Amyotrophic lateral sclerosis
Conditions
Interventions
Sponsors
Xingtai People's Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Inclusion criteria
Inclusion criteria: 1.Able to understand and voluntarily sign the informed consent form, the informed consent form must be signed before performing any clinical trail procedures; 2.18~65 years old (including 16 and 65 years old), both male and female; 3.Must have been diagnosed with clinically probable ALS or clinically definite ALS according to the revisedversion of the El Escorial World Federation of Neurology criteria (22), detailed in Appendix1; 4.Less than or equal to 24 months (inclusive) after the onset of symptoms of amyotrophic lateral sclerosis. 5.BMI=19 kg/m2; 6.The forced vital capacity (FVC) in the screening period is greater than or equal to 70% of the estimated vital capacity; 7. ?FS=(48-ALSFRS-R at the screening visit )\Duration from onset to screening visit (months) = 1.0 points/month, ALSFRS-R total score = 26 points. 8. Subjects are not currently receiving riluzole or have been receiving a stable dose of riluzole for at least 4 weeks prior to the screening visit. Subjects treated with riluzole are expected to remain on the same dose throughout the study period.Subjects being treated with edaravone must have been receiving a stable dose of edaravone for at least 4 weeks prior to the Screening Visit and and must have discontinued edaravone from 4 weeks before to 8 weeks after the invention drug (inclusive) and maintained the same dose of edaravone for the remainder of the study period. 9.Good bone marrow and organ function: A. Hematology (no blood products allowed within 14 days prior to administration): Absolute Neutrophil Count (ANC) 1.5x109L; Platelet Count (PLT) 100x109L; Hemoglobin (HGB) =110g/L; B. Liver and Kidney Function: Glutamyltransferase (?-GT) = Upper Limit of Normal (ULN); Total Bilirubin (TBIL) = ULN; Glutaminase (ALT) and Glutaminase (AST) = ULN; Serum creatinine (Cr) = 1.5xULN; C. Coagulation function: International Normalised Ratio (INR) = 1.5xULN and activated partial thromboplastin time (APTT) and plasminogen time (PT) < 1.5xULN (without anticoagulation treatment) ; 10.Women of childbearing age must have a negative blood pregnancy test during the screening period and be non-lactating. Female subjects of childbearing age (women of childbearing age include premenopausal women and women within 2 years after menopause, except those who have undergone bilateral tubal ligation, complete oophorectomy or hysterectomy.) and male subjects whose partners are women of childbearing age must Agree to use effective contraceptive methods throughout the study period, such as abstinence, double barrier contraceptive methods, condoms, intrauterine devices and other non-drug contraceptive measures, and are not allowed to donate sperm or eggs.
Exclusion criteria
Exclusion criteria: 1. Serum anti-AAV9 neutralizing antibody (Nab) titer > 1:100 at the time of screening. 2. There are contraindications to lumbar puncture during the screening period (including but not limited to skin infection at the administration site and signs or symptoms of increased intracranial pressure), receiving any active intrathecal therapy, and having implants for drainage of cerebrospinal fluid (CSF). Inserted shunt, presence of implanted central nervous system (CNS) cannula, or any condition that prevents CSF collection. 3. There are other diseases related to motor neuron dysfunction (progressive bulbar palsy, primary lateral sclerosis, cervical spondylosis, lumbar spondylosis, etc., idiopathic inflammatory myopathy), which may confuse or cover up the diagnosis of ALS. 4. Previously required invasive ventilation or tracheotomy due to ALS disease, or currently using non-invasive ventilation support with an average of =16 hours/day. 5. Previous history of gene therapy, hematopoietic stem cell transplantation, and solid organ transplantation. 6. The patient has poorly controlled acute or chronic respiratory diseases, including but not limited to: chronic obstructive pulmonary disease, severe asthma, severe pneumonia, active tuberculosis. 7. Those who have been implanted or the researchers estimate that they will need to implant a diaphragmatic pacing system during the study period. 8. Any thromboembolic events occurred within 6 months before the first administration, such as deep vein thrombosis, pulmonary arteriovenous embolism, jugular vein embolism, etc.. 9. Received another drug for the treatment of ALS disease (including but not limited to sodium phenylbutyrate (PB), taurine diol (TURSO), tauroursodeoxycholic acid (TUDCA) within 4 weeks before the first dose ) or ursodeoxycholic acid (UDCA), biologics, etc. except riluzole and edaravone). 10. Autoimmune disease within 30 days prior to the Screening Period, or ongoing immune-related therapy (e.g., corticosteroids, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous immunoglobulin, rituximab, etc.), except for intranasal, inhaled, ocular, topical, intra-articular corticosteroid therapy, or physiologic replacement therapy with corticosteroids. 11. Suffering from active or uncontrolled infection (including but not limited to: infectious pneumonia, sepsis, herpes zoster infection) within 4 weeks before the first administration, or chronic bacterial infection that is considered unacceptable according to the investigator's judgment ( medical history such as tuberculosis). 12. Have undergone major surgery within 4 weeks before the first administration, or have not recovered from previous treatment-related adverse events (AE) to = grade 1 (CTCAE version 5.0), except hair loss. 13. Participated in another clinical study within 4 weeks before the first administration, unless it is an observational (non-intervention) clinical study. 14. Any febrile illness occurred within 14 days before the first administration. 15. Have been vaccinated within 14 days before the first dose. 16. Patients with poorly controlled hypertension (refers to resting blood pressure after treatment: systolic blood pressure (SBP) > 160 mmHg or diastolic blood pressure (DBP) > 100 mmHg). 17. Have clinically significant low hypoxaemia state (arterial oxygen saturation <93%) at the time of screening, as judged by the investigator. 18. Hypersensitivity to prednisolone, other glucocorticoids or their excipients. 1
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety evaluation; | — |
Secondary
| Measure | Time frame |
|---|---|
| Efficacy evaluation;Immunological evaluation; | — |
Countries
China
Contacts
Public ContactXipeng Li
Xingtai People's Hospital
Outcome results
None listed