Evaluation of Safety and Efficacy of Gene Therapy Drug in the Treatment of Spinal Muscular Atrophy (SMA) Type 1 Patients

April 22, 2023 updated by: GeneCradle Inc

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 1 Patients

The study will evaluate safety and efficacy of intrathecal delivery of GC101 gene therapy drug as a treatment of spinal muscular atrophy Type 1 (SMA 1) patients.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The purpose of this trial is to evaluate safety and efficacy of gene therapy drug GC101 in SMA 1 patients. Open-label, dose-escalation clinical trial 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 on various time points.

The primary analysis for efficacy will be assessed when all patients reach 18 months of age on the motor milestone of sit unassisted for at least 10 seconds.

Study Type

Interventional

Enrollment (Anticipated)

18

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
      • Beijing, China, 100034
        • Recruiting
        • Peking University， First Hospital, Department of Pediatrics
        • Principal Investigator:
          • Hui Xiong
        • Contact:
      • Beijing, China, 100700
        • Recruiting
        • Bayi Children's Hospital, Seventh Medical Center, PLA general hospital
        • Contact:
        • Principal Investigator:
          • Zhicun Feng
      • Shenyang, China, 110004
        • Recruiting
        • Shengjing Hospital of China Medical University
        • Contact:
        • Principal Investigator:
          • Hua Wang
      • Suzhou, China, 215025
        • Recruiting
        • Children's Hospital of Soochow University
        • Contact:
        • Principal Investigator:
          • Jihong Tang

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Six months of age and younger on day of vector infusion with Type 1 SAM 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 SMN2;
    • Onset of disease before 6 months of age
  • 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.

Exclusion Criteria:

  • Patient who has participated in a previous gene therapy research trials;
  • Patient who has received Nusinersen and Risdiplam treatment;
  • Patient who has AAV9 neutralizing antibody titer ≥1:200;
  • Patient who requires non-invasive ventilatory support averaging≥16 hours/day;
  • Patient with a point mutation in SMN2 (c.859G>C);
  • Patient who requires non-invasive ventilatory support averaging≥16 hours/day at screening;
  • Patient who 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 <183x10^9/L or 614x10^9/L;
  • 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.

Note: Other protocol defined inclusion/exclusion criteria may apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Low dosage group
2.4x10^14 vg/person of GC101 delivered one-time intrathecally (n=3)
Genetic: GC101
Self-complementary AAV9 carrying a codon-optimized SMN coding sequence(coSMN1) driven by CMV enhancer and chicken β-actin promoter
Experimental: High dosage group
4.8x10^14 vg/person of GC101 delivered one-time intrathecally (n=3)
Genetic: GC101
Self-complementary AAV9 carrying a codon-optimized SMN coding sequence(coSMN1) driven by CMV enhancer and chicken β-actin promoter

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients treated with GC101 who achieve motor milestone of sit unassisted for at least 10 seconds at 18 months of age
Time Frame: when patient reaches 18 months of age
when patient reaches 18 months of age
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time Frame: when patient reaches 18 months of age
Frequency of treatment-related adverse events (AEs), serious adverse events (SAEs), and changes from baseline in relevant clinical laboratory tests
when patient reaches 18 months of age

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Ability to thrive
Time Frame: when patient reaches 18 months of age
Ability to thrive is defined as the following at 18 months of age: does not receive nutrition through mechanical support or other non-oral method; maintains weight
when patient reaches 18 months of age
Proportion of event-free survival patients
Time Frame: when patient reaches 14 months of age
when patient reaches 14 months of age
Changes from baseline Children's hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) score
Time Frame: when patient reaches 18 months of age
CHOP INTEND score ranges from 0 to 64 with higher scores indicating higher motor function
when patient reaches 18 months of age

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients who achieve the World Health Organization (WHO) Multicenter Growth Reference Study (MGRS) motor milestones
Time Frame: when patient reaches 18 months of age
WHO MGRS gross motor milestones and performance criteria included sitting without support for at least 10 seconds, Hands-and-knees crawling at least three in a row, standing with assistance for at least 10 seconds, walking with assistance at least five steps, standing alone for at least 10 seconds, and walking alone.
when patient reaches 18 months of age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

GeneCradle Inc

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 25, 2023

Primary Completion (Anticipated)

December 1, 2025

Study Completion (Anticipated)

December 1, 2025

Study Registration Dates

First Submitted

April 10, 2023

First Submitted That Met QC Criteria

April 10, 2023

First Posted (Actual)

April 21, 2023

Study Record Updates

Last Update Posted (Actual)

April 25, 2023

Last Update Submitted That Met QC Criteria

April 22, 2023

Last Verified

April 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • JLJY-GC101-SMA-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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