Back to resultsFirst-in-Human Study of TSHA-101 Gene Therapy for Treatment of Infantile Onset GM2 Gangliosidosis
Primary Purpose
Infantile GM2 Gangliosidosis (Disorder)
Status
Active
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
TSHA-101
Sponsored by
About this trial
This is an interventional treatment trial for Infantile GM2 Gangliosidosis (Disorder) focused on measuring Tay-Sachs disease, Sandhoff disease, GM2 gangliosidosis
Eligibility Criteria
Key Inclusion Criteria:
- male or female with age less than or equal to 15 months
- diagnosis of GM2 gangliosidosis with genetic and enzymatic documentation of infantile disease
Key Exclusion Criteria:
- a second neurodevelopmental disorder independent of the HEXA or HEXB
- inability to tolerate sedation or intrathecal administration
- invasive ventilatory support
- concomitant illness, allergies or known hypersensitivity to the required immunosuppression regimen
Sites / Locations
- Queen's University/Kingston Health Sciences Centre
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
TSHA-101
Arm Description
Subjects who will receive one-time intrathecal TSHA-101, brain volume based sliding scale for dosage
Outcomes
Primary Outcome Measures
Safety and tolerability: Treatment-emergent Adverse Events (TEAEs)
Incidence, severity, and relatedness of TEAEs
Safety and Tolerability: Number of participants with abnormal Laboratory assessments
Number of participants with Changes from Baseline in laboratory assessments
Safety and Tolerability: Electrocardiogram (ECG)
Changes from Baseline in 12-lead ECG findings in QT interval
Secondary Outcome Measures
Safety and tolerability: Viral shedding analysis
Positive presence of viral DNA from biological fluids (whole blood, urine, saliva, and stool)
Assessment of Immunogenicity: Biomarkers in serum
Summary of neutralizing antibodies (NAbs) titers for adeno-associated virus, serotype 9 (AAV9) and Hex A
Assessment of Immunogenicity: Biomarkers in serum
Summary of total antibodies (TAbs) titers for AAV9 and Hex A
Assessment of Immunogenicity: Biomarkers in peripheral blood mononuclear cells (PBMCs
Summary of PBMCs for enzyme-linked immune absorbent spot (ELISpot) assays for cytokine secretion against AAV9 and Hex A
Overall Survival
Estimated using the Kaplan-Meier method
Hex A Enzyme Activity: Cerebrospinal fluid (CSF) and serum
Change from baseline
Head Control: Number of events for abnormal head control
change from Baseline
Change from Baseline in motor function: Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND)
The test consists of 16 items (body parts), where each item is tested for both sides of the body, left and right. The best score is taken for each item (with a maximum score of 4), and the scores are summed over all 16 items with a possible total CHOP-INTEND score of 64.
Change from Baseline in Motor Function: Modified Ashworth Scale
change from Baseline. Increase or decrease of muscle tone will be measured by the Modified Ashworth Scale. Frequency counts and percentages will be presented by score (0, 1, 1+, 2, 3, and 4), muscle, side, and visit for the safety population. Flexion and extension of the knee and elbow will be measured on both sides, along with hip adduction and abduction on both sides of the body.
Clinical Efficacy Assessment: Progression of Hypotonia
Assessed through neurological examinations as present or absent. Baseline to each post-Baseline visit
Clinical Efficacy Assessment: Dysphagia
Assessment of the dysphagia events- assessed as present or absent.
