Evaluation of Safety and Efficacy of Gene Therapy Drug in the Treatment of Spinal Muscular Atrophy (SMA) Type 2 Patients

NCT05901987 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: JLJY-GC101-SMA-003
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 5

Brief Summary

The study will evaluate safety and efficacy of intrathecal delivery of GC101 gene therapy drug as a treatment of spinal muscular atrophy Type 2 (SMA 2) patients.

Conditions

SMA II

Outcome Measures

Primary Outcomes (3)

• Incidence of Treatment-Emergent Adverse Events

  Frequency of treatment-related adverse events (AEs), serious adverse events (SAEs), and changes from baseline in relevant clinical laboratory tests

  52 weeks

• Proportion of patients who can stand unassisted for at least 3 seconds at Month 12

  52 weeks

• Change from baseline on Hammersmith Functional Motor Scale - Expanded (HFMSE) scores at Month 12

  HFMSE consists of 33 activities that can be scored one of three ways: 0 for unable to perform, 1 for performs with modification/adaptation, and 2 for performs without modification.

  52 weeks

Secondary Outcomes (1)

• Proportion of patients treated with GC101 who achieve motor milestone of walk alone for 5 steps at Month 12

  52 weeks

Other Outcomes (2)

• Change from baseline in independent ventilatory support time at Month 12

  52 weeks

• Number of patients whose HFMSE scores improve more than 3 at Month 12

  52 weeks

Study Arms (3)

Low dosing group

EXPERIMENTAL

1.2x10\^14 vg/person of GC101 delivered one-time intrathecally (n=3)

Genetic: GC101

Medium dosing group

EXPERIMENTAL

2.4x10\^14 vg/person of GC101 delivered one-time intrathecally (n=3)

Genetic: GC101

High dosing group

EXPERIMENTAL

4.8x10\^14 vg/person of GC101 delivered one-time intrathecally (n=3)

Genetic: GC101

Interventions

GC101 GENETIC

Self-complementary AAV9 carrying a codon-optimized SMN coding sequence(coSMN1) driven by CMV enhancer and chicken β-actin promoter

High dosing group; Low dosing group; Medium dosing group

Eligibility Criteria

• Age: 6 Months - 60 Months
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Between 6 months and 60 months of age on day of signing informed consent form;
• Patient with SMA Type 2 as defined by the following features:
• Diagnosis of SMA based on gene mutation analysis with bi-allelic SMN1 mutations (deletion or point mutations) and 2 copies of SMN
• Onset of disease between 6 and 18 months of age
• Patient who can sit alone but never be able to stand or walk alone ;
• The patient's legal guardian(s) must be able to understand the purpose and risks of the study and voluntarily provide signed and dated informed consent prior to any study-related procedures being performed.

You may not qualify if:

• Patient who has participated in any previous gene therapy research trials;
• Patient who has received Nusinersen within 4 months and Risdiplam within 15 days before treatment;
• Patient who has AAV9 neutralizing antibody titer ≥1:200;
• Patient with a point mutation in SMN2 (c.859G\>C);
• Patient who requires non-invasive ventilatory support averaging≥12 hours/day at screening, or use invasive ventilatory support or pulse oximetry \< 95% saturation while awake and calm at screening;
• Patient who is positive for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen, hepatitis C antibody, or treponema pallidum antibody;
• Abnormal laboratory values considered clinically significant, including gamma-glutamyl transferase(GGT), Aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin \> 3x upper limit of normal (ULN), Hemoglobin (Hgb)\< 110 or \>150 g/L, platelet \<lower limit of normal (LLN);Class IV patient based on Modified Ross Heart Failure Classification for Children;
• Patient with a history of glucocorticoid allergy;
• Contraindication that would interfere with the lumbar puncture procedures;
• Presence of an untreated active infection requiring systemic antiviral therapy at any time during the screening period;
• Vaccination less than 2 weeks before infusion of vector;
• Patient who has any concurrent clinically significant major disease or any other condition that, in the opinion of the Investigator, makes the subject unsuitable for participation in the study.

Sponsors & Collaborators

• GeneCradle Inc: lead

Study Sites (5)

Peking University， First Hospital, Department of Pediatrics

Beijing, 100034, China

Location

Bayi Children's Hospital, Seventh Medical Center, PLA general hospital

Beijing, 100700, China

Location

West China Second University Hospital, Sichuan University

Chengdu, China

Location

Children's Hospital of Chongqing Medical University

Chongqing, China

Location

Tongji Medical college of Huazhong University of Science&Technology, Affiliated Children's Hospital

Wuhan, China

Location

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: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2023
• First Posted: June 13, 2023
• Study Start: August 1, 2023
• Primary Completion: April 22, 2025
• Study Completion (Estimated): December 1, 2028
• Last Updated: July 3, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (5)