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Evaluation of Safety and Efficacy of Gene Therapy Drug in the Treatment of Spinal Muscular Atrophy (SMA) Type 3 Patients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT06421831
Recruitment Status : Recruiting
First Posted : May 20, 2024
Last Update Posted : May 20, 2024
Information provided by (Responsible Party):
GeneCradle Inc

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 3 (SMA 3) patients.

Condition or disease Intervention/treatment Phase
Spinal Muscular Atrophy Type 3 Genetic: GC101 Phase 1 Phase 2

Detailed Description:

The purpose of this trial is to evaluate safety and efficacy of gene therapy drug GC101 in SMA 3 patients. Open-label, dose-escalation clinical trials of GC101 will be conducted in multiple centers in China.

GC101 will be administrated intrathecally. Short-term safety will be evaluated in 52 weeks and enter long-term follow-up study of 5 years at will. Patients will be tested at baseline and followed up at various time points.

The primary analysis for efficacy will be assessed at 12 months after treatment with GC101 on the changes from baseline HFMSE (Hammersmith Functional Motor Scale Expanded) and RULM(Revised Upper Limb Module) scores for patients of age ≥ 6 years old.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 21 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multi-center, Open Label, Single-arm, Dose Ascending Clinical Trial for Evaluation of Safety and Efficacy of Gene Therapy Drug GC101 in the Treatment of Spinal Muscular Atrophy (SMA) Type 3 Patients
Actual Study Start Date : May 10, 2024
Estimated Primary Completion Date : December 2026
Estimated Study Completion Date : December 2028

Arm Intervention/treatment
Experimental: single dose cohort
1.2x10^14 vg/person of GC101 delivered one-time intrathecally
Genetic: GC101
Self-complementary AAV9 carrying a codon-optimized SMN coding sequence(coSMN1) driven by CMV enhancer and chicken β-actin promoter

Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events [ Time Frame: 52 weeks ]
    Frequency of treatment-related adverse events (AEs), serious adverse events (SAEs), and changes from baseline in relevant clinical laboratory tests

  2. Change from baseline on Hammersmith Functional Motor Scale - Expanded (HFMSE) scores at Month 12 [ Time Frame: 52 weeks ]
    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.

Secondary Outcome Measures :
  1. The proportion of patients whose HFMSE improvement ≥ 3 points at Month 12 [ Time Frame: 52 weeks ]
    HFMSE ≥3 points:minimal clinically important differences (MCID) were considered for the outcomes:

  2. Change from baseline on Revised Upper Limb Module (RULM) scores at Month 12 [ Time Frame: 52 weeks ]
    RULM is a 20-item evaluation of upper limb function primarily used for those with SMA who are non-ambulatory (young children through adults).

Other Outcome Measures:
  1. The proportion of patients whose Clinical Global Impression (CGI) is improved at Month 12 [ Time Frame: 52 weeks ]
  2. The proportion of patients whose Motor Function Measure (MFM) is improved or maintained at Month 12 [ Time Frame: 52 weeks ]
  3. Change from baseline of Forced Vital Capacity (FVC) at Month 12 ( for patients > 6 years) [ Time Frame: 52 weeks ]
  4. Change from baseline of Forced Expiratory Volume in 1 Second (FEV1) at Month 12 ( for patients > 6 years) [ Time Frame: 52 weeks ]
  5. Change from baseline of Maximal Inspiratory Pressure (MIP) at Month 12 ( for patients > 6 years) [ Time Frame: 52 weeks ]
  6. Change from baseline of Maximal Expiratory Pressure (MEP) at Month 12 ( for patients > 6 years) [ Time Frame: 52 weeks ]
  7. Change from baseline of 6 minutes walk test (6MWT) at Month 12 (for ambulatory patients) [ Time Frame: 52 weeks ]
    The 6MWT is used for ambulatory participants with SMA and measures the total distance walked in 6 minutes.

  8. Change from baseline of SMA Independence Scale (SMAIS) at Month 12 [ Time Frame: 52 weeks ]

    The SMA Independence Scale (SMAIS) is a self-reported questionnaire to assess the amount of assistance patients require to perform daily activities. Higher SMAIS scores indicate greater independence.

    (range: 0-44).

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   2 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • ≥2 years of age on the day of signing the informed consent form;
  • Genetic and clinical diagnosis of type 3 SMA with bi-allelic deletion of SMN1 of 5qSMA;
  • Hammersmith Functional Motor Scale - Expanded (HFMSE) score is between 10 and 54 at screening;
  • Female patients of childbearing age who are pregnant or lactating, as well as all enrolled patients (both male and female), should take effective contraceptive measures within 6 months after the treatment;
  • Patients or 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.

Exclusion Criteria:

  • Patient who has participated in any previous gene therapy research trials;
  • Patient who has AAV9 neutralizing antibody titer ≥1:200;
  • Patient who has received Nusinersen within 120 days and Risdiplam within 15 days before treatment;
  • Patient who requires invasive or non-invasive ventilatory support averaging≥16 hours/day at screening;
  • SMN2 copy numbers >4;
  • Patient who needs nasal or gastric tube feeding for eating;
  • Patient who is positive for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen, hepatitis C antibody, or treponema pallidum antibody;
  • Known allergy or hypersensitivity to prednisolone or other glucocorticosteroids or their excipients
  • Severe contractures at screening that interfere with either the ability to attain/demonstrate functional measures or with the ability to receive intrathecal (IT) dosing;
  • Patient who has other serious diseases, such as severe cardiovascular and cerebrovascular diseases, digestive system diseases, urinary system diseases, endocrine system diseases, hematological diseases, immune system diseases, nervous system diseases (including but not limited to epilepsy, meningitis, history of convulsions or seizures, cerebrospinal fluid circulation disorders), and mental illnesses, etc.;
  • Patient with previous injuries (such as upper or lower limb fractures) or surgical operations that have not fully recovered or reached a stable state;
  • Vaccination no longer than 2 weeks before treatment;
  • Patient who has any other condition that, in the opinion of the investigator, makes the subject unsuitable for participation in the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT06421831

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Contact: GeneCradle, Inc China +8613501380583

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China, Beijing
Beijing Tiantan Hospital, Capital Medical University Recruiting
Beijing, Beijing, China
Contact: Kang Zhang         
Principal Investigator: Zaiqiang Zhang         
Principal Investigator: Yajie Wang         
Sponsors and Collaborators
GeneCradle Inc
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Responsible Party: GeneCradle Inc Identifier: NCT06421831    
Other Study ID Numbers: JLJY-GC101-SMA-010
First Posted: May 20, 2024    Key Record Dates
Last Update Posted: May 20, 2024
Last Verified: May 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GeneCradle Inc:
SMA type 3
Additional relevant MeSH terms:
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Muscular Atrophy
Muscular Atrophy, Spinal
Pathological Conditions, Anatomical
Neuromuscular Manifestations
Neurologic Manifestations
Nervous System Diseases
Spinal Cord Diseases
Central Nervous System Diseases
Motor Neuron Disease
Neurodegenerative Diseases
Neuromuscular Diseases