Amyotrophic lateral sclerosis
Conditions
Interventions
Experimental group:Calculate the dosage according to body weight. Dissolve ALT001 in 100ml of normal saline injection and administer it by intravenous once daily.Single-dose administration.
Multiple-
Placebo group:Calculate the dosage according to body weight. Dissolve Placebo Product in 100ml of normal saline injection and administer it by intravenous once daily.Single-dose administration.
Multi
Sponsors
Beijing Tiantan Hospital, Capital Medical University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: (1) The subject or their legal guardian must be able to understand the procedures and methods of this study, communicate effectively with the investigator, be willing to strictly adhere to the clinical trial protocol, and voluntarily provide written informed consent or provide oral consent in the presence of their guardian. (2) Aged 18 to 75 years (inclusive), both male and female. (3)Have a definite, or probable diagnosis of sporadic amyotrophic lateral sclerosis (ALS) according to the World Federation of Neurology revised EI Escorial diagnostic criteria for ALS, including both familial and sporadic ALS patients. (4)(FVC) at screening must be =50% of the predicted value; (5)The total ALSFRS-R score at baseline must be >=30 and =3; (6)If the subject is receiving riluzole or edaravone treatment prior to enrollment, a stable dose must have been maintained for =30 days before Day 1 of the study and should be continued until the final study visit. (7)No severe hematopoietic dysfunction; cardiac, pulmonary, hepatic, renal, and other organ functions, as well as bone marrow function, are essentially normal. Laboratory values within 7 days prior to administration must meet the following criteria: 1)Hematology:? Absolute neutrophil count (ANC) >= 1.5×10^9/L, platelet count (PLT) >= 100×10^9/L, hemoglobin (Hb) >=100 g/L. 2)Liver Function:? Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) 60 mL/min/1.73 m² (calculated using the Cockcroft-Gault formula). 4)Coagulation:? International normalized ratio (INR) <= 1.5 × ULN, activated partial thromboplastin time (APTT) <= 1.5 × ULN. (8) Subjects of childbearing potential must agree to use a medically accepted effective method of contraception throughout the study period and for 3 months after the last dose, and female subjects must have a negative blood pregnancy test at the time of enrollment.
Exclusion criteria
Exclusion criteria: (1) Diagnosis of other known diseases associated with motor neuron dysfunction that could confuse or obscure the diagnosis of ALS. (2)History of alcohol dependence or drug abuse within 6 months prior to screening, which in the investigator's judgment would render the subject unsuitable for the study (3)Presence of significant cognitive impairment, as defined by Mini-Mental State Examination (MMSE) scores (<=19 for the illiterate group, <=22 for the primary school group, <=26 for the junior high school and above group [with more than 8 years of education]), or other unstable psychiatric disorders deemed by the investigator as unsuitable for study participation (including suicidal intent, untreated major depression, etc.). (4)Planned continuous use of non-invasive ventilation (NIV), a diaphragm pacing system, or invasive ventilation (tracheostomy) during the screening period or the study period. (5) Presence of severe autoimmune diseases, myeloproliferative disorders, leukemia or lymphoma, malignant tumors, fractures, or severe scoliosis at screening, which, in the investigator's opinion, may affect the study evaluation. (6)Concurrent severe and/or uncontrolled diseases of major organs or unstable systemic diseases, including but not limited to: uncontrolled diabetes, unstable angina, cerebrovascular accident or transient ischemic attack (within 6 months prior to screening), myocardial infarction (within 6 months prior to screening), severe congestive heart failure, uncontrolled hypertension, uncontrolled active infection, hepatic, renal, or other severe metabolic diseases, and severe gastrointestinal diseases. (7)Positive hepatitis B surface antigen (HBsAg) with HBV-DNA levels above the upper limit of normal (no HBV-DNA test required if HBsAg is negative); positive hepatitis C virus (HCV) antibody with HCV-RNA levels above the upper limit of normal (no HCV-RNA test required if Anti-HCV is negative); positive human immunodeficiency virus (HIV) antibody; or positive Treponema pallidum serology. (8) Women who are pregnant, breastfeeding, or planning to conceive during the medication period or within 3 months after discontinuing the medication. (9) Participation in other interventional clinical trials within 4 weeks prior to the study; or previous receipt of small interfering RNA (siRNA) therapy, stem cell therapy, or gene therapy. (10) Patients deemed by the investigator as unsuitable for participation in this study (e.g., due to clinically significant abnormalities in physical examination or laboratory tests).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Occurrence of Adverse Events (AEs) and Serious Adverse Events (SAEs): including the frequency, type, severity, duration, relationship to the drug, and relationship to dose and duration of treatment; the proportion of patients discontinuing treatment due to drug toxicity.;During the dose escalation observation period, the incidence of significant intolerable events (SIE) in each dose cohort, exploration of the Maximum Tolerated Dose (MTD), and evaluation of the Recommended Dose (RD) for subsequent studies.; | — |
Secondary
| Measure | Time frame |
|---|---|
| Biomarkers: NFLTDP43SOD1 in plasma,Cytokines(IFN-?IL-10IL-13IL-1ßIL-4IL-5IL-6GRO-aTNF-a,IL2) and Immune Function Parameters(IgGIgMIgACD3+CD4+CD3+CD8+CD3+CD4+/CD3+CD8+CD28+CD16+);Efficacy Endpoints: ALSFRS-R,ALSAQ-40,Norris,HAMA,HAMD,FVC, Muscle Strength/ (EMG), Grip Strength, ALS Clinical Staging, Disease Deterioration Events, and Survival; | — |
Countries
China
Contacts
Public ContactYilong Wang
Capital Medical University Affiliated Beijing Tiantan Hospital
Outcome results
None listed