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

Amyotrophic Lateral Sclerosis Clinical Trial

— HIMALAYA  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05237284
• Other study ID #: ACT16970
• Secondary ID: U1111-1263-57662
• Status: Terminated
• Phase: Phase 2
• Start date: April 13, 2022
• Est. completion date: March 7, 2024

Study information

• Verified date: April 2024
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 305
• Est. completion date: March 7, 2024
• Est. primary completion date: March 7, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

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.

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• SAR443820
Tablet oral
• Placebo
Tablet

Locations

Country	Name	City	State
Belgium	Investigational Site Number : 0560001	Leuven
Canada	Investigational Site Number : 1240004	Edmonton	Alberta
Canada	Investigational Site Number : 1240007	Hamilton	Ontario
Canada	Investigational Site Number : 1240006	London	Ontario
Canada	Investigational Site Number : 1240002	Montreal	Quebec
Canada	Investigational Site Number : 1240001	Quebec
Canada	Investigational Site Number : 1240008	Toronto	Ontario
China	Investigational Site Number : 1560001	Beijing
China	Investigational Site Number : 1560003	Chengdu
China	Investigational Site Number : 1560005	Guangzhou
China	Investigational Site Number : 1560002	Hangzhou
China	Investigational Site Number : 1560004	Wuhan
China	Investigational Site Number : 1560006	Xi'An
France	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
Germany	Investigational Site Number : 2760004	Berlin
Germany	Investigational Site Number : 2760003	Dresden
Germany	Investigational Site Number : 2760008	Haag In OB
Germany	Investigational Site Number : 2760005	Hannover
Germany	Investigational Site Number : 2760002	Lübeck
Germany	Investigational Site Number : 2760001	Ulm
Germany	Investigational Site Number : 2760009	Würzburg
Italy	Investigational Site Number : 3800001	Milano
Italy	Investigational Site Number : 3800004	Milano
Italy	Investigational Site Number : 3800002	Torino
Japan	Investigational Site Number : 3920005	Fuchu-shi	Tokyo
Japan	Investigational Site Number : 3920004	Ichikawa-shi	Chiba
Japan	Investigational Site Number : 3920002	Koshi-shi
Japan	Investigational Site Number : 3920003	Nagoya-shi	Aichi
Japan	Investigational Site Number : 3920001	Ota-ku	Tokyo
Japan	Investigational Site Number : 3920006	Tokushima-shi	Tokushima
Netherlands	Investigational Site Number : 5280001	Utrecht
Poland	Investigational Site Number : 6160001	Krakow
Poland	Investigational Site Number : 6160002	Ksawerow
Spain	Investigational Site Number : 7240005	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240002	Hospitalet de Llobregat	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240003	Madrid
Spain	Investigational Site Number : 7240001	Valencia
Sweden	Investigational Site Number : 7520002	Stockholm
Sweden	Investigational Site Number : 7520001	Umea
United Kingdom	Investigational Site Number : 8260002	Plymouth	Devon
United Kingdom	Investigational Site Number : 8260003	Stoke-on-Trent	Staffordshire
United States	University of Colorado Site Number : 8400025	Aurora	Colorado
United States	Johns Hopkins University Site Number : 8400028	Baltimore	Maryland
United States	Massachusetts General Hospital Site Number : 8400001	Boston	Massachusetts
United States	Northwestern Medical Group, Department of Neurology Site Number : 8400003	Chicago	Illinois
United States	Penn State Milton S. Hershey Medical Center Site Number : 8400004	Hershey	Pennsylvania
United States	Mayo Clinic Site Number : 8400029	Jacksonville	Florida
United States	UC San Diego Health Site Number : 8400022	La Jolla	California
United States	USC Site Number : 8400008	Los Angeles	California
United States	Froedtert Hospital & Medical College of Wisconsin Site Number : 8400010	Milwaukee	Wisconsin
United States	Mount Sinai - Union Square Site Number : 8400002	New York	New York
United States	University of California Irvine Site Number : 8400012	Orange	California
United States	Thomas Jefferson University Hospital Site Number : 8400014	Philadelphia	Pennsylvania
United States	University of Pennsylvania Site Number : 8400021	Philadelphia	Pennsylvania
United States	University of Utah Site Number : 8400009	Salt Lake City	Utah
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	AdventHealth Medical Group - Neurology at Winter Park Site Number : 8400006	Winter Park	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Belgium,  Canada,  China,  France,  Germany,  Italy,  Japan,  Netherlands,  Poland,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in the ALSFRS-R total score -Part A		From baseline to Week 24
Primary	Combined assessment of the function and survival (CAFS) score -Part B		Week 52
Secondary	Combined assessment of the function and survival (CAFS) score -Part A		Week 24
Secondary	Change from baseline in slow vital capacity (SVC) -Part A		From baseline to Week 24
Secondary	Muscle Strength - Part A	Measured using a grip dynamometer and a handheld dynamometer (HHD)	From baseline to Week 24
Secondary	Change from baseline in Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ5) -Part A		From baseline to Week 24
Secondary	Change from baseline in serum neurofilament light chain (NfL) -Part A		From baseline to Week 24
Secondary	Number of patients with treatment emergent adverse events (TEAE) and Serious adverse event (SAE) - Part A		Up to Week 24
Secondary	Assessment of pharmacokinetic parameter -Plasma concentration of SAR443820 -Part A		Day 1, Week 2, Week 8
Secondary	Combined assessment of the function and survival (CAFS) score - Part B		Week 76, Week 104
Secondary	Change from baseline in the ALSFRS R total score-Part B		From baseline to Week 52 and Week 76 and Week 104
Secondary	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
Secondary	Time from baseline to the occurrence of death-Part B		Up to Week 106
Secondary	Change from baseline in slow vital capacity (SVC)-Part B		From baseline to Week 52, Week 76 and Week 104
Secondary	Change from baseline in Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-5)-Part B		From baseline to Week 52, Week 76 and Week 104
Secondary	Change from baseline in serum neurofilament light chain (NfL)-Part B		Week 52
Secondary	Number of patients with treatment emergent adverse events (TEAE) and Serious adverse event (SAE) -Part B		Up to Week 106
Secondary	Assessment of pharmacokinetic parameter Plasma concentration of SAR443820 -Part B		Week 28

External Links

•   ACT16970 (Himalaya study)-Amyotrophic Lateral Sclerosis website