An IIT Clinical Study to Evaluate the Safety, Tolerability, and Preliminary Efficacy of a Single Intrathecal Injection of SNUG01 in Patients with Amyotrophic Lateral Sclerosis

NCT06645197 | Not Yet Recruiting Early Phase 1

• 1 other identifier: CTP-SNUG01-IIT-02
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 5

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).

Conditions

Amyotrophic Lateral Sclerosis (ALS)

Keywords

Gene therapy; AAV (adeno-associated virus); ALS; Neuromuscular Diseases; Motor Neuron Disease; Nervous System Diseases

Outcome Measures

Primary Outcomes (1)

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

  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.

  Each visit in 1 year after administration

Secondary Outcomes (5)

• Characterization of Immune Response to SNUG01

  up to 1 years

• Characterization of the Effect of intrathecally administered SNUG01

  3 months, 6months

• Characterization of the Effect of intrathecally administered SNUG01

  3 months, 6 months,12 months

• 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

Other Outcomes (2)

• To evaluate the viral shedding after SNUG01 treatment

  Up to 5 years

• To explore the potential biomarkers in ALS subjects

  6 months, 12 months

Study Arms (1)

3 single Ascending Dose Levels

EXPERIMENTAL

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.

Drug: SNUG01

Interventions

SNUG01 DRUG

Recombinant adeno-associated virus serotype 9 capsid containing human SG001 expression cassette

3 single Ascending Dose Levels

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand and voluntarily sign the informed consent form, the informed consent form must be signed before performing any clinical trail procedures.
• \~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.
• Less than or equal to 36 months (inclusive) after the onset of symptoms of amyotrophic lateral sclerosis.
• Body Mass Index (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.
• 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.
• 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 are not currently treated with edaravone or are being treated with the approved standard regimen of edaravone. Subjects being treated with edaravone must have completed at least 1 cycle of treatment prior to the Screening Visit and are expected to continue treatment with edaravone throughout the study period.
• 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.

You may not qualify if:

• 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.
• 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).
• 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 5.0), except alopecia.
• Participated in another clinical study within 4 weeks before the first administration, unless it is an observational (non-intervention) clinical study.
• Any febrile illness occurred within 14 days before the first administration.
• Have been vaccinated within 14 days before the first dose.

Sponsors & Collaborators

• Peking University Third Hospital: lead
• SineuGene Therapeutics Co., Ltd.: collaborator

Study Sites (5)

Peking University Third Hospital

Beijing, Beijing Municipality, 100000, China

Location

Fujian Medical University Union Hospital

Fujian, Fuzhou, 350000, China

Location

JiangSu Provincce Hospital

Nanjing, Jiangsu, 210000, China

Location

West China Hospital of Sichuan University

Chengdu, Sichuan, 610000, China

Location

Second Affiliated Hospital Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310000, China

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Neuromuscular Diseases; Motor Neuron Disease; Nervous System Diseases

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Neurodegenerative Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Peking University Third Hospital

CONTACT

15710013912; neurbj@126.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Chief Physician

Study Record Dates

• First Submitted: October 11, 2024
• First Posted: October 16, 2024
• Study Start: October 16, 2024
• Primary Completion: April 15, 2025
• Study Completion (Estimated): October 15, 2029
• Last Updated: October 16, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5)