0
Week 76-12.0 ± 10.1-13.3 ± 9.0
SecondaryParts A and B: Change From Baseline to Weeks 24, 52, 76, and 104 in Amyotrophic Lateral Sclerosis Assessment Questionnaire 5 Items (ALSAQ-5)

The ALSAQ-5 is a patient-reported outcome that consists of 5 items derived from the ALSAQ-40. The 5 items closely resemble those of the 5-dimension scores of the ALSAQ-40: eating and drinking; communication; activities of daily living/independence; physical mobility; and emotional functioning. Each item was scored on a 5-point Likert scale ranging from 0 (never) to 4 (always or cannot do at all) according to the frequency of a particular problem. The total scores was the sum of the individual items score and it ranges from 0 to 20, with higher scores indicative of greater physical and emotional limitations. Baseline was defined as the Day 1 pre-dose value.

Time frame:
Baseline (Day 1, pre-dose) and Part A: Week 24, Part B: Weeks 52, 76 and 104
Reported as:
Mean · score on a scale
Parts A and B: Change From Baseline to Weeks 24, 52, 76, and 104 in Amyotrophic Lateral Sclerosis Assessment Questionnaire 5 Items (ALSAQ-5)
score on a scalePart A: PlaceboPart A: SAR443820Part B: Placebo/SAR443820Part B: SAR443820/SAR443820
Week 242.1 ± 3.12.4 ± 3.1——
Week 52——4.1 ± 4.24.4 ± 3.5
Week 76——5.0 ± 3.55.8 ± 5.3
Statistical analysis
  • Part A: Placebo vs Part A: SAR443820 · MMRM · p = 0.2182 · Ls mean difference: 0.520 · 95% CI -0.310 to 1.350
SecondaryParts A and B: Change From Baseline to Weeks 24, 52, 76, and 104 in Percent Predicted Slow Vital Capacity (SVC)

SVC is the maximum volume of air that can be slowly exhaled after slow, maximal inhalation. SVC is measured in participants while they are in an upright position at least 3 trials per assessment or up to 5 trials when the highest and second highest of the first 3 measurements differ by 10% or more. Baseline was defined as the Day 1 pre-dose value.

Time frame:
Baseline (Day 1, pre-dose) and Part A: Week 24, Part B: Weeks 52, 76 and 104
Reported as:
Mean · percentage of predicted volume
Parts A and B: Change From Baseline to Weeks 24, 52, 76, and 104 in Percent Predicted Slow Vital Capacity (SVC)
percentage of predicted volumePart A: PlaceboPart A: SAR443820Part B: Placebo/SAR443820Part B: SAR443820/SAR443820
Week 24-13.43 ± 14.66-11.24 ± 13.35——
Week 52——-22.44 ± 16.35-18.29 ± 15.75
Week 76——-31.30 ± 30.72-22.68 ± 15.93
Statistical analysis
  • Part A: Placebo vs Part A: SAR443820 · MMRM · p = 0.8134 · Ls mean difference: 0.419 · 95% CI -3.075 to 3.914
SecondaryParts A and B: Change From Baseline to Weeks 24 and 52 in Serum Neurofilament Light Chain (NfL)

Serum blood samples were collected at indicated time points to measure changes in NfL, a marker of neuronal injury. Baseline was defined as the Day 1 pre-dose value.

Time frame:
Baseline (Day 1, pre-dose) and Part A: Week 24 and Part B: Week 52
Reported as:
Geometric mean · picograms per milliliter (pg/mL)
Parts A and B: Change From Baseline to Weeks 24 and 52 in Serum Neurofilament Light Chain (NfL)
picograms per milliliter (pg/mL)Part A: PlaceboPart A: SAR443820Part B: Placebo/SAR443820Part B: SAR443820/SAR443820
Week 241.016 ± 5853.6450.996 ± 6136.969——
Week 52——0.925 ± -709.9570.887 ± -1488.592
Statistical analysis
  • Part A: Placebo vs Part A: SAR443820 · MMRM · p = 0.2356 · Ratio of the ls geometric mean ratios: 0.961 · 95% CI 0.899 to 1.027
SecondaryPart A: Change From Baseline to Week 24 in Muscle Strength

