A Multicenter, Single-Arm, Open-Label, IIT Clinical Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of a Single Intrathecal Injection of SNUG01 in Patients with Amyotrophic Lateral Sclerosis (ALS)

Peking University Third Hospital5 sites in 1 country7 target enrollmentOctober 16, 2024

ConditionsAmyotrophic Lateral Sclerosis (ALS)

InterventionsSNUG01

Overview

Phase: Early Phase 1
Intervention: SNUG01
Conditions: Amyotrophic Lateral Sclerosis (ALS)
Sponsor: Peking University Third Hospital
Enrollment: 7
Locations: 5
Primary Endpoint: To evaluate the safety and tolerability of ascending doses of intrathecally administered SNUG01 in Participants with ALS
Status: Not yet recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

This is a multicenter, open-label, single-arm investigator-initiated clinical study designed to evaluate the safety, tolerability, and preliminary efficacy of SNUG01 in patients with Amyotrophic Lateral Sclerosis (ALS).

Detailed Description

SNUG01 is a gene therapy designed to deliver a protective protein gene to the central nervous system. Safety will be the primary focus during the initial 24 weeks post-treatment (primary study period). After the primary study period, participants will be assessed for both safety and efficacy for up to a total of 5 years following SNUG01 treatment.

Registry

clinicaltrials.gov

Start Date

October 16, 2024

End Date

October 15, 2029

Last Updated

last year

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

Peking University Third Hospital

Responsible Party

Principal Investigator

Fan Dongsheng

Professor, Chief Physician

Peking University Third Hospital

Eligibility 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\~80 years old (including 18 and 80 years old), both male and female. 3.Must have been diagnosed with clinically probable ALS, clinically possible laboratory-supported ALS, or clinically definite ALS according to the revised version of the El Escorial World Federation of Neurology criteria.
•4.Less than or equal to 36 months (inclusive) after the onset of symptoms of amyotrophic lateral sclerosis.
•5.Body Mass Index (BMI) ≥19 kg/m
•6.The forced vital capacity (FVC) in the screening period is greater than or equal to 70% of the estimated vital capacity.
•7.Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) score ≥ 26 during the screening period, with scores of ≥ 4 in the three respiratory items (dyspnea, orthopnea, and respiratory insufficiency) on the ALSFRS-R.
•Adequate organ function: Hematological: Neutrophil count≥1.5 × 10⁹/L, platelet count≥ 100 × 10⁹/L, Hemoglobin ≥90 g/L. Renal: Creatinine ≤1.5×ULN or creatinine clearance (CCr) ≥50 ml/min using the Cockcroft-Gault formula.
•Hepatic: Total bilirubin (TBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST)≤2 × ULN, alkaline phosphatase (ALP) ≤ 3 × ULN.
•Coagulation: International Normalized Ratio (INR), Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) ≤1.5 × ULN.
•9.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.

Exclusion Criteria

•Serum anti-AAV9 neutralizing antibody (Nab) titer \> 1:100 at the time of screening.
•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.
•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.
•Previously required invasive ventilation or tracheotomy due to ALS disease, or currently using non-invasive ventilation support with an average of ≥16 hours/day.
•Previous history of gene therapy, hematopoietic stem cell transplantation, and solid organ transplantation.
•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.
•Those who have been implanted or the researchers estimate that they will need to implant a diaphragmatic pacing system during the study period.
•Any thromboembolic events occurred within 6 months before the first administration, such as deep vein thrombosis, pulmonary arteriovenous embolism, jugular vein embolism, etc..
•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).
•Autoimmune disease (e.g., rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease, scleroderma, inflammatory myopathies, mixed connective tissue disease, overlap syndrome, etc.) within 30 days prior to the Screening Period, or ongoing immune-related therapy (e.g., corticosteroids, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, intravenous immunoglobulin, rituximab, leflunomide, hydroxychloroquine, interleukin 2 antagonists, etc.), except for intranasal, inhaled, ocular, topical topical, intra-articular corticosteroid therapy, or physiologic replacement therapy with corticosteroids.

Arms & Interventions

3 single Ascending Dose Levels

The study will be open-label with an initial plan to explore 3 dose levels of SNUG01 in approximately 7 to 10 Participants in total. Each Participant will receive a single dose of SNUG01 delivered via intrathecal (IT) infusion and will be followed for up to 5 years after administration.

Intervention: SNUG01

Outcomes

Primary Outcomes

To evaluate the safety and tolerability of ascending doses of intrathecally administered SNUG01 in Participants with ALS

Time Frame: Each visit in 1 year after administration

Safety and tolerability, including adverse events (AE), vital signs, physical examination, clinical laboratory tests (hematology, blood chemistry, urinalysis, coagulation, cardiac enzymes, etc.) and 12 electrocardiograms,etc.

Secondary Outcomes

Characterization of Immune Response to SNUG01(up to 1 years)
Characterization of the Effect of intrathecally administered SNUG01(3 months, 6 months,12 months)
Evaluate the long-term safety and tolerability of intrathecally administered SNUG01 in Participants with ALS(up to 5 years)