Amyotrophic Lateral Sclerosis (ALS)
Conditions
Interventions
Test Group:SNUG01
Sponsors
Peking University Third Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1.Subjects who are able to provide written informed consent form (ICF); 2.Subjects who are males or females must be >= 18 years and = 19 kg/m2 at the screening visit; 6.Subjects whose percent-predicted Forced Vital Capacity (%FVC) is >= 70% or percent-predicted Slow Vital Capacity (%SVC) is >= 60%,adjusted for sex, age, and height at the screening visit. 7.The ALSFRS-R score >= 30 during the screening period, and the three respiratory scores (dyspnea, upright respiration, and respiratory insufficiency) must be full marks. 8.Subjects have been on a stable dose of Riluzole for at least 4 weeks or have not received it before the screening visit. Subjects receiving Riluzole are expected to maintain the same dose throughout the duration of the study. 9.Subjects have been on the approved standard treatment schedule of Edaravone for at least 4 weeks or are currently not receiving it before the screening visit. Subjects receiving Edaravone are expected to continue treatment regimen throughout the duration of the study. 10.Subjects have been on the approved standard treatment schedule of Tofersen for at least 4 weeks or are currently not receiving it before the screening visit. Subjects receiving Tofersen are expected to continue treatment regimen throughout the duration of the study. 11.Males and all females of childbearing potential must be willing to use effective contraception at the time of administration of gene transfer and for the 48 weeks following administration of SNUG01 to prevent the potential transmission of the AAV vector.
Exclusion criteria
Exclusion criteria: 1.Serum Anti-AAV9 neutralizing antibody titer >= 1:100 as determined by Enzyme-linked Immunosorbent Assay (ELISA) binding immunoassay. 2.Contraindications for a lumbar puncture process (including but not limited to signs or symptoms of skin infection at the injection site and increased intracranial pressure), receiving any active intrathecal therapy, presence of implanted shunt for draining CSF, embedded CNS catheter, or any condition that hinders CSF collection. 3.Other diseases related to motor neuron dysfunction (primary lateral sclerosis, cervical spondylosis, lumbar spine disease, idiopathic inflammatory myopathy, etc.) may confuse or obscure the diagnosis of ALS. 4.Current or previous exposure to gene therapy, stem cell products, and solid organ transplantation. 5.Subjects who have implanted or are estimated to require a diaphragmatic pacing system during the study period. 6.Any thromboembolic event, such as deep vein thrombosis, pulmonary arteriovenous embolism, and jugular vein embolism, has occurred within 6 months before the administration. 7.Have received any other drug for ALS within 4 weeks prior to administration (including but not limited to sodium phenylbutyrate [PB], taurursodiol [TURSO], tauroursodeoxycholic acid [TUDCA], ursodeoxycholic acid [UDCA], biological agents, etc.), excluding Riluzole, Edaravone, and Tofersen. 8.Suffering from autoimmune diseases (for example rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, scleroderma, inflammatory myopathy, mixed connective tissue disease, overlap syndrome) within 30 days before the screening period, etc.) or ongoing immune-related therapy (e.g., corticosteroids, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous immune globulin, rituximab, leflunomide, hydroxy Chloroquine, Interleukin [IL]-2 antagonists, etc.), except intranasal, inhalation, ocular, topical, intra-articular corticosteroid therapy or corticosteroid physiological replacement therapy. 9.Active or chronic uncontrolled infection (including but not limited to pneumonia, sepsis, herpes zoster infection, tuberculosis), within 4 weeks before the administration, deemed unacceptable in the discretion of the investigator. 10.Having major surgery within 4 weeks prior to the administration or not recovering from previous TRAEs to Grade 1 (CTCAE version 5.0), except for alopecia. 11.Participation in another clinical study within 4 weeks prior to the administration, unless it was an observational (non-intervention) clinical study. 12.Presence of fever >= 38? within 14 days prior to the administration. 13.Vaccination within 14 days before the administration. 14.Clinically significant abnormal findings in the following the laboratory parameters: a)Neutrophil count = 1.5× upper limit of normal (ULN) or creatinine clearance (CCr) = 2×ULN, Alkaline phosphatase (ALP) >= 3×ULN. d)Prothrombin time international normalized ratio (INR), Activated partial thromboplastin time (APTT), and / or Prothrombin time >= 1.5×ULN. 15.Uncontrolled hypertension (systolic blood pressure [SBP] > 160 millimeters of mercury [mm Hg], diastolic blood pressure [DBP] >100 mmHg) despite maximal medical treatment. 16.Pulse oximetry saturation < 93% at the screening visit. NOTE: If the investigator d
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety;Pharmacokinetic (PK) characteristics; | — |
Secondary
| Measure | Time frame |
|---|---|
| Immunogenicity; | — |
Countries
China
Contacts
Public ContactDongsheng Fan
Peking University Third Hospital
Outcome results
None listed