The muscles measured in the study included upper limb and lower-limb muscle groups. Bilateral hand grip were measured using a grip dynamometer and all other muscles were measured using a handheld dynamometer (HHD). Nine upper and lower extremity muscles or muscle groups were examined: shoulder flexion, elbow flexion, wrist extension, first dorsal interosseous contraction, hip flexion, knee extension, and ankle dorsiflexion. Each group was measured at least twice bilaterally and the average of the 2 highest measurements were analyzed. Individual muscles are standardized into the corresponding Z-scores using data from standard sample of healthy participants. A Z-score of 0 in a muscle measurement is equal to the mean of that measurement from the standard sample. Negative numbers indicate decreased muscle strength. For analysis, individual Z-scores were averaged to produce a total megascore including all available muscle groups. Baseline was defined as the Day 1 pre-dose value.

Time frame:
Baseline (Day 1, pre-dose) and Week 24
Reported as:
Mean · score on a scale
Part A: Change From Baseline to Week 24 in Muscle Strength
score on a scalePart A: PlaceboPart A: SAR443820
Part A: Change From Baseline to Week 24 in Muscle Strength-0.498 ± 0.960-0.495 ± 0.704
Statistical analysis
  • Part A: Placebo vs Part A: SAR443820 · MMRM · p = 0.9565 · Ls mean difference: -0.005 · 95% CI -0.193 to 0.183
SecondaryPart B: Time From Baseline to Occurrence of Either Death or Permanent Assisted Ventilation

The survival endpoint was defined as the time to death or permanent assisted ventilation (\>22 hours a day for \>7 consecutive days), whichever comes first. Baseline was defined as the Day 1 pre-dose value.

Time frame:
Baseline (Day 1, pre-dose) up to early termination of study, approximately 84 weeks
Reported as:
Mean · weeks
Part B: Time From Baseline to Occurrence of Either Death or Permanent Assisted Ventilation
weeksPart B: Placebo/SAR443820Part B: SAR443820/SAR443820
Part B: Time From Baseline to Occurrence of Either Death or Permanent Assisted Ventilation31.90 ± 16.7131.54 ± 18.82
SecondaryPart B: Time From Baseline to the Occurrence of Death

Time to the occurrence of death from baseline due to any reason has been reported. Baseline was defined as the Day 1 pre-dose value.

Time frame:
Baseline (Day 1, pre-dose) up to early termination of study, approximately 84 weeks
Reported as:
Mean · weeks
Part B: Time From Baseline to the Occurrence of Death
weeksPart B: Placebo/SAR443820Part B: SAR443820/SAR443820
Part B: Time From Baseline to the Occurrence of Death38.30 ± 16.4529.93 ± 17.13
SecondaryParts B and A+B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) After SAR443820 Initiation

An adverse event (AE) was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. TEAEs were defined as the AEs that developed, worsened or became serious during the treatment-emergent period (defined as time from first administration of study treatment (Day 1) to last administration of study treatment + 14 days). Serious adverse events (SAE): Any AE that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was a medically important event. All TEAE occurring after SAR443820 initiation are provided for both randomized treatment arms in this endpoint.

Time frame:
From first dose of SAR443820 up to 14 days after last dose of SAR443820 administration in Part B, approximately 82 weeks for Parts A+B combined Arm (SAR443820/SAR443820), approximately 58 weeks for Part B Arm (Placebo/SAR443820)
Reported as:
Count of participants · Participants
Parts B and A+B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) After SAR443820 Initiation
ParticipantsPart B (Placebo/SAR443820)Parts A+B: SAR443820/SAR443820
TEAEs51183
TESAEs1353
SecondaryParts A and B: Plasma Concentration of SAR443820

Plasma samples were collected at specified timepoints to determine plasma concentrations of SAR443820.