Full Information
NCT ID
NCT04798235
First Posted
February 22, 2021
Last Updated
May 8, 2023
Sponsor
Dr. Anupam Sehgal
Collaborators
Taysha Gene Therapies, Inc., GlycoNet
1. Study Identification
Unique Protocol Identification Number
NCT04798235
Brief Title
First-in-Human Study of TSHA-101 Gene Therapy for Treatment of Infantile Onset GM2 Gangliosidosis
Official Title
Phase 1/2, Open-Label Clinical Study to Evaluate the Safety and Efficacy of Intrathecal TSHA-101 Gene Therapy for Treatment of Infantile Onset GM2 Gangliosidosis
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 12, 2021 (Actual)
Primary Completion Date
March 12, 2027 (Anticipated)
Study Completion Date
March 12, 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Dr. Anupam Sehgal
Collaborators
Taysha Gene Therapies, Inc., GlycoNet
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
GM2 gangliosidoses are a group of autosomal recessive neurodegenerative diseases characterized by a deficiency of the Hex A enzyme to catabolize GM2, thereby causing GM2 accumulation within cellular lysosomes.Hex A is composed of 2 subunits, α- and β-, coded by the HEXA and HEXB genes, respectively. The primary purpose of the current study is to assess the safety and tolerability of TSHA101 administered via IT injection.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infantile GM2 Gangliosidosis (Disorder)
Keywords
Tay-Sachs disease, Sandhoff disease, GM2 gangliosidosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Actual)
8. Arms, Groups, and Interventions
Arm Title
TSHA-101
Arm Type
Experimental
Arm Description
Subjects who will receive one-time intrathecal TSHA-101, brain volume based sliding scale for dosage
Intervention Type
Biological
Intervention Name(s)
TSHA-101
Intervention Description
AAV9 viral vector containing HEXA and HEXB genes to be administered via Intrathecal injection
Primary Outcome Measure Information:
Title
Safety and tolerability: Treatment-emergent Adverse Events (TEAEs)
Description
Incidence, severity, and relatedness of TEAEs
Time Frame
1 year
Title
Safety and Tolerability: Number of participants with abnormal Laboratory assessments
Description
Number of participants with Changes from Baseline in laboratory assessments
Time Frame
1 year
Title
Safety and Tolerability: Electrocardiogram (ECG)
Description
Changes from Baseline in 12-lead ECG findings in QT interval
Time Frame
1 year
Secondary Outcome Measure Information:
Title
Safety and tolerability: Viral shedding analysis
Description
Positive presence of viral DNA from biological fluids (whole blood, urine, saliva, and stool)
Time Frame
1 year
Title
Assessment of Immunogenicity: Biomarkers in serum
Description
Summary of neutralizing antibodies (NAbs) titers for adeno-associated virus, serotype 9 (AAV9) and Hex A
Time Frame
1 year
Title
Assessment of Immunogenicity: Biomarkers in serum
Description
Summary of total antibodies (TAbs) titers for AAV9 and Hex A
Time Frame
1 year
Title
Assessment of Immunogenicity: Biomarkers in peripheral blood mononuclear cells (PBMCs
Description
Summary of PBMCs for enzyme-linked immune absorbent spot (ELISpot) assays for cytokine secretion against AAV9 and Hex A
Time Frame
5 years
Title
Overall Survival
Description
Estimated using the Kaplan-Meier method
Time Frame
treatment to death from any cause, up to 5 years
Title
Hex A Enzyme Activity: Cerebrospinal fluid (CSF) and serum
Description
Change from baseline
Time Frame
1 year
Title
Head Control: Number of events for abnormal head control
Description
change from Baseline
Time Frame
1 year
Title
Change from Baseline in motor function: Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND)
Description
The test consists of 16 items (body parts), where each item is tested for both sides of the body, left and right. The best score is taken for each item (with a maximum score of 4), and the scores are summed over all 16 items with a possible total CHOP-INTEND score of 64.
Time Frame
1 year
Title
Change from Baseline in Motor Function: Modified Ashworth Scale
Description
change from Baseline. Increase or decrease of muscle tone will be measured by the Modified Ashworth Scale. Frequency counts and percentages will be presented by score (0, 1, 1+, 2, 3, and 4), muscle, side, and visit for the safety population. Flexion and extension of the knee and elbow will be measured on both sides, along with hip adduction and abduction on both sides of the body.
Time Frame
1 year
Title
Clinical Efficacy Assessment: Progression of Hypotonia
Description
Assessed through neurological examinations as present or absent. Baseline to each post-Baseline visit
Time Frame
1 year
Title
Clinical Efficacy Assessment: Dysphagia
Description
Assessment of the dysphagia events- assessed as present or absent.
Time Frame
From onset up to 3 years, if present
10. Eligibility
Sex
All
Maximum Age & Unit of Time
15 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
male or female with age less than or equal to 15 months
diagnosis of GM2 gangliosidosis with genetic and enzymatic documentation of infantile disease
Key Exclusion Criteria:
a second neurodevelopmental disorder independent of the HEXA or HEXB
inability to tolerate sedation or intrathecal administration
invasive ventilatory support
concomitant illness, allergies or known hypersensitivity to the required immunosuppression regimen
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anupam Sehgal, MBBS
Organizational Affiliation
Queen's University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Queen's University/Kingston Health Sciences Centre
City
Kingston
State/Province
Ontario
ZIP/Postal Code
K7L 2V7
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
First-in-Human Study of TSHA-101 Gene Therapy for Treatment of Infantile Onset GM2 Gangliosidosis
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