A Study of VRG50635 in Participants With Amyotrophic Lateral Sclerosis (ALS)

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.
• •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
• •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 \[MDRD\])