Time frame:
Part A: Day 1: 0.25- 1 hour and 1-3 hours post-dose; Weeks 2 and 8: pre-dose; Week 8: 0.25-3 hours post-dose; Part B: Week 28: pre-dose
Reported as:
Mean · nanogram (ng)/mL
Parts A and B: Plasma Concentration of SAR443820
nanogram (ng)/mLPart A: SAR443820Part B: SAR443820
Day 1: 0.25- 1 hours post-dose181.500 ± 169.940—
Day 1: 1-3 hours post-dose250.188 ± 95.867—
Week 2: pre-dose165.833 ± 91.355—
Week 8: pre-dose165.089 ± 92.686—
Week 8: 0.25- 3 hours post-dose365.488 ± 198.609—
Week 28: pre-dose—171.865 ± 104.304
PrimaryPart A: Change From Baseline to Week 24 in the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) Total Score

The ALSFRS-R is an instrument to evaluate the functional status of participants with ALS. It consists of 12 items across 4 sub-domains of bodily function: bulbar, fine motor, gross motor, and breathing. Each item was scored on an ordinal scale from 0 (total loss of function) to 4 (no loss of function). The total scores was the sum of the individual items score and it ranges from 0 to 48, with a higher score indicating better function. The analysis was performed using mixed-effect model with repeated measures (MMRM). Baseline was defined as the Day 1 pre-dose value.

Time frame:
Baseline (Day 1, pre-dose) and Week 24
Reported as:
Mean · score on a scale
Part A: Change From Baseline to Week 24 in the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) Total Score
score on a scalePart A: PlaceboPart A: SAR443820
Part A: Change From Baseline to Week 24 in the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) Total Score-5.9 ± 5.9-6.1 ± 5.4
Statistical analysis
  • Part A: Placebo vs Part A: SAR443820 · MMRM · p = 0.5289 · Least square (ls) mean difference: -0.414 · 95% CI -1.706 to 0.878
PrimaryPart B: Combined Assessment of the Function and Survival (CAFS) Score at Week 52

The CAFS at Week 52 is a composite endpoint based on time to earlier occurrence of death or permanent assisted ventilation (\>22 hours a day for \>7 consecutive days) and change from baseline in ALSFRS-R score up to Week 52. ALSFRS-R is a rating scale where 12 functions are rated on 5-point scales (from 0 to 4) with a maximum score of 48 (sum of all 12 items), with a higher score indicating better function. Each participant's outcome was compared to every other participant's outcome by time to death or permanent assisted ventilation and change on ALSFRS-R if survived without permanent assisted ventilation, assigned a score which is sum of comparisons (+1 \[better\], 0 \[tie\], -1 \[worse\]), and summed scores were ranked, from 1 to 296 (modified ITT\[mITT\] population) lowest rank corresponds to participant who died first and highest rank to 1 with best ALSFRS-R outcome among those who survived. A higher rank is considered a better outcome.

Time frame:
Week 52
Reported as:
Mean · score on a scale
Part B: Combined Assessment of the Function and Survival (CAFS) Score at Week 52
score on a scalePlacebo/SAR443820SAR443820/SAR443820
Part B: Combined Assessment of the Function and Survival (CAFS) Score at Week 52154.89 ± 92.16145.24 ± 82.09
Statistical analysis
  • Placebo/SAR443820 vs SAR443820/SAR443820 · ANCOVA · p = 0.1830

Adverse events

Collected over Adverse events were collected from first dose of study treatment (Day 1) up to 14 days after last dose of study treatment administration, up to 26 weeks for Part A, and 58 weeks for Part B. All-cause mortality (death) was assessed from signing of the informed consent form to study termination, approximately 99 weeks.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Part A: Placebo5/102 (4.9%)17/102 (16.7%)56/102 (54.9%)
Part A: SAR44382011/202 (5.4%)34/202 (16.8%)116/202 (57.4%)
Part B: Placebo/SAR4438209/79 (11.4%)17/79 (21.5%)29/79 (36.7%)
Part B: SAR443820/SAR44382012/136 (8.8%)26/136 (19.1%)43/136 (31.6%)
Most frequent serious events
Showing 10 of 66
Most frequent serious events
EventPart A: PlaceboPart A: SAR443820Part B: Placebo/SAR443820Part B: SAR443820/SAR443820
Respiratory FailureRespiratory, thoracic and mediastinal disorders2/1027/2023/7912/136
Amyotrophic Lateral SclerosisNervous system disorders0/1022/2023/791/136
Hepatic Enzyme IncreasedInvestigations0/1025/2023/790/136
Pneumonia AspirationInfections and infestations1/1020/2022/792/136
Pulmonary EmbolismRespiratory, thoracic and mediastinal disorders1/1024/2022/792/136
PneumoniaInfections and infestations1/1024/2021/792/136
Covid-19Infections and infestations2/1021/2020/790/136
DysphagiaGastrointestinal disorders2/1020/2020/790/136
Covid-19 PneumoniaInfections and infestations0/1020/2021/790/136
Gastrointestinal InfectionInfections and infestations0/1020/2021/790/136
Most frequent other events
Showing 10 of 13
Most frequent other events
EventPart A: PlaceboPart A: SAR443820Part B: Placebo/SAR443820Part B: SAR443820/SAR443820
FallInjury, poisoning and procedural complications22/10244/20210/7911/136
Hepatic Enzyme IncreasedInvestigations2/10230/20210/797/136
HeadacheNervous system disorders9/10225/2023/792/136
Covid-19Infections and infestations9/10220/2023/793/136
ConstipationGastrointestinal disorders10/10214/2026/797/136
CoughRespiratory, thoracic and mediastinal disorders9/1026/2022/791/136
ContusionInjury, poisoning and procedural complications9/10211/2022/793/136
DiarrhoeaGastrointestinal disorders7/10213/2021/798/136
NauseaGastrointestinal disorders7/1026/2023/793/136
NasopharyngitisInfections and infestations4/1028/2025/794/136

