Amyotrophic Lateral Sclerosis (ALS)
Conditions
Brief summary
The goal of this clinical trial is to evaluate the safety, tolerability and preliminary efficacy of SNUG01 in in adult subjects with Amyotrophic Lateral Sclerosis (ALS).
Detailed description
This is a 52-week, multicenter, open-label, single-arm, dose escalation and expansion Phase Ⅰ/Ⅱa study of SNUG01 in adults with ALS. Safety will be the primary focus, with secondary emphasis on immunogenicity, PK and preliminary clinical efficacy of SNUG01.
Interventions
DRUGSNUG01
AAV (adeno-associated virus) Gene therapy
Sponsors
SineuGene Therapeutics Co., Ltd.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Key Inclusion Criteria\*\*: * Subjects who are able to provide written informed consent form (ICF). * Subjects who are males or females must be ≥ 18 years and ≤ 80 years of age at the screening visit. * Subjects who have clinically definite ALS, clinically probable ALS, or clinically probable-laboratory supported ALS as specified in the revised version of the El Escorial World Federation of Neurology criteria. * Subjects must have an ALS disease duration (from first symptom onset to the screening visit) ≤ 2 years. * Subjects with a body mass index (BMI) ≥ 19 kg/m2 at the screening visit. * 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. * The ALSFRS-R score ≥ 30 during the screening period, and the three respiratory scores (dyspnea, upright respiration, and respiratory insufficiency) must be full marks. * Key
Exclusion criteria
\*\*: * Serum Anti-AAV9 neutralizing antibody titer ≥ 1:100. * Current or previous exposure to gene therapy, stem cell products, and solid organ transplantation. * Subjects who have implanted or are estimated to require a diaphragmatic pacing system during the study period. * Any thromboembolic event, such as deep vein thrombosis, pulmonary arteriovenous embolism, and jugular vein embolism, has occurred within 6 months before the administration. * Suffering from autoimmune diseases or ongoing immune-related therapy, except intranasal, inhalation, ocular, topical, intra-articular corticosteroid therapy or corticosteroid physiological replacement therapy. * Active or chronic uncontrolled infection within 4 weeks before the administration, deemed unacceptable in the discretion of the investigator. * Evidence of human immunodeficiency virus (HIV) and treponema pallidum (TP) infection, as documented by the treatment for HIV or TP, or by HIV or TP antibodies positivity at the screening visit. * Has a positive serum pregnancy test at screening (females of childbearing potential only), a positive urine or serum pregnancy test at baseline (Day -1. females of childbearing potential only), or is nursing.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The safety and tolerability of SNUG01 administered by intrathecal. | up to 1 year after administration | Dose-limiting toxicity (DLT), adverse events (AEs), clinically significant changes in vital signs, physical examination, clinical laboratory tests (hematology, biochemistry, urinalysis, coagulation, cardiac enzymes, etc.) and 12-lead ECG, etc. |
| To recommend the optimal expansion dose of SNUG01 that demonstrates acceptable safety with maximum preliminary efficacy administered by IT. | up to 1 years | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Immunogenicity of SNUG01 | up to 1 years | Change of anti-SG001 antibody and anti-AAV9 neutralizing antibody in serum, change of anti-AAV9 neutralizing antibody in CSF. |
| PK of SNUG01 (Biodistribution and Viral Shedding) | up to 1 years | SG001 protein level in CSF, viral vector DNA in serum, viral shedding in saliva, urine, and feces. |
| Preliminary Clinical Efficacy of SNUG01 | up to 1 years | Change in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) , the Amyotrophic Lateral Sclerosis Assessment Questionnaire-40 (ALSAQ-40) , the percent-predicted Forced Vital Capacity (%FVC) / percent-predicted Slow Vital Capacity (%SVC) and muscle strength, the Patient Health Questionnaire (PHQ-9) and NfL level in CSF and serum from baseline to Week 48 after administration. |
Countries
China, United States
Contacts
Primary ContactJi Shen
Outcome results
None listed