Clinical Trial to Assess the Safety and Efficacy of EXG001-307 in Patients with Spinal Muscular Atrophy Type 1

NCT05614531 | Enrolling By Invitation Phase 1 DMC

• 2 other identifiers: EXG001-307-1022022LP00989
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this trial is to evaluate safety and efficacy of intravenous delivery of EXG001-307 as a treatment of spinal muscular atrophy Type 1 (SMN1).

Conditions

Spinal Muscular Atrophy Type I

Keywords

SMA，SMA1

Outcome Measures

Primary Outcomes (1)

• To evaluate the safety and tolerability of EXG001-307 following a single intravenous infusion

  including type and incidence of AE, SAE, AESI, vital signs, physical/neurological examination, immunogenicity, virology, injection/infusion site reactions, 12-lead electrocardiogram, and safety laboratory results recorded

  During each visit

Secondary Outcomes (2)

• Patients number who survival at 14 month of age

  up to 14 month of age

• Number of patients who were able to sit unsupported for ≥30 seconds

  From Day 1 up to 18 Months of Age Visit

Study Arms (3)

Dose escalation- Cohort 1

EXPERIMENTAL

dose 1 of EXG001-307 delivered one-time through a venous catheter inserted into a peripheral vein (n=3\~6)

Genetic: EXG001-307 injection

Dose escalation-Cohort 2

EXPERIMENTAL

dose 2 of EXG001-307 delivered one-time through a venous catheter inserted into a peripheral vein (n=6\~12)

Genetic: EXG001-307 injection

Dose escalation-Cohort 3

EXPERIMENTAL

dose 3 of EXG001-307 delivered one-time through a venous catheter inserted into a peripheral vein (n=3\~6)

Genetic: EXG001-307 injection

Interventions

EXG001-307 injection GENETIC

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

Dose escalation- Cohort 1; Dose escalation-Cohort 2; Dose escalation-Cohort 3

Eligibility Criteria

• Age: 1 Day - 180 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• SMA was diagnosed by a bilaterally allelic SMN1 mutation (deletion or point mutation) gene with 2 copies of the SMN2 gene.
• On the day of dosing, the subject ' s age did not exceed postnatal Day 180.
• The clinical history and signs were consistent with type 1 SMA manifestations, i.e. hypotonia, delayed motor function development, poor head control, round shoulder posture, and joint hypermobility.
• 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:

• Gestational age at birth was less than 35 weeks (245 days).
• At screening, the subject had an oxygen saturation \< 96% 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 ≥ 16 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, COVID-19, hepatitis B or C seropositivity, torch virus, Epstein-Barr virus, and syphilis).
• Serious non-respiratory disease within 2 weeks prior to screening.
• Upper respiratory tract infection or lower respiratory tract infection within 4 weeks prior to screening.
• Current presence of other severe infections or diseases.
• Known cardiac disease or ECG abnormalities that are clinically significant.
• Known hypersensitivity to prednisolone, other glucocorticoids, or its excipients.
• Immunosuppressive therapy (eg, cyclosporine, tacrolimus, methotrexate, cyclophosphamide, rituximab) other than protocol-required prophylaxis within 3 months prior to dosing.
• Immunomodulatory drugs (eg, thymosin, interferon, etc.) are being used to treat myopathy, neuritis, diabetes mellitus (eg, immunosuppressants, glucocorticoids, insulin).
• Anti-AAV9 antibody titer \> 1: 50 (as determined by ECL). If the potential subject has an anti-AAV9 antibody titer \> 1: 50, it can be retested during the screening period. If the anti-AAV9 antibody titer is ≤ 1: 50 at the retest, the subject may continue to participate in the screening.
• Clinically significant abnormal laboratory values (GGT, ALT, and AST \> 2.5 × ULN, bilirubin ≥ 3.0 mg/dL, creatinine ≥ 1.0 mg/dL, hemoglobin \< 8 or \> 18 g/dL; white blood cell count \> 20,000/cm3; platelet count \< 100,000/cm3).

Sponsors & Collaborators

• Hangzhou Jiayin Biotech Ltd: lead

Study Sites (2)

The Children's Hospital of Fudan University

Shanghai, Shanghai Municipality, 201100, China

Location

The Children'S Hospital Zhejiang University of Medicine

Hangzhou, Zhejiang, 310051, China

Location

Related Publications (1)

• Song C, Wang Q, Zhu P, Li J, Dai L, Hu W, Yang W, Zhang R, Wang D, Li Z, Chen S, Wang L, Ye G, Wu Z. Efficacy and preliminary safety assessment of EXG001-307 AAV gene therapy for spinal muscular atrophy. Mol Ther Methods Clin Dev. 2025 Apr 18;33(2):101475. doi: 10.1016/j.omtm.2025.101475. eCollection 2025 Jun 12.

  PMID: 40458203 DERIVED

MeSH Terms

Conditions

Spinal Muscular Atrophies of Childhood

Condition Hierarchy (Ancestors)

Muscular Atrophy, Spinal; Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Motor Neuron Disease; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Design

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

Study Record Dates

• First Submitted: November 2, 2022
• First Posted: November 14, 2022
• Study Start: February 16, 2023
• Primary Completion: August 1, 2025
• Study Completion: August 1, 2025
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (2)