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Trial record 1 of 6 for:    gene therapy | GM2 Gangliosidosis
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First-in-Human Study of TSHA-101 Gene Therapy for Treatment of Infantile Onset GM2 Gangliosidosis

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. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT04798235
Recruitment Status : Active, not recruiting
First Posted : March 15, 2021
Last Update Posted : May 9, 2023
Taysha Gene Therapies, Inc.
Information provided by (Responsible Party):
Dr. Anupam Sehgal, Queen's University

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.

Condition or disease Intervention/treatment Phase
Infantile GM2 Gangliosidosis (Disorder) Biological: TSHA-101 Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 12, 2021
Estimated Primary Completion Date : March 12, 2027
Estimated Study Completion Date : March 12, 2027

Arm Intervention/treatment
Experimental: TSHA-101
Subjects who will receive one-time intrathecal TSHA-101, brain volume based sliding scale for dosage
Biological: TSHA-101
AAV9 viral vector containing HEXA and HEXB genes to be administered via Intrathecal injection

Primary Outcome Measures :
  1. Safety and tolerability: Treatment-emergent Adverse Events (TEAEs) [ Time Frame: 1 year ]
    Incidence, severity, and relatedness of TEAEs

  2. Safety and Tolerability: Number of participants with abnormal Laboratory assessments [ Time Frame: 1 year ]
    Number of participants with Changes from Baseline in laboratory assessments

  3. Safety and Tolerability: Electrocardiogram (ECG) [ Time Frame: 1 year ]
    Changes from Baseline in 12-lead ECG findings in QT interval

Secondary Outcome Measures :
  1. Safety and tolerability: Viral shedding analysis [ Time Frame: 1 year ]
    Positive presence of viral DNA from biological fluids (whole blood, urine, saliva, and stool)

  2. Assessment of Immunogenicity: Biomarkers in serum [ Time Frame: 1 year ]
    Summary of neutralizing antibodies (NAbs) titers for adeno-associated virus, serotype 9 (AAV9) and Hex A

  3. Assessment of Immunogenicity: Biomarkers in serum [ Time Frame: 1 year ]
    Summary of total antibodies (TAbs) titers for AAV9 and Hex A

  4. Assessment of Immunogenicity: Biomarkers in peripheral blood mononuclear cells (PBMCs [ Time Frame: 5 years ]
    Summary of PBMCs for enzyme-linked immune absorbent spot (ELISpot) assays for cytokine secretion against AAV9 and Hex A

  5. Overall Survival [ Time Frame: treatment to death from any cause, up to 5 years ]
    Estimated using the Kaplan-Meier method

  6. Hex A Enzyme Activity: Cerebrospinal fluid (CSF) and serum [ Time Frame: 1 year ]
    Change from baseline

  7. Head Control: Number of events for abnormal head control [ Time Frame: 1 year ]
    change from Baseline

  8. Change from Baseline in motor function: Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP-INTEND) [ Time Frame: 1 year ]
    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.

  9. Change from Baseline in Motor Function: Modified Ashworth Scale [ Time Frame: 1 year ]
    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.

  10. Clinical Efficacy Assessment: Progression of Hypotonia [ Time Frame: 1 year ]
    Assessed through neurological examinations as present or absent. Baseline to each post-Baseline visit

  11. Clinical Efficacy Assessment: Dysphagia [ Time Frame: From onset up to 3 years, if present ]
    Assessment of the dysphagia events- assessed as present or absent.

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 15 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

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 ClinicalTrials.gov identifier (NCT number): NCT04798235

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Canada, Ontario
Queen's University/Kingston Health Sciences Centre
Kingston, Ontario, Canada, K7L 2V7
Sponsors and Collaborators
Dr. Anupam Sehgal
Taysha Gene Therapies, Inc.
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Principal Investigator: Anupam Sehgal, MBBS Queen's University
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Responsible Party: Dr. Anupam Sehgal, Primary Investigator, Queen's University
ClinicalTrials.gov Identifier: NCT04798235    
Other Study ID Numbers: TSHA-101-IST-001
First Posted: March 15, 2021    Key Record Dates
Last Update Posted: May 9, 2023
Last Verified: May 2023
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 Dr. Anupam Sehgal, Queen's University:
Tay-Sachs disease
Sandhoff disease
GM2 gangliosidosis
Additional relevant MeSH terms:
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Gangliosidoses, GM2
Tay-Sachs Disease
Lysosomal Storage Diseases, Nervous System
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders