Clinical Trial to Assess the Safety and Efficacy of EXG001-307 in Patients With Spinal Muscular Atrophy

NCT06888661 | Enrolling By Invitation Early Phase 1 DMC

• 1 other identifier: EXG001-307-011
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this trial is to evaluate safety and efficacy of intrathecal delivery of EXG001-307 as a treatment of spinal muscular atrophy .

Conditions

Spinal Muscular Atrophy (SMA)

Keywords

SMA; AAV9; gene therapy

Outcome Measures

Primary Outcomes (1)

• To evaluate the safety and tolerability of EXG001-307 following a single intrathecal injection

  Adverse events (AES), serious adverse events (SAEs), dose-limited toxicity types, severity, incidence, and drug relevance were evaluated after treatment.（Evaluate through examinations such as electrocardiogram, echocardiography, blood routine, blood biochemistry, coagulation function, etc. conducted during each visit）

  up to 52 weeks after treatment

Secondary Outcomes (3)

• Evaluate the improvement of motor function in subjects after treatment: assessed with the BSID-III scale

  up to 52 weeks after treatment

• Evaluate the improvement of motor function in subjects after treatment: assessed with the CHOP-INTEND scale

  up to 52 weeks after treatment

• Evaluate the improvement of motor function in subjects after treatment: assessed with the HINE-2 scale

  up to 52 weeks after treatment

Study Arms (1)

Dose escalation- Cohort 1

EXPERIMENTAL

Dose 1 Intrathecal administration dose 1 of EXG001-307 to SMA patient (type I \&type II)

Biological: EXG001-307 injection

Interventions

EXG001-307 injection BIOLOGICAL

non-replicating, rAAV vector based on AAV9 containing cDNA encoding the human SMN protein.

Dose escalation- Cohort 1

Eligibility Criteria

• Age: 1 Day - 2 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• On the day of dosing, type 1 SMA age ≤180 days, type 2 SMA age \> 180 days ≤2 years, male or female.
• Clinical history and physical signs are consistent with SMA manifestations; SMA was diagnosed by bilateral allelic SMN1 mutation (deletion or point mutation). Type 1 has 2 copies of SMN2 gene. Type 2 has ≤3 copies of SMN2 gene.
• The subject's legal guardian understands the purpose, possible risks and interests of the study, agrees to participate in the study, completes all study procedures, tests and visits, and voluntarily signs the informed consent form.
• During the study, the subject's legal guardian was willing to perform standard treatment requirements such as nasogastric feeding, noninvasive mechanical ventilation, and expectoration machine as recommended by the investigator.

You may not qualify if:

• The presence of contraindications to lumbar puncture (including, but not limited to, signs or symptoms of skin infection at the administration site and elevated intracranial pressure), the receipt of any active intrathecal therapy, the presence of an implantable shunt tube for draining CSF, the presence of an implantable central nervous system (CSF) cannula, or any condition that interferes with CSF collection.
• Imaging shows severe scoliosis (defined as curvature of the spine ≥ 50°).
• Gestational age at birth was less than 35 weeks (245 days).
• At screening, the subject had an oxygen saturation \< 95% while awake or sleeping and did not receive any supplemental oxygen or respiratory support.
• Requirement of invasive ventilation or tracheotomy, or current use of noninvasive ventilatory support for an average of ≥ 12 hours/day.
• Weighed below the 3rd percentile by age according to the WHO Child Growth Criteria (WHO 2009).
• Before administration, if the subject has not received or delayed vaccination according to the current month-old national vaccination plan, it will significantly affect the safety of the subject as assessed by the investigator and the medical manager of the project team;
• Active viral infections (including HIV, hepatitis B or C seropositivity, torch virus, Epstein-Barr virus, and syphilis).
• Serious non-respiratory disease within 2 weeks prior to screening.
• EXG001-307 has had an upper respiratory tract infection or lower respiratory tract infection within 4 weeks prior to administration, and still has relevant clinical symptoms or is still in an unstable state of disease.
• Other severe infections or illnesses within 4 weeks prior to administration of EXG001-307.
• A history of bacterial meningitis or brain or spinal cord disease, including tumors, or abnormalities found on an MRI or computed tomography scan that interfere with a lumbar puncture procedure or cerebrospinal fluid circulation.
• There are currently clinically significant heart disease or electrocardiogram abnormalities that may affect the safety assessment of subjects.
• Known hypersensitivity to prednisolone, other glucocorticoids, or its excipients；Or cannot tolerate oral or gastrostomy tube administration of corticosteroids.
• Immunosuppressive therapy (eg, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, rituximab) other than protocol-required prophylaxis within 3 months prior to dosing.

Sponsors & Collaborators

• Hangzhou Jiayin Biotech Ltd: lead

Study Sites (2)

Shanghai Children's Medical Center Affiliated to Shanghai Jiao Tong University School of Medicine

Shanghai, Shanghai Municipality, 201100, China

Location

The Children's Hospital of Fudan University

Shanghai, Shanghai Municipality, 201100, China

Location

MeSH Terms

Conditions

Muscular Atrophy, Spinal

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Motor Neuron Disease; Neurodegenerative Diseases; Neuromuscular Diseases

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 3, 2025
• First Posted: March 21, 2025
• Study Start: March 10, 2025
• Primary Completion: March 1, 2026
• Study Completion (Estimated): December 30, 2026
• Last Updated: March 21, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)