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Active, Not Recruiting

NCT Number: NCT04798235

First-in-Human Study of TSHA-101 Gene Therapy for Treatment of Infantile Onset GM2 Gangliosidosis

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

Key information

Conditions

Infantile GM2 Gangliosidosis (Disorder) Brain Diseases Brain Diseases, Metabolic Brain Diseases, Metabolic, Inborn Central Nervous System Diseases Congenital, Hereditary, and Neonatal Diseases and Abnormalities Gangliosidoses Gangliosidoses, GM2 Genetic Diseases, Inborn Lipid Metabolism Disorders Lipid Metabolism, Inborn Errors Lipidoses Lysosomal Storage Diseases Lysosomal Storage Diseases, Nervous System Metabolic Diseases Metabolism, Inborn Errors Nervous System Diseases Nutritional and Metabolic Diseases Sandhoff Disease Sphingolipidoses Tay-Sachs Disease

Age range

Up to 15 month

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Queen's University/Kingston Health Sciences Centre

Kingston, Ontario, K7L 2V7, Canada

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

TSHA-101

Biological

AAV9 viral vector containing HEXA and HEXB genes to be administered via Intrathecal injection

Primary outcomes

  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 outcomes

  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.

Sponsors and collaborators

Lead sponsor

Dr. Anupam Sehgal

Other

Collaborators

  • GlycoNet
  • Taysha Gene Therapies, Inc.

Registry information

Official study 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

Important dates

Study start
2021
Primary completion
2027
Study completion
2027
First posted
Mar 15, 2021
Registry last updated
May 9, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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