Amyotrophic Lateral Sclerosis
Conditions
Interventions
Experimental group1:VGN-R13 was injected intrathecally with VGN-R13, 6×10^13 vg, 1 subject was enrolled first, and after completing the evaluation of the safety data of the first subject for at least
Experimental group2:VGN-R13 was injected intrathecally with VGN-R13, 2×10^14 vg, 1 subject was enrolled first, and after completing the evaluation of the safety data of the first subject for at least
Sponsors
Tongji Hospital, Tongji Medical College ,Huazhong University of Science and Technology
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Fully understand the purpose and risks of the study and voluntarily provide signed and dated informed consent; 2. Age >=18 years old at the time of signing informed consent, male or female; 3. Patients diagnosed with ALS according to the El Escorial criteria of the World Federation of Neurology (as amended by the 1998 Airlie House meeting [Brooks2000]) with a confirmed diagnosis of the exception of pathogenic mutations in the genes superoxide dismutase 1 (SOD1) and/or FUS genes; 4. Duration of illness = 2 years (first onset of symptoms to screening); 5. Forced vital capacity (FVC) adjusted for sex, age, and height (sitting position) > = 50% of predicted; 6. Riluzole has been discontinued for more than 5 half-lives prior to the screening visit (no reuse is expected to be expected during the study), or is receiving a stable dose of riluzole for >=30 days and is expected to remain on that dose until the end of the last visit; 7. Have discontinued edaravone for more than 5 half-lives prior to the screening visit (no re-use of edaravone is expected during the study), or are receiving standard treatment regimen for edaravone at screening and are on a stable dose >=60 days prior to dosing (2 treatment cycles) and are expected to maintain that dose until the end of the last visit; 8. Males and females of childbearing potential must consistently and correctly use one highly effective contraceptive method during the screening period until at least 1 year after medication, males must agree not to donate sperm during the screening period until at least 1 year after medication, and females must agree not to donate eggs during the screening period until at least 1 year after medication; 9. Subject is willing and able to comply with visit schedules, dosing schedules, laboratory tests, and other clinical trial steps.
Exclusion criteria
Exclusion criteria: 1.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. 2.Presence of risk for increased or uncontrolled bleeding and/or risk of bleeding that is not managed optimally and could place a participant at an increased risk for intraoperative or postoperative bleeding. These could include, but are not limited to, anatomical factors at or near the LP site (e.g., vascular abnormalities, neoplasms, or other abnormalities) and underlying disorders of the coagulation cascade, platelet function, or platelet count (e.g., hemophilia, Von Willebrand’s disease, liver disease). 3.Current severe liver or kidney or cardiovascular disease or coagulation dysfunction, autoimmune deficiency, or uncontrolled autoimmune disease or need immunosuppressive long-term treatment, poorly controlled diabetes (HBA1C >=7% at screening) or high blood pressure, presence of sever gastrointestinal ulcers or history of gastrointestinal bleeding; 4.Presence of active infection that needs system treatment; 5.Presence or history of malignant tumors within 5 years prior to screening; 6.Significant cognitive impairment, clinical dementia, or unstable psychiatric illness, including psychosis, suicidal ideation, suicide attempt, or untreated major depression = 90 days, as determined by the Investigator. 7.Current using medications including, drugs, herbal or OTC medications that strongly inhibit or induce CYP3A4 or P-glycoprotein (P-gp), e.g., metoclopramide, grapefruit juice, ketoconazole, erythromycin; 8.Received another drug for the treatment of ALS disease (including but not limited to sodium phenylbutyrate (PB), taurine diol (TURSO), tauroursodeoxycholic acid (TUDCA) within 1 month before the first dose) or ursodeoxycholic acid (UDCA), biologics or Other investigational drugs with a discontinuation period shorter than five half-lives; 9.Anticipated need, in the opinion of the Investigator, for administration of any antiplatelet or anticoagulant medication (e.g., clopidogrel) for 7 days before or 48 hours after an LP; 10.Received systemic immunosuppressive therapy within 3 months prior to screening; 11.Presence of an implanted shunt for the drainage of CSF or an implanted CNS catheter; 12.Presence of an implanted shunt for the drainage of CSF or an implanted CNS catheter; 13.Participation in gene therapy or stem cell transduction therapy at any time prior to screening; 14.Positive test result for HIV, positive treponemal antibody for syphilis, Active hepatitis B or hepatitis C infection, Active tuberculosis infection; 15.Clinically significant abnormalities in hematology or clinical chemistry parameters, as determined by the Investigator, which would render the participant unsuitable for enrollment; 16.Clinically significant, as determined by the Investigator, 12-lead ECG abnormalities, including corrected QT interval using Fridericia’s correction method of > 450 ms for males and > 470 ms for females; 17.History of systemic hypersensitivity reaction to investigational product, the excipients contained in the formulation, or prophylactic immunosuppressant; 18.Contraindicated use of corticosteroids and sirolimus; 19.History of drug abuse or alcoholism within = 6 months of study enrollment that would limit participation in the study, as determined by the Investigator; 20.Alcohol abuse (dr
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of adverse events; | — |
Secondary
| Measure | Time frame |
|---|---|
| Changes in the ALSFRS-R total score;Changes in forced vital capacity; | — |
Countries
China
Contacts
Public ContactHong Chen
Tongji Hospital, Tongji Medical College ,Huazhong University of Science and Technology
Outcome results
None listed