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

Phase 2

Terminated

• Conditions: Amyotrophic Lateral Sclerosis
• Interventions: Drug: SAR443820; Drug: Placebo

• Registration Number: NCT05237284
• Lead Sponsor: Sanofi

Brief Summary

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 open-label, long-term 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), 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 will attend 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 will rollover to open-label extension Part B. The Week 24 Visit is the end of Part A and the beginning of Part B.

Part B is an open-label, long-term extension period that starts from Week 24 and continues up to Week 106. The objectives of Part B are 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 will remain blinded to Investigators, participants, and site personnel until the end of Part B. Every participant, except those who discontinue Investigational Medicinal Product (IMP) treatment permanently in Part A, will receive BID oral tablets of SAR443820 in Part B.

Detailed Description

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 Timeline

• Study First Submitted: 2022-02-02
• Study First Submitted QC: 2022-02-02
• Study First Posted: 2022-02-14
• Study Start: 2022-04-13
• Primary Completion: 2024-03-07
• Study Completion: 2024-03-07
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-02
• Last Update Posted: 2024-04-03

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 305

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.
• 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.
• 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 are 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 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.

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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 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 are pregnant or are 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 have 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 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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SAR443820	SAR443820	twice daily (BID) oral SAR443820
Placebo	Placebo	twice daily (BID) oral placebo

Primary Outcome Measures

Name	Time	Method
Combined assessment of the function and survival (CAFS) score -Part B	Week 52
Change from baseline in the ALSFRS-R total score -Part A	From baseline to Week 24

Secondary Outcome Measures

Name	Time	Method
Muscle Strength - Part A	From baseline to Week 24	Measured using a grip dynamometer and a handheld dynamometer (HHD)
Change from baseline in the ALSFRS R total score-Part B	From baseline to Week 52 and Week 76 and Week 104
Change from baseline in serum neurofilament light chain (NfL)-Part B	Week 52
Combined assessment of the function and survival (CAFS) score -Part A	Week 24
Change from baseline in serum neurofilament light chain (NfL) -Part A	From baseline to Week 24
Change from baseline in Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ5) -Part A	From baseline to Week 24
Assessment of pharmacokinetic parameter -Plasma concentration of SAR443820 -Part A	Day 1, Week 2, Week 8
Time from baseline to the occurrence of death-Part B	Up to Week 106
Number of patients with treatment emergent adverse events (TEAE) and Serious adverse event (SAE) -Part B	Up to Week 106
Assessment of pharmacokinetic parameter Plasma concentration of SAR443820 -Part B	Week 28
Change from baseline in slow vital capacity (SVC) -Part A	From baseline to Week 24
Combined assessment of the function and survival (CAFS) score - Part B	Week 76, Week 104
Change from baseline in slow vital capacity (SVC)-Part B	From baseline to Week 52, Week 76 and Week 104
Number of patients with treatment emergent adverse events (TEAE) and Serious adverse event (SAE) - Part A	Up to Week 24
Time from baseline to the occurrence of either death, or permanent assisted ventilation (>22 hours daily for >7 consecutive days), whichever comes first - Part B	Up to Week 106
Change from baseline in Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-5)-Part B	From baseline to Week 52, Week 76 and Week 104

Trial Locations

Locations (63)

University of Pennsylvania Site Number : 8400021; 🇺🇸 Philadelphia, Pennsylvania, United States

Thomas Jefferson University Hospital Site Number : 8400014; 🇺🇸 Philadelphia, Pennsylvania, United States

Investigational Site Number : 1240008; 🇨🇦 Toronto, Ontario, Canada

USC Site Number : 8400008; 🇺🇸 Los Angeles, California, United States

AdventHealth Medical Group - Neurology at Winter Park Site Number : 8400006; 🇺🇸 Winter Park, Florida, United States

Johns Hopkins University Site Number : 8400028; 🇺🇸 Baltimore, Maryland, United States

Massachusetts General Hospital Site Number : 8400001; 🇺🇸 Boston, Massachusetts, United States

Investigational Site Number : 3800001; 🇮🇹 Milano, Italy

Investigational Site Number : 2760009; 🇩🇪 Würzburg, Germany

Investigational Site Number : 0560001; 🇧🇪 Leuven, Belgium

University of Colorado Site Number : 8400025; 🇺🇸 Aurora, Colorado, United States

Investigational Site Number : 3920006; 🇯🇵 Tokushima-shi, Tokushima, Japan

Investigational Site Number : 8260003; 🇬🇧 Stoke-on-Trent, Staffordshire, United Kingdom

