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

Study of an Investigational Medication in Individuals with Amyotrophic Lateral Sclerosis (ALS)

Not Recruiting
18 years - 80 years
All
Phase 2
305 participants needed
19 Locations

Study Overview

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.

Study Details

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.

Eligibility Criteria

You may be eligible for this study if you meet the following criteria:

  • Conditions: Amyotrophic Lateral Sclerosis
  • Age: 18 years - 80 years
  • Gender: All

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:

  • 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.

This study investigates an investigational medication for individuals with Amyotrophic Lateral Sclerosis (ALS). The purpose of this study is to assess the efficacy, safety, and tolerability of the investigational medication compared to a placebo in participants aged 18 to 80 years. Participants were randomly assigned to receive either the investigational medication or a placebo in a blinded manner, meaning neither the participants nor the researchers knew who was receiving the actual medication.

Participants underwent various study procedures, including regular in-clinic assessments to monitor their health and the effects of the treatment. These assessments took place at multiple intervals throughout the study, starting from the baseline visit on Day 1 and continuing through Weeks 2, 4, 6, 8, 10, 12, 16, 20, 21, 22, 23, and 24. After completing the initial 24-week period, participants could enter an open-label extension phase, where all received the investigational medication to further evaluate its long-term safety and efficacy.

  • Who can participate: Eligible participants are adults aged 18 to 80 years diagnosed with ALS according to specific criteria, with symptoms for 2 years or less, and a Slow Vital Capacity of at least 60%. They must be able to swallow tablets and meet specific medication stability requirements.
  • Study details: Participants took oral tablets twice daily. Those in the placebo arm received an inactive substance resembling the investigational medication. The study involved regular in-clinic visits for health assessments and monitoring treatment effects.
  • Study timelines and visits: The study will last 110 weeks. The study requires 13 visits.
Updated on 05 Apr 2025. Study ID: NCT05237284