Baseline characteristics

Randomized population=all participants from screened population who had been allocated to a randomized study treatment by interactive response technology (IRT) regardless of whether study treatment was received. Participants from Part A were allowed to transition to Part B per the study design hence baseline characteristics collected at the beginning of the study applies to both Part A and Part B.

Age, Continuous
Age, Continuous(years)Part A: PlaceboPart A: SAR443820Total
Mean56.7 ± 11.557.0 ± 11.656.9 ± 11.5
Sex: Female, Male
Sex: Female, Male(Participants)Part A: PlaceboPart A: SAR443820Total
Female3884122
Male64119183
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Part A: PlaceboPart A: SAR443820Total
American Indian or Alaska Native000
Asian265278
Native Hawaiian or Other Pacific Islander112
Black or African American134
White69126195
More than one race000
Unknown or Not Reported52126
Baseline Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) Total Score
Baseline Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) Total Score(score on a scale)Part A: PlaceboPart A: SAR443820Total
Mean36.23 ± 5.0035.97 ± 4.4136.06 ± 4.61
08

Study locations

63 sites
  • UC San Diego Health Site Number : 8400022
    La Jolla, California 92121, United States
  • USC Site Number : 8400008
    Los Angeles, California 90033, United States
  • University of California Irvine Site Number : 8400012
    Orange, California 92868, United States
  • California Pacific Medical Center Site Number : 8400015
    San Francisco, California 94115, United States
  • University of Colorado Site Number : 8400025
    Aurora, Colorado 80045, United States
  • Georgetown University Medical Center Site Number : 8400020
    Washington, District of Columbia 20007, United States
  • Mayo Clinic Site Number : 8400029
    Jacksonville, Florida 32224, United States
  • AdventHealth Medical Group - Neurology at Winter Park Site Number : 8400006
    Winter Park, Florida 32789, United States
  • Northwestern Medical Group, Department of Neurology Site Number : 8400003
    Chicago, Illinois 60611, United States
  • Johns Hopkins University Site Number : 8400028
    Baltimore, Maryland 21287, United States
  • Massachusetts General Hospital Site Number : 8400001
    Boston, Massachusetts 02114, United States
  • Mount Sinai - Union Square Site Number : 8400002
    New York, New York 10003, United States
  • Penn State Milton S. Hershey Medical Center Site Number : 8400004
    Hershey, Pennsylvania 17033, United States
  • University of Pennsylvania Site Number : 8400021
    Philadelphia, Pennsylvania 19104, United States
  • Thomas Jefferson University Hospital Site Number : 8400014
    Philadelphia, Pennsylvania 19107, United States
  • University of Utah Site Number : 8400009
    Salt Lake City, Utah 84132, United States
  • Froedtert Hospital & Medical College of Wisconsin Site Number : 8400010
    Milwaukee, Wisconsin 53226, United States
  • Investigational Site Number : 0560001
    Leuven, 3000, Belgium
  • Investigational Site Number : 1240004
    Edmonton, Alberta T6G 2C8, Canada
  • Investigational Site Number : 1240007
    Hamilton, Ontario L8N 3Z5, Canada
  • Investigational Site Number : 1240006
    London, Ontario N6A 5A5, Canada
  • Investigational Site Number : 1240008
    Toronto, Ontario M4N 3M5, Canada
  • Investigational Site Number : 1240002
    Montreal, Quebec H3A 2B4, Canada
  • Investigational Site Number : 1240001
    Quebec, G1J 1Z4, Canada
  • Investigational Site Number : 1560001
    Beijing, 100191, China
