A Study to Evaluate the Efficacy and Safety of Different Doses of CB03-154 in Adult Patients With Amyotrophic Lateral Sclerosis (ALS)

Exclusion Criteria

• •1. Significant cognitive impairment, mental disorders (such as schizophrenia, bipolar disorder), other neurodegenerative diseases (such as Parkinson's disease, Alzheimer's disease, frontotemporal dementia, etc.), substance abuse or other causes leading to neuromuscular weakness (such as myasthenia gravis), or other conditions that may interfere with the participants' participation in clinical study or, in the investigator's judgment, may interfere with outcome assessment or affect the completion of the trial.
• •2. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), or bilirubin\>2.0× upper limit of normal at screening.
• •3. Estimated glomerular filtration rate \<59 mL/min/1.73m2 at Screening (using the Cockcroft-Gault formula to calculate eGFR: eGFR (mL/min/1.73m2) = Ccr × 0.84 × 1.73 / BSA; Ccr (mL/min) = \[(140 - age) × weight (kg)\] / \[72 × Scr (mg/dL)\], females multiply the result by 0.85, and Scr is the serum creatinine; BSA (m2) = 0.007184 × weight (kg)\^0.425 × height (cm)\^0.725).
• •4. D-dimer\>2.0× upper limit of normal or venous ultrasound of the lower limbs shows deep vein thrombosis at screening or a history of venous thrombosis.
• •5. Assistance with ventilation support or tracheostomy or tube feeding status or having a central venous catheter is required at screening.
• •6. A history of unexplained syncope, family history of syncope, or a history of convulsions or epilepsy (excluding the history of febrile seizures in childhood), or unstable medical condition, serious heart issues (e.g., corrected QTcF interval: males \>450ms, females \>470ms, torsades de pointes, NYHA class 3 or higher heart failure, myocardial infarction or unstable angina within 6 months prior to screening), lung, liver, kidney diseases, or tumors, or other clinically significant diseases or medical history (excluding ALS), participation in this study could threaten the safety of the participants.
• •7. Current clinically significant urinary retention, or current use of medications for urinary retention, or clinically significant abnormalities in residual urinary bladder ultrasound at screening.
• •8. Clinically significant ophthalmological abnormalities found in visual acuity examination (best corrected visual acuity), fundus photography, OCT examination, etc. during screening period, or clinically significant fundus lesions or retinopathy known or recorded in medical history.
• •9. Hepatitis B surface antigen (HBsAg) positive, or hepatitis C antibody (HCVAb) positive and hepatitis C virus ribonucleic acid (HCV-RNA) test higher than the lower limit of detection, or human immunodeficiency virus antibody (HIVAb) positive, or Treponema pallidum (TP) antibody positive (also judged as active infection by the investigator) at screening.
• •10. Severe infections (e.g., infectious pneumonia, sepsis) within 4 weeks prior to screening, or infections requiring hospitalization or intravenous administration of antibiotics, antiviral drugs, or antifungal medications, or chronic active bacterial infections (e.g., tuberculosis) deemed by the investigator to be unsuitable for participation in this trial.
• •11. Received Tofersen treatment before screening.
• •12. Significant risk of suicidality based on the Investigator's opinion or with an answer of "yes" on either item 4 or item 5 of the Suicidal Ideation Section of the Columbia Suicide Severity Rating Scale (C-SSRS) or any answer of "yes" within the Suicidal Behavior Section of the C SSRS within the 6 months before Screening.
• •13. Exposure to any other investigational medicinal product or product within 4 weeks or 5 half-lives of the investigational product (whichever is longer) prior to Screening; or exposure to monoclonal antibody drug within 6 months prior to Screening (or if the washout period at the time of screening has not reached more than 3 months), or had received cell therapy or gene therapy at any time in the past.
• •14. Treatment with CYP3A4 strong inducers or strong inhibitors prior to screening, and washout time of more than 5 half-lives of the drug was not reached before enrollment。
• •15. Pregnant, currently breastfeeding women or women with a positive pregnancy test at screening.
• •16. Known history of allergy to any component of the investigational medicinal product.
• •17. History of drug abuse within 12 months of Screening.
• •18. Anything else that, in the opinion of the Investigator, would place the participant at increased risk or preclude the participant's full compliance with or completion of the trial.