search
Back to results

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

Primary Purpose

SMA II

Status
Recruiting
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
GC101
Sponsored by
GeneCradle Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for SMA II

Eligibility Criteria

6 Months - 60 Months (Child)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Peking University, First Hospital, Department of PediatricsRecruiting
  • Bayi Children's Hospital, Seventh Medical Center, PLA general hospitalRecruiting
  • West China Second University Hospital, Sichuan University
  • Children's Hospital of Chongqing Medical University
  • Tongji Medical college of Huazhong University of Science&Technology, Affiliated Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Low dosing group

Medium dosing group

High dosing group

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
June 4, 2023
Last Updated
September 11, 2023
Sponsor
GeneCradle Inc
search

1. Study Identification

Unique Protocol Identification Number
NCT05901987
Brief Title
Evaluation of Safety and Efficacy of Gene Therapy Drug in the Treatment of Spinal Muscular Atrophy (SMA) Type 2 Patients
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 2 Patients
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
August 1, 2023 (Actual)
Primary Completion Date
May 2025 (Anticipated)
Study Completion Date
December 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GeneCradle Inc

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
The purpose of this trial is to evaluate safety and efficacy of gene therapy drug GC101 in SMA 2 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 at 12 months after treatment with GC101 on the motor milestone of stand unassisted for at least 3 seconds for patients of age between 6 and 24 months, or changes from baseline HFMSE scores for patients of age between 24 and 60 months.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
SMA II

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
33 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Low dosing group
Arm Type
Experimental
Arm Description
1.2x10^14 vg/person of GC101 delivered one-time intrathecally (n=3)
Arm Title
Medium dosing group
Arm Type
Experimental
Arm Description
2.4x10^14 vg/person of GC101 delivered one-time intrathecally (n=3)
Arm Title
High dosing group
Arm Type
Experimental
Arm Description
4.8x10^14 vg/person of GC101 delivered one-time intrathecally (n=3)
Intervention Type
Genetic
Intervention Name(s)
GC101
Intervention Description
Self-complementary AAV9 carrying a codon-optimized SMN coding sequence(coSMN1) driven by CMV enhancer and chicken β-actin promoter
Primary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events
Description
Frequency of treatment-related adverse events (AEs), serious adverse events (SAEs), and changes from baseline in relevant clinical laboratory tests
Time Frame
52 weeks
Title
Proportion of patients who can stand unassisted for at least 3 seconds at Month 12
Time Frame
52 weeks
Title
Change from baseline on Hammersmith Functional Motor Scale - Expanded (HFMSE) scores at Month 12
Description
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.
Time Frame
52 weeks
Secondary Outcome Measure Information:
Title
Proportion of patients treated with GC101 who achieve motor milestone of walk alone for 5 steps at Month 12
Time Frame
52 weeks
Other Pre-specified Outcome Measures:
Title
Change from baseline in independent ventilatory support time at Month 12
Time Frame
52 weeks
Title
Number of patients whose HFMSE scores improve more than 3 at Month 12
Time Frame
52 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Months
Maximum Age & Unit of Time
60 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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. 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 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. Note: Other protocol defined inclusion/exclusion criteria may apply.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
GeneCradle, Inc. China
Phone
86-13501380583
Email
ind@bj-genecradle.com
Facility Information:
Facility Name
Peking University, First Hospital, Department of Pediatrics
City
Beijing
ZIP/Postal Code
100034
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yanbin Fan
Phone
86-13126582705
Email
fanyanbin0323@163.com
First Name & Middle Initial & Last Name & Degree
Hui Xiong
Facility Name
Bayi Children's Hospital, Seventh Medical Center, PLA general hospital
City
Beijing
ZIP/Postal Code
100700
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Xiuwei Ma
Phone
86-1361111080
Email
pony007@vip.sina.com
First Name & Middle Initial & Last Name & Degree
Zhicun Feng
Facility Name
West China Second University Hospital, Sichuan University
City
Chengdu
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Zhuo Chen
Phone
028-85503776
Email
hxeygcp@163.com
First Name & Middle Initial & Last Name & Degree
Rong Luo
Facility Name
Children's Hospital of Chongqing Medical University
City
Chongqing
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bennian Huo
Phone
023-63619303
Email
gcpchcmu@126.com
First Name & Middle Initial & Last Name & Degree
Li Jiang
Facility Name
Tongji Medical college of Huazhong University of Science&Technology, Affiliated Children's Hospital
City
Wuhan
Country
China
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jing Wang
Phone
13296528475
Email
270519624@qq.com
First Name & Middle Initial & Last Name & Degree
Dan Sun

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

We'll reach out to this number within 24 hrs