  • Investigational Site Number : 1560003
    Chengdu, 610041, China
  • Investigational Site Number : 1560005
    Guangzhou, 510515, China
  • Investigational Site Number : 1560002
    Hangzhou, 310009, China
  • Investigational Site Number : 1560004
    Wuhan, 430030, China
  • Investigational Site Number : 1560006
    Xi'An, 710061, China
  • Investigational Site Number : 2500007
    Caen, 14033, France
  • Investigational Site Number : 2500006
    Lille, 59037, France
  • Investigational Site Number : 2500002
    Marseille, 13385, France
  • Investigational Site Number : 2500003
    Montpellier, 34295, France
  • Investigational Site Number : 2500004
    Tours, 37044, France
  • Investigational Site Number : 2500005
    Vandoeuvre-les-nancy, 54511, France
  • Investigational Site Number : 2760004
    Berlin, 13353, Germany
  • Investigational Site Number : 2760003
    Dresden, 01307, Germany
  • Investigational Site Number : 2760008
    Haag In OB, 83527, Germany
  • Investigational Site Number : 2760005
    Hannover, 30625, Germany
  • Investigational Site Number : 2760002
    Lübeck, 23538, Germany
  • Investigational Site Number : 2760001
    Ulm, 89081, Germany
  • Investigational Site Number : 2760009
    Würzburg, 97074, Germany
  • Investigational Site Number : 3800001
    Milano, 20132, Italy
  • Investigational Site Number : 3800004
    Milano, 20138, Italy
  • Investigational Site Number : 3800002
    Torino, 10126, Italy
  • Investigational Site Number : 3920003
    Nagoya-shi, Aichi 466-8560, Japan
  • Investigational Site Number : 3920004
    Ichikawa-shi, Chiba 272-0827, Japan
  • Investigational Site Number : 3920006
    Tokushima-shi, Tokushima 770-8503, Japan
  • Investigational Site Number : 3920005
    Fuchu-shi, Tokyo 183-0042, Japan
  • Investigational Site Number : 3920001
    Ota-ku, Tokyo 143-8541, Japan
  • Investigational Site Number : 3920002
    Koshi-shi, 861-1196, Japan
  • Investigational Site Number : 5280001
    Utrecht, 3584 CX, Netherlands
  • Investigational Site Number : 6160001
    Krakow, 31-503, Poland
  • Investigational Site Number : 6160002
    Ksawerow, 95-054, Poland
  • Investigational Site Number : 7240005
    Barcelona, Barcelona [Barcelona] 08035, Spain
  • Investigational Site Number : 7240002
    Hospitalet de Llobregat, Barcelona [Barcelona] 08907, Spain
  • Investigational Site Number : 7240003
    Madrid, 28029, Spain
  • Investigational Site Number : 7240001
    Valencia, 46026, Spain
  • Investigational Site Number : 7520002
    Stockholm, 113 61, Sweden
  • Investigational Site Number : 7520001
    Umea, SE-901 85 Umea, Sweden
  • Investigational Site Number : 8260002
    Plymouth, Devon PL6 8DH, United Kingdom
  • Investigational Site Number : 8260003
    Stoke-on-Trent, Staffordshire ST46QG, United Kingdom
09

References and documents

Study documents

  • Study protocol · Dec 13, 2023
  • Statistical analysis plan · Jan 8, 2024

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — 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

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 21, 2025, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT05237284
Lead sponsor
Sanofi
Responsible party
Sponsor
First posted
Feb 14, 2022
Start date
Apr 13, 2022
Primary completion
Mar 7, 2024
Completion
Mar 7, 2024
Results posted
Mar 21, 2025
Last update
Mar 21, 2025

Study contacts

Clinical Sciences & Operations
study director · Sanofi

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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