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 open label, longterm extension period.Study ACT16970 consists of 2 parts (A and B) as follows:
Part A is a 24week, 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 8, Week 16, and Week 24, and will receive a phone call at Week 12 and Week 20. All ongoing participants in Part A 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, except those who discontinued Investigational Medicinal Product (IMP) treatment permanently in Part A , will receive BID oral tablets of SAR443820 in Part B.
Study Status:
Active, Not Recruiting
Disease:
Amyotrophic Lateral Sclerosis
Study Type:
Interventional
Type of Intervention:
Drug
Intervention Name:
SAR443820, Placebo
Placebo:
Yes
Phase:
Phase 2
Study Chair(s)/Principal Investigator(s):
Clinical Sciences & Operations, Sanofi
Clinicaltrials.gov ID:
Neals Affiliated?
Yes
Coordinating Center Contact Information
Sanofi
Trial Transparency email recommended (Toll free for US & Canada) / email hidden; JavaScript is required / 800-633-1610
Full Study Summary:
Part A of the study will last for 24 weeks, and participants will receive BID oral SAR443820 or placebo in a double-blind fashion for 24 weeks. All ongoing participants in Part A will rollover to Part B.
Part B begins at the end of Week 24 and continues up to Week 106. All participants except those who discontinued Investigational Medicinal Product (IMP) treatment permanently in Part A 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.
Part B begins at the end of Week 24 and continues up to Week 106. All participants except those who discontinued Investigational Medicinal Product (IMP) treatment permanently in Part A 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
Estimated Enrollment:
261
Estimated Study Start Date:
04 / 13 / 2022
Estimated Study Completion Date:
08 / 12 / 2025
Posting Last Modified Date:
05 / 03 / 2023
Date Study Added to neals.org:
02 / 14 / 2022
For more information, visit the Himalaya study website: www.sanofistudies.com/ALS
Minimum Age:
18 Years
Maximum Age:
80 Years
Can participants use Riluzole?
Yes
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 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 (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.
St. Joseph's Hospital and Medical Center-Site Number:8400016 | Recruiting
Phoenix, Arizona
85013
United States
Phoenix Neurological Associates-Site Number:8400018 | Recruiting
Phoenix, Arizona
85018
United States
UC San Diego Health-Site Number:8400022 | Recruiting
La Jolla, California
92121
United States
USC-Site Number:8400008 | Recruiting
Los Angeles, California
00000
United States
University of California Irvine-Site Number:8400012 | Recruiting
Orange, California
92868
United States
California Pacific Medical Center-Site Number:8400015 | Recruiting
San Francisco, California
94115
United States
University of Colorado-Site Number:8400025 | Recruiting
Aurora, Colorado
80045
United States
Georgetown University Medical Center-Site Number:8400020 | Recruiting
Washington, District of Columbia
20007
United States
AdventHealth Medical Group - Neurology at Winter Park-Site Number:8400006 | Recruiting
Winter Park, Florida
32789
United States
Mayo Clinic-Site Number:8400029 | Recruiting
Jacksonville, Florida
32224
United States
Northwestern Medical Group, Department of Neurology-Site Number:8400003 | Recruiting
Chicago, Illinois
60611
United States
Johns Hopkins University-Site Number:8400028 | Recruiting
Baltimore, Maryland
21287
United States
Massachusetts General Hospital-Site Number:8400001 | Recruiting
Boston, Massachusetts
02114
United States
Mount Sinai Beth Israel Medical Center-Site Number:8400002 | Recruiting
New York, New York
10003
United States
Penn State Milton S. Hershey Medical Center-Site Number:8400004 | Recruiting
Hershey, Pennsylvania
17033
United States
University of Pennsylvania-Site Number:8400021 | Recruiting
Philadelphia, Pennsylvania
19104
United States
Thomas Jefferson University Hospital-Site Number:8400014 | Recruiting
Philadelphia, Pennsylvania
19107
United States
University of Utah-Site Number:8400009 | Recruiting
Salt Lake City, Utah
84132
United States
Froedtert Hospital & Medical College of Wisconsin-Site Number:8400010 | Recruiting
Milwaukee, Wisconsin
53226
United States
Investigational Site Number :0560001 | Recruiting
Leuven 3000
Belgium
Investigational Site Number :1240004 | Recruiting
Edmonton, Alberta
T6G 2C8
Canada
Investigational Site Number :1240007 | Recruiting
Hamilton, Ontario
L8N 3Z5
Canada
Investigational Site Number :1240006 | Recruiting
London, Ontario
N6A 5A5
Canada
Investigational Site Number :1240008 | Recruiting
Toronto, Ontario
M4N 3M5
Canada
Investigational Site Number :1240003 | Recruiting
Gatineau, Quebec
J8Y 1W2
Canada
Investigational Site Number :1240002 | Recruiting
Montreal, Quebec
H3A 2B4
Canada
Investigational Site Number :1560006 | Recruiting
Xi'An 710061
China
Investigational Site Number :1560004 | Recruiting
Wuhan 430030
China
Investigational Site Number :1560002 | Recruiting
Hangzhou 310009
China
Investigational Site Number :1560005 | Recruiting
Guangzhou 510515
China
Investigational Site Number :1560003 | Recruiting
Chengdu 610041
China
Investigational Site Number :1560001 | Recruiting
Beijing 100191
China
Investigational Site Number :2500007 | Recruiting
Caen 14033
France
Investigational Site Number :2500006 | Recruiting
Lille 59037
France
Investigational Site Number :2500002 | Recruiting
Marseille 13385
France
Investigational Site Number :2500003 | Recruiting
Montpellier 34295
France
Investigational Site Number :2500004 | Recruiting
Tours 37044
France
Investigational Site Number :2500005 | Recruiting
Vandoeuvre-les-nancy 54511
France
Investigational Site Number :2760009 | Recruiting
Würzburg 97074
Germany
Investigational Site Number :2760001 | Recruiting
Ulm 89081
Germany
Investigational Site Number :2760002 | Recruiting
Lübeck 23538
Germany
Investigational Site Number :2760005 | Recruiting
Hannover 30625
Germany
Investigational Site Number :2760003 | Recruiting
Dresden 01307
Germany
Investigational Site Number :2760004 | Recruiting
Berlin 13353
Germany
Investigational Site Number :2760008 | Recruiting
Haag In OB 83527
Germany
Investigational Site Number :3800001 | Recruiting
Milano 20132
Italy
Investigational Site Number :3800004 | Recruiting
Milano 20138
Italy
Investigational Site Number :3800002 | Recruiting
Torino 10126
Italy
Investigational Site Number :3920005 | Recruiting
Fuchu-shi, Tokyo
183-0042
Japan
Investigational Site Number :3920001 | Recruiting
Ota-ku, Tokyo
143-8541
Japan
Investigational Site Number :3920002 | Recruiting
Koshi-shi 861-1196
Japan
Investigational Site Number :3920006 | Recruiting
Tokushima-shi, Tokushima
770-8503
Japan
Investigational Site Number :3920004 | Recruiting
Ichikawa-shi, Chiba
272-0827
Japan
Investigational Site Number :3920003 | Recruiting
Nagoya-shi, Aichi
466-8560
Japan
Investigational Site Number :5280001 | Recruiting
Utrecht 3584 CX
Netherlands
Investigational Site Number :6160001 | Recruiting
Krakow 31-503
Poland
Investigational Site Number :6160002 | Recruiting
Ksawerow 95-054
Poland
Investigational Site Number :7240005 | Recruiting
Barcelona, Barcelona [Barcelona]
08035
Spain
Investigational Site Number :7240002 | Recruiting
Hospitalet de Llobregat, Catalunya [Cataluña]
08907
Spain
Investigational Site Number :7240003 | Recruiting
Madrid 28029
Spain
Investigational Site Number :7240001 | Recruiting
Valencia 46026
Spain
Investigational Site Number :7520002 | Recruiting
Stockholm 113 61
Sweden
Investigational Site Number :7520001 | Recruiting
Umea SE-901 85 Umea
Sweden
Investigational Site Number :8260002 | Recruiting
Plymouth, Devon
PL6 8DH
United Kingdom
Investigational Site Number :8260003 | Recruiting
Stoke-on-Trent, Staffordshire
ST46QG
United Kingdom