Safety and Efficacy Evaluation of GC101 Gene Therapy Via Intrathecal (IT) Injectionin the Treatment of Patients With Type 2 Spinal Muscular Atrophy (SMA) - Phase III

NCT06971094 | Recruiting Phase 3 DMC

• 1 other identifier: JLJY-GC101-SMA-011
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 7

Brief Summary

This trial employs a multicenter, randomized, open-label, standard-of-care-controlled design and plans to enroll 50 patients with Type 2 SMA aged 2 to 12 years who have previously received nusinersen. The primary objective of the trial is to evaluate the efficacy of GC101 in treating Type 2 SMA. The secondary objectives are to assess the efficacy, safety, and pharmacokinetic (PK) profile of GC101 in treating Type 2 SMA.

Conditions

SMA - Spinal Muscular Atrophy

Keywords

SMA, type II, AAV gene therapy; Genecradle

Outcome Measures

Primary Outcomes (1)

• HFMSE score change from baseline

  HFMSE Motor Function Assessment (Hammersmith Functional Motor Scale Expanded) is a standardized tool specifically designed to evaluate motor function in patients with spinal muscular atrophy (SMA). It includes 33 test items covering actions such as head control, sitting, standing, walking, stair climbing, jumping, as well as balance and coordination, providing a comprehensive assessment of motor function in the trunk and limbs. The maximum total score is 66 points, with higher scores indicating better motor capabilities.

  52 weeks

Secondary Outcomes (6)

• HFMSE score change from baseline

  26 weeks

• The proportion of participants with an increase in HFMSE score of ≥3 points from baseline.

  26 and 52 weeks

• Changes in WHO-MGRS motor milestones from baseline.

  26 and 52 weeks

• RULM score change from baseline.

  26 and 52 weeks

• SMAIS score change from baseline.

  26 and 52 weeks

Study Arms (2)

GC101

EXPERIMENTAL

single dose of GC101 at dosage of 1.2E+14 vg per person via intrathecal injection

Genetic: GC101 adeno-associated virus injection

Control

NO INTERVENTION

Participants will continue to receive treatment according to their previous standard-of-care regimen with nusinersen.

Interventions

GC101 adeno-associated virus injection GENETIC

Self-complementary recombinant adeno-associated viral vector (scAAV) containing a single-stranded transgene encoding a codon-optimized human SMN1 gene

GC101

Eligibility Criteria

• Age: 2 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Patients with a confirmed diagnosis of Type 2 5q-SMA through clinical phenotype and genetic testing.
• Patients who have been receiving regular treatment with nusinersen for more than one year prior to screening.
• Patients who have not received treatment with risdiplam within 2 months prior to screening and have no plans to receive risdiplam treatment within 12 months after enrollment.
• Patients who can sit independently but cannot walk independently at the time of screening (according to the definitions of independent sitting and walking in the WHO-MGRS motor milestones scale), and have an HFMSE score of ≥10 points.
• Patients and/or their legal guardians are able to understand and are willing to comply with the requirements and procedures of the trial protocol, and voluntarily participate and sign the informed consent form

You may not qualify if:

• Patients with serum anti-AAV9 neutralizing antibody titers \> 1:50 at the time of screening.
• Patients who have received nusinersen treatment within 2 months prior to enrollment.
• Patients with any medical conditions that may affect the interpretation of study results or pose a risk to the safety of the participants, including but not limited to organ dysfunction of any cause, acute infectious diseases, primary/acquired immunodeficiency diseases, severe cardiovascular/cerebrovascular diseases, gastrointestinal diseases, diabetes, known epilepsy, meningitis, seizure or convulsion history, or a family history of psychiatric disorders; and those with cerebrospinal fluid circulation disorders.
• Patients with severe liver injury/hepatic insufficiency of any cause, including but not limited to alanine aminotransferase (ALT), aspartate aminotransferase (AST) ≥3 times the upper limit of normal (ULN); total bilirubin (TBil) ≥1.5 times the ULN.
• Patients deemed by the investigator to have contraindications to glucocorticoid use, such as severe hypertension, diabetes, systemic infectious diseases, fungal infections, glaucoma, osteoporosis, peptic ulcer disease, tuberculosis, etc.
• Patients with contraindications to lumbar puncture or intrathecal injection therapy.
• Patients with any medical conditions that may affect the assessment of motor function, such as severe scoliosis, severe joint contracture deformities, planned spinal correction surgery during the trial period, severe osteoporosis, or a history of fractures.
• Patients positive for hepatitis B surface antigen (HBsAg), human immunodeficiency virus (HIV) antibodies, hepatitis C virus (HCV) antibodies, or syphilis antibodies.
• Patients who have received vaccinations within 2 weeks prior to dosing.
• Patients who have previously received gene therapy or participated in any clinical trial within 3 months prior to screening.
• Patients deemed by the investigator to be unsuitable for participation in this study.

Sponsors & Collaborators

• GeneCradle Inc: lead

Study Sites (7)

The Seventh Medical Center of Chinese PLA General Hospital

Beijing, 100700, China

RECRUITING

Children's Medical Center of Peking University First Hospital

Beijing, 102699, China

RECRUITING

Beijing Children's Hospital, Capital Medical University

Beijing, China

RECRUITING

National Children's Medical Center，Shanghai Jiaotong University

Shanghai, 200127, China

RECRUITING

Shenzhen Children's Hospital

Shenzhen, China

RECRUITING

Children's Hospital of Soochow University

Suzhou, China

RECRUITING

Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science & Technology

Wuhan, 430015, China

RECRUITING

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

Central Study Contacts

GeneCradle, Inc China

CONTACT

+8613501380583; ind@bj-genecradle.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This trial employs a multicenter, randomized, open-label, standard-of-care-controlled design and plans to enroll 50 patients with Type 2 SMA aged 2 to 12 years who have previously received treatment. The trial consists of two groups: one group will receive a single intrathecal injection of GC101 at a dose of 1.2E+14 vg per person and discontinue their previous standard-of-care treatment with nusinersen; the other group will continue their previous standard-of-care treatment with nusinersen. Participants will be randomly assigned to the trial group or the control group in a 1:1 ratio.

Study Record Dates

• First Submitted: May 6, 2025
• First Posted: May 14, 2025
• Study Start: May 27, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: June 5, 2025

Record last verified: 2025-06

Locations

CN (7)