Investigational Site Number : 3920005; 🇯🇵 Fuchu-shi, Tokyo, Japan

Investigational Site Number : 1240004; 🇨🇦 Edmonton, Alberta, Canada

Investigational Site Number : 3920004; 🇯🇵 Ichikawa-shi, Chiba, Japan

Froedtert Hospital & Medical College of Wisconsin Site Number : 8400010; 🇺🇸 Milwaukee, Wisconsin, United States

UC San Diego Health Site Number : 8400022; 🇺🇸 La Jolla, California, United States

University of California Irvine Site Number : 8400012; 🇺🇸 Orange, California, United States

California Pacific Medical Center Site Number : 8400015; 🇺🇸 San Francisco, California, United States

Georgetown University Medical Center Site Number : 8400020; 🇺🇸 Washington, District of Columbia, United States

Mayo Clinic Site Number : 8400029; 🇺🇸 Jacksonville, Florida, United States

Northwestern Medical Group, Department of Neurology Site Number : 8400003; 🇺🇸 Chicago, Illinois, United States

Mount Sinai - Union Square Site Number : 8400002; 🇺🇸 New York, New York, United States

University of Utah Site Number : 8400009; 🇺🇸 Salt Lake City, Utah, United States

Penn State Milton S. Hershey Medical Center Site Number : 8400004; 🇺🇸 Hershey, Pennsylvania, United States

Investigational Site Number : 1240007; 🇨🇦 Hamilton, Ontario, Canada

Investigational Site Number : 1240002; 🇨🇦 Montreal, Quebec, Canada

Investigational Site Number : 1240006; 🇨🇦 London, Ontario, Canada

Investigational Site Number : 1560001; 🇨🇳 Beijing, China

Investigational Site Number : 1240001; 🇨🇦 Quebec, Canada

Investigational Site Number : 1560005; 🇨🇳 Guangzhou, China

Investigational Site Number : 1560002; 🇨🇳 Hangzhou, China

Investigational Site Number : 1560003; 🇨🇳 Chengdu, China

Investigational Site Number : 1560004; 🇨🇳 Wuhan, China

Investigational Site Number : 1560006; 🇨🇳 Xi'An, China

Investigational Site Number : 2500007; 🇫🇷 Caen, France

Investigational Site Number : 2500006; 🇫🇷 Lille, France

Investigational Site Number : 2500002; 🇫🇷 Marseille, France

Investigational Site Number : 2500003; 🇫🇷 Montpellier, France

Investigational Site Number : 2500004; 🇫🇷 Tours, France

Investigational Site Number : 2500005; 🇫🇷 Vandoeuvre-les-nancy, France

Investigational Site Number : 2760004; 🇩🇪 Berlin, Germany

Investigational Site Number : 2760003; 🇩🇪 Dresden, Germany

Investigational Site Number : 2760008; 🇩🇪 Haag In OB, Germany

Investigational Site Number : 2760002; 🇩🇪 Lübeck, Germany

Investigational Site Number : 2760001; 🇩🇪 Ulm, Germany

Investigational Site Number : 2760005; 🇩🇪 Hannover, Germany

Investigational Site Number : 7240001; 🇪🇸 Valencia, Spain

Investigational Site Number : 3800002; 🇮🇹 Torino, Italy

Investigational Site Number : 3800004; 🇮🇹 Milano, Italy

Investigational Site Number : 3920003; 🇯🇵 Nagoya-shi, Aichi, Japan

Investigational Site Number : 3920001; 🇯🇵 Ota-ku, Tokyo, Japan

Investigational Site Number : 3920002; 🇯🇵 Koshi-shi, Japan

Investigational Site Number : 6160002; 🇵🇱 Ksawerow, Poland

Investigational Site Number : 5280001; 🇳🇱 Utrecht, Netherlands

Investigational Site Number : 6160001; 🇵🇱 Krakow, Poland

Investigational Site Number : 7520002; 🇸🇪 Stockholm, Sweden

Investigational Site Number : 7240005; 🇪🇸 Barcelona, Barcelona [Barcelona], Spain

Investigational Site Number : 7520001; 🇸🇪 Umea, Sweden

Investigational Site Number : 7240002; 🇪🇸 Hospitalet de Llobregat, Barcelona [Barcelona], Spain

Investigational Site Number : 7240003; 🇪🇸 Madrid, Spain

Investigational Site Number : 8260002; 🇬🇧 Plymouth, Devon, United Kingdom