Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ZYIL1 in Patients With Amyotrophic Lateral Sclerosis

Exclusion Criteria

• •1. With significant cognitive impairment, psychiatric disease, other neurodegenerative disorder (e.g., 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.
• •2. History of recent serious infection (e.g., 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
• •3. With active herpes zoster infection within 2 months prior to the screening visit
• •4. A documented history of attempted suicide within 6 months prior to the screening visit, or in the Investigator's judgment are at risk for a suicide attempt
• •5. 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
• •6. Participants who are pregnant or are currently breastfeeding
• •7. A known history of allergy to any ingredients of ZYIL1
• •8. Patients taking concomitant medicines within 7 days or 5 half-lives of the medication (whichever is longer) prior to first dose of study drug administration till end of the study, which are substrate of CYP1A2 enzymes (e.g., alosetron, caffeine, duloxetine, melatonin, ramelteon, tasimelteon, tizanidine etc.) and CYP2B6 enzymes (e.g., bupropion, efavirenz etc.).
• •9. Use of any steroids, colchicine or anti-IL-1 inhibitors within 7 days or 5 half-lives of the medication (whichever is longer) prior to first dose of study drug administration.
• •10. Use of any investigational drugs concurrently or within 4 weeks or 5 half-lives (whichever is longer), prior to first dose of study drug administration.
• •11. Any clinically significant and/or laboratory significant value or other instability that would prevent the patient from participating in the study as determined by the Investigator.
• •12. Received a live vaccine within 14 days before the screening visit or planning to receive during the study
• •13. Participants who have received stem cell or gene therapy for ALS at any time in the past
• •14. Any of the following laboratory values at screening
• •* 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%)
• •* Estimated glomerular filtration rate \<60 mL/min/1.73 m2 (Modification of Diet in Renal Disease \[MDRD\])
• •15. QT interval corrected for heart rate using Fridericia's method (QTcF) \> 450 msec at screening.
• •16. Contraindications to lumbar puncture including but not limited to lumbar scoliosis, coagulopathy, infection at site of puncture, use of anticoagulants at the time of study enrolment.
• •17. Participant with seizure disorder or history of seizures within 6 months.
• •18. Surgery within last 3 months or planned major surgery within next 3 months from the date of screening (other than minor cosmetic surgery and minor dental surgery).
• •19. Use or intended use of any medications/products known to alter drug absorption, metabolism, or elimination processes including St John's Wort within 4 weeks prior to receiving study drug and up to end of study. Use of such medication will be considered on a case-by-case basis as per the opinion of the Investigator and/or independent medical monitor.
• •20. Use of grapefruit or similar substances (Seville oranges or marmalade, grapefruit juice, grapefruit hybrids, pomelos, exotic citrus fruits or fruit juices) within 7 days prior to first dose of study drug until last dose administration.
• •21. Donation of blood or blood products within 3 months prior to screening.
• •22. History of, or positive screening test for, hepatitis C infection (defined as positive for hepatitis C virus antibody), hepatitis B infection (defined as positive for hepatitis B surface antigen), or human immunodeficiency virus I or II.
• •23. Use or intended use of any over-the-counter (vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations) or prescription medications within 7 days or 5 half-lives (whichever is longer) prior to receiving study drug, with the exception of hormone replacement therapy and therapies for chronic stable diseases that have been stable for at least 30 days prior to screening and until Day 1, unless deemed acceptable by the Investigator.
• •24. Inability to be venipunctured or tolerate venous puncture.