A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of SAR443820 in Adult Participants With Amyotrophic Lateral Sclerosis, Followed by an Open-label Extension (HIMALAYA)

Study Purpose:

This is 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 openlabel, longterm extension period.

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

Part A is 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 will be 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 will be stratified by the geographic region of the study site, region of ALS onset (bulbar vs other areas), use of riluzole (yes vs no), and use of edaravone (yes vs no). Participants will attend inclinic study assessments at baseline (Day 1), Week 2, Week 4, Week 8, Week 16, and Week 24, and will receive a phone call at Week 12 and Week 20. After successful completion of Part A, all participants will rollover to Part B. The Week 24 Visit is the end of Part A and the beginning of Part B.

Part B is an open label, longterm extension period that starts from the end of Part A (Week 24) and continues up to Week 106. The objectives of Part B are to further determine the safety and efficacy of longterm SAR443820 treatment. The treatment assignment of participants in Part A will remain blinded to Investigators, participants, and site personnel until the end of Part B. Every participant will receive BID oral tablets of SAR443820 in Part B.

Disease:

Amyotrophic Lateral Sclerosis (ALS),  Familial ALS,  Sporadic ALS

Study Type:

Interventional Trial

Study Category:

Drug Trial

Study Status:

Enrolling

Phase:

Phase II

Study Chair(s)/Principal Investigator(s):

Clinicaltrials.gov ID (11 digit #):

NCT05237284

Neals Affiliated?

No

Coordinating Center Contact Information

Sanofi
.(JavaScript must be enabled to view this email address) / 800-633-1610 ext option 6
.(JavaScript must be enabled to view this email address)

Full Study Summary:

Part A of the study will last for 24 weeks, and participants will receive BID oral SAR443820 or placebo in a doubleblind fashion for 24 weeks. Participants who successfully complete double blind Part A will rollover to open label Part B.

Part B begins at the end of Week 24 and continues up to Week 106. All participants will receive BID oral tablets of SAR443820 in Part B.

The study duration includes 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.

Study Sponsor:

Sanofi

Participant Duration:

Estimated Enrollment:

261

Estimated Study Start Date:

04/13/2022

Estimated Study Completion Date:

04/29/2025

Posting Last Modified Date:

05/13/2022

Date Study Added to alsconsortium.org:

05/13/2022
  • Eligibility Criteria

    Gender:

    Female, Male

    Minimum Age:

    18

    Maximum Age:

    80

    Min Vital Capacity (% predicted normal):

    60

    Time since Symptom Onset:

    <24 months

    Time since Diagnosis:

    Can participants use Riluzole?

    Yes


    Inclusion Criteria:

    Type of participant and disease characteristics

    • Male or female, 18-80 years of age (inclusive)
    • Diagnosis of possible, clinically probable ALS, clinically probable laboratorysupported 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.
    • 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 are 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 must have completed at least 1 cycle of treatment before the screening visit and are expected to continue edaravone treatment throughout the duration of the study.

    Weight : Participants with a body weight no less than 45 kg and body mass index no less than 18 kg/m2 .

    Female participants with childbearing potential are eligible to participate if they are not pregnant or breastfeeding and agree to use adequate contraceptive method during study intervention period and for at least 32 days after the last dose of study drug.

    Male participants must 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 must 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 is allowed).

    Having central IV lines, such as a peripherally inserted central catheter (PICC) or midline or port a cath lines.

    With significant cognitive impairment, psychiatric disease, other neurodegenerative disorder (eg, Parkinson disease or AD), substance abuse, 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 (C-SSRS ), 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 are pregnant or are currently breastfeeding.

    A known history of allergy to any ingredients of SAR443820.

    Prior/concomitant therapy :

    Currently or previously treated with any strong or moderate CYP3A4 inhibitors or strong CYP3A4 inducers listed in Appendix 10 of the protocol 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 have received treatment with another investigational drug within 4 weeks or 5 halflives of the investigational agent before the screening visit, whichever is longer.

    Participants who have 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 has documented Gilbert syndrome (isolated bilirubin >1.5 × ULN is acceptable if bilirubin is 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 is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

  • Site Contact Information

    Investigational Site
    New York, New York 10003
    United States

    Investigational Site
    Leuven,
    Belgium

    Investigational Site
    Hamilton, Ontario
    Canada

    Investigational Site
    London, Ontario
    Canada

    Investigational Site
    Tours,
    France

    Investigational Site
    Berlin,
    Germany

    Investigational Site
    Dresden,
    Germany

    Investigational Site
    Hannover,
    Germany

    Investigational Site
    L├╝beck,
    Germany

    Investigational Site
    Ulm,
    Germany

    Investigational Site
    Utrecht,
    Netherlands

    Investigational Site
    Plymouth, Devon
    United Kingdom