Condition médicale (spécialité visée)
Choix aire thérapeutique
Système Nerveux Central / Neurologie
Maladies neuromusculaires et SLA
Profil des participants
Sexe(s) des participants
TOUS
Aptitude des participants
Majeurs aptes
Critères de sélection
Critères d'inclusion
Critères d'inclusion :
* Avoir un diagnostic de SLA selon les Critères Diagnostiques de Gold Coast.
* Avoir soit une sclérose latérale amyotrophique sporadique (sSLA) soit une sclérose latérale amyotrophique familiale (fSLA).
* Profil de risque de l'Initiative de Recherche pour le Traitement et la Guérison de la SLA (TRICALS) > -6 et < -2.
* Avoir une capacité vitale lente (SVC) ≥ 75% de la valeur prédite.
* Avoir un score de 3 ou 4 à l'article #3 (Déglutition) du Harmonized ALS-FRS-R. Les participants avec un score de 3 peuvent être inscrits avec l'approbation du sponsor seulement s'ils sont capables d'avaler en sécurité les capsules.
* Avoir un poids corporel ≥ 45 kg et un indice de masse corporelle (IMC) ≥ 18 kg/m^2.
Critères d'exclusion :
* Avoir une maladie psychiatrique active, un abus de substances, une faiblesse neuromusculaire autre que la SLA, ou toute autre condition médicale qui, selon l'opinion de l'investigateur, pourrait confondre les résultats de l'étude ou interférer avec l'ingestion ou l'absorption du médicament de l'étude ou la participation pendant toute la durée de l'étude.
* Avoir des antécédents de maladie cardiaque, pulmonaire, neurologique, oncologique, hépatique ou rénale instable ou grave, ou une autre maladie médicalement significative autre que la SLA empêchant leur participation sécurisée à cette étude.
* Avoir des antécédents de trouble de l'usage de substances ou de consommation de drogues illicites au cours de la dernière année.
* Avoir des antécédents d'infection grave (par exemple, pneumonie, septicémie) ≤ 4 semaines avant le dépistage; infection nécessitant une hospitalisation ou un traitement avec des antibiotiques, des antiviraux ou des antifongiques par voie intraveineuse (IV) dans les 4 semaines précédant le dépistage; ou infection bactérienne chronique (par exemple, tuberculose) jugée inacceptable selon le jugement de l'investigateur.
Des critères supplémentaires définis par le protocole peuvent s'appliquer.
Inclusion Criteria:
1. Provide written informed consent and be willing and able to comply with the requirements of the study protocol.
2. Must be ≥ 18 and ≤ 75 years of age at the time of signing the informed consent form (ICF).
3. Have a diagnosis of ALS according to the Gold Coast Diagnostic Criteria.
4. Have either sporadic amyotrophic lateral sclerosis (sALS) or familial amyotrophic lateral sclerosis (fALS).
5. Treatment Research Initiative to Cure ALS (TRICALS) risk profile \> -6.00 and \< -2.00.
6. Have slow vital capacity (SVC) ≥ 60% of the predicted value.
7. Have a score of 3 or 4 on Item #3 (Swallowing) of the Harmonized ALS Functional Rating Scale-Revised (ALS-FRS-R). Participants with a score of 3 can be enrolled with the Sponsor's approval only if they are able to safely swallow capsules.
8. Have a body weight ≥ 45 kg and body mass index (BMI) ≥ 18 kg/m2.
9. Participants of childbearing potential are eligible to participate if they are not pregnant or breastfeeding and agree to use one highly effective method of contraception, if sexually active, for the duration of the study through 90 days after the last study drug administration. Participants must not donate eggs for the duration of study through 90 days after the last dose of study drug.
10. Participants capable of producing sperm and their partners of childbearing potential must agree to use condoms and one highly effective method of contraception, respectively, for the duration of the study through 90 days after the last study drug administration. Participants must not donate sperm for the duration of study through 90 days after the last dose of study drug.
11. Be able and willing to undergo measurement of at-home mobility using contactless sensors connected to the internet.
12. Be able and willing to have clinic or at-home visits during the study.
Exclusion Criteria:
1. Have active psychiatric disease, substance abuse, neuromuscular weakness other than ALS, or any other medical condition that, in the opinion of the Investigator, might confound the results of the study or interfere with the intake or absorption of the study drug or participation for the full duration of the study.
2. Have a history of unstable or severe cardiac, pulmonary, neurological, oncological, hepatic, or renal disease or another medically significant illness other than ALS precluding their safe participation in this study.
3. Have a history of substance use disorder or illicit drug use in the last year (medically prescribed or over-the-counter cannabis use is allowed, if legal in the country).
4. Have a history of serious infection (e.g., pneumonia, septicemia) ≤ 4 weeks of Screening; infection requiring hospitalization or treatment with intravenous (IV) antibiotics, antivirals, or antifungals within 4 weeks of Screening; or chronic bacterial infection (e.g., tuberculosis) deemed unacceptable as per the Investigator's judgment.
5. Had major surgery ≤ 4 weeks before Screening.
6. Be currently taking or planning to take strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers.
7. Be currently taking or have discontinued treatment with riluzole \< 4 weeks before Screening. Participants who have been taking a stable dose of riluzole for ≥ 4 weeks are eligible if they remain on the same dose throughout the duration of the study.
8. Be taking Radicava (administered orally or IV as approved in the participant's country), Relyvrio, any other approved standard of care treatment, or tauroursodeoxycholic acid (TUDCA) as a dietary supplement administered for \< 4 weeks prior to Screening or on a schedule of treatment different from the approved standard schedule of treatment. Participants who have completed ≥ 4 weeks of treatment before Screening are eligible if they plan to continue treatment at a stable dose throughout the duration of the study.
9. Have an active malignancy or history (≤ 1 years prior to enrollment) of solid, metastatic, or hematologic malignancy. Exception: basal cell carcinoma in situ of the skin that has been adequately treated.
10. Be diagnosed with long QT syndrome. Any history of clinically significant ventricular arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes) should be discussed with and approved by the study medical monitor prior to enrollment.
11. Have a prolonged corrected QT interval using Fridericia's formula (QTcF) at the Screening visit ECG \> 450 ms for male participants and \> 470 ms for female participants.
12. Have an active SARS-CoV-2 infection or positive COVID-19 test at Screening.1
13. Have one or more of the following laboratory test abnormalities at Screening: (a) Positive hepatitis C virus (HCV) antibodies with confirmation by HCV-RNA polymerase chain reaction (PCR) reflex testing; (b) Positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Note: If a participant is negative for HBsAg but positive for HBcAb, the participant is eligible if the participant tests positive for the antibody to HBsAg reflex testing.
14. Have uncontrolled seizures.
15. Have a documented history of attempted suicide within 6 months prior to the Screening visit, or suicidal ideation of category 4 or 5 on the screening Columbia-Suicide Severity Rating Scale (C-SSRS), or be at significant risk for suicide, in the opinion of the Investigator.
16. For participants of childbearing potential, be pregnant or breastfeeding.
17. Have received a live vaccine within 14 days before Screening.
18. Be concurrently participating in any other interventional clinical study or have received treatment with another investigational drug within 4 weeks or 5 half-lives of the investigational agent before the Screening visit, whichever is longer. Participation in observational studies is allowed.
19. Have received stem cell or gene therapy for ALS at any time in the past.
20. At the Screening visit, have one or more of the following:
1. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 3.0 × upper limit of normal (ULN)
2. 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%)
3. Serum albumin \< 3 g/dL
4. Hemoglobin \< 9.0 g/dL
5. Platelets \< 30,000/μL
6. Estimated glomerular filtration rate \< 90 mL/min/1.73 m2 (Modification of Diet in Renal Disease \[MDRD\])
Critères d'exclusion
- Have active psychiatric disease - substance abuse - neuromuscular weakness other than ALS - or any other medical condition that--in the opinion of the Investigator--might confound the results of the study or interfere with the intake or absorption of the study drug or participation for the full duration of the study,
- Have a history of unstable or severe cardiac - pulmonary - neurological - oncological - hepatic - or renal disease or another medically significant illness other than ALS precluding their safe participation in this study,
- Have a history of serious infection (e.g., pneumonia, septicemia) ≤ 4 weeks of Screening,
- Be currently taking or planning to take prohibited concomitant medications,
- Be currently taking or have discontinued treatment with riluzole < 4 weeks before Screening,
- Be taking Radicava (administered orally or IV -- as approved in the participant’s country) -- Relyvrio or tauroursodeoxycholic acid (TUDCA) as a dietary supplement administered for < 4 weeks prior to Screening,
- Have an active malignancy or history (≤ 1 years prior to enrollment) of solid, metastatic, or hematologic malignancy.
Exception: basal cell carcinoma in situ of the skin that has been adequately treated,
- Have an active SARS-CoV-2 infection or positive COVID-19 test at Screening,
- Have one or more laboratory test abnormalities at Screening,
- Have a documented history of attempted suicide within 6 months prior to the Screening visit,
- For participants of childbearing potential, be pregnant or breastfeeding,
- Have received a live vaccine within 14 days before Screening,
- Be concurrently participating in any other interventional clinical study or have received treatment with another investigational drug within 4 weeks or 5 half-lives of the investigational agent before the Screening visit, whichever is longer,
- Have received stem cell or gene therapy for ALS at any time in the past.