Amyotrophic lateral sclerosis MedDRA version: 21.1 Level: PT Classification code 10002026 Term: Amyotrophic lateral sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Code: SAR443820
Pharmaceutical Form: Film-coated tablet
CAS Number: 2252271-93-3
Current Sponsor code: SAR443820
Other descriptive name: RA15804589, C19061501-F, DNL788, DN2489, DN0002489
Conc
Sponsors
Sanofi-aventis recherche & développement
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Male or female, 18-80 years of age (inclusive) • 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. Weight : 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 85 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 176
Exclusion criteria
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, -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 (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 (eg sodium phenylbutyrate or taurursodiol) within 4 weeks or 5 half-lives 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part A To assess the effect of SAR443820 compared to placebo in reducing ALS progression as measured by the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) Part B To assess the long-term effects of SAR443820 on function and survival;Secondary Objective: Part A - To assess the effect of SAR443820 compared to placebo on a combined assessment of function and survival, respiratory function, muscle strength, and quality of life (QoL) - To assess the pharmacodynamic (PD) effect of SAR443820 compared to placebo on a key disease biomarker - To assess the safety and tolerability of SAR443820 compared to placebo - To assess the pharmacokinetics (PK) of SAR443820 Part B - To assess the long-term effects of SAR443820 on disease progression, survival, respiratory function, and quality of life (QoL) - To assess the long-term effect of SAR443820 on a key disease biomarker - To assess the long-term safety and tolerability of SAR443820 - To assess the pharmacokinetics (PK) of SAR443820;Primary end point(s): 1) Change from baseline in the ALSFRS-R total score -Part A 2) Combined assessment of the function and survival (CAFS) score -Part B;Timepoint(s) of evaluation of this end point: 1)From baseline to Week 24 2)Week 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| Timepoint(s) of evaluation of this end point: 1) Week 24 2) From baseline to Week 24 3) From baseline to Week 24 4) From baseline to Week 24 5) From baseline to Week 24 6) Up to Week 24 7) Day 1, Week 2, Week 8 8) Week 76, Week 104 9) From baseline to Week 52 and Week 76 and Week 104 10) Up to week 106 11) Up to week 106 12) From baseline to Week 52, Week 76 and Week 104 13) From baseline to Week 52, Week 76 and Week 104 14) Week 52 15) Up to Week 106 16) Week 28 ;Secondary end point(s): 1) Combined assessment of the function and survival (CAFS) score -Part A 2) Change from baseline in slow vital capacity (SVC) -Part A 3) Muscle Strength – Part A 4) Change from baseline in Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-5) -Part A 5) Change from baseline in serum neurofilament light chain (NfL) -Part A 6) Number of patients with treatment-emergent adverse events (TEAE) and Serious adverse event (SAE) – Part A 7) Assessment of pharmacokinetic parameter - Plasma concentration of SAR443820 -Part A 8) Combined assessment of the function and survival (CAFS) score – Part B 9) Change from baseline in the ALSFRS R total score-Part B 10) 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 11) Time from baseline to the occurrence of death- Part B 12) Change from baseline in slow vital capacity (SVC)-Part B 13) Change from baseline in Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-5)-Part B 14) Change from baseline in serum neurofilament light chain (NfL)-Part B 15) Number of patients with treatment emergent adverse events (TEAE) and Serious adverse event (SAE) -Part B 16) Assessment of pharmacokinetic parameter Plasma concentration of SAR443820 -Part B | — |
Countries
Belgium, Canada, China, France, Germany, Italy, Japan, Netherlands, Poland, Spain, Sweden, United Kingdom, United States
Outcome